1
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IT IS  MY PLEASURE TO INTRODUCE
LORI 

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ISOM AND HEATHER MEF FORD.  LORI

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IS THE TREASURER OF THE 

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DEPARTMENT OF PHARMACOLOGY.  I 

5
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ALMOST SAID PHARMACY 

6
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I KNEW THAT WASN'T RIGHT AT THE 

7
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UNIVERSITY OF MICHIGAN AND AT 

8
00:00:31,240 --> 00:00:33,042
HEATHER IS AT ST. JUDE'S 

9
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HOSPITAL AND SO I WILL TURN IT 

10
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OVER TO YOU TWO TO MODERATE.

11
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>> GREAT, VICKY AND I WILL
ECHO 

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THAT SENT SENTIMENT.  YESTERDAY 

13
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WE RERPED A LOT FROM PEOPLE IN 

14
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ADJACENT TO EPILEPSY FIELDS. 

15
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AND I THINK WE WILL HAVE A 

16
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LITTLE MORE EPILEPSY FOCUS TODAY

17
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TO ROUND OUT THE ENTIRE MEETING 

18
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AND REALLY LEARN ABOUT 

19
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STRATEGIES FOR TREATING THESE 

20
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DIFFICULT TO TREAT DISEASES.  SO

21
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LORI AND I PUT THIS SESSION 

22
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TOGETHER THINKING ABOUT WHAT IS 

23
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IT THAT WE NEED TO THINK ABOUT 

24
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AS WE DESIGN THESE THERAPIES 

25
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SPECIFICALLY FOR EPILEPSIES AND 

26
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AS WE THINK ABOUT HOW DO WE 

27
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DESIGN TARGETED THERAPIES FOR 

28
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THESE GENETIC CONDITIONS THERE 

29
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ARE MANY, MANY CONSIDERATIONS 

30
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AND MOST OF THESE WERE TOUCHED 

31
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ON YESTERDAY IF NOT IN DETAIL AT

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LEAST AT A HIGH LEVEL.  AS THING

33
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TO THINK ABOUT AS WE DEVELOP 

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THERAPIES AND I THINK THE WAY I 

35
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THINK ABOUT IT WE NEED TO THINK 

36
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ABOUT WHAT IS THE INHERENT 

37
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PATTERN FOR THE DISEASE IS IT DE

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NOVO DOMINANT.  THAT'S WHEN WE 

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DIAGNOSE PATIENTS BECAUSE WE 

40
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HAVE NO IDEA UNTIL THEY 

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REPRESENT WITH

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INSUFFICIENCY WE HAD HEARD.  WE 

43
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HEARD YESTERDAY FOR SOME OF 

44
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THESE FUNCTION YOU NEED TO GET 

45
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RID OF THAT RATHER THAN REPLACE 

46
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FOR HAPPEN LOIN SUFFICIENCY AND 

47
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THE DISORDERS WE HEARD ABOUT 

48
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THAT YESTERDAY.  THE GENE 

49
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REPLACEMENT STRATEGY BUT IF YOU 

50
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HAVE THE PARTIALLY FUNCTIONAL 

51
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ALLELE THAT'S STILL THERE YOU 

52
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CAN THINK ABOUT STRATEGY.  IT'S 

53
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JUST TO UPREGULATE THAT FOR 

54
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PARTIALLY FUNCTIONAL ALLELE.  

55
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AND SO THESE ARE SOME OF THE 

56
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APPROACHES, RIGHT, UPREGULATION,

57
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GENE REPLACEMENT, IF YOU GAIN A 

58
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FUNCTION OR KNOCK IT DOWN.  IF 

59
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WE'RE UPREGULATING OR WANT MORE 

60
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GENE PRODUCT WE CAN TARGET AT 

61
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THE DNA LEVEL.  TARGET AN AT RNA

62
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LEVEL OR USE ENZYME REPLACEMENT 

63
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WHICH IS SOMETHING WITH PROTEIN.

64
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BUT WE HAVE TO TAKE ALL OF THESE

65
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INTO ACCOUNT AND THIS IS 

66
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THINKING ABOUT HOW DO WE TARGET 

67
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THE -- THERE'S AN ECHO, YEAH?  

68
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HOW DO WE TARGET THE MUTATION OR

69
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THE GENE BUT THERE ARE OTHER 

70
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MORE COMPLICATED THINGS WE HAVE 

71
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TO THINK ABOUT AS WELL.  SO WHEN

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CAN WE TREAT AND THEN HOW DO WE 

73
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TREAT?  WE HEARD ABOUT SOME 

74
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GREAT STRATEGIES YESTERDAY EVEN 

75
00:03:28,918 --> 00:03:30,353
TREATING, YOU KNOW, PRENATALLY 

76
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WHICH I THINK IS AMAZING.  BUT 

77
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CAN WE TREAT -- HOW EARLY CAN WE

78
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TREAT AND HOW EARLY DO WE NEED 

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TO TREAT?  HOW FREQUENTLY DO WE 

80
00:03:39,061 --> 00:03:40,463
NEED TO TREAT IF IT'S NOT A 

81
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PERMANENT TREATMENT LIKE A GENE 

82
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REPLACEMENT?  HOW DO WE REACH 

83
00:03:46,235 --> 00:03:47,103
THOSE IMPORTANT LEVELS IN THE 

84
00:03:47,103 --> 00:03:49,839
BRAIN THAT WE NEED TO GET TO TO 

85
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REALLY HAVE AN EFFECTIVE THERAPY

86
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FOR EPILEPSY?  AND SO HOW DO YOU

87
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DELIVER IT.  CAN WE DO THIS 

88
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SYSTEMICALLY AND I THINK 

89
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YESTERDAY WAS REALLY INFORMATIVE

90
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FOR ME IN THINKING ABOUT SOME OF

91
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THESE THINGS AND THEN THE 

92
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SESSION THIS MORNING WE'RE GOING

93
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TO TRY TO I THINK TOUCH ON ALL 

94
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OF THESE IN DIFFERENT WAYS.  SO 

95
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WE HAVE THREE GREAT SPEAKERS 

96
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THIS MORNING.  OUR FIRST SPEAKER

97
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WILL BE GEMMA CARVILL WHO IS AN 

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ASSISTANT PROFESSOR AT 

99
00:04:16,632 --> 00:04:18,067
NORTHWESTERN UNIVERSITY WHO IS 

100
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GOING TO TOUCH ON HOW DO WE 

101
00:04:21,303 --> 00:04:23,272
THINK ABOUT THOSE MUTATIONAL 

102
00:04:23,272 --> 00:04:25,274
MECHANISMS?  HOW DO WE IDENTIFY 

103
00:04:25,274 --> 00:04:27,042
WHAT MUTATIONS ARE ACTUALLY 

104
00:04:27,042 --> 00:04:28,978
PATHOGENIC VERSUS BENIGN.  THIS 

105
00:04:28,978 --> 00:04:32,014
IS OFTEN A FRUSTRATION FOR US IN

106
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GENETICS ESPECIALLY AS WE GET TO

107
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THIS.  CAN WE GET PAST THAT AND 

108
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TEST ALL THE MUTATIONS AND 

109
00:04:40,222 --> 00:04:42,057
PREDICT WHEN THE PATIENT HAS A 

110
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TEST WHETHER IT'S BENIGN OR 

111
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PATHOGENIC AND THINKING ABOUT 

112
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THOSE BEING A FUNCTION OR NOT 

113
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AND THEN WE'RE GOING TO HEAR 

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FROM ISABEL AZNAREZ WHO LORI 

115
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WILL INTRODUCE LATER ABOUT 

116
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SPECIFIC STRATEGY FOR TREATING 

117
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EPILEPSIES AND WILL TALK ABOUT 

118
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THE STORY.  AND THEN GAIA COLA 

119
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SAN TODAY WHO WILL DIVE INTO 

120
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TIMING OF TREATMENT AND 

121
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DELIVERY.  OF GENETIC THERAPIES 

122
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FOR EPILEPSY SO I AM GOING TO 

123
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START BY BRINGING GEMMA CARVILL 

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WHO IS NOT HERE IN PERSON BUT 

125
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WHO IS HERE ONLINE AND GIVE US 

126
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OUR FIRST TALK THIS MORNING.  SO

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GEMMA, I THINK I WILL GET YOU 

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TAKE IT AWAY.  THERE SHE IS, 

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GREAT.  

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>> GEMMA: GOOD MORNING, 

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EVERYBODY, I CAN SEE YOU ALL.  

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CAN YOU GIVE ME A WAVE IF YOU 

133
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HEAR ME?  HOPEFULLY SEE YOU ALL 

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IN-PERSON SOON BUT IT'S GREAT TO

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SEE YOU YOU FROM FAR IN THE 

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LITTLE CORNER HERE I'M HERE TO 

137
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SET THE STAGE OF WHERE WE'RE AT 

138
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IN TERMS OF THE GENETIC 

139
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LANDSCAPE OF THE EPILEPSIES.  

140
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AND SO TO KICK OFF.  I SKIPPED 

141
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THE SLIDE THAT I LOVE THAT SHOWS

142
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THE PROGRESS THAT WE'VE MADE IN 

143
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TERMS OF THE GENE DISCOVERY AND 

144
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THE GENES IDENTIFIED FOR 

145
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EPILEPSY BUT IN THE INTEREST OF 

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TIME WHAT I AM REALLY GOING TO 

147
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JUMP INTO TODAY IS THINKING 

148
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ABOUT THE DIFFERENT PATHOGENIC 

149
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MECHANISMS THAT ALL OF THE 

150
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EPILEPSY RELATED GENES CONFER.  

151
00:06:30,232 --> 00:06:32,301
I LIKE TO GET EVERYBODY ON THE 

152
00:06:32,301 --> 00:06:33,335
SAME PAGE BY INTRUSION THE TYPES

153
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OF MECHANISMS AND I AM FOCUSING 

154
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ON THE ATE SOEMS BUT THIS APPLY 

155
00:06:37,973 --> 00:06:39,942
TO THE X CHROMOSOME AS WELL AND 

156
00:06:39,942 --> 00:06:43,045
THERE ARE MANY X LINKED EPILEPSY

157
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GENES AND THERE CAN BE LOSS OF 

158
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FUNCTION SO RECESSIVE IN WHICH 

159
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CASE THERE'S NO FUNCTIONAL 

160
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PROTEIN MARRIED FROM EARLY 

161
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ALLELE AND THERE ARE A NUMBER OF

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RECESSIVE EPILEPSY RELATED 

163
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GENES.  I WILL NAME JUST TWO 

164
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HERE AND THERE ARE MANY HAPPEN 

165
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LOW INSUFFICIENT GENE Z ALE W. 

166
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THESE ARE DE NOVO AND RESULT IN 

167
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ABOUT 50% OF PROTEIN LEVELS AS 

168
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COMPARED TO THE WILD TYPE.  ALSO

169
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PRETTY COMMON PARTICULARLY IN 

170
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CHANNELS OF THE EPILEPSIES ARE 

171
00:07:20,215 --> 00:07:23,552
GAIN OF FUNCTION.  THE LEVEL OF 

172
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PROTEIN IS THE SAME AS WE 

173
00:07:27,089 --> 00:07:28,757
CALL "WILD TYPE" BUT THERE ARE 

174
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THOSE MISSING VARIANTS ALTER 

175
00:07:32,194 --> 00:07:34,797
PROTEINS.  SO THEY ACT IN A GAIN

176
00:07:34,797 --> 00:07:36,599
OF FUNCTION MANNER.  AND LASTLY 

177
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THE PROBABLY THE MOST DIFFICULT 

178
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TO THINK ABOUT FROM A 

179
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THERAPEUTIC STANDPOINT ARE THE 

180
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DOMINANT NEGATIVE AND SO AGAIN 

181
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THESE TEND TO BE DE NOVO 

182
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VARIANTS THAT OCCUR IN THE TWO 

183
00:07:47,710 --> 00:07:49,278
ALLELES AND THE INHERENT 

184
00:07:49,278 --> 00:07:53,482
PROPERTY OF DOMINANT NEGATIVE 

185
00:07:53,482 --> 00:07:55,351
MECHANISMS IS THAT VARIANT TENDS

186
00:07:55,351 --> 00:07:57,286
TO INTERFERE WITH THE FUNCTION 

187
00:07:57,286 --> 00:08:01,357
OF THE WILD TYPE SUCH THAT THE 

188
00:08:01,357 --> 00:08:04,226
AMOUNT OF PROTEIN IS 30% AS COME

189
00:08:04,226 --> 00:08:09,765
FIRE DEPARTMENT -- COMPARED TO 

190
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THE WILD TYPE. 

191
00:08:10,699 --> 00:08:12,167
THINKING ABOUT THE MECHANISM IS 

192
00:08:12,167 --> 00:08:15,137
REALLY, REALLY KEY WHEN WE'RE 

193
00:08:15,137 --> 00:08:16,572
SELECTING THE TYPE OF 

194
00:08:16,572 --> 00:08:17,172
THERAPEUTIC APPROACH AND WE 

195
00:08:17,172 --> 00:08:18,941
HEARD NICE STORIES ABOUT THIS 

196
00:08:18,941 --> 00:08:20,976
YESTERDAY AND OTHER NEUROLOGICAL

197
00:08:20,976 --> 00:08:21,910
DISORDERS AND OF COURSE IT'S 

198
00:08:21,910 --> 00:08:24,780
TRUE IN EPILEPSY AS WELL AND SO 

199
00:08:24,780 --> 00:08:26,949
FOR THE LOSS OF FUNCTION 

200
00:08:26,949 --> 00:08:28,250
ESSENTIALLY ALL WE HAVE TO DO IS

201
00:08:28,250 --> 00:08:29,018
INCREASE THE AMOUNT OF PROTEIN 

202
00:08:29,018 --> 00:08:31,053
LEVELS AND RECESSIVE.  WE NEED 

203
00:08:31,053 --> 00:08:33,989
TO GET TO ABOUT 50% BECAUSE WE 

204
00:08:33,989 --> 00:08:37,326
KNOW THAT CARE OWE ROTES IN 

205
00:08:37,326 --> 00:08:43,132
GENERAL ARE NOT AFFECTED.  AND 

206
00:08:43,132 --> 00:08:44,933
IN THE DOMINANT NEGATIVE IDEALLY

207
00:08:44,933 --> 00:08:47,002
WHAT WE WANT TO DO IS HAVE A 

208
00:08:47,002 --> 00:08:48,537
DISEASE ALLELE SPECIFIC 

209
00:08:48,537 --> 00:08:51,373
KNOCKDOWN AND/OR IDEALLY A 

210
00:08:51,373 --> 00:08:52,775
CORRECTION.  AND SO I LIKE TO 

211
00:08:52,775 --> 00:08:55,210
USE THE SODIUM CHANNELS AS A 

212
00:08:55,210 --> 00:08:56,779
REALLY NICE EXAMPLE OF HOW 

213
00:08:56,779 --> 00:08:58,380
INCREASING AND DECREASING THE 

214
00:08:58,380 --> 00:09:01,750
AMOUNT OF PROTEIN IS REALLY 

215
00:09:01,750 --> 00:09:03,485
IMPORTANT DEPENDENT ON THE 

216
00:09:03,485 --> 00:09:06,355
PATHOGENIC MECHANISM.  AND SO I 

217
00:09:06,355 --> 00:09:08,223
AM SHOWING YOU TWO EPILEPSY 

218
00:09:08,223 --> 00:09:16,565
RELATED GENES HERE.  SCN 21A AND

219
00:09:16,565 --> 00:09:18,867
2A.  BUT THESE DO SO IN A LOSS 

220
00:09:18,867 --> 00:09:20,135
OF FUNCTION MANNER.  SO WITH 

221
00:09:20,135 --> 00:09:21,470
THIS LOSS OF FUNCTION, THIS 

222
00:09:21,470 --> 00:09:22,571
MEANS THAT ESSENTIALLY THERE IS 

223
00:09:22,571 --> 00:09:24,907
A DECREASE IN THE AMOUNT OF 

224
00:09:24,907 --> 00:09:27,676
SODIUM THAT IS ENTERING THE 

225
00:09:27,676 --> 00:09:29,244
INTRACELLULAR SPACE AND SO THIS 

226
00:09:29,244 --> 00:09:31,413
IS PROBABLY WHY WHEN WE USE 

227
00:09:31,413 --> 00:09:33,015
SODIUM CHANNEL BLOCKERS THIS CAN

228
00:09:33,015 --> 00:09:34,850
ACTUALLY EXACERBATE THE 

229
00:09:34,850 --> 00:09:37,786
SEIZURES, CONVERSELY WE THINK 

230
00:09:37,786 --> 00:09:39,722
ABOUT GAIN OF FUNCTION VARIANTS 

231
00:09:39,722 --> 00:09:42,024
IN SCN 2A.  IN THIS INSTANCE 

232
00:09:42,024 --> 00:09:43,959
THERE'S ACTUALLY AN INCREASE 

233
00:09:43,959 --> 00:09:46,328
INFLUX OF THE SODIUM.  SO THIS 

234
00:09:46,328 --> 00:09:49,498
IS PROBABLY WHY WE USE SODIUM 

235
00:09:49,498 --> 00:09:50,799
CHANNEL BLOCKERS.  THERE'S AT 

236
00:09:50,799 --> 00:09:53,769
LEAST SOME EFFICACY IN TERMS OF 

237
00:09:53,769 --> 00:09:55,871
TREATING THE SEIZURES FOR 

238
00:09:55,871 --> 00:09:57,806
INDIVIDUALS WITH GAIN OF 

239
00:09:57,806 --> 00:10:01,243
FUNCTION VARIANTS AND SO THIS IS

240
00:10:01,243 --> 00:10:03,746
IN IMPLICATIONS WHEN THINKING 

241
00:10:03,746 --> 00:10:05,347
ABOUT WHAT TO USE AND IN GENE 

242
00:10:05,347 --> 00:10:06,648
TARGETING THERAPIES THIS MEANS 

243
00:10:06,648 --> 00:10:09,318
THE INSTANCE OF SCN 1A WHAT WE 

244
00:10:09,318 --> 00:10:12,621
WANT TO DO IS INCREASE THE 

245
00:10:12,621 --> 00:10:15,457
AMOUNT OF NAV 1.1 WHEREAS 

246
00:10:15,457 --> 00:10:17,126
IDEALLY WE WANT TO DECREASE THE 

247
00:10:17,126 --> 00:10:21,930
AMOUNT OF NAV 1.2 IN THE SECOND 

248
00:10:21,930 --> 00:10:24,700
ONE.  ONE OF THE MAJOR 

249
00:10:24,700 --> 00:10:26,935
CHALLENGES THAT WE HAVE IN THE 

250
00:10:26,935 --> 00:10:29,471
EPILEPSIES IS THAT MANY GENES 

251
00:10:29,471 --> 00:10:32,207
CAN CONFER MORE THAN ONE 

252
00:10:32,207 --> 00:10:34,343
PATHOGENIC MECHANISM AND THAT 

253
00:10:34,343 --> 00:10:35,878
THEY REALLY ARE VARIANT SPECIFIC

254
00:10:35,878 --> 00:10:38,046
EFFECTS.  I THINK 2A WHICH I 

255
00:10:38,046 --> 00:10:39,715
HIGHLIGHTED IS A REALLY NICE 

256
00:10:39,715 --> 00:10:44,219
EXAMPLE OF THIS.  WHERE GAIN OF 

257
00:10:44,219 --> 00:10:47,756
FUNCTION THROUGHOUT THE GENE 

258
00:10:47,756 --> 00:10:50,759
CONFER A DEE TYPE OF PHENOTYPE. 

259
00:10:50,759 --> 00:10:52,528
WHEREAS LOSS OF FUNCTION 

260
00:10:52,528 --> 00:10:55,664
VARIANCE ALSO DE NOVO TEND TO 

261
00:10:55,664 --> 00:10:57,332
CAUSE AUTISM SPECTRUM DISORDERS 

262
00:10:57,332 --> 00:10:58,967
AND INTELLECTUAL DISABILITY AND 

263
00:10:58,967 --> 00:11:02,137
SO THIS IS AN EXAMPLE OF 2A 

264
00:11:02,137 --> 00:11:03,939
ANOTHER GOOD EXAMPLE IS Q2 WHERE

265
00:11:03,939 --> 00:11:06,041
LOSS OF FUNCTION VARIANTS ARE 

266
00:11:06,041 --> 00:11:07,943
ASSOCIATED WITH THE SELF 

267
00:11:07,943 --> 00:11:08,977
LIMITING EPILEPSIES AND DOMINANT

268
00:11:08,977 --> 00:11:10,546
NEGATIVE VARIANTS ARE ASSOCIATED

269
00:11:10,546 --> 00:11:16,618
WITH THE DEES.  AND SO THIS IS 

270
00:11:16,618 --> 00:11:18,954
TRUE FOR MANY OTHER CHANNELS AND

271
00:11:18,954 --> 00:11:20,155
OTHERS TOO WE'RE STARTING TO 

272
00:11:20,155 --> 00:11:22,791
FIND MORE AND MORE THAT THERE 

273
00:11:22,791 --> 00:11:25,794
ARE DIFFERENT PATHOGENIC 

274
00:11:25,794 --> 00:11:27,196
MECHANISMS THAT ARE BASED ON THE

275
00:11:27,196 --> 00:11:28,463
SPECIFIC VARIANT.  AND SO ONE OF

276
00:11:28,463 --> 00:11:30,999
THE CHALLENGES THAT WE HAVE IN 

277
00:11:30,999 --> 00:11:33,068
THE FIELD IS HOW DO WE DETERMINE

278
00:11:33,068 --> 00:11:35,337
THE PATHOGENIC EFFECT OF A 

279
00:11:35,337 --> 00:11:36,638
SPECIFIC VARIANT.  SO GAIN 

280
00:11:36,638 --> 00:11:39,341
VERSUS LOSS OR DOMINANT 

281
00:11:39,341 --> 00:11:40,442
NEGATIVE.  AND REALLY 

282
00:11:40,442 --> 00:11:42,411
IMPORTANTLY A HUGE CHALLENGE FOR

283
00:11:42,411 --> 00:11:44,646
OUR FIELD IS AND GENETICS IN 

284
00:11:44,646 --> 00:11:49,585
GENERAL I'D SAY IS HOW DO WE 

285
00:11:49,585 --> 00:11:50,752
RESOLVE THOSE VARIANTS OF 

286
00:11:50,752 --> 00:11:51,620
UNCERTAIN SIGNIFICANCE.  THOSE 

287
00:11:51,620 --> 00:11:53,188
WHERE WE DON'T HAVE ENOUGH 

288
00:11:53,188 --> 00:11:55,090
INFORMATION TO CALL IT AS 

289
00:11:55,090 --> 00:11:56,792
PATHOGENIC OR BENIGN ONE WAY OR 

290
00:11:56,792 --> 00:11:59,795
THE OTHER AND THESE VARIANTS 

291
00:11:59,795 --> 00:12:01,930
OVERWHELMINGLY ARE MISSING 

292
00:12:01,930 --> 00:12:04,166
VARIANTS IN THESE GENES AND THE 

293
00:12:04,166 --> 00:12:06,368
FOCUS OF MY GROUP AND MANY 

294
00:12:06,368 --> 00:12:08,070
GROUPS ARE TO RESOLVE THOSE AND 

295
00:12:08,070 --> 00:12:09,972
DETERMINE THE PATHOGENIC 

296
00:12:09,972 --> 00:12:12,808
EFFECTS.  BUT BEFORE I JUMP INTO

297
00:12:12,808 --> 00:12:14,009
THE WORK THAT WE'VE BEEN DOING I

298
00:12:14,009 --> 00:12:15,811
WANT TO THINK CONCEPTUALLY ABOUT

299
00:12:15,811 --> 00:12:17,012
WHAT ARE THE DIFFERENT TOOLS 

300
00:12:17,012 --> 00:12:19,081
THAT WE HAVE TO BE ABLE TO DO 

301
00:12:19,081 --> 00:12:20,649
THIS?  AND THE FIRST IS GENOTYPE

302
00:12:20,649 --> 00:12:22,985
PHENOTYPE CORRELATIONS.  I 

303
00:12:22,985 --> 00:12:27,256
SHOWED YOU ON THE PRECEDING 

304
00:12:27,256 --> 00:12:28,857
SLIDE HOW THERE ARE LOSS OF 

305
00:12:28,857 --> 00:12:32,094
FUNCTION THAT GIVES US TWO VERY 

306
00:12:32,094 --> 00:12:32,728
DISTINCT CLINICAL FEATURES AND 

307
00:12:32,728 --> 00:12:34,296
THIS WORKS REALLY WELL WHEN WE 

308
00:12:34,296 --> 00:12:36,565
HAVE LARGE GROUPS OF PATIENTS 

309
00:12:36,565 --> 00:12:38,233
FOR A SPECIFIC GENE.  THAT, 

310
00:12:38,233 --> 00:12:40,569
HOWEVER, TAKES TIME AND OF 

311
00:12:40,569 --> 00:12:42,404
COURSE IS NOT ALWAYS CLEARCUT 

312
00:12:42,404 --> 00:12:44,573
FROM THE OUTSET.  WE'VE KNOWN 

313
00:12:44,573 --> 00:12:50,612
ABOUT SEN 2A FOR A LONG TIME AND

314
00:12:50,612 --> 00:12:52,915
NOW ARE WE ONLY STARTING TO 

315
00:12:52,915 --> 00:12:54,349
TEASE APART THOSE EFFECTS.  ONE 

316
00:12:54,349 --> 00:12:57,686
OF THE WAYS IN WHICH WE THINK 

317
00:12:57,686 --> 00:12:59,087
ABOUT DETERMINING VARIANT EFFECT

318
00:12:59,087 --> 00:13:00,122
IS THROUGH FUNCTIONAL 

319
00:13:00,122 --> 00:13:01,189
CHARACTERIZATION AND I WOULD SAY

320
00:13:01,189 --> 00:13:02,424
TRADITIONALLY IN THE FIELD KIND 

321
00:13:02,424 --> 00:13:05,928
OF HOW WE THOUGHT ABOUT 

322
00:13:05,928 --> 00:13:07,629
MODELLING IS REALLY LOW 

323
00:13:07,629 --> 00:13:09,698
THROUGHPUT MODELING.  MODELING 

324
00:13:09,698 --> 00:13:10,666
OF SPECIFIC VARIETIES IN PRIMARY

325
00:13:10,666 --> 00:13:15,637
CELL LINES OR IPSCS, SO INHERENT

326
00:13:15,637 --> 00:13:17,339
PROTEIN STEM CELLS AS WELL AS 

327
00:13:17,339 --> 00:13:18,840
ANIMAL MODELS AND THESE MODELS 

328
00:13:18,840 --> 00:13:20,842
ARE GREAT FOR MODELING LARGE 

329
00:13:20,842 --> 00:13:22,577
NUMBER OF VARIANTS, OFTEN 

330
00:13:22,577 --> 00:13:26,315
BECAUSE WE CAN MODEL THESE 

331
00:13:26,315 --> 00:13:29,351
VARIANTS IN A NEURONAL BRAIN 

332
00:13:29,351 --> 00:13:31,019
TYPE CELL SO IT'S A LITTLE BIT 

333
00:13:31,019 --> 00:13:32,287
CLOSER TO THE PATHOLOGY IN TERMS

334
00:13:32,287 --> 00:13:34,890
OF WHAT MAY BE CAUSING EPILEPSY 

335
00:13:34,890 --> 00:13:37,092
BUT I THINK INCREASINGLY WE NEED

336
00:13:37,092 --> 00:13:38,860
TO START LEVERAGING HIGH 

337
00:13:38,860 --> 00:13:41,330
THROUGHPUT MODELING IN ORDER TO 

338
00:13:41,330 --> 00:13:43,432
STUDY THE EFFECT OF THE VARIANTS

339
00:13:43,432 --> 00:13:47,069
ON PROTEIN FUNCTION THAT IS 

340
00:13:47,069 --> 00:13:48,737
CONSERVED IN A VARIETY OF 

341
00:13:48,737 --> 00:13:50,205
DIFFERENT CELL TYPES.  IN 

342
00:13:50,205 --> 00:13:52,274
ADDITION, I THINK THAT WE NEED 

343
00:13:52,274 --> 00:13:54,376
TO START LEVERAGING MACHINE 

344
00:13:54,376 --> 00:13:55,477
LEARNING PREDICTORS, WE'RE KIND 

345
00:13:55,477 --> 00:13:57,045
OF GETTING TO A STAGE WHERE 

346
00:13:57,045 --> 00:13:59,247
THERE'S SO MUCH GENOMIC DATA OUT

347
00:13:59,247 --> 00:14:00,782
THERE AND THAT WE CAN START 

348
00:14:00,782 --> 00:14:02,851
HARNESSING IT TO BE ABLE TO USE 

349
00:14:02,851 --> 00:14:05,520
MACHINE LEARNING PREDICTORS TO 

350
00:14:05,520 --> 00:14:07,389
DETERMINE WHICH VARIETIES ARE 

351
00:14:07,389 --> 00:14:08,890
PATHOGENIC OR BENIGN AND WHICH 

352
00:14:08,890 --> 00:14:10,058
HAVE DIFFERENT PROPERTIES OR 

353
00:14:10,058 --> 00:14:11,827
UNIQUE PROPERTY ON THE EFFECT OF

354
00:14:11,827 --> 00:14:13,996
SPECIFIC PROTEINS.  AND SO OF 

355
00:14:13,996 --> 00:14:17,099
COURSE THERE ARE GLOBAL 

356
00:14:17,099 --> 00:14:24,106
PREDICTORS, LIKE CLINIC PRED, 

357
00:14:24,106 --> 00:14:26,241
THESE ARE GENE AGNOSTIC AND AS 

358
00:14:26,241 --> 00:14:28,076
OTHERS ARE STARTING TO THINK 

359
00:14:28,076 --> 00:14:31,346
ABOUT USING GENE SPECIFIC 

360
00:14:31,346 --> 00:14:37,386
PREDICTORS.  THESE ARE TO WORK 

361
00:14:37,386 --> 00:14:38,787
WITH THAT JEEP AND ARE HIGHLY 

362
00:14:38,787 --> 00:14:42,491
SPECIFIC FOR THAT DISEASE GENE 

363
00:14:42,491 --> 00:14:45,327
THAT YOU'RE INTERESTED IN.  SO I

364
00:14:45,327 --> 00:14:47,496
WILL TAKE YOU THROUGH A COUPLE 

365
00:14:47,496 --> 00:14:49,031
EXAMPLES.  THE OTHER THING TO 

366
00:14:49,031 --> 00:14:50,766
THINK ABOUT IS IS THE IMPORTANCE

367
00:14:50,766 --> 00:14:51,933
OF NOT CONSIDERING THESE IN 

368
00:14:51,933 --> 00:14:54,269
SILOS AND THE POWER OF ITERATING

369
00:14:54,269 --> 00:14:56,238
THROUGH THESE DIFFERENT MODEL 

370
00:14:56,238 --> 00:14:57,239
SYSTEMS AND COMPUTATIONAL AND 

371
00:14:57,239 --> 00:15:02,044
CLINICAL APPROACHES.  TO BEST 

372
00:15:02,044 --> 00:15:06,114
RESOLVE THE VARIETY AFFECT.  AND

373
00:15:06,114 --> 00:15:08,116
SO THE FIRST KIND OF HIGH 

374
00:15:08,116 --> 00:15:09,351
THROUGHPUT APPROACH THAT I'M 

375
00:15:09,351 --> 00:15:11,887
GOING TO TALK ABOUT ON MAVES, 

376
00:15:11,887 --> 00:15:13,722
THESE ARE MULTIPLEX ASSAY OF 

377
00:15:13,722 --> 00:15:17,726
VARIANT EFFECT THIS WAS WORK LED

378
00:15:17,726 --> 00:15:19,494
BY JEFF CALHOUN AND KARINA IN MY

379
00:15:19,494 --> 00:15:21,863
LAB AND WHAT THEY DEVELOPED WAS 

380
00:15:21,863 --> 00:15:24,299
A VERY HIGH THROUGHPUT ASSAY FOR

381
00:15:24,299 --> 00:15:26,234
ASSESSING THE AFFECT OF THE 

382
00:15:26,234 --> 00:15:29,304
VARIANCE IN TSC 2 AND SO WHAT 

383
00:15:29,304 --> 00:15:31,640
JEFF AND KARINA DID WAS 

384
00:15:31,640 --> 00:15:36,378
INTRODUCED OVER 200 EDITS INTO 

385
00:15:36,378 --> 00:15:38,180
HAPLOID CELL.  SO ONLY ONE COPY 

386
00:15:38,180 --> 00:15:40,082
OF THE HUMAN GENOME WHICH IS 

387
00:15:40,082 --> 00:15:41,316
VERY HELPFUL FOR DOING THESE 

388
00:15:41,316 --> 00:15:43,785
TYPES OF HIGH THROUGHPUT ASSAYS 

389
00:15:43,785 --> 00:15:45,821
AND SO THEY INTRODUCED THESE 

390
00:15:45,821 --> 00:15:48,323
VARIANTS INTO THE ENDOGENOUS TSC

391
00:15:48,323 --> 00:15:50,592
2 LOCUS AND CREATED A POOL OF 

392
00:15:50,592 --> 00:15:54,129
CELLS THAT HAD A VARIETY OF 

393
00:15:54,129 --> 00:15:55,063
DIFFERENT EDITS. 

394
00:15:55,063 --> 00:15:57,232
THEY THEN DEVELOPED AN ASSAY 

395
00:15:57,232 --> 00:15:58,567
CALLED -- WHICH IS ESSENTIALLY 

396
00:15:58,567 --> 00:16:02,370
JUST LOOKING AT LEVELS OF 

397
00:16:02,370 --> 00:16:03,772
PHOSPHOR RESSICS WHICH IS A 

398
00:16:03,772 --> 00:16:07,375
READOUT FOR ACTIVITY AND TOOK 

399
00:16:07,375 --> 00:16:11,813
THIS POOL OF CELLS AND USE A 

400
00:16:11,813 --> 00:16:14,015
FLORA FORD TO SORT THOSE CELLS 

401
00:16:14,015 --> 00:16:19,754
THAT HAD HIGH M TORC ACTIVITY.  

402
00:16:19,754 --> 00:16:22,057
AND YOU CAN TAKE THESE POOLS OF 

403
00:16:22,057 --> 00:16:23,325
CELLS AND PERFORM NEXT 

404
00:16:23,325 --> 00:16:24,092
GENERATION SEQUENCING AND COME 

405
00:16:24,092 --> 00:16:26,261
UP WITH A VARIETY OF SCORING 

406
00:16:26,261 --> 00:16:28,897
METRICS THAT YOU CAN PUT THE 

407
00:16:28,897 --> 00:16:30,365
VARIANTS INTO BASICALLY TWO 

408
00:16:30,365 --> 00:16:32,234
BUCKETS.  WHOOPS.  THE FIRST AND

409
00:16:32,234 --> 00:16:34,369
WE CAN USE EMBEDDED IN THE 

410
00:16:34,369 --> 00:16:36,438
DESIGN, WE HAVE A NUMBER OF 

411
00:16:36,438 --> 00:16:38,073
SYNONYMOUS AND PROTEIN 

412
00:16:38,073 --> 00:16:39,975
TRUNCATING VARIANTS AND YOU CAN 

413
00:16:39,975 --> 00:16:42,611
USE THESE VARIANT TO SET YOUR 

414
00:16:42,611 --> 00:16:43,879
THRESHOLDS FOR WHAT YOU CONSIDER

415
00:16:43,879 --> 00:16:46,014
TO BE PATHOGENIC OVER HERE AND 

416
00:16:46,014 --> 00:16:46,648
WHAT YOU CONSIDER TO BE BENIGN 

417
00:16:46,648 --> 00:16:49,618
OVER HERE.  YOU CAN THEN TAKE 

418
00:16:49,618 --> 00:16:51,453
THOSE TWO HUNDRED VARIANTS AND 

419
00:16:51,453 --> 00:16:53,855
THIS IS WHAT JEFF AND KARINA 

420
00:16:53,855 --> 00:16:55,390
DID.  THEY TOOK THOSE TWO 

421
00:16:55,390 --> 00:16:56,691
HUNDRED VARIANTS, PUT THEM 

422
00:16:56,691 --> 00:16:59,494
THROUGH THE SYSTEM, DID MULTIPLE

423
00:16:59,494 --> 00:17:00,395
ITERATIONS, DID FIVE REPS OF 

424
00:17:00,395 --> 00:17:02,964
EACH OF THESE AND WITH SOME 

425
00:17:02,964 --> 00:17:04,900
CONFIDENCE YOU CAN -- YOU CAN 

426
00:17:04,900 --> 00:17:06,368
ASSIGN VARIANTS TO ONE CATEGORY 

427
00:17:06,368 --> 00:17:07,936
OR ANOTHER AND SO YOU CAN SEE 

428
00:17:07,936 --> 00:17:10,639
HERE THE PATHOGENIC AND LIKELY 

429
00:17:10,639 --> 00:17:12,807
PATHOGENIC VARIETY E VARIANTS 

430
00:17:12,807 --> 00:17:14,242
CLUSTER ON THIS SIDE AND THE 

431
00:17:14,242 --> 00:17:16,511
BENIGN OR LIKELY BENIGN VARIANTS

432
00:17:16,511 --> 00:17:19,881
CLUSTER ON THIS SIDE WITH 

433
00:17:19,881 --> 00:17:20,715
SYNONYMOUS VARIANTS YOU CAN ALSO

434
00:17:20,715 --> 00:17:22,083
SEE HERE IN GRAY THAT WE WERE 

435
00:17:22,083 --> 00:17:25,187
ABLE TO RECLASSIFY A NUMBER OF 

436
00:17:25,187 --> 00:17:26,888
THESE.  SO IN THIS PARTICULAR 

437
00:17:26,888 --> 00:17:31,159
ASSAY WE COULD RECLASSIFY THESE 

438
00:17:31,159 --> 00:17:33,061
VARIANTS AS EITHER PATHOGENIC OR

439
00:17:33,061 --> 00:17:36,198
BENIGN BASED ON THIS ONE METRIC 

440
00:17:36,198 --> 00:17:39,868
OF MTOR ACTIVITY AND THEREFORE 

441
00:17:39,868 --> 00:17:41,469
GENE FUNCTION.  AND SO I ELUDED 

442
00:17:41,469 --> 00:17:45,507
EARLIER TO THE POWER OF 

443
00:17:45,507 --> 00:17:46,541
INTEGRATING THESE DIFFERENT 

444
00:17:46,541 --> 00:17:48,910
METHODS SO I THINK THE MAVE IS A

445
00:17:48,910 --> 00:17:52,581
GREAT FIRST STEP IN TERMS OF 

446
00:17:52,581 --> 00:17:53,848
TRYING TO DETERMINE VARIANT 

447
00:17:53,848 --> 00:17:56,251
EFFECT.  BUT I THINK IT'S BEST 

448
00:17:56,251 --> 00:17:57,519
USED IN CONJUNCTION WITH 

449
00:17:57,519 --> 00:17:59,621
MULTIPLE DIFFERENT TYPES OF 

450
00:17:59,621 --> 00:18:00,956
INFORMATION.  AND SO I WANT TO 

451
00:18:00,956 --> 00:18:02,490
SHOW YOU AN EXAMPLE HERE OF 

452
00:18:02,490 --> 00:18:04,292
INTEGRATING THESE DIFFERENT 

453
00:18:04,292 --> 00:18:10,365
METHODS.  WITH THE EXAMPLE OF 

454
00:18:10,365 --> 00:18:14,069
THE EPI-MVP WHICH IS LED IN THE 

455
00:18:14,069 --> 00:18:15,036
UNIVERSITY OF MICHIGAN.  THIS 

456
00:18:15,036 --> 00:18:16,404
HAS BEEN A HUGE COLLABORATIVE 

457
00:18:16,404 --> 00:18:18,240
AND A FUN PROJECT TO WORK ON FOR

458
00:18:18,240 --> 00:18:21,009
THE LAST COUPLE OF YEARS IT 

459
00:18:21,009 --> 00:18:23,778
CONSIST OF MYSELF AT 

460
00:18:23,778 --> 00:18:25,614
NORTHWESTERN, PROJECT ONE IS 

461
00:18:25,614 --> 00:18:28,450
BETTY ROSS AT CORNELL, PROJECT 

462
00:18:28,450 --> 00:18:30,785
TWO AND PROJECT THREE, DOWN ON 

463
00:18:30,785 --> 00:18:36,424
THE BOTTOM THERE ARE LED BY JACK

464
00:18:36,424 --> 00:18:44,199
AT THE UNIVERSITY OF MI CHIGAN -

465
00:18:44,199 --> 00:18:45,400
THESE ARE USING MACHINE LEARNING

466
00:18:45,400 --> 00:18:49,204
AND THEN TEST OUR PREDICTIONS IN

467
00:18:49,204 --> 00:18:50,905
MULTIPLE DIFFERENT SYSTEMS.  SO 

468
00:18:50,905 --> 00:18:52,741
PRIMARY, IPS AND ANIMAL MODELS. 

469
00:18:52,741 --> 00:18:54,943
AND TO USE THIS ITERATIVE 

470
00:18:54,943 --> 00:18:56,645
PROCESS TO REALLY REFINE THE WAY

471
00:18:56,645 --> 00:19:00,148
IN WHICH WE CAN CLASSIFY 

472
00:19:00,148 --> 00:19:01,416
VARIANCE IN CERTAIN SIGNIFICANCE

473
00:19:01,416 --> 00:19:02,550
AND DETERMINE VARIANT EFFECT AND

474
00:19:02,550 --> 00:19:04,019
SO WE'RE WORKING WITH FOUR 

475
00:19:04,019 --> 00:19:04,886
DIFFERENT GENES I'M GOING TO 

476
00:19:04,886 --> 00:19:07,555
SHOW YOU TODAY OUR RESULTS WITH 

477
00:19:07,555 --> 00:19:11,660
THE FIRST GENE WHICH IS STXBP 1 

478
00:19:11,660 --> 00:19:14,195
AND OUR FIRST STEP WAS TO BUILD 

479
00:19:14,195 --> 00:19:16,598
A CLASSIFIER.  WE CURATED KNOWN 

480
00:19:16,598 --> 00:19:20,101
PATHOGENIC AND BENIGN VARIANTS 

481
00:19:20,101 --> 00:19:25,674
FROM THE LITERATURE.  WE 

482
00:19:25,674 --> 00:19:27,509
ANNOTATED THEM WITH PROPERTIES, 

483
00:19:27,509 --> 00:19:29,110
PROTEIN STRUCTURE AND BUILT A 

484
00:19:29,110 --> 00:19:30,312
CLASSIFIER AND THIS IS SHOUP 

485
00:19:30,312 --> 00:19:31,446
HERE AND ESSENTIALLY WHAT I'M 

486
00:19:31,446 --> 00:19:32,881
SHOWING YOU IS THE SENSITIVITY 

487
00:19:32,881 --> 00:19:36,084
AND THE SPECIFICITY OF OUR 

488
00:19:36,084 --> 00:19:37,686
CLASSIFIER TO ACCURATELY 

489
00:19:37,686 --> 00:19:40,889
CLASSIFY A VARIANT AS 

490
00:19:40,889 --> 00:19:42,090
PATHOGENIC.  SO THE DIAGONAL 

491
00:19:42,090 --> 00:19:43,625
LINE HERE WOULD BE JUST A COIN 

492
00:19:43,625 --> 00:19:45,660
TOSS OF HOW GOOD THE PREDICTOR 

493
00:19:45,660 --> 00:19:49,698
IS.  AND THE CLOSER TO ONE THE 

494
00:19:49,698 --> 00:19:52,300
CLOSER YOU ARE TO A 100% 

495
00:19:52,300 --> 00:19:53,968
ACCURACY FOR THAT PARTICULAR 

496
00:19:53,968 --> 00:19:55,070
CLASSIFIER.  WE NEVER WANT TO BE

497
00:19:55,070 --> 00:19:57,405
AT 100% BECAUSE THEN SOMETHING 

498
00:19:57,405 --> 00:19:58,973
IS BROKEN AND DOESN'T GENERALIZE

499
00:19:58,973 --> 00:20:00,875
WELL AND YOU GO BACK TO THE LAB 

500
00:20:00,875 --> 00:20:05,413
AND TRY TO FIX IT SO I BUILT IN 

501
00:20:05,413 --> 00:20:06,314
CLASSIFIER THAT WORKS PRETTY 

502
00:20:06,314 --> 00:20:10,352
WELL AND OUTPERFORMS ALL OTHER 

503
00:20:10,352 --> 00:20:11,820
PREDICTORS THAT ARE TRAINED ON 

504
00:20:11,820 --> 00:20:15,457
MUCH, MUCH LARGER GENE WIDE 

505
00:20:15,457 --> 00:20:17,292
DATASETS.  AND SO WE WERE QUITE 

506
00:20:17,292 --> 00:20:18,360
EXCITED A BY THIS BUT OF COURSE 

507
00:20:18,360 --> 00:20:20,628
THE PROOF IS IN THE PUDDING AND 

508
00:20:20,628 --> 00:20:22,931
WE NEED TO TEST THESE PREDICTION

509
00:20:22,931 --> 00:20:25,800
USING FUNCTIONAL ASSAYS AND SO 

510
00:20:25,800 --> 00:20:28,136
THIS IS A SYNAPTIC PROTEIN THAT 

511
00:20:28,136 --> 00:20:29,938
INTERACTS WITH A COMPLEX TO 

512
00:20:29,938 --> 00:20:33,341
RELEASE VESICALS AT THE SYNAPTIC

513
00:20:33,341 --> 00:20:35,577
MEMBRANE AND SO BETTY'S GROUP 

514
00:20:35,577 --> 00:20:38,546
CAME UP WITH FOUR FUNCTIONAL 

515
00:20:38,546 --> 00:20:39,314
READ OOUT TO DETERMINE THE 

516
00:20:39,314 --> 00:20:41,149
ACCURACY OF OUR PREDICTIONS AND 

517
00:20:41,149 --> 00:20:42,384
SO THESE ARE THE FOUR DIFFERENT 

518
00:20:42,384 --> 00:20:45,353
ASSAYS THAT WE USED.  MIKE AT 

519
00:20:45,353 --> 00:20:51,793
THE HETC WHICH IS THE OTHER CORE

520
00:20:51,793 --> 00:20:56,164
GENERATED ALL THE VARIANTS.  

521
00:20:56,164 --> 00:20:57,065
EVERYTHING WAS BLINDED AND 

522
00:20:57,065 --> 00:20:58,900
QUANTIFIED BY TWO DIFFERENT 

523
00:20:58,900 --> 00:21:00,068
SCIENTISTS OVERALL WHAT WE HAD 

524
00:21:00,068 --> 00:21:02,303
SHOWN WAS A GOOD AGREEMENT 

525
00:21:02,303 --> 00:21:03,972
BETWEEN THE RAW FUNCTIONAL 

526
00:21:03,972 --> 00:21:04,773
SCORES AND THE PREDICTIONS AND 

527
00:21:04,773 --> 00:21:05,974
TO WALK YOU THROUGH ONE OF THE 

528
00:21:05,974 --> 00:21:08,309
OUTCOMES OF ONE OF THE ASSAYS, 

529
00:21:08,309 --> 00:21:10,278
SO THE EXPRESSION ASSAY WHAT I'M

530
00:21:10,278 --> 00:21:12,647
SHOWING YOU HERE IS ALL THE VUSS

531
00:21:12,647 --> 00:21:14,849
ON THE SIDE.  THE WILD TYPE IS 

532
00:21:14,849 --> 00:21:17,352
OVER HERE AND IN GREEN ARE ALL 

533
00:21:17,352 --> 00:21:19,621
OF THE KNOWN BENIGN VARIANT 

534
00:21:19,621 --> 00:21:20,989
WHICH IS YOU CAN SEE CLUSTER 

535
00:21:20,989 --> 00:21:23,525
VERY NICELY WITH THE WILD TYPE 

536
00:21:23,525 --> 00:21:26,294
ALL OF THE KNOWN PATHOGENIC 

537
00:21:26,294 --> 00:21:27,862
VARIANTS HAD A DECREASE IN THE 

538
00:21:27,862 --> 00:21:28,997
AMOUNT OF EXPRESSION AND WHAT 

539
00:21:28,997 --> 00:21:31,399
YOU CAN SAY HERE IN LIGHT GREEN 

540
00:21:31,399 --> 00:21:33,802
AND LIGHT PURPLE OR PINK ARE THE

541
00:21:33,802 --> 00:21:38,072
VUSS THAT WERE PREDICTED TO BE 

542
00:21:38,072 --> 00:21:41,042
PATHOGENIC, ALL CLUSTERED WITH 

543
00:21:41,042 --> 00:21:43,011
THE KNOWN BENIGN VARIANTS AND 

544
00:21:43,011 --> 00:21:47,081
THE PATHOGENIC VARIANT, THE 

545
00:21:47,081 --> 00:21:50,051
PREDICTED PATHOGENIC VARIANT 

546
00:21:50,051 --> 00:21:51,352
HAVE THE SAME PROPERTIES AND WE 

547
00:21:51,352 --> 00:21:53,154
DID THIS ACROSS FOUR DIFFERENT 

548
00:21:53,154 --> 00:21:55,757
ASSAYS AND OVERALL THERE WAS A 

549
00:21:55,757 --> 00:21:59,060
REALLY GOOD AGREEMENT BETWEEN EP

550
00:21:59,060 --> 00:22:01,062
PE PRED AND THE FUNCTIONAL 

551
00:22:01,062 --> 00:22:05,600
READOUTS.  AND SO AGAIN, WE ARE 

552
00:22:05,600 --> 00:22:11,806
PRETTY EXCITED ABOUT THIS.  AND 

553
00:22:11,806 --> 00:22:14,442
THEN WE DID A WHOLE NEW DATA SET

554
00:22:14,442 --> 00:22:17,512
AND SUDDENLY EP PE PRED WAS NOT 

555
00:22:17,512 --> 00:22:18,413
PERFORMING AS WELL AS SOME OF 

556
00:22:18,413 --> 00:22:21,049
THE OTHER GLOBAL PREDICTORS AND 

557
00:22:21,049 --> 00:22:22,150
SO WE WERE QUITE INTRIGUED BY 

558
00:22:22,150 --> 00:22:23,718
THIS AND DUG INTO THE DATA A 

559
00:22:23,718 --> 00:22:25,553
LITTLE BIT MORE AND WHAT WE 

560
00:22:25,553 --> 00:22:27,956
ACTUALLY FOUND WAS THAT THE 

561
00:22:27,956 --> 00:22:29,891
TRAININGINGS OR THE HOLDOUT 

562
00:22:29,891 --> 00:22:32,260
DATASETS THAT WE USED WERE FROM 

563
00:22:32,260 --> 00:22:33,828
PUBLISHED DATA AND THE VARIANTS 

564
00:22:33,828 --> 00:22:35,897
WERE CALLED PATHOGENIC IN THE 

565
00:22:35,897 --> 00:22:38,299
PUBLISHED DATA BUT WERE BEING 

566
00:22:38,299 --> 00:22:40,735
CALLED BENIGN BY EPIPRED AND SO 

567
00:22:40,735 --> 00:22:42,937
WHEN WE DUG INTO THIS WE FOUND 

568
00:22:42,937 --> 00:22:44,672
THEY TEND TO LOCALIZE IN CERTAIN

569
00:22:44,672 --> 00:22:46,307
PARTS OF THE PROTEIN OR CERTAIN 

570
00:22:46,307 --> 00:22:48,076
AMINO ACID AND THAT MANY OF 

571
00:22:48,076 --> 00:22:50,311
THESE VARIANTS WERE ACTUALLY AT 

572
00:22:50,311 --> 00:22:52,447
RELATIVELY HIGH ALLELE 

573
00:22:52,447 --> 00:22:55,016
FREQUENCIES AND/OR THE 

574
00:22:55,016 --> 00:22:57,685
INDIVIDUAL HAD A VERY ATYPICAL 

575
00:22:57,685 --> 00:23:00,722
PHENOTYPE SO NOT INCLUDING 

576
00:23:00,722 --> 00:23:03,024
EPILEPSY BUT HAVING SOME OTHER 

577
00:23:03,024 --> 00:23:05,627
DISORDER.  AND SO SO TO TEST 

578
00:23:05,627 --> 00:23:07,195
WHAT THESE VARIANTS ARE DOING 

579
00:23:07,195 --> 00:23:08,997
WE'RE NOW MODELING THESE IN 

580
00:23:08,997 --> 00:23:11,399
PRIMARY AND HOPEFULLY THE IPSC 

581
00:23:11,399 --> 00:23:14,502
MODELS AS WELL TO GET A FEEL FOR

582
00:23:14,502 --> 00:23:16,371
WHAT THESE VARIETIES ARE DOING 

583
00:23:16,371 --> 00:23:18,039
BY I THINK THAT THIS EXAMPLE IS 

584
00:23:18,039 --> 00:23:19,274
A REALLY NICE, IT'S A REALLY 

585
00:23:19,274 --> 00:23:21,175
NICE EXAMPLE OF HOW WE CAN 

586
00:23:21,175 --> 00:23:22,343
ITERATE BETWEEN USING MACHINE 

587
00:23:22,343 --> 00:23:24,546
LEARNING APPROACHES AND 

588
00:23:24,546 --> 00:23:25,280
FUNCTIONAL APPROACHES.  TO FIND 

589
00:23:25,280 --> 00:23:29,450
THE PARTS OF THE PROTEIN THAT 

590
00:23:29,450 --> 00:23:30,451
REALLY NEED A DEEP DIVE IN TERMS

591
00:23:30,451 --> 00:23:33,388
OF RESOLVING PROTEIN FUNCTION.  

592
00:23:33,388 --> 00:23:34,322
BECAUSE THESE PARTS OF THE 

593
00:23:34,322 --> 00:23:40,728
PROTEIN ARE MANY OF THE 

594
00:23:40,728 --> 00:23:43,431
CLASSIFIERS STRUGGLE WITH.  THE 

595
00:23:43,431 --> 00:23:46,067
ONLY ONE THAT DIDN'T WAS ALMA 

596
00:23:46,067 --> 00:23:48,002
AND WE KNOW THIS WAY OVERCALLS 

597
00:23:48,002 --> 00:23:50,471
ON PATHOGENIC VARIANTS IN MOST 

598
00:23:50,471 --> 00:23:54,175
OF OUR EPILEPSY RELATED GENES.  

599
00:23:54,175 --> 00:23:56,344
AND SO TO KIND OF SUMMARIZE THIS

600
00:23:56,344 --> 00:23:59,847
FIRST PART OF THE TALK, I REALLY

601
00:23:59,847 --> 00:24:02,317
THINK I WANTED TO HIGHLIGHT HOW 

602
00:24:02,317 --> 00:24:04,819
THE PATHOGENIC MECHANISM REALLY 

603
00:24:04,819 --> 00:24:05,386
DETERMINES THE APPROPRIATE 

604
00:24:05,386 --> 00:24:06,688
TREATMENT TYPE AND THAT WE 

605
00:24:06,688 --> 00:24:08,756
REALLY NEED TO BE THINKING ABOUT

606
00:24:08,756 --> 00:24:11,492
MANY OF THESE GENES HAVE VARIANT

607
00:24:11,492 --> 00:24:14,028
CLASS SPECIFIC AND NOT GENE 

608
00:24:14,028 --> 00:24:15,530
SPECIFIC PATHOGENIC MECHANISMS 

609
00:24:15,530 --> 00:24:17,165
AND SO OF COURSE GENE EDITING 

610
00:24:17,165 --> 00:24:19,634
WOULD BE THE HOLY GRAIL AND WE 

611
00:24:19,634 --> 00:24:21,169
COULD CHANGE THE VARIANT TO WILD

612
00:24:21,169 --> 00:24:22,403
TYPE AND THAT WOULD BE GREAT AND

613
00:24:22,403 --> 00:24:24,072
WE'RE GOING TO REQUIRE DIFFERENT

614
00:24:24,072 --> 00:24:25,640
STRATEGIES TO BE DEPENDENT ON 

615
00:24:25,640 --> 00:24:27,809
THE PATHOGENIC MECHANISM.  AND 

616
00:24:27,809 --> 00:24:31,846
SO, I THINK SOME OF THE MOST 

617
00:24:31,846 --> 00:24:38,353
CHALLENGING, SO ALL WE NEED TO 

618
00:24:38,353 --> 00:24:41,122
DO IS UPREGULATE THE AMOUNT OF 

619
00:24:41,122 --> 00:24:42,123
PROTEIN AND DOMINANT NEGATIVE 

620
00:24:42,123 --> 00:24:44,192
ARE GOING TO NEED A BIT MORE 

621
00:24:44,192 --> 00:24:50,264
THOUGHT AND SO THINGS LIKE ASO 

622
00:24:50,264 --> 00:24:51,899
DEPLETION WOULD BE IDEAL.  BUT I

623
00:24:51,899 --> 00:24:53,901
THINK ONE OF THE BIG QUESTIONS 

624
00:24:53,901 --> 00:24:57,271
IS WHETHER WE ALSO NEED TO 

625
00:24:57,271 --> 00:25:00,074
UPREGULATE TO GET TO 100% OF 

626
00:25:00,074 --> 00:25:01,709
WILD TYPE FUNCTION ESSENTIALLY. 

627
00:25:01,709 --> 00:25:03,011
BECAUSE WHAT WE'RE ASSUMING HERE

628
00:25:03,011 --> 00:25:05,713
IS THAT LOSS OF FUNCTION IS NOT 

629
00:25:05,713 --> 00:25:06,714
ALSO ASSOCIATED WITH A 

630
00:25:06,714 --> 00:25:08,216
NEUROLOGICAL PHENOTYPE.  AND WE 

631
00:25:08,216 --> 00:25:09,584
KNOW THAT THAT'S NOT TRUE.  SO 

632
00:25:09,584 --> 00:25:10,885
IN THE LAST TWO MINUTES I JUST 

633
00:25:10,885 --> 00:25:12,820
WANT TO TOUCH ON ONE OF THE 

634
00:25:12,820 --> 00:25:14,155
OTHER CHALLENGES I THINK WE FACE

635
00:25:14,155 --> 00:25:16,958
IN EPILEPSY IS THAT MANY OF THE 

636
00:25:16,958 --> 00:25:19,227
GENES DE -- DOSAGE SENSITIVITY 

637
00:25:19,227 --> 00:25:21,562
AND THAT BOTH TOO MUCH AND TOO 

638
00:25:21,562 --> 00:25:23,297
LITTLE PROTEIN IS DETRIMENTAL IN

639
00:25:23,297 --> 00:25:24,699
TERMS OF NEUROLOGICAL FUNCTION. 

640
00:25:24,699 --> 00:25:27,001
AND I'D LIKE TO REALLY HIGHLIGHT

641
00:25:27,001 --> 00:25:30,538
THIS WITH A SPECIFIC CASE, SO OF

642
00:25:30,538 --> 00:25:34,942
CHD 2 WHICH IS THE EPILEPSY 

643
00:25:34,942 --> 00:25:37,078
RELATED GENE WHERE DE NOVO 

644
00:25:37,078 --> 00:25:39,547
PATHOGENIC LOSS OF FUNCTION 

645
00:25:39,547 --> 00:25:41,349
VARIETIES IN CHD 2 CAUSE A 

646
00:25:41,349 --> 00:25:47,021
CLASSIC AND FAIRLY RECOGNIZABLE 

647
00:25:47,021 --> 00:25:50,358
DEVELOPMENTAL.  AND IMPORTANTLY 

648
00:25:50,358 --> 00:25:51,592
THE PATHOGENIC MECHANISM IS 

649
00:25:51,592 --> 00:25:55,329
HAPPEN LOW INSUFFICIENCY SO MOST

650
00:25:55,329 --> 00:25:57,965
OF THE VARIANTS IS TRUNCATIONS. 

651
00:25:57,965 --> 00:26:01,536
SO HERE IS THE CLINICAL PICTURE 

652
00:26:01,536 --> 00:26:06,374
OF CHD 2 RELATED.  MORE 

653
00:26:06,374 --> 00:26:07,875
RECENTLY, THROUGH A 

654
00:26:07,875 --> 00:26:12,613
COLLABORATION WITH ANN AND 

655
00:26:12,613 --> 00:26:14,849
VEEJAY WE IDENTIFIED THESE 

656
00:26:14,849 --> 00:26:17,018
INDIVIDUALS WITH DE NOVO 

657
00:26:17,018 --> 00:26:19,220
DELETION.  IN INDIVIDUALS WITH A

658
00:26:19,220 --> 00:26:21,289
MUCH MORE SEVERE NEUROLOGICAL 

659
00:26:21,289 --> 00:26:22,690
PRESENTATION THAN THOSE 

660
00:26:22,690 --> 00:26:25,426
INDIVIDUALS WITH CHD 2 VARIANTS.

661
00:26:25,426 --> 00:26:28,629
AND SO THESE INDIVIDUALS ALL HAD

662
00:26:28,629 --> 00:26:30,998
SEVERE HYPO TONE YA FROM BIRTH, 

663
00:26:30,998 --> 00:26:34,402
THEY'RE ALL NONVERBAL, NON 

664
00:26:34,402 --> 00:26:37,238
AMBULATORY AND HAVE SEVERE 

665
00:26:37,238 --> 00:26:42,443
DELAYS AND HAVE ATROPHY AS WELL 

666
00:26:42,443 --> 00:26:44,579
AS HYPO MYELINATION.  SO WE WERE

667
00:26:44,579 --> 00:26:46,380
INTRIGUED TO FIGURE OUT WHAT 

668
00:26:46,380 --> 00:26:48,783
EXACTLY WERE THESE DELETION 

669
00:26:48,783 --> 00:26:51,152
UPSTREAM DOING.  AND THIS JUST 

670
00:26:51,152 --> 00:26:53,721
SHOWS YOU A CARICATURE OF THE 

671
00:26:53,721 --> 00:26:58,392
CHD 2 IN FRONT OF IT IS A, RNA 

672
00:26:58,392 --> 00:27:01,262
CALLED A CHASER AND YOU CAN SEE 

673
00:27:01,262 --> 00:27:03,164
THOSE THREE DELETION ALL 

674
00:27:03,164 --> 00:27:05,466
ENCOMPASS THE FIRST THREE AXONS 

675
00:27:05,466 --> 00:27:08,136
OF THIS LONG CODING CHASER AND 

676
00:27:08,136 --> 00:27:12,106
WE KNOW FROM THIS WORK IN ISRAEL

677
00:27:12,106 --> 00:27:18,379
THAT IN MICE WHICH YOU DELETE 

678
00:27:18,379 --> 00:27:24,552
THIS CHASER YOU HAVE THE SEVERE 

679
00:27:24,552 --> 00:27:27,088
GROWTH DEFECTS AND SO WE TESTED 

680
00:27:27,088 --> 00:27:27,989
THIS FROM TWO DIFFERENT PATIENTS

681
00:27:27,989 --> 00:27:31,292
AND SHOWED INDEED, IN -- AS WITH

682
00:27:31,292 --> 00:27:33,995
THE MICE, HERE YOUR WILD TYPE 

683
00:27:33,995 --> 00:27:35,296
LEVELS ARE, HERE'S PATIENT ONE 

684
00:27:35,296 --> 00:27:37,331
AND PATIENT TWO YOU CAN SEE 

685
00:27:37,331 --> 00:27:37,965
THERE WAS A REALLY CONSISTENT 

686
00:27:37,965 --> 00:27:40,701
INCREASE IN THE AMOUNT OF CHD 2 

687
00:27:40,701 --> 00:27:42,570
PROTEIN AS COMPARED TO A WILD 

688
00:27:42,570 --> 00:27:45,606
TYPE SO TO A LEVEL ABOUT 1.8 

689
00:27:45,606 --> 00:27:49,443
FOLD AND SO OUR TAKEAWAY FROM 

690
00:27:49,443 --> 00:27:54,382
THIS IS THAT BOTH HAPPEN LOW 

691
00:27:54,382 --> 00:27:56,217
INSUFFICIENCY BUT ALSO THAT 

692
00:27:56,217 --> 00:27:58,386
OVEREXPRESSION OF CHD 2 CAN BE 

693
00:27:58,386 --> 00:27:59,420
ASSOCIATED WITH AN EVEN MORE 

694
00:27:59,420 --> 00:28:07,862
SEVERE NEUROLOGICAL PHENOTYPE.  

695
00:28:07,862 --> 00:28:10,264
THIS IS IMPORTANT FOR CHD 2 AND 

696
00:28:10,264 --> 00:28:13,267
FOR OTHERS.  SO I SHOWED YOU THE

697
00:28:13,267 --> 00:28:18,372
EXAMPLE OF SCN 2A AND MECP 2 IS 

698
00:28:18,372 --> 00:28:21,642
ANOTHER WELL-KNOWN GENE WHERE 

699
00:28:21,642 --> 00:28:25,713
THERE'S LET SYNDROME AND 

700
00:28:25,713 --> 00:28:26,380
DUPLICATIONS THAT CAUSED A 

701
00:28:26,380 --> 00:28:29,083
DISORDER IN MALES THERE WAS ALSO

702
00:28:29,083 --> 00:28:32,019
A RECENT GENOME WIDE STUDY THAT 

703
00:28:32,019 --> 00:28:34,388
SHOWED THAT MANY HAPPEN LOW 

704
00:28:34,388 --> 00:28:35,056
INSUFFICIENT GENES ARE ALSO 

705
00:28:35,056 --> 00:28:37,525
SENSITIVE SO IF WE LOOK AT SOME 

706
00:28:37,525 --> 00:28:39,427
OF THE MOST COMMONLY HAPPEN LOW 

707
00:28:39,427 --> 00:28:41,262
INSUFFICIENT OR LOSS OF FUNCTION

708
00:28:41,262 --> 00:28:42,997
GENES, FOR THE EPILEPSY RELATED 

709
00:28:42,997 --> 00:28:45,566
GENES, WE SEE THAT MANY OF THESE

710
00:28:45,566 --> 00:28:50,771
ARE IN THE TOP TEN PER TENSI TI 

711
00:28:50,771 --> 00:28:53,107
OF SENSITIVE GENES WE NEED TO BE

712
00:28:53,107 --> 00:28:56,677
CAREFUL ABOUT DESAMING SPECIFIC 

713
00:28:56,677 --> 00:28:58,746
GENE THERAPIES AND BEING 

714
00:28:58,746 --> 00:29:00,615
COGNIZANT OF TOO MUCH MAY ALSO 

715
00:29:00,615 --> 00:29:02,450
BE BAD.  

716
00:29:02,450 --> 00:29:04,852
AND ALSO TAILORING OUR 

717
00:29:04,852 --> 00:29:06,387
THERAPEUTICS TO BE ABLE TO 

718
00:29:06,387 --> 00:29:07,955
OPERATE WITHIN A VERY FINE 

719
00:29:07,955 --> 00:29:10,024
DOSAGE SENSITIVE WINDOW AND SO 

720
00:29:10,024 --> 00:29:11,959
LASTLY J TO CONCLUDE I THINK 

721
00:29:11,959 --> 00:29:14,962
I'VE -- KIND OF HIGHLIGHTED HOW 

722
00:29:14,962 --> 00:29:17,031
IT'S REALLY IMPORTANT IN THE 

723
00:29:17,031 --> 00:29:20,134
EPILEPSY GENES AND FOR SPECIFIC 

724
00:29:20,134 --> 00:29:22,236
VARIANTS TO THINK ABOUT HOW 

725
00:29:22,236 --> 00:29:23,704
THOSE MECHANISMS DETERMINE THE 

726
00:29:23,704 --> 00:29:26,507
APPROPRIATE TREATMENT STRATEGY. 

727
00:29:26,507 --> 00:29:35,249
>> TO TO CONSIDER THAT
THEY ALL 

728
00:29:35,249 --> 00:29:40,655
NOT HAVE THE SAME DISH SHOWED 

729
00:29:40,655 --> 00:29:43,257
YOU ONE OR TWO ASSAYS.  I THINK 

730
00:29:43,257 --> 00:29:45,192
MULTIMODAL IS ALSO KEY.  WE NEED

731
00:29:45,192 --> 00:29:49,230
TO BE USING A VARIETY OF 

732
00:29:49,230 --> 00:29:51,799
DIFFERENT ASSAYS.  BECAUSE I -- 

733
00:29:51,799 --> 00:29:53,067
GEORGE'S GROUP AND OTHERS HAVE 

734
00:29:53,067 --> 00:29:54,869
SHOWN THAT DEPENDING ON THE 

735
00:29:54,869 --> 00:29:56,604
ASSAY THAT YOU USE YOU CAN GET A

736
00:29:56,604 --> 00:30:01,542
LOSS OF FUNCTION VERSUS A GAIN 

737
00:30:01,542 --> 00:30:02,310
OF FUNCTION EFFECT DEPENDING ON 

738
00:30:02,310 --> 00:30:04,011
THE ASSAY SO WE NEED TO WORK 

739
00:30:04,011 --> 00:30:05,212
TOGETHER TO TACKLE THE IMPORTANT

740
00:30:05,212 --> 00:30:07,915
PARTS OF THE PROTEINS AND LASTLY

741
00:30:07,915 --> 00:30:10,217
TO SHOW YOU THAT GENE DOSAGE IS 

742
00:30:10,217 --> 00:30:12,086
IMPORTANT FOR EPILEPSY RELATED 

743
00:30:12,086 --> 00:30:14,322
GENES THE WITH THAT I WILL END. 

744
00:30:14,322 --> 00:30:16,157
I WILL THANK MY LAB LAB.  IT'S 

745
00:30:16,157 --> 00:30:18,392
BEEN A FABULOUS COLLABORATION OF

746
00:30:18,392 --> 00:30:20,394
LOVE WORKING WITH EVERYBODY AND 

747
00:30:20,394 --> 00:30:23,264
LASTLY JUST TO SAY EPIPRED WILL 

748
00:30:23,264 --> 00:30:24,298
BE AVAILABLE SOON WHERE 

749
00:30:24,298 --> 00:30:26,267
EVERYBODY CAN COME IN AND PUT IN

750
00:30:26,267 --> 00:30:27,468
YOUR MISSING VARIANTS AND FIGURE

751
00:30:27,468 --> 00:30:31,539
OUT WHAT IT DOES.  THANKS FOR 

752
00:30:31,539 --> 00:30:39,046
YOUR ATTENTION.  

753
00:30:39,046 --> 00:30:40,948
>> LORI: THANKS VERY MUCH.
THAT

754
00:30:40,948 --> 00:30:42,416
WAS WONDERFUL.  WE HAVE ABOUT 

755
00:30:42,416 --> 00:30:52,893
FIVE MINUTES FOR QUESTIONS.

756
00:30:59,400 --> 00:30:59,967
>> AUDIENCE: (SPEAKER FAR
FROM 

757
00:30:59,967 --> 00:31:03,504
MIC).  

758
00:31:03,504 --> 00:31:04,438
>> GEMMA: CAN YOU SPEAK
UP, I 

759
00:31:04,438 --> 00:31:08,376
CAN'T HEAR.  

760
00:31:08,376 --> 00:31:10,378
>> LORI: HOLD ON, GEMMA.  

761
00:31:10,378 --> 00:31:14,382
>> GEMMA: LORI, COULD YOU
JUST 

762
00:31:14,382 --> 00:31:19,453
REPEAT THE QUESTION FOR ME?

763
00:31:19,453 --> 00:31:21,622
>> AUDIENCE: I WORK WITH 

764
00:31:21,622 --> 00:31:23,391
JENNIFER AND I BUILT THIS.  WHAT

765
00:31:23,391 --> 00:31:26,394
AN AMAZING TALK.  YOU SHOW NICE 

766
00:31:26,394 --> 00:31:28,295
DATA IN THESE HAPPEN ONE CELLS 

767
00:31:28,295 --> 00:31:30,097
BUT YOU CAN MODEL THE AFFECT OF 

768
00:31:30,097 --> 00:31:30,398
THE VARIANT 

769
00:31:30,398 --> 00:31:32,867
GREAT BY WAY OF BUILDING A 

770
00:31:32,867 --> 00:31:34,935
PIPELINE WHERE DE NOVO DIAGNOSED

771
00:31:34,935 --> 00:31:36,370
CHILD WHO HAS TWO MONTHS CAN GO 

772
00:31:36,370 --> 00:31:39,140
THROUGH THAT PIPELINE TO MODEL 

773
00:31:39,140 --> 00:31:41,542
THE VARIANT.  WE COULD USE THAT 

774
00:31:41,542 --> 00:31:44,045
SAME GUIDE RNA WITH 

775
00:31:44,045 --> 00:31:45,880
MODIFICATIONS AS A THERAPEUTIC. 

776
00:31:45,880 --> 00:31:47,348
SO QUESTION FOR YOU, DO WE NEED 

777
00:31:47,348 --> 00:31:55,723
TO DO THE MODELING OF THE PURE 

778
00:31:55,723 --> 00:31:57,725
OF THE NEURON BECAUSE IF THE 

779
00:31:57,725 --> 00:31:58,826
ANSWER IS YES WE CAN BUILD A 

780
00:31:58,826 --> 00:32:01,762
PIPELINE THAT COMPLEMENTS YOUR 

781
00:32:01,762 --> 00:32:03,497
PIPELINE WHERE AS SOON AS YOU 

782
00:32:03,497 --> 00:32:06,067
SHOW IN YOUR HAPLOID CELLS 

783
00:32:06,067 --> 00:32:08,669
THAT'S THE MUTATION WE CAN 

784
00:32:08,669 --> 00:32:10,371
REPAIR THAT INTO A MORE SPECIFIC

785
00:32:10,371 --> 00:32:12,740
CELL TYPE, QUESTION FOR YOU WHAT

786
00:32:12,740 --> 00:32:14,375
IS THAT CELL TYPE?  

787
00:32:14,375 --> 00:32:16,110
>> GEMMA: GREAT QUESTION I

788
00:32:16,110 --> 00:32:17,711
COMPLETELY AGREE WITH YOU AND 

789
00:32:17,711 --> 00:32:21,916
THE GOAL OF THE MAVES IS TO KNOW

790
00:32:21,916 --> 00:32:24,018
THE GENE AND WHAT IT DOES.  THAT

791
00:32:24,018 --> 00:32:26,220
IS OUR GOAL IS TO HAVE A GUIDE 

792
00:32:26,220 --> 00:32:28,656
RNA THAT EDITS THAT PARTICULAR 

793
00:32:28,656 --> 00:32:30,357
LOCUS READY TO GO BUT TO ANSWER 

794
00:32:30,357 --> 00:32:32,026
YOUR QUESTION, WHICH CELL TYPE 

795
00:32:32,026 --> 00:32:34,395
IS THAT?  THAT WILL DEPEND ON 

796
00:32:34,395 --> 00:32:36,063
THE GENE AND SO FOR CERTAIN 

797
00:32:36,063 --> 00:32:37,798
GENES, AND, AGAIN, AND THIS IS 

798
00:32:37,798 --> 00:32:39,767
WHY I WAS CAREFUL TO POINT OUT 

799
00:32:39,767 --> 00:32:43,370
THAT IN THE HAP ONES THERE ARE 

800
00:32:43,370 --> 00:32:47,074
ONLY CERTAIN PROPERTIES OF THE 

801
00:32:47,074 --> 00:32:48,209
PROTEIN THAT WE CAN ASSAY.  

802
00:32:48,209 --> 00:32:49,577
THAT'S ONLY ONE READOUT AND SO 

803
00:32:49,577 --> 00:32:51,979
WE NEED TO HAVE MULTIPLE 

804
00:32:51,979 --> 00:32:56,183
DIFFERENT READ OITS AND MULTIPLE

805
00:32:56,183 --> 00:32:58,586
CELLS IDEALLY WE WILL DO THESE 

806
00:32:58,586 --> 00:33:02,356
DERIVED NEURONS AND MAYBE TWO 

807
00:33:02,356 --> 00:33:08,362
NEURONS TO START TO DO THIS.  

808
00:33:08,362 --> 00:33:09,563
BUT TO ANSWER YOUR QUESTION A. 

809
00:33:09,563 --> 00:33:13,634
THAT WILL DEPEND.  IT THAT'S 

810
00:33:13,634 --> 00:33:15,136
KIND OF, I HOPE WHAT GAIA IS 

811
00:33:15,136 --> 00:33:16,403
GOING TO TALK ABOUT IN THE THIRD

812
00:33:16,403 --> 00:33:21,509
TALK IS WHAT ARE THE CELL TYPES.

813
00:33:21,509 --> 00:33:23,777
>> AUDIENCE: TERRIFIC.  WE
HAVE 

814
00:33:23,777 --> 00:33:29,049
THE PIPELINES TO KNOCK THE 

815
00:33:29,049 --> 00:33:29,683
MUTATIONS AND LONGITUDINALLY.  I

816
00:33:29,683 --> 00:33:33,287
WOULD LOVE TO DIAGRAM WHAT YOU 

817
00:33:33,287 --> 00:33:34,388
HAVE DONE THANK YOU.  

818
00:33:34,388 --> 00:33:37,591
>> GEMMA: I'D LOVE TO
CHAT.  

819
00:33:37,591 --> 00:33:38,993
>> LORI: THANKS, GEMMA,
LET'S 

820
00:33:38,993 --> 00:33:41,128
HAVE ONE MORE QUESTION.

821
00:33:41,128 --> 00:33:43,397
>> AUDIENCE: HI, I'M LEAH
MYERS,

822
00:33:43,397 --> 00:33:45,232
I REALLY LIKED YOUR TALK AND I 

823
00:33:45,232 --> 00:33:47,001
JUST WANT TO DO JUST SAY FOR 

824
00:33:47,001 --> 00:33:48,335
EVERYONE HERE THIS IS A REALLY 

825
00:33:48,335 --> 00:33:51,205
IMPORTANT TOPIC IN OUR COMMUNITY

826
00:33:51,205 --> 00:33:52,473
RIGHT NOW.  AS PRECISION 

827
00:33:52,473 --> 00:33:54,108
MEDICINE IS COMING DOWN THE 

828
00:33:54,108 --> 00:33:55,976
PIPELINE FOR US WE'RE IN 

829
00:33:55,976 --> 00:33:57,344
CLINICAL TRIALS.  FOR CERTAIN 

830
00:33:57,344 --> 00:33:59,480
ONES AND WE ARE REALLY CONCERNED

831
00:33:59,480 --> 00:34:02,383
ABOUT THIS AS A COMMUNITY.  

832
00:34:02,383 --> 00:34:06,287
BECAUSE WE -- WITH AL GEORGE 

833
00:34:06,287 --> 00:34:08,022
ANALYZING OUR VARIANTS AND 

834
00:34:08,022 --> 00:34:10,391
INDUSTRY GROUPS ANALYZING THE 

835
00:34:10,391 --> 00:34:12,059
CHANNEL WE'RE GETTING SOME 

836
00:34:12,059 --> 00:34:14,128
DIFFERENT RESULTS LIKE POLAR 

837
00:34:14,128 --> 00:34:14,929
OPPOSITE DIFFERENT RESULTS AND 

838
00:34:14,929 --> 00:34:16,630
THAT'S REALLY SCARY BECAUSE THEY

839
00:34:16,630 --> 00:34:18,866
WANT TO PUT A KID IN A GENE 

840
00:34:18,866 --> 00:34:20,701
THERAPY TRIAL AND THE OTHER ONE 

841
00:34:20,701 --> 00:34:22,403
SAYING IT'S A COMPLETE LOSS OF 

842
00:34:22,403 --> 00:34:24,405
FUNCTION SO I JUST WANTED TO 

843
00:34:24,405 --> 00:34:26,173
EXPRESS THAT THIS IS A VERY 

844
00:34:26,173 --> 00:34:29,276
NEEDED TOPIC FOR THE PATIENTE 

845
00:34:29,276 --> 00:34:33,981
ADVOCACY  GROUPS WE'RE WILLING 

846
00:34:33,981 --> 00:34:34,381
TO SUPPORT.  

847
00:34:34,381 --> 00:34:35,983
>> GEMMA: I THINK YOU HIT
THE 

848
00:34:35,983 --> 00:34:37,818
NAIL ON THE HEAD.  I THINK 

849
00:34:37,818 --> 00:34:39,353
WHAT'S REALLY IMPORTANT IS DATA 

850
00:34:39,353 --> 00:34:41,855
SHARING.  RIGHT?  WE NEED TO 

851
00:34:41,855 --> 00:34:42,790
MAKE SURE THAT EVERYBODY IS 

852
00:34:42,790 --> 00:34:46,093
SHARING THEIR DATA IN A ROBUST 

853
00:34:46,093 --> 00:34:49,496
WAY.  AND I DON'T KNOW THE BEST 

854
00:34:49,496 --> 00:34:51,131
FORUM TAD  TO DO THAT BUT I 

855
00:34:51,131 --> 00:34:52,299
THINK THAT'S SOMETHING WE HAVE 

856
00:34:52,299 --> 00:34:53,734
TO FIGURE OUT. 

857
00:34:53,734 --> 00:34:56,370
AND THIS IS SOMETHING YOU CAN 

858
00:34:56,370 --> 00:34:59,106
CHAMPION FOR US.  SNA

859
00:34:59,106 --> 00:35:02,376
>> AUDIENCE: I AGREE, WE
DID 

860
00:35:02,376 --> 00:35:04,011
JUST PUBLISH WHERE IT WAS 

861
00:35:04,011 --> 00:35:07,815
ANALYZED IN EACH ONE AND WE DID 

862
00:35:07,815 --> 00:35:10,317
A DEEP DIVE INTO THEM AND I'M 

863
00:35:10,317 --> 00:35:11,785
PRESSING THE INDUSTRY GROUP TO 

864
00:35:11,785 --> 00:35:14,154
SHARE THEIRS BUT THAT'S REALLY 

865
00:35:14,154 --> 00:35:15,089
DIFFICULT FOR US TO DO AND SEEMS

866
00:35:15,089 --> 00:35:17,091
LIKE WE'RE NOT MAKING A LOT OF 

867
00:35:17,091 --> 00:35:18,626
PROGRESS THERE BUT I AGREE.  

868
00:35:18,626 --> 00:35:19,960
IT'S THE ONLY WAY TO MOVE 

869
00:35:19,960 --> 00:35:21,195
FORWARD AND I DO THINK THERE ARE

870
00:35:21,195 --> 00:35:22,763
SOME PEOPLE IN THIS ROOM THAT 

871
00:35:22,763 --> 00:35:24,498
ALSO HAVE OTHER IDEAS ON HOW WE 

872
00:35:24,498 --> 00:35:27,468
CAN PUT THAT DATA ALTOGETHER 

873
00:35:27,468 --> 00:35:31,071
LIKE THE PORTALS.  THANK YOU.  

874
00:35:31,071 --> 00:35:41,615
>> LORI: THANKS, LEE
YACLEAH.   

875
00:35:41,615 --> 00:35:45,052
ARE CONTEXT DEPENDENT.  SO IT'S 

876
00:35:45,052 --> 00:35:47,488
WHAT ACTS ON THE INITIAL SEGMENT

877
00:35:47,488 --> 00:35:49,423
VERSUS DENDRITES VERSUS CELL 

878
00:35:49,423 --> 00:35:50,557
BODY I THINK IT'S AN IMPORTANT 

879
00:35:50,557 --> 00:35:53,894
PROBLEM.  LET'S MOVE ON, THANKS,

880
00:35:53,894 --> 00:35:57,631
GEMMA.  IT'S MY HONOR TO 

881
00:35:57,631 --> 00:36:00,234
INTRODUCE ISABEL AZNAREZ WHO IS 

882
00:36:00,234 --> 00:36:02,336
COFOUNDER OF STOKE THEIR PIEKTS 

883
00:36:02,336 --> 00:36:03,937
AND WILL TALK ABOUT THE 

884
00:36:03,937 --> 00:36:06,206
DEVELOPMENT OF THE FIRST GENE 

885
00:36:06,206 --> 00:36:07,975
MODIFYING THERAPY FOR EPILEPSY.

886
00:36:07,975 --> 00:36:18,419
>> AUDIENCE: (APPLAUSE).  

887
00:36:21,989 --> 00:36:23,023
>> ISABEL: THANK YOU IT'S
A 

888
00:36:23,023 --> 00:36:25,359
PLEASURE TO BE HERE AND REALLY 

889
00:36:25,359 --> 00:36:27,161
ENJOYED THE PRESENTATIONS TODAY 

890
00:36:27,161 --> 00:36:28,595
AND GEMMA ALWAYS A FANTASTIC JOB

891
00:36:28,595 --> 00:36:32,166
AND SUPER IMPORTANT WORK.  AND I

892
00:36:32,166 --> 00:36:34,401
WILL TOUCH A LITTLE BIT ON THAT 

893
00:36:34,401 --> 00:36:42,109
IN THE NEXT FEW SLIDES.  JUST TO

894
00:36:42,109 --> 00:36:45,646
INTRODUCE, OH, FIRST I HAVE SOME

895
00:36:45,646 --> 00:36:47,548
DISCLAIMERS.  AS LORI MENTIONED 

896
00:36:47,548 --> 00:36:49,950
I'M A FULL-TIME EMPLOYEE OF 

897
00:36:49,950 --> 00:36:50,951
STOKE AS PART OF THIS 

898
00:36:50,951 --> 00:36:51,585
PRESENTATION I WILL BE MAKING 

899
00:36:51,585 --> 00:36:57,057
SOME FORWARD LOOKING STATEMENTS.

900
00:36:57,057 --> 00:36:59,827
THE TECHNOLOGY THAT WE DEVELOPED

901
00:36:59,827 --> 00:37:02,429
IS CALLED TANGO, TARGETED 

902
00:37:02,429 --> 00:37:03,997
AUGMENTATION OF NUCLEAR GENE 

903
00:37:03,997 --> 00:37:05,432
OUTPUT.  A MOUTHFUL WHICH WE AIM

904
00:37:05,432 --> 00:37:10,604
TO ADDRESS THE UNDERLYING CAUSE 

905
00:37:10,604 --> 00:37:13,607
OF DISEASES BY UPREGULATING 

906
00:37:13,607 --> 00:37:17,311
PROTEIN BY USING NUCLEOTIDES AND

907
00:37:17,311 --> 00:37:20,013
YOU PROBABLY HEARD A LOT ABOUT 

908
00:37:20,013 --> 00:37:24,485
THIS IN THE VAST MAJORITY OF 

909
00:37:24,485 --> 00:37:28,789
APPLICATIONS TO DOWN REGULATE 

910
00:37:28,789 --> 00:37:30,324
GENE EXPRESSION.  WE'RE TABLE 

911
00:37:30,324 --> 00:37:31,825
LEVERAGE THE COPY AND I WILL GET

912
00:37:31,825 --> 00:37:34,695
INTO THE DETAILS IN A FEW 

913
00:37:34,695 --> 00:37:37,765
SLIDES.  TO UPREGULATE FULLY 

914
00:37:37,765 --> 00:37:41,668
FUNCTIONAL PROTEIN.  WE DO SO BY

915
00:37:41,668 --> 00:37:43,804
USING NUCLEOTIDES TO PREVENT 

916
00:37:43,804 --> 00:37:46,273
WHAT WE CALL NONPRODUCTIVE 

917
00:37:46,273 --> 00:37:47,374
SPLICING AND AGAIN I WILL 

918
00:37:47,374 --> 00:37:50,644
EXPLAIN THAT IN THE NEXT SLIDE 

919
00:37:50,644 --> 00:37:54,381
TO PROMOTE THE PRODUCTION OF 

920
00:37:54,381 --> 00:37:56,250
PRODUCTIVE RNA WHICH WOULD THEN 

921
00:37:56,250 --> 00:38:01,588
LEAD TO AN INCREASED PRODUCTION 

922
00:38:01,588 --> 00:38:06,360
OF PROTEIN.  BUT BECAUSE OUR 

923
00:38:06,360 --> 00:38:07,461
NUCLEOTIDES ARE LIKE ANY OTHER 

924
00:38:07,461 --> 00:38:10,431
AND OPERATE AT THE LEVEL OF RNA 

925
00:38:10,431 --> 00:38:13,367
THE TECHNOLOGY SELECTIVELY 

926
00:38:13,367 --> 00:38:14,401
UPREGULATE GENE EXPRESSION ONLY 

927
00:38:14,401 --> 00:38:16,703
WHERE THAT GENE IS EXPRESSED SO 

928
00:38:16,703 --> 00:38:19,273
WE DON'T NEED TO WORRY ABOUT 

929
00:38:19,273 --> 00:38:20,874
ATOPIC EXPRESSION OR 

930
00:38:20,874 --> 00:38:21,675
OVEREXPRESSION ITSELF WHERE THAT

931
00:38:21,675 --> 00:38:27,414
GENE IS NOT NEEDED.  AND THEN BY

932
00:38:27,414 --> 00:38:29,216
TARGETING OR LEVERAGING THAT 

933
00:38:29,216 --> 00:38:31,485
WILD TYPE COPY IN THE CONTEXT OF

934
00:38:31,485 --> 00:38:33,353
HAPPEN LOW INSUFFICIENT DISEASES

935
00:38:33,353 --> 00:38:35,489
WE'RE ABLE TO DEVELOP ONE DRUG 

936
00:38:35,489 --> 00:38:37,157
FOR AN ENTIRE PATIENT POPULATION

937
00:38:37,157 --> 00:38:41,061
OF COURSE PROVIDED THAT THE 

938
00:38:41,061 --> 00:38:42,296
MUTATION AFFECTING THE PATIENT 

939
00:38:42,296 --> 00:38:46,867
ARE LOSS OF FUNCTION MUTATIONS. 

940
00:38:46,867 --> 00:38:52,372
AND THEN AGAIN THE TYPE OF 

941
00:38:52,372 --> 00:38:53,006
MODALITY BEING NUCLEOTIDES WE 

942
00:38:53,006 --> 00:38:54,274
DON'T NEED TO WORRY ABOUT THE 

943
00:38:54,274 --> 00:38:56,410
SIZE OR THE FUNCTION OF THE GENE

944
00:38:56,410 --> 00:38:58,378
AS WELL AS WE HAVE EVENTS TO 

945
00:38:58,378 --> 00:39:01,448
TARGET, WE CAN UPREGULATE THEIR 

946
00:39:01,448 --> 00:39:07,387
EXPRESSION.  SO JUST BRIEFLY HOW

947
00:39:07,387 --> 00:39:11,692
THE TECHNOLOGY WORKS.  WE HAVE 

948
00:39:11,692 --> 00:39:12,593
THE HAPPEN LOW INSUFFICIENT 

949
00:39:12,593 --> 00:39:14,394
DISEASE WHICH YOU ALL KNOW THE 

950
00:39:14,394 --> 00:39:24,638
DISEASE IS CAUSED BY MUTATIONS. 

951
00:39:24,638 --> 00:39:26,173
AND THIS PARTICULAR EXAMPLE 

952
00:39:26,173 --> 00:39:32,379
THERE'S BOTH ALLELE CODE CONTAIN

953
00:39:32,379 --> 00:39:34,882
A NONPRODUCTIVE AX ON, THERE ARE

954
00:39:34,882 --> 00:39:36,984
MANY NAME TO THE SAME TYPE OF AX

955
00:39:36,984 --> 00:39:39,486
ONS AND WHEN THESE AX ONS ARE 

956
00:39:39,486 --> 00:39:42,422
INCLUDED IN MRNA THEY LEAD TO 

957
00:39:42,422 --> 00:39:45,859
THE INTRODUCTION OF OF THIS.  

958
00:39:45,859 --> 00:39:47,794
AND THIS IS WHAT IS HAPPENING 

959
00:39:47,794 --> 00:39:48,795
HERE WE SEE THIS IS SPLICED IN 

960
00:39:48,795 --> 00:39:50,898
TWO DIFFERENT WAYS AND THE M RAN

961
00:39:50,898 --> 00:39:53,300
LAN THAT CONTAINS THAT AX ON 

962
00:39:53,300 --> 00:39:55,602
GETS DEGRADED AND THIS IS 

963
00:39:55,602 --> 00:39:56,403
NATURALLY OCCURRING, THIS IS -- 

964
00:39:56,403 --> 00:39:58,372
UP RELATED TO THE DISEASE STATE 

965
00:39:58,372 --> 00:40:01,642
AND MORE OFTEN THAN NOT THOSE 

966
00:40:01,642 --> 00:40:03,710
NONPRODUCTIVE SPLICING EVENTS 

967
00:40:03,710 --> 00:40:06,413
ARE THERE TO REGULATE GENE 

968
00:40:06,413 --> 00:40:09,550
EXPRESSION SO WE'RE ABLE TO 

969
00:40:09,550 --> 00:40:14,221
PREVENT THE INCLUSION OF THIS 

970
00:40:14,221 --> 00:40:19,960
AND THEN ALMOST SCLIFLY HAVE THE

971
00:40:19,960 --> 00:40:22,863
PRODUCTIVE MRNA AND THE MUTANT 

972
00:40:22,863 --> 00:40:25,232
ALLELE IS STILL USELESS BUT THE 

973
00:40:25,232 --> 00:40:26,934
INCREASED MRNA LEVELS FROM THE 

974
00:40:26,934 --> 00:40:29,803
WILD TYPE ALLELE CAN NOW MAKE 

975
00:40:29,803 --> 00:40:30,470
MORE PROTEIN WHICH CAN THEN MAKE

976
00:40:30,470 --> 00:40:33,407
UP FOR THE LOSS OF THE MUTANT 

977
00:40:33,407 --> 00:40:34,608
ALLELE AND BRING LEVELS BACK TO 

978
00:40:34,608 --> 00:40:37,978
HAVING EFFECT.  SO THIS IS IN A 

979
00:40:37,978 --> 00:40:38,645
NUTSHELL HOW THE CONCEPT OF 

980
00:40:38,645 --> 00:40:45,719
TANGO WORKS.  TO FIND THOSE 

981
00:40:45,719 --> 00:40:48,822
EVENTS WE DEVELOPED A 

982
00:40:48,822 --> 00:40:50,190
BIOINFORMATICS PIPELINE FOR 

983
00:40:50,190 --> 00:40:52,526
WHICH WE UTILIZE OUR DATASETS 

984
00:40:52,526 --> 00:40:54,695
AND THEN WE HAVE FOUND WHAT WE 

985
00:40:54,695 --> 00:40:56,430
CALL THE UNIVERSE OF 

986
00:40:56,430 --> 00:40:58,365
NONPRODUCTIVE SPLICING EVENTS 

987
00:40:58,365 --> 00:41:01,535
WHICH GO BEYOND THE AXONS, THERE

988
00:41:01,535 --> 00:41:02,469
ARE ALL KINDS OF ALTERNATIVE 

989
00:41:02,469 --> 00:41:05,839
SPLICE SPLICING EVENTS AND THE 

990
00:41:05,839 --> 00:41:06,907
TRANSCRIPT DEGRADATION AND 

991
00:41:06,907 --> 00:41:10,344
QUESTION FOUND THEM IN 50% OF 

992
00:41:10,344 --> 00:41:11,345
CODING GENES.  BECAUSE WE WANT 

993
00:41:11,345 --> 00:41:13,680
TO TREAT GENETIC DISEASES WE 

994
00:41:13,680 --> 00:41:19,219
CROSS-REFERENCE THOSE LISTS OF 

995
00:41:19,219 --> 00:41:20,687
GENES THAT CONTAIN NONPRODUCTIVE

996
00:41:20,687 --> 00:41:23,090
SPLICING EVENTS WITH GENETIC 

997
00:41:23,090 --> 00:41:25,626
DISEASE, ET CETERA.  AND WE 

998
00:41:25,626 --> 00:41:29,096
FOUND THAT 2900, THE DISEASE 

999
00:41:29,096 --> 00:41:32,366
CODES IN GENES ALSO HAVE THESE 

1000
00:41:32,366 --> 00:41:33,233
NONPRODUCTIVE SPLICING EVENTS 

1001
00:41:33,233 --> 00:41:34,568
THAT WE CAN LEVERAGE TO INCREASE

1002
00:41:34,568 --> 00:41:37,270
GENE EXPRESSION BY OF COURSE WE 

1003
00:41:37,270 --> 00:41:39,673
CAN'T AND DON'T WANT TO 

1004
00:41:39,673 --> 00:41:40,774
UPREGULATE 2900 DISEASE GENES 

1005
00:41:40,774 --> 00:41:45,579
AND THIS IS WHEN IF THEY -- 

1006
00:41:45,579 --> 00:41:46,380
CONSIDERATIONS BECOME VERY, VERY

1007
00:41:46,380 --> 00:41:48,949
POOR AND A LOT OF THESE THINGS 

1008
00:41:48,949 --> 00:41:51,585
WERE TOUCHED UPON BY GEMMA 

1009
00:41:51,585 --> 00:41:52,686
EARLIER.  BUT I WANT TO DOUBLE 

1010
00:41:52,686 --> 00:41:56,089
DOWN ON SOME OF THOSE THINGS.  

1011
00:41:56,089 --> 00:42:02,729
SO FOR US, IT'S IMPORTANT TO 

1012
00:42:02,729 --> 00:42:04,197
UNDERSTAND THE GENETIC DISEASE 

1013
00:42:04,197 --> 00:42:06,800
CAME UP ON THOSE LISTS.  BECAUSE

1014
00:42:06,800 --> 00:42:09,836
ARE THEY A DOMINANT DISEASE.  DO

1015
00:42:09,836 --> 00:42:11,538
THEY HAVE SUFFICIENCY OR USED TO

1016
00:42:11,538 --> 00:42:15,008
A DOMINANT NEGATIVE OR A GAIN.  

1017
00:42:15,008 --> 00:42:15,842
OF COURSE DOMINANT ANYTHING GAVE

1018
00:42:15,842 --> 00:42:17,310
GAIN OF FUNCTION LIMITATIONS IS 

1019
00:42:17,310 --> 00:42:19,646
OUT OF THE QUESTION FOR US AND 

1020
00:42:19,646 --> 00:42:21,081
IT'S VERY, VERY IMPORTANT TO 

1021
00:42:21,081 --> 00:42:22,849
KNOW THAT PRECISELY BECAUSE WE 

1022
00:42:22,849 --> 00:42:26,386
DO NOT WANT TO HARM PATIENTS BY 

1023
00:42:26,386 --> 00:42:27,421
UPREGULATING THEIR EXPRESSION.  

1024
00:42:27,421 --> 00:42:30,390
IS A RECESSIVE DISEASE THAT 

1025
00:42:30,390 --> 00:42:31,858
UPREGULATION IS COULD HAVE A 

1026
00:42:31,858 --> 00:42:34,227
BENEFIT AND GEMMA POINTED IT OUT

1027
00:42:34,227 --> 00:42:36,630
ALSO SAME WITH THE NEXT DISEASE 

1028
00:42:36,630 --> 00:42:40,367
WE HAVE THE SYNDROME IN OUR 

1029
00:42:40,367 --> 00:42:44,438
PIPELINE AS WELL.  THE BIOLOGY 

1030
00:42:44,438 --> 00:42:47,274
IS A VERY IMPORTANT.  GENOTYPE 

1031
00:42:47,274 --> 00:42:49,676
PHENOTYPE CORRELATION, HOW MUCH 

1032
00:42:49,676 --> 00:42:52,713
UPREGULATION IS NECESSARY.  IF 

1033
00:42:52,713 --> 00:42:54,214
TOO MUCH HOW MUCH IS TOO MUCH?  

1034
00:42:54,214 --> 00:42:56,450
AND THEN, YOU KNOW, WHAT IS THE 

1035
00:42:56,450 --> 00:42:58,785
EXPRESSION PATTERN OF THE GENE? 

1036
00:42:58,785 --> 00:43:00,921
THE GENE IS VERY HIGHLY 

1037
00:43:00,921 --> 00:43:03,790
EXPRESSED PRENATALLY AND 

1038
00:43:03,790 --> 00:43:04,391
POSTNATALLY ALMOST NOTHING?  

1039
00:43:04,391 --> 00:43:09,362
WELL THAT TELLS YOU THAT MAYBE 

1040
00:43:09,362 --> 00:43:09,996
RESTORING A LEVEL AFTER A 

1041
00:43:09,996 --> 00:43:12,599
PERSON, A BABY IS BORN, MAY NOT 

1042
00:43:12,599 --> 00:43:16,470
DO THE TRICK.  SO THAT SPEAKS TO

1043
00:43:16,470 --> 00:43:19,506
WHERE IS THE TREATMENT 

1044
00:43:19,506 --> 00:43:20,941
OPPORTUNITY WINDOW BASICALLY.  

1045
00:43:20,941 --> 00:43:21,775
THE DISEASE PREVALENCE OF COURSE

1046
00:43:21,775 --> 00:43:23,677
YOU MAY SAY, WELL, YOU'RE A 

1047
00:43:23,677 --> 00:43:25,645
COMPANY, YOU NEED TO MAKE A 

1048
00:43:25,645 --> 00:43:27,948
PROFIT BUT THE DISEASE 

1049
00:43:27,948 --> 00:43:32,452
PREVALENCE IS ALSO IMPORTANT TO 

1050
00:43:32,452 --> 00:43:33,587
DESIGN PROPER CLINICAL TRIALS TO

1051
00:43:33,587 --> 00:43:35,589
HAVE THE TREATING PHYSICIANS AND

1052
00:43:35,589 --> 00:43:37,691
TO BE ABLE TO HAVE ENOUGH 

1053
00:43:37,691 --> 00:43:39,693
PATIENT TO HAVE A POWER AT 

1054
00:43:39,693 --> 00:43:40,927
CLINICAL TRIAL SO IT'S AN 

1055
00:43:40,927 --> 00:43:43,864
IMPORTANT FACTOR NO MATTER WHAT 

1056
00:43:43,864 --> 00:43:45,031
UNLESS YOU DEVELOP A TREATMENT 

1057
00:43:45,031 --> 00:43:46,233
AND THEN, YOU KNOW, OF COURSE 

1058
00:43:46,233 --> 00:43:48,068
YOU DON'T NEED TO WORRY ABOUT 

1059
00:43:48,068 --> 00:43:55,742
THAT, THE TARGET ORGAN, VERY --E

1060
00:43:55,742 --> 00:43:58,645
MODALITY BECAUSE WE NEED TO IF 

1061
00:43:58,645 --> 00:44:00,147
WE CAN DELIBERATE INTO THE 

1062
00:44:00,147 --> 00:44:02,449
DISEASE AND IF THAT'S A 

1063
00:44:02,449 --> 00:44:04,484
CONSIDERATION THE CLINICAL 

1064
00:44:04,484 --> 00:44:06,987
DEVELOPMENT IS ALSO WAY AHEAD OF

1065
00:44:06,987 --> 00:44:09,022
TIME.  ARE THEY MODELS?  ARE 

1066
00:44:09,022 --> 00:44:12,626
THEY WELL VALIDATED MODELS THAT 

1067
00:44:12,626 --> 00:44:14,694
CAN TRANSLATE INTO WHAT -- YOU 

1068
00:44:14,694 --> 00:44:15,862
WILL BE -- WE WILL BE MEASURING 

1069
00:44:15,862 --> 00:44:18,231
IN THE CLINIC AND THEN FROM THE 

1070
00:44:18,231 --> 00:44:19,900
CLINICAL DEVELOPMENT, THERE ARE 

1071
00:44:19,900 --> 00:44:22,269
END POINTS THAT ARE ALREADY 

1072
00:44:22,269 --> 00:44:25,872
ACCEPTED BY THE FDA WHAT WOULD 

1073
00:44:25,872 --> 00:44:28,008
BE THE DURATION OF THE TRIAL, ET

1074
00:44:28,008 --> 00:44:28,942
CETERA, ET CETERA.  ALL OF THESE

1075
00:44:28,942 --> 00:44:30,377
ARE IMPORTANT CONSIDERATIONS 

1076
00:44:30,377 --> 00:44:32,746
WHEN DECIDING WHAT TO TARGET.  

1077
00:44:32,746 --> 00:44:35,816
WITH WHATEVER APPROACH YOU 

1078
00:44:35,816 --> 00:44:42,389
REACH.  ONCE WE DECIDE TO WORK 

1079
00:44:42,389 --> 00:44:46,393
ON A TARGET WE WORK ON THE 

1080
00:44:46,393 --> 00:44:52,566
PREDICTIONS.  IDENTIFY THE HITS 

1081
00:44:52,566 --> 00:44:54,034
AND PRIORITIZE A PIPELINE.  WE 

1082
00:44:54,034 --> 00:44:56,203
HAVE SEVERAL TARGETS IN OUR 

1083
00:44:56,203 --> 00:44:57,637
PIPELINE.  TODAY I'M GOING TO 

1084
00:44:57,637 --> 00:45:01,141
TELL YOU WHAT I THINK IS SUPER 

1085
00:45:01,141 --> 00:45:05,178
EXCITING STORY ABOUT TREATING 

1086
00:45:05,178 --> 00:45:08,448
DRAVET SYNDROME.  WE ARE 

1087
00:45:08,448 --> 00:45:10,383
TARGETING WITH OUR BRAND NEW 

1088
00:45:10,383 --> 00:45:20,927
NAME SOR REVENUE NEVER SEN.  I'M

1089
00:45:23,997 --> 00:45:26,233
GOING QUIZ YOU.  A LOT OF THE 

1090
00:45:26,233 --> 00:45:27,801
BOXES, THAT WE WANTED TO CHECK 

1091
00:45:27,801 --> 00:45:31,304
IN WHAT IS THE RIGHT TARGET FOR.

1092
00:45:31,304 --> 00:45:33,807
IT'S A CLEAR HAPPEN LOW INSIEVE 

1093
00:45:33,807 --> 00:45:35,809
SI WHICH HALLS HAS -- WHEN IT 

1094
00:45:35,809 --> 00:45:39,246
HAS MUTATIONS THAT LEAD TO GAIN 

1095
00:45:39,246 --> 00:45:42,415
OF FUNCTION.  AND -- BUT THE 

1096
00:45:42,415 --> 00:45:43,984
PHENOTYPE ASSOCIATED WITH THOSE 

1097
00:45:43,984 --> 00:45:45,085
MUTATIONS IS VERY, VERY 

1098
00:45:45,085 --> 00:45:45,819
DIFFERENT AND SO WE'RE CONFIDENT

1099
00:45:45,819 --> 00:45:49,055
THAT WITH THE GENETIC AND THE 

1100
00:45:49,055 --> 00:45:50,624
CLINICAL DIAGNOSIS, WE CAN 

1101
00:45:50,624 --> 00:45:51,491
IDENTIFY THE RIGHT PATIENT WHICH

1102
00:45:51,491 --> 00:45:55,028
IS ARE THE MAJORITY OF THE 

1103
00:45:55,028 --> 00:45:57,964
PATIENTS.  THAT HAVE THE 

1104
00:45:57,964 --> 00:45:58,732
INSUFFICIENCY.  IT'S 

1105
00:45:58,732 --> 00:46:00,734
SUFFICIENTLY PREVALENT TO HAVE 

1106
00:46:00,734 --> 00:46:02,068
ENOUGH PATIENTS TO HAVE CLINICAL

1107
00:46:02,068 --> 00:46:03,737
TRIALS AND THERE'S A HIGH UNMET 

1108
00:46:03,737 --> 00:46:06,373
NEED THE PATIENTS THAT ARE NOT 

1109
00:46:06,373 --> 00:46:08,441
IN CONTROL WITH EPILEPTIC DRUGS 

1110
00:46:08,441 --> 00:46:12,245
AND 20% OF PATIENTS DON'T REACH 

1111
00:46:12,245 --> 00:46:17,584
TO ADULTHOOD BECAUSE OF 

1112
00:46:17,584 --> 00:46:24,791
COMPLICATIONS SUDEP OR SEIZURE 

1113
00:46:24,791 --> 00:46:25,692
COMPLICATIONS.  DRAVET IS NOT 

1114
00:46:25,692 --> 00:46:27,227
JUST A SEIZURE DISEASE.  THERE'S

1115
00:46:27,227 --> 00:46:29,262
A LOT OF DIFFERENT COMPONENTS BY

1116
00:46:29,262 --> 00:46:30,931
TARGETING THE ROOT CAUSE OF THE 

1117
00:46:30,931 --> 00:46:32,365
DISEASE WE'RE TABLE TREAT BOTH 

1118
00:46:32,365 --> 00:46:34,801
THE EPILEPSY AND THE COGNITIVE 

1119
00:46:34,801 --> 00:46:38,071
AND BEHAVIORAL ASPECTS OF IT.  

1120
00:46:38,071 --> 00:46:40,206
SO ONE OF THE FIRST THINGS WE 

1121
00:46:40,206 --> 00:46:44,444
NEEDED TO DO WAS TO DEMONSTRATE 

1122
00:46:44,444 --> 00:46:48,348
AND CLINICALLY WHETHER WE HAVE 

1123
00:46:48,348 --> 00:46:52,085
THE PROTEIN CODED LED TO A 

1124
00:46:52,085 --> 00:46:53,954
PHENOTYPIC RESCUE AND WE DID 

1125
00:46:53,954 --> 00:46:56,222
THIS WORK IN COLLABORATION AS 

1126
00:46:56,222 --> 00:46:59,292
WELL AS.  AND SO HERE WE USE 

1127
00:46:59,292 --> 00:47:01,261
THAT AS VERY WELL-ESTABLISHED 

1128
00:47:01,261 --> 00:47:05,832
AND ROBUST MOUSE MODEL THAT 

1129
00:47:05,832 --> 00:47:07,567
PRESENTS WITH SEIZURES AS WELL 

1130
00:47:07,567 --> 00:47:10,103
AS THE TWO OF THE PHENOTYPES 

1131
00:47:10,103 --> 00:47:13,206
THAT ARE OF COURSE PRESENT IN 

1132
00:47:13,206 --> 00:47:18,712
PATIENTS AND WE ADMINISTER THE 

1133
00:47:18,712 --> 00:47:21,948
SEW REV NEVER SEN AND SEVEN 

1134
00:47:21,948 --> 00:47:23,149
WEEKS OR FOURTEEN WEEKS LATER WE

1135
00:47:23,149 --> 00:47:28,221
MEASURE PROTEIN.  THE PROTEIN, 

1136
00:47:28,221 --> 00:47:30,190
WHAT WE WANT IT TO SEE IS 

1137
00:47:30,190 --> 00:47:32,325
WHETHER WE CAN RESTORE PROTEINS 

1138
00:47:32,325 --> 00:47:33,560
BACK TO NORMAL AND HERE WHAT 

1139
00:47:33,560 --> 00:47:35,862
YOU'RE SEEING IS THE LINE AT 

1140
00:47:35,862 --> 00:47:38,264
100% IS THE WILD TYPE LEVELS AND

1141
00:47:38,264 --> 00:47:42,402
THEN THE PLACEBO TREATED MICE 

1142
00:47:42,402 --> 00:47:45,605
WERE HAVE THE PROTEIN LEVELS 

1143
00:47:45,605 --> 00:47:48,041
AROUND 50%.  AND WE SEE AN 

1144
00:47:48,041 --> 00:47:50,276
INCREASE ALMOST BACK TO 100% 

1145
00:47:50,276 --> 00:47:53,580
BOTH AT SEVEN WEEKS AND THAT 

1146
00:47:53,580 --> 00:47:55,515
INCREASE WAS THE SAME ALMOST 

1147
00:47:55,515 --> 00:47:58,184
ENTIRELY AT 14 WEEKS SO WE KNEW 

1148
00:47:58,184 --> 00:48:02,389
THAT ONE DOSE WAS SUFFICIENT AND

1149
00:48:02,389 --> 00:48:02,989
THAT THAT AFFECT WAS HIGHLY 

1150
00:48:02,989 --> 00:48:07,727
CONTROLLED.  WHAT DID THIS DO TO

1151
00:48:07,727 --> 00:48:12,999
THE SUDEP PHENOTYPE OF THESE 

1152
00:48:12,999 --> 00:48:16,770
MICE THE RED LINE IS THE MICE 

1153
00:48:16,770 --> 00:48:20,040
AND THEN YOU SEE AROUND DAY 

1154
00:48:20,040 --> 00:48:23,443
THIRTY BUT THE -- THE SEW REV 

1155
00:48:23,443 --> 00:48:25,378
NONER SEN TREATED, ALL BY ONE 

1156
00:48:25,378 --> 00:48:32,485
SURVIVED SO VERY CLEARLY THE 

1157
00:48:32,485 --> 00:48:33,820
DOSE HELPS WITH THE SURVIVAL OF 

1158
00:48:33,820 --> 00:48:36,790
THE MOUSE AND WE ALSO LOOKED AT 

1159
00:48:36,790 --> 00:48:38,992
THE SPONTANEOUS SEIZURES, WE 

1160
00:48:38,992 --> 00:48:42,395
IMPLANTED ELECTRODES IN THE 

1161
00:48:42,395 --> 00:48:48,001
BRAIN.  SO INTRACRANIAL AND WE 

1162
00:48:48,001 --> 00:48:50,136
MEASURE SPONTANEOUS SEIZURES AT 

1163
00:48:50,136 --> 00:48:53,006
TWO DIFFERENT TIME POINTS FROM 

1164
00:48:53,006 --> 00:48:57,043
30 TO 20 AND 20 TO 40 AND YOU 

1165
00:48:57,043 --> 00:49:00,013
SEE HERE AT THE EARLIER TIME 

1166
00:49:00,013 --> 00:49:01,815
POINT YOU SEE THE TREATED MICE 

1167
00:49:01,815 --> 00:49:04,984
HAVE NO SEIZURES WHATSOEVER 

1168
00:49:04,984 --> 00:49:07,987
WHEREAS THE UNTREATED MICE HAVE 

1169
00:49:07,987 --> 00:49:10,223
A SEIZURE FREQUENCY AND THIS 

1170
00:49:10,223 --> 00:49:12,125
SHOWS A SIGNIFICANT REDUCTION IN

1171
00:49:12,125 --> 00:49:14,294
SEIZURE FREQUENCY FOR THE 

1172
00:49:14,294 --> 00:49:15,929
TREATED MICE IN ORANGE COMPARED 

1173
00:49:15,929 --> 00:49:19,966
TO THE DARK BLUE GRAYISH DOT.  

1174
00:49:19,966 --> 00:49:25,505
SO AGAIN WITH A SINGLE DOSE OF 

1175
00:49:25,505 --> 00:49:26,739
STK-001 WE WERE ABLE TO 

1176
00:49:26,739 --> 00:49:29,442
SIGNIFICANTLY REDUCE THE SEIZURE

1177
00:49:29,442 --> 00:49:32,278
PHENOTYPE SO THAT MOUSE MODEL 

1178
00:49:32,278 --> 00:49:36,983
DATA BOTH THE SEIZURES GAVE US 

1179
00:49:36,983 --> 00:49:40,687
CONFIDENCE THAT THE UPREGULATION

1180
00:49:40,687 --> 00:49:42,622
WAS ABLE TO AFFECT THIS IN A 

1181
00:49:42,622 --> 00:49:44,424
POSITIVE WAY AND WE'RE ABLE TO 

1182
00:49:44,424 --> 00:49:48,061
RESTORE PROTEIN LEVELS IN THAT 

1183
00:49:48,061 --> 00:49:57,570
EFFECT IT'S DURABLE AND THAT IN 

1184
00:49:57,570 --> 00:49:59,105
THE PREMISE WE SEE THAT.  AND 

1185
00:49:59,105 --> 00:50:02,375
WHEN WE LOOK AT THE STUDIES WE 

1186
00:50:02,375 --> 00:50:06,179
WERE ABLE TO HAVE A TALK READOUT

1187
00:50:06,179 --> 00:50:08,615
SUPPORT THE CURRENT DOSES THAT 

1188
00:50:08,615 --> 00:50:12,285
WE HAVE ONGOING IN THE FIELD.  

1189
00:50:12,285 --> 00:50:14,320
SO TO SWITCH GEARS AND SHOW YOU 

1190
00:50:14,320 --> 00:50:16,189
A LITTLE BIT OF THE CLINICAL 

1191
00:50:16,189 --> 00:50:18,391
DATA.  I'M NOT A CLINICIAN SO I 

1192
00:50:18,391 --> 00:50:24,564
WILL TRY TO DO MY BEST HERE.  

1193
00:50:24,564 --> 00:50:26,432
THE CLINICAL TRIALS ARE SHOWN 

1194
00:50:26,432 --> 00:50:28,001
HERE.  WE HAVE THE TRIAL IN 

1195
00:50:28,001 --> 00:50:30,370
WHICH WE -- THERE WAS A SINGLE 

1196
00:50:30,370 --> 00:50:32,305
DOSE ARM AND A MULTIPLE DOSE ARM

1197
00:50:32,305 --> 00:50:36,109
OF DOSES UP TO 70 MILLIGRAM 

1198
00:50:36,109 --> 00:50:37,810
THESE -- THE PATIENTS WERE DOSED

1199
00:50:37,810 --> 00:50:41,281
AND AFTER THE LAST DOSE, THERE 

1200
00:50:41,281 --> 00:50:43,349
WAS A 6 MONTHS OBSERVATIONAL 

1201
00:50:43,349 --> 00:50:49,923
PERIOD IN WHICH PATIENTS DID NOT

1202
00:50:49,923 --> 00:50:51,491
RECEIVE ANY SEW VE NEVER SEN 

1203
00:50:51,491 --> 00:50:52,692
DOSES AND RIGHT AT THE GOING ALL

1204
00:50:52,692 --> 00:51:02,468
THE PATIENTS AT THE TRIAL WERE 

1205
00:51:02,468 --> 00:51:04,704
CONTINUING THEIR ANTIEPILEPTIC 

1206
00:51:04,704 --> 00:51:06,206
DRUGS AND MANY OF THESE PATIENTS

1207
00:51:06,206 --> 00:51:08,441
WERE ON THE THREE OR FOUR DRUGS 

1208
00:51:08,441 --> 00:51:09,542
ALREADY AND STILL HAVING 

1209
00:51:09,542 --> 00:51:13,313
NUMEROUS SEIZURES.  AFTER THE 

1210
00:51:13,313 --> 00:51:18,051
SIX MONTHS PERIOD THEY WERE ABLE

1211
00:51:18,051 --> 00:51:20,420
TO GO TO THE EXTENSION AND HERE 

1212
00:51:20,420 --> 00:51:25,124
THE DOSES WERE 30 MILLIGRAMS 45 

1213
00:51:25,124 --> 00:51:27,961
MIL GRAMS AND AGAIN PATIENTS 

1214
00:51:27,961 --> 00:51:30,663
CONTINUE ON THEIR NORMAL 

1215
00:51:30,663 --> 00:51:34,100
REGIMENT OF ANTIEPILEPTIC DRUGS.

1216
00:51:34,100 --> 00:51:34,500
I. 

1217
00:51:34,500 --> 00:51:36,469
WILL WALK YOU THROUGH THE DATA. 

1218
00:51:36,469 --> 00:51:38,271
HERE YOU SEE PATIENTS IN THE 

1219
00:51:38,271 --> 00:51:39,706
INITIAL PHASE OF ONE, TWO OR 

1220
00:51:39,706 --> 00:51:44,110
THREE DOSES FOLLOWED BY THE SIX 

1221
00:51:44,110 --> 00:51:54,621
MONTHS OBSERVATIONAL PERIOD.  

1222
00:51:55,955 --> 00:51:58,291
THE LINE IS NO CHANGE.  THE RED 

1223
00:51:58,291 --> 00:52:02,161
IS 45 MILLIGRAMS AND THE GREEN 

1224
00:52:02,161 --> 00:52:06,833
IS 71 MILLIGRAMS AND THE DOSING 

1225
00:52:06,833 --> 00:52:08,268
REGIMENT, THE FIRST DOSE AND 

1226
00:52:08,268 --> 00:52:11,037
THEN TWO MONTHS THE SECOND DOSE,

1227
00:52:11,037 --> 00:52:13,640
ONE MONTH LATER THE THIRD DOSE 

1228
00:52:13,640 --> 00:52:15,275
AND THE SIX MONTHS OBSERVATIONAL

1229
00:52:15,275 --> 00:52:17,010
PERIOD.  SO HERE WHAT YOU CAN 

1230
00:52:17,010 --> 00:52:23,716
SEE IS, FIRST THE EFFECT SEW 

1231
00:52:23,716 --> 00:52:25,051
REVIEW NEVER SEN.  YOU SEE THE 

1232
00:52:25,051 --> 00:52:27,420
REDUCTION AND THE EFFECT 

1233
00:52:27,420 --> 00:52:28,288
SUSTAINED BEYOND THE LAST DOSE 

1234
00:52:28,288 --> 00:52:32,425
INTO THE SIX MONTHS OF 

1235
00:52:32,425 --> 00:52:41,401
OBSERVATIONAL PERIOD.  AND YOU 

1236
00:52:41,401 --> 00:52:44,304
SEE THE DECREASE IN SEIZURES 

1237
00:52:44,304 --> 00:52:47,407
WHICH IS A DRAMATIC DECREASE.  

1238
00:52:47,407 --> 00:52:49,876
IN SEIZURES, IF WE ZOOM IN THE 

1239
00:52:49,876 --> 00:52:52,812
PATIENTS WHO WERE DOZED WITH 

1240
00:52:52,812 --> 00:52:54,914
DOSES OF 70 MILLIGRAMS ON THE 

1241
00:52:54,914 --> 00:52:55,948
LEFT-HAND SIDE YOU CAN SEE 

1242
00:52:55,948 --> 00:52:58,084
PATIENTS THAT RECEIVE ONE DOSE 

1243
00:52:58,084 --> 00:53:00,653
OF 70 MILLIGRAMS AND THEN 

1244
00:53:00,653 --> 00:53:01,554
OBSERVE THAT THREE MONTHS AND 

1245
00:53:01,554 --> 00:53:05,291
THEN AT SIX MONTHS POST SINGLE 

1246
00:53:05,291 --> 00:53:06,793
DOSE WHICH WE ALREADY SAW AN 

1247
00:53:06,793 --> 00:53:08,027
EFFECT OF A SINGLE DOSE BUT WHEN

1248
00:53:08,027 --> 00:53:10,063
WE LOOK AT TWO AND THREE DOSES 

1249
00:53:10,063 --> 00:53:11,431
AND COMBINED THE DATA BECAUSE 

1250
00:53:11,431 --> 00:53:12,965
THERE WAS NO DIFFERENCE IN THE 

1251
00:53:12,965 --> 00:53:15,335
EFFECT OF TWO OR THREE DOSES YOU

1252
00:53:15,335 --> 00:53:17,570
CAN SEE THAT IN THREE MONTHS 

1253
00:53:17,570 --> 00:53:20,473
THERE'S AN 85% REDUCTION IN 

1254
00:53:20,473 --> 00:53:21,474
SEIZURE FREQUENCY AND THAT 

1255
00:53:21,474 --> 00:53:23,876
REDUCTION IS SUSTAINED THROUGH 

1256
00:53:23,876 --> 00:53:26,379
THE SIX MONTHS OBSERVATIONAL 

1257
00:53:26,379 --> 00:53:34,620
PERIOD.  WE THEN GO INTO THE 

1258
00:53:34,620 --> 00:53:35,988
EXTENSION PERIOD.  ANYTHING 

1259
00:53:35,988 --> 00:53:37,890
BELOW IS A REDUCTION AND THE 

1260
00:53:37,890 --> 00:53:40,293
OPEN LEVEL EXTENSION IN ORANGE 

1261
00:53:40,293 --> 00:53:42,428
ARE THE PATIENTS THAT WE SEE 30 

1262
00:53:42,428 --> 00:53:45,898
OR 45 MILLIGRAM DOSES AND THEN 

1263
00:53:45,898 --> 00:53:48,067
WENT ONTO THE LABEL EXTENSION 30

1264
00:53:48,067 --> 00:53:53,873
OR 45.  AND THEN IN GREEN WE'RE 

1265
00:53:53,873 --> 00:53:55,608
SEEING THE 70 MILLIGRAM COHORT 

1266
00:53:55,608 --> 00:54:00,446
THAT RECEIVED THREE DOSES OF 70 

1267
00:54:00,446 --> 00:54:02,448
MILLIGRAMS AND THEN WENT ONTO AN

1268
00:54:02,448 --> 00:54:06,652
OPEN LABEL EXTENSION OF 45 

1269
00:54:06,652 --> 00:54:10,189
MILLIGRAMS JUST ONE DOSE WHEN 

1270
00:54:10,189 --> 00:54:11,457
THE DATA HAPPENED.  HERE YOU CAN

1271
00:54:11,457 --> 00:54:12,925
SEE FIRST OF ALL THE EFFECT FROM

1272
00:54:12,925 --> 00:54:14,761
THE INITIAL DOSING, SIX MONTHS 

1273
00:54:14,761 --> 00:54:18,264
AND THEN THE OPEN LABEL 

1274
00:54:18,264 --> 00:54:19,665
EXTENSION, IT SUSTAINED SO THE 

1275
00:54:19,665 --> 00:54:22,635
EFFECT DIDN'T GO AWAY AS A 

1276
00:54:22,635 --> 00:54:25,972
POTENTIAL PLACEBO EFFECT AND 

1277
00:54:25,972 --> 00:54:28,374
SECOND THE 75 LOADING DOSE 

1278
00:54:28,374 --> 00:54:30,343
FOLLOWED BY 45 MILLIGRAM OPEN 

1279
00:54:30,343 --> 00:54:31,911
LABEL EXTENSION SEEMED TO 

1280
00:54:31,911 --> 00:54:34,247
MAINTAIN THE SEIZURE FREQUENCY 

1281
00:54:34,247 --> 00:54:35,381
REDUCTION WHICH IS REALLY 

1282
00:54:35,381 --> 00:54:36,783
IMPORTANT FOR US TO SEE BECAUSE 

1283
00:54:36,783 --> 00:54:39,886
IT'S VERY INFORMATIVE FOR WHAT 

1284
00:54:39,886 --> 00:54:50,396
WE CAN DO IN THE TRIALS.  NOW 

1285
00:54:51,297 --> 00:54:52,765
MOVING ONTO TO COGNITIVE PARTS 

1286
00:54:52,765 --> 00:54:54,367
OF THE DISEASE.  PATIENTS, FIRST

1287
00:54:54,367 --> 00:54:57,270
OF ALL, SEIZURES DON'T CHANGE.  

1288
00:54:57,270 --> 00:54:59,071
THEY CONTINUE TO HAVE SEIZURES. 

1289
00:54:59,071 --> 00:55:02,375
THE SEIZURE FREQUENCY DOES NOT 

1290
00:55:02,375 --> 00:55:04,010
CHANGE OVER TIME IN OUR HISTORY 

1291
00:55:04,010 --> 00:55:05,978
STUDY AND FROM THE COGNITIVE 

1292
00:55:05,978 --> 00:55:08,448
PERSPECTIVE HERE EVERYTHING IS 

1293
00:55:08,448 --> 00:55:12,084
TO THE RIGHT.  WHICH EVERYTHING 

1294
00:55:12,084 --> 00:55:14,153
IMPROVES IN THE NATURAL HISTORY 

1295
00:55:14,153 --> 00:55:16,589
EVERYTHING GOES TO THE LEFT AND 

1296
00:55:16,589 --> 00:55:18,357
THINGS DEVIATE FROM THE NORM AND

1297
00:55:18,357 --> 00:55:20,927
SO WHAT WE SAW AFTER TREATMENT 

1298
00:55:20,927 --> 00:55:22,929
AND THESE ARE PATIENTS THAT WENT

1299
00:55:22,929 --> 00:55:24,897
ONTO THE OPEN LABEL AND SAY THE 

1300
00:55:24,897 --> 00:55:26,365
EXTENSION ON THE 30 MILLIGRAMS 

1301
00:55:26,365 --> 00:55:29,135
AND 45 MIL GRAMS DOSE IS DATA 

1302
00:55:29,135 --> 00:55:31,971
THAT DOES NOT INCLUDE THE 70 

1303
00:55:31,971 --> 00:55:33,439
MILLIGRAM DOSE YET. 

1304
00:55:33,439 --> 00:55:37,276
WE SAW A CLINICAL AND MEANINGFUL

1305
00:55:37,276 --> 00:55:38,644
IMPROVEMENT IN RECEPTIVE 

1306
00:55:38,644 --> 00:55:40,146
COMMUNICATION, IN PERSONAL 

1307
00:55:40,146 --> 00:55:41,647
SKILLS, INTERPERSONAL 

1308
00:55:41,647 --> 00:55:44,150
RELATIONSHIPS, AND SOME SIGNS OF

1309
00:55:44,150 --> 00:55:46,385
IMPROVEMENT IN THE OTHER TWO 

1310
00:55:46,385 --> 00:55:50,223
MEASUREMENTS.  WE DID THESE 

1311
00:55:50,223 --> 00:55:53,025
MEASUREMENTS SIMILAR TO WHAT 

1312
00:55:53,025 --> 00:55:53,893
OTHER SECTION WAS DONE YESTERDAY

1313
00:55:53,893 --> 00:55:55,261
AND WE'RE SUPER EXCITED TO BE 

1314
00:55:55,261 --> 00:55:58,231
ABLE TO SEE THAT OUR TREATMENTS 

1315
00:55:58,231 --> 00:55:59,765
ARE ONLY ADDRESSED THE SEIZURE 

1316
00:55:59,765 --> 00:56:03,069
FREQUENCY BUT THERE ARE 

1317
00:56:03,069 --> 00:56:09,942
IMPROVEMENTS IN COGNITION IN 

1318
00:56:09,942 --> 00:56:11,244
BEHAVIOR THAT ARE EXTREMELY 

1319
00:56:11,244 --> 00:56:12,645
IMPORTANT.  AND WE LOOKED AT 

1320
00:56:12,645 --> 00:56:15,581
WHAT CLINICAL AND MEANINGFUL 

1321
00:56:15,581 --> 00:56:17,216
IMPROVEMENTS IN THE OVERALL 

1322
00:56:17,216 --> 00:56:18,384
POSITION AND THESE WERE 

1323
00:56:18,384 --> 00:56:20,453
MEASUREMENT BY CLINICIANS AND 

1324
00:56:20,453 --> 00:56:22,755
CAREGIVERS ON THE LEFT-HAND SIDE

1325
00:56:22,755 --> 00:56:24,657
ARE THE CLINICAL GLOBAL 

1326
00:56:24,657 --> 00:56:26,325
IMPRESSION CHANGES AND AS YOU 

1327
00:56:26,325 --> 00:56:29,295
CAN SEE IN THE DARK BLUE GRAY 

1328
00:56:29,295 --> 00:56:33,199
THESE ARE THE NATURAL HISTORY 

1329
00:56:33,199 --> 00:56:36,335
PATIENTS.  AND THERE'S LITTLE TO

1330
00:56:36,335 --> 00:56:39,205
NO IMPROVEMENT ACROSS TIME BUT 

1331
00:56:39,205 --> 00:56:44,443
THEN THE PATIENTS TREATED WITH 

1332
00:56:44,443 --> 00:56:47,046
SEW REV NEVER SEN WE SEE A VERY 

1333
00:56:47,046 --> 00:56:50,483
CLEAR IMPROVEMENT OVER TIME.  

1334
00:56:50,483 --> 00:56:59,091
THE SAME IMPRESSION IN THE 

1335
00:56:59,091 --> 00:57:00,459
NATURAL HISTORY STUDY DID NOT 

1336
00:57:00,459 --> 00:57:03,062
SHOW ANY IMPROVEMENT WHEREAS 

1337
00:57:03,062 --> 00:57:05,831
PATIENTS IN THE -- TREATED WITH 

1338
00:57:05,831 --> 00:57:09,068
SEW REV UNER SEN WERE SHOWING 

1339
00:57:09,068 --> 00:57:12,638
IMPROVEMENT.  JUST TO SUM PRIZE,

1340
00:57:12,638 --> 00:57:14,874
SORRY, 50 DATA.  SO ALL SINGLE 

1341
00:57:14,874 --> 00:57:18,311
AND MULTIPLE DOSE AFTER 70 

1342
00:57:18,311 --> 00:57:19,111
MILLIGRAMS WERE GENERALLY WELL 

1343
00:57:19,111 --> 00:57:20,413
TOLERATED WHICH IS GREAT.  WE 

1344
00:57:20,413 --> 00:57:25,251
DID SEE TREATMENT EMERGING 

1345
00:57:25,251 --> 00:57:29,288
ADVERSE EFFECTS.  THAT WERE 

1346
00:57:29,288 --> 00:57:31,123
MOSTLY PROCEDURAL AS WELL AS THE

1347
00:57:31,123 --> 00:57:36,429
PROTEIN ELEVATIONS.  AND THEN 

1348
00:57:36,429 --> 00:57:39,265
ALSO TREATMENT OH SEVERE ADVERSE

1349
00:57:39,265 --> 00:57:41,267
EFFECTS BUT THEY WERE NOT DEEMED

1350
00:57:41,267 --> 00:57:45,137
TO BE DRUG RELATED WITH THE 

1351
00:57:45,137 --> 00:57:48,040
EXCEPTION OF THE PATIENT WHO 

1352
00:57:48,040 --> 00:57:49,575
EXPERIENCED THIS.  IN THE OPEN 

1353
00:57:49,575 --> 00:57:52,578
LABEL EXTENSION WE DID SEE 

1354
00:57:52,578 --> 00:57:54,880
ELEVATION OF CSF PROTEIN LEVELS 

1355
00:57:54,880 --> 00:57:58,117
BUT THIS DOESN'T SEEM TO BE 

1356
00:57:58,117 --> 00:58:00,686
SPECIFIC TO THE SEW REV NEVER 

1357
00:58:00,686 --> 00:58:04,190
SUN AND THIS IS FOR SPINAL 

1358
00:58:04,190 --> 00:58:05,257
MUSCULAR ATROPHY AND OTHERS HAVE

1359
00:58:05,257 --> 00:58:07,426
SEEN THIS PROTEIN ELEVATION AND 

1360
00:58:07,426 --> 00:58:09,795
THERE IS NO CLINICAL CORRELATION

1361
00:58:09,795 --> 00:58:12,131
AT ALL WITH THIS ELEVATED 

1362
00:58:12,131 --> 00:58:15,067
PROTEIN.  AND SO WE ARE NOT 

1363
00:58:15,067 --> 00:58:17,803
CONCERNED ABOUT THIS.  SO JUST 

1364
00:58:17,803 --> 00:58:21,307
TO SUMMARIZE, WE HAVE SEEN A 

1365
00:58:21,307 --> 00:58:22,441
SIGNIFICANT REDUCTION IN SEIZURE

1366
00:58:22,441 --> 00:58:26,278
FREQUENCY DOWN TO 85%.  WE ALSO 

1367
00:58:26,278 --> 00:58:29,715
SEE A SUSTAINED EFFECT IN THE 

1368
00:58:29,715 --> 00:58:31,917
OPEN LABEL EXTENSION AND WE SEE 

1369
00:58:31,917 --> 00:58:35,121
IMPROVEMENT IN COGNITIVE AND 

1370
00:58:35,121 --> 00:58:36,322
BEHAVIORAL PHENOTYPES OF DRUGS 

1371
00:58:36,322 --> 00:58:39,692
IN THE PATIENTS.  WE'RE 

1372
00:58:39,692 --> 00:58:40,960
CURRENTLY GEARING UP FOR 

1373
00:58:40,960 --> 00:58:42,928
CONVERSATIONS WITH THE FDA TO 

1374
00:58:42,928 --> 00:58:44,330
FOLLOW OUR CLINICAL TRIALS AND 

1375
00:58:44,330 --> 00:58:45,998
OUR DATA SUPPORTS A LOADING DOSE

1376
00:58:45,998 --> 00:58:49,468
OF 70 MILLIGRAMS FOLLOWED BY 

1377
00:58:49,468 --> 00:58:51,103
MAINTENANCE DOSE OF 45 

1378
00:58:51,103 --> 00:58:56,475
MILLIGRAMS EVERY FOUR MONTHS.  

1379
00:58:56,475 --> 00:58:58,844
THAT I WOULD LIKE TO THANK YOU 

1380
00:58:58,844 --> 00:58:59,912
FOR YOUR ATTENTION AND MORE 

1381
00:58:59,912 --> 00:59:03,149
IMPORTANTLY THE FAMILY WHO IS EM

1382
00:59:03,149 --> 00:59:05,918
BARKED ON THIS ADVENTURE WITH US

1383
00:59:05,918 --> 00:59:08,454
AND TRUST IN US WITH THEIR KIDS.

1384
00:59:08,454 --> 00:59:18,664
THANK YOU.

1385
00:59:21,667 --> 00:59:23,869
>> I'M NOT A CLINICIAN SO
THE 

1386
00:59:23,869 --> 00:59:26,939
DATA ARE INCREDIBLY INSPIRING.  

1387
00:59:26,939 --> 00:59:28,941
KRRGS.  I THINK YOU SOLVED ONE 

1388
00:59:28,941 --> 00:59:32,445
OF THE MAJOR CHALLENGES FOR A 

1389
00:59:32,445 --> 00:59:34,380
BROAD FIELD OF TREATMENT FOR 

1390
00:59:34,380 --> 00:59:35,681
EPILEPSIES AND I WOULD LIKE TO 

1391
00:59:35,681 --> 00:59:37,483
CONFIRM THIS IS THE CASE.  THERE

1392
00:59:37,483 --> 00:59:39,685
IS NO MONKEY.

1393
00:59:39,685 --> 00:59:41,287
>> OH, THERE IS?

1394
00:59:41,287 --> 00:59:42,388
>> THERE IS NO MONKEY THAT

1395
00:59:42,388 --> 00:59:43,489
YOU'RE USING.

1396
00:59:43,489 --> 00:59:45,157
>> OH, YES, SO, NO.

1397
00:59:45,157 --> 00:59:51,564
>> SO MY QUESTION IS, SOR
--

1398
00:59:51,564 --> 00:59:55,201
>> YOU SOMEHOW MANAGED TO
BRIDGE

1399
00:59:55,201 --> 00:59:57,970
A PLACEBO PHARMACOLOGY IN A 

1400
00:59:57,970 --> 01:00:02,241
MOUSE MODEL WITH A STARTING DOSE

1401
01:00:02,241 --> 01:00:05,010
IN A HUMAN.  SO IF YOU'RE AT 

1402
01:00:05,010 --> 01:00:07,179
LIBERTY TO SAY JUST SO THAT 

1403
01:00:07,179 --> 01:00:09,215
EVERYBODY CAN LEARN AS WE'RE 

1404
01:00:09,215 --> 01:00:14,353
BUILDING WHATEVER DID YOU HAVE A

1405
01:00:14,353 --> 01:00:18,991
MY BIOMARKER?  HOW DID YOU 

1406
01:00:18,991 --> 01:00:21,660
BRIDGE?  

1407
01:00:21,660 --> 01:00:23,129
>> ISABEL: GREAT QUESTION.
NOW 

1408
01:00:23,129 --> 01:00:24,430
THERE IS BUT NOT WHEN WE STARTED

1409
01:00:24,430 --> 01:00:26,098
SO THE MOUSE WE WERE ABLE TO 

1410
01:00:26,098 --> 01:00:30,236
CONNECT THE DOTS BECAUSE THERE 

1411
01:00:30,236 --> 01:00:32,238
IS TARGETING ENGAGEMENT AND 

1412
01:00:32,238 --> 01:00:36,008
PROTEIN UPREGULATION IN THE 

1413
01:00:36,008 --> 01:00:37,143
PRIMATE.  TO --

1414
01:00:37,143 --> 01:00:39,645
>> AUDIENCE: DID YOU SAY
THERE 

1415
01:00:39,645 --> 01:00:40,880
IS EVIDENCE?  

1416
01:00:40,880 --> 01:00:41,413
>> ISABEL: YES.

1417
01:00:41,413 --> 01:00:44,450
>> AUDIENCE: WHAT IS THAT 

1418
01:00:44,450 --> 01:00:46,018
EVIDENCE?  

1419
01:00:46,018 --> 01:00:47,319
>> ISABEL: YEAH.  YEAH. 
THE 

1420
01:00:47,319 --> 01:00:49,855
SEQUENCE THAT WE USE THE FULLY 

1421
01:00:49,855 --> 01:00:54,360
CONSERVED ACROSS ALL SPECIES SO 

1422
01:00:54,360 --> 01:00:57,530
MOUSE, NONHUMAN PRIMATES THAT 

1423
01:00:57,530 --> 01:01:01,467
MADE CONNECTING THE DOTS VERY 

1424
01:01:01,467 --> 01:01:02,134
EASY.  THANK YOU.

1425
01:01:02,134 --> 01:01:03,335
>> AUDIENCE: THAT WAS THE 

1426
01:01:03,335 --> 01:01:05,704
IDENTICAL THING DONE.  IS IN THE

1427
01:01:05,704 --> 01:01:09,575
NORMAL MONKEY.  THEY WERE ABLE 

1428
01:01:09,575 --> 01:01:11,610
TO LOOK AT THE BREAKDOWN OF THE 

1429
01:01:11,610 --> 01:01:13,045
RNA AND INCREASES IN THE 

1430
01:01:13,045 --> 01:01:20,319
PROTEIN.  BUT I HAVVHAVE A COUP 

1431
01:01:20,319 --> 01:01:22,321
QUESTIONS.  THE PROTEIN 

1432
01:01:22,321 --> 01:01:23,756
INCREASE, THAT WAS THE HARBINGER

1433
01:01:23,756 --> 01:01:29,628
IN THE IMPLEMENT ASO, THAT'S THE

1434
01:01:29,628 --> 01:01:32,932
HARBINGER OF THE LEG WEAKNESS 

1435
01:01:32,932 --> 01:01:35,301
HAVE YOU SEEN THOSE AFFECTS IN 

1436
01:01:35,301 --> 01:01:38,404
YOUR ASO OR MOU?  

1437
01:01:38,404 --> 01:01:39,471
>> ISABEL: YEAH, SHOULD
HAVE 

1438
01:01:39,471 --> 01:01:42,441
MENTIONED THAT, THIS IS FULLY 

1439
01:01:42,441 --> 01:01:46,111
MODIFIED MOE, IT'S AN 18.  AND 

1440
01:01:46,111 --> 01:01:55,421
WE DIDN'T SEE, NO, NONE OF THAT.

1441
01:01:55,421 --> 01:01:58,424
AND THIS IS THE THING, EVEN 

1442
01:01:58,424 --> 01:01:59,525
THOUGH THE CHEMISTRY MIGHT BE 

1443
01:01:59,525 --> 01:02:01,126
THE SAME, WE KNOW THE SEQUENCE 

1444
01:02:01,126 --> 01:02:02,294
HAS EFFECTS.  THE SEQUENCE OF 

1445
01:02:02,294 --> 01:02:06,565
THE ASOS.  AND WE'VE SEEN IN 

1446
01:02:06,565 --> 01:02:10,736
CLINICAL STUDIES WE PUT ASOS FOR

1447
01:02:10,736 --> 01:02:14,373
THE SAME TARGET IN SOME HAVE 

1448
01:02:14,373 --> 01:02:16,809
VERY TRANSIENT BUT STILL SOME 

1449
01:02:16,809 --> 01:02:18,911
ADVERSE EFFECTS IN MICE, IN WILD

1450
01:02:18,911 --> 01:02:21,647
TYPE MICE AND SOME DON'T.  VERY 

1451
01:02:21,647 --> 01:02:24,683
CLEARLY RIGHT FROM THE GET-GO 

1452
01:02:24,683 --> 01:02:29,722
THE SAME CHEMISTRY LEAD TO TWO 

1453
01:02:29,722 --> 01:02:30,522
DIFFERENT AFFECTS AND SOME MAY 

1454
01:02:30,522 --> 01:02:33,058
HAVE THE SAME SIDE EFFECTS AND 

1455
01:02:33,058 --> 01:02:34,126
SOME MAY NOT.

1456
01:02:34,126 --> 01:02:38,097
>> AUDIENCE: HOW MUCH WAS
THE 

1457
01:02:38,097 --> 01:02:39,031
PROTEIN ELEVATION?  

1458
01:02:39,031 --> 01:02:40,933
>> ISABEL: LET ME GO BACK.

1459
01:02:40,933 --> 01:02:43,102
>> AUDIENCE: I CAN TALK TO
YOU 

1460
01:02:43,102 --> 01:02:43,903
MAYBE LATER.  

1461
01:02:43,903 --> 01:02:45,137
>> ISABEL: I DON'T KNOW
OFF THE 

1462
01:02:45,137 --> 01:02:46,372
TOP OF MY HEAD.

1463
01:02:46,372 --> 01:02:48,240
>> AUDIENCE: THAT'S A
RELATIVELY

1464
01:02:48,240 --> 01:02:50,542
SMALL AMOUNT AND I CAN TALK TO 

1465
01:02:50,542 --> 01:02:52,645
YOU LATER.  I'M INTERESTED IN 

1466
01:02:52,645 --> 01:02:54,546
HOW MUCH MORE THAT IS THAN IN 

1467
01:02:54,546 --> 01:03:05,090
NATURAL HISTORY.  I A.M. ASS

1468
01:03:06,959 --> 01:03:08,961
ASSUME -- 

1469
01:03:08,961 --> 01:03:10,829
>> ISABEL: YOU CAN DO THE
LINE 

1470
01:03:10,829 --> 01:03:13,032
ACROSS AND IT DOESN'T GET BETTER

1471
01:03:13,032 --> 01:03:17,069
AND THIS IS THE COGNITIVE AND 

1472
01:03:17,069 --> 01:03:18,938
BEHAVIORAL.  AND SO, NOW, TRY TO

1473
01:03:18,938 --> 01:03:20,506
REMEMBER, YOU KNOW, THE OTHER 

1474
01:03:20,506 --> 01:03:22,374
ONES WERE GOING ON THE OTHER 

1475
01:03:22,374 --> 01:03:25,044
DIRECTION BASICALLY, YEP.

1476
01:03:25,044 --> 01:03:27,947
>> AUDIENCE: THEY'RE
ACTUALLY 

1477
01:03:27,947 --> 01:03:29,682
GOING DOWN.  

1478
01:03:29,682 --> 01:03:30,582
>> ISABEL: MOST OF THEM
ARE 

1479
01:03:30,582 --> 01:03:32,651
GETTING WORSE.  THE PATIENTS ARE

1480
01:03:32,651 --> 01:03:35,821
BASICALLY, THEY KEEP, THE 

1481
01:03:35,821 --> 01:03:39,124
DISTANCE BETWEEN THE STANDARD 

1482
01:03:39,124 --> 01:03:41,860
NORMAL, YOU KNOW, COGNITIVE IN 

1483
01:03:41,860 --> 01:03:44,997
THESE PATIENTS, IT GETS WIDENED 

1484
01:03:44,997 --> 01:03:46,365
BASICALLY OF THE AGE AND SO 

1485
01:03:46,365 --> 01:03:50,235
THAT'S WHY THINGS GET WORSE AND 

1486
01:03:50,235 --> 01:03:55,140
WORSE, YEAH.  ABSOLUTELY.  

1487
01:03:55,140 --> 01:03:59,878
WHOOPS.  CAN I GO BACKWARDS?  

1488
01:03:59,878 --> 01:04:04,216
YES, I CAN.  YES I CAN.  OH, THE

1489
01:04:04,216 --> 01:04:06,618
DIFFERENT ANTIEPILEPTIC DRUGS.  

1490
01:04:06,618 --> 01:04:11,256
CLOSE TO 50% ARE ALREADY ON 

1491
01:04:11,256 --> 01:04:11,457
THESE.

1492
01:04:11,457 --> 01:04:12,257
>> AUDIENCE: IF YOU CAN
COMMENT 

1493
01:04:12,257 --> 01:04:13,826
ON THE AGE OF THE PATIENTS THAT 

1494
01:04:13,826 --> 01:04:14,827
WERE TREATED IN THE TRIAL AND IF

1495
01:04:14,827 --> 01:04:16,895
YOU SEE ANY DIFFERENCES IN THE 

1496
01:04:16,895 --> 01:04:19,298
RESPONSE?  AND THEN SECONDLY, 

1497
01:04:19,298 --> 01:04:20,666
THE INCLUSION CRITERIA AS FAR AS

1498
01:04:20,666 --> 01:04:23,602
TYPE OF MUTATIONS YOU INCLUDED 

1499
01:04:23,602 --> 01:04:26,338
BOTH THE TRUNCATIONS?  

1500
01:04:26,338 --> 01:04:28,907
>> ISABEL: YEAH, YEAH, WE 

1501
01:04:28,907 --> 01:04:31,610
INCLUDED THE TRUNCATIONS AND 

1502
01:04:31,610 --> 01:04:32,678
THAT'S A GOOD QUESTION.  WE KNEW

1503
01:04:32,678 --> 01:04:34,246
THERE WERE LOTS OF FUNCTIONS 

1504
01:04:34,246 --> 01:04:35,214
BECAUSE OF THE CLINICAL 

1505
01:04:35,214 --> 01:04:36,815
PHENOTYPE AND WHAT WAS KNOWN 

1506
01:04:36,815 --> 01:04:38,717
ALREADY.  BUT BECAUSE WE'RE 

1507
01:04:38,717 --> 01:04:42,388
UPREGULATING BOTH, WE DIDN'T 

1508
01:04:42,388 --> 01:04:46,225
KNOW THEY WERE GOING TO TAKE THE

1509
01:04:46,225 --> 01:04:48,761
SPOTS BUT WHEN WE SEPARATED, 

1510
01:04:48,761 --> 01:04:49,728
THERE WERE NO DIFFERENCES SO WE 

1511
01:04:49,728 --> 01:04:51,363
WERE SUPER EXCITED ABOUT THAT.  

1512
01:04:51,363 --> 01:04:55,067
SO THAT WAS ONE OF THE 

1513
01:04:55,067 --> 01:04:58,003
QUESTIONS.  NOW I -- OH SO THE 

1514
01:04:58,003 --> 01:05:00,205
PATIENTS ARE 2-18 AND I THINK I 

1515
01:05:00,205 --> 01:05:01,607
HAVE ANOTHER SLIDE THIS THE 

1516
01:05:01,607 --> 01:05:03,575
BACKUP JUST IN CASE.  SO THIS IS

1517
01:05:03,575 --> 01:05:06,378
BROKEN DOWN IN DOSES.  TWO 

1518
01:05:06,378 --> 01:05:08,580
DOSES, THREE DOSES, TWO MONTHS, 

1519
01:05:08,580 --> 01:05:10,349
THREE MONTHS, SIX MONTHS BASED 

1520
01:05:10,349 --> 01:05:12,251
ON AGE.  YOU CAN SEE IN THE 

1521
01:05:12,251 --> 01:05:15,120
HIGHEST RESPONDING GROUPS, THEY 

1522
01:05:15,120 --> 01:05:20,492
ARE 14 YEAR OLDS.  AGAIN, NO 

1523
01:05:20,492 --> 01:05:21,627
CLEAR EFFECT ON AGE EITHER.  

1524
01:05:21,627 --> 01:05:24,830
YEP.

1525
01:05:24,830 --> 01:05:27,032
>> AUDIENCE: EXCITING DATA
ON 

1526
01:05:27,032 --> 01:05:30,369
THE TRIAL.  I WAS VERY 

1527
01:05:30,369 --> 01:05:34,373
INTERESTED IN THE POSSIBLE 

1528
01:05:34,373 --> 01:05:38,677
VARIABILITY RESPONSE BETWEEN 

1529
01:05:38,677 --> 01:05:40,879
PATIENTS.  THERE WERE SOME THAT 

1530
01:05:40,879 --> 01:05:42,381
RESPONDED, SOME DID NOT.  DID 

1531
01:05:42,381 --> 01:05:48,187
YOU SEE ANYTHING LIKE THAT?  

1532
01:05:48,187 --> 01:05:49,988
>> ISABEL: OF COURSE THERE
WAS 

1533
01:05:49,988 --> 01:05:54,359
VARIABILITY AND IF WE GO TO, I 

1534
01:05:54,359 --> 01:06:01,100
THINK.  HERE IN THE SEIZURES, 

1535
01:06:01,100 --> 01:06:03,402
FOR EXAMPLE, YOU CAN CLEARLY SEE

1536
01:06:03,402 --> 01:06:05,137
THAT NOT ALL PATIENTS RESPOND AT

1537
01:06:05,137 --> 01:06:07,973
EXACTLY 85% BUT THE VARIABILITY 

1538
01:06:07,973 --> 01:06:09,641
ACROSS THE 70 MILLIGRAM GROUP 

1539
01:06:09,641 --> 01:06:11,210
THIS IS WHERE THINGS GOT A 

1540
01:06:11,210 --> 01:06:13,579
LITTLE BIT MORE NARROW SO THE 

1541
01:06:13,579 --> 01:06:15,714
HIGHER THE DOSE THAN THE 

1542
01:06:15,714 --> 01:06:17,616
VARIABILITY WOULD BE DOWN.

1543
01:06:17,616 --> 01:06:20,119
>> AUDIENCE: INTERESTING. 

1544
01:06:20,119 --> 01:06:22,054
>> ISABEL: THANK YOU.

1545
01:06:22,054 --> 01:06:25,724
>> ONE MORE QUESTION.

1546
01:06:25,724 --> 01:06:26,859
>> AUDIENCE: CAN YOU
COMMENT ON 

1547
01:06:26,859 --> 01:06:29,394
WHAT SORTS OF PHASE THREE 

1548
01:06:29,394 --> 01:06:30,362
DESIGNS ARE YOU CONSIDER 

1549
01:06:30,362 --> 01:06:32,498
SOMETHING ARE YOU GOING A RUN IN

1550
01:06:32,498 --> 01:06:38,504
STUDY OR A RANDOM CONTROL TRIAL?

1551
01:06:38,504 --> 01:06:44,510
>> ISABEL: WE ARE
CONSIDERING A 

1552
01:06:44,510 --> 01:06:46,845
PLACEBO RANDOMIZED CONTROL.  

1553
01:06:46,845 --> 01:06:48,180
THOSE ARE CONVERSATIONS WE'RE 

1554
01:06:48,180 --> 01:06:49,915
GOING TO BE HAVING WITH THE FDA 

1555
01:06:49,915 --> 01:06:50,883
TO UNDERSTAND, YOU KNOW, BUT, 

1556
01:06:50,883 --> 01:06:54,052
YES, IT'S GOING TO HAVE A FULL, 

1557
01:06:54,052 --> 01:06:56,622
YEP.  THANK YOU.  THANKS FOR THE

1558
01:06:56,622 --> 01:06:58,357
QUESTIONS.

1559
01:06:58,357 --> 01:07:07,533
>> AUDIENCE: (APPLAUSE).  

1560
01:07:07,533 --> 01:07:10,235
>> LORI: I ADMIT THAT'S
BIASED 

1561
01:07:10,235 --> 01:07:13,872
BUT THAT'S PRETTY IMPRESSIVE.  

1562
01:07:13,872 --> 01:07:15,908
NEXT IS DR. GAIA WHO IS GOING TO

1563
01:07:15,908 --> 01:07:17,643
TELL US HOW TO TARGET THE RIGHT 

1564
01:07:17,643 --> 01:07:20,479
CELLS AT THE RIGHT TIME.  GAIA, 

1565
01:07:20,479 --> 01:07:25,284
THANK YOU 

1566
01:07:25,284 --> 01:07:31,356
>> KATIE: THANK YOU.  SO I
WILL 

1567
01:07:31,356 --> 01:07:34,359
TALK TODAY ABOUT SOMETHING WE 

1568
01:07:34,359 --> 01:07:40,866
TAL

1569
01:07:40,866 --> 01:07:42,401
TALKED ABOUT WITH GENE THERAPY 

1570
01:07:42,401 --> 01:07:45,137
DEVELOPMENT.  ALL RIGHT, CAN I 

1571
01:07:45,137 --> 01:07:54,379
GO ON?  READY?  OKAY.  THIS ONE?

1572
01:07:54,379 --> 01:07:58,650
OKAY.  THANK YOU.  SO WE STARTED

1573
01:07:58,650 --> 01:08:02,354
THINKING WHY GENE THERAPIES 

1574
01:08:02,354 --> 01:08:07,426
MIGHT BE INEFFECTIVE AND THIS IS

1575
01:08:07,426 --> 01:08:08,493
SOMETHING THAT MIGHT BE 

1576
01:08:08,493 --> 01:08:10,395
POSSIBLE.  THERE MAY BE 

1577
01:08:10,395 --> 01:08:12,531
LIMITATIONS THAT WE ARE ADOPTING

1578
01:08:12,531 --> 01:08:14,366
SO WE ARE NOT ACHIEVING THE 

1579
01:08:14,366 --> 01:08:16,034
CORRECT LEVEL OR GENE EXPRESSION

1580
01:08:16,034 --> 01:08:17,970
THAT WE WOULD LIKE IN THE CELL 

1581
01:08:17,970 --> 01:08:20,505
SO IT'S TOO LOW OR TOO MUCH OR 

1582
01:08:20,505 --> 01:08:22,374
LOW DELIVERY EFFICIENCY SO WE 

1583
01:08:22,374 --> 01:08:25,577
ARE TALKING ABOUT THE IMPORTANCE

1584
01:08:25,577 --> 01:08:31,984
OF CHOOSING THE RIGHT AMOUNT TO 

1585
01:08:31,984 --> 01:08:33,385
TARGET THE PART OF THE TRAIN 

1586
01:08:33,385 --> 01:08:35,254
THAT WE WANT TO TARGET AND WE 

1587
01:08:35,254 --> 01:08:37,189
MAY HAVE LOW SPECIFICITY, WE MAY

1588
01:08:37,189 --> 01:08:39,658
TARGET MOST OF THE BRAIN BUT NOT

1589
01:08:39,658 --> 01:08:41,760
THE RIGHT.  WE WANT TO TARGET ON

1590
01:08:41,760 --> 01:08:44,963
THE RIGHT CIRCUITS.  OR LAST ON 

1591
01:08:44,963 --> 01:08:47,366
THE LIST, WE MAY HAVE A PROBLEM 

1592
01:08:47,366 --> 01:08:50,369
IN TIMING IN GENE THERAPY 

1593
01:08:50,369 --> 01:08:53,839
DELIVERY AND SO WHY TIMING IS 

1594
01:08:53,839 --> 01:08:57,042
IMPORTANT?  IT IS IMPORTANT IN 

1595
01:08:57,042 --> 01:08:59,311
PATHOLOGY BECAUSE WE SHOULD KNOW

1596
01:08:59,311 --> 01:09:02,314
THAT, OR DO KNOW THAT THE 

1597
01:09:02,314 --> 01:09:03,915
INITIAL PATHOLOGICAL MECHANISM 

1598
01:09:03,915 --> 01:09:06,652
IS MAYBE A GENE MUTATION 

1599
01:09:06,652 --> 01:09:09,921
FOLLOWED BY MANY CHANGES IN 

1600
01:09:09,921 --> 01:09:11,123
SEQUENCE.  SOME OF THEM ARE MORE

1601
01:09:11,123 --> 01:09:15,093
ADAPTIVE CHANGES AND SO THIS 

1602
01:09:15,093 --> 01:09:17,529
MODIFICATION LEADS TO A 

1603
01:09:17,529 --> 01:09:18,830
SITUATION THAT MAY BE DIFFERENT 

1604
01:09:18,830 --> 01:09:20,532
FROM THE ONES THAT YOU INITIALLY

1605
01:09:20,532 --> 01:09:22,601
TARGETED SO WE MAY HAVE A DESIGN

1606
01:09:22,601 --> 01:09:24,236
IN GENE THERAPY STRATEGIES THAT 

1607
01:09:24,236 --> 01:09:25,404
HAVE NOT EVIDENCE FOR THE 

1608
01:09:25,404 --> 01:09:28,106
CONDITION OF THE BRAIN THAT WE 

1609
01:09:28,106 --> 01:09:31,076
ACHIEVED.  AND THIS IS EVEN MORE

1610
01:09:31,076 --> 01:09:34,346
IMPORTANT.  WE CAN SEE THE 

1611
01:09:34,346 --> 01:09:39,251
DEVELOPMENT TA AND EPILEPTIC 

1612
01:09:39,251 --> 01:09:41,186
ENRECEIVE LOP PA THINK BECAUSE 

1613
01:09:41,186 --> 01:09:43,155
THERE'S CHANGES IN THE PROCEDURE

1614
01:09:43,155 --> 01:09:45,190
BUT ALSO ADDING DISFUNCTION INTO

1615
01:09:45,190 --> 01:09:47,326
IN THE DEVELOPMENT PROCESS. 

1616
01:09:47,326 --> 01:09:50,362
SO GENE MUTATION IN THESE 

1617
01:09:50,362 --> 01:09:58,837
SPECIFIC JEEP MAY HAVE AN IM

1618
01:09:58,837 --> 01:10:04,109
IMPACT.  AND THIS IS DURING THE 

1619
01:10:04,109 --> 01:10:06,478
RODENTS AND SO IT IS PART OF THE

1620
01:10:06,478 --> 01:10:08,513
DEVELOPMENTAL PROPERTY THAT CAN 

1621
01:10:08,513 --> 01:10:11,483
BE ALSO WORSENED BY THE 

1622
01:10:11,483 --> 01:10:14,219
PROCEDURE AND SO WE BRING TO YOU

1623
01:10:14,219 --> 01:10:18,357
AGAIN A SPECIFIC EXAMPLE OF THE 

1624
01:10:18,357 --> 01:10:23,695
DRAVET SYNDROME.  AND THIS IS 

1625
01:10:23,695 --> 01:10:25,897
SHOWN BY HAPPEN LO 

1626
01:10:25,897 --> 01:10:26,598
INSUFFICIENCY.  AND YOU SEE THIS

1627
01:10:26,598 --> 01:10:31,903
IN THE MAIN LOCALIZED IN THE 

1628
01:10:31,903 --> 01:10:39,177
SPECIFIC AREA WHERE THIS IS 

1629
01:10:39,177 --> 01:10:41,413
RELEVANT.  AND THERE'S AN 

1630
01:10:41,413 --> 01:10:44,049
ESSENTIAL ROLE BECAUSE YOU 

1631
01:10:44,049 --> 01:10:44,816
LOCALIZE. WHERE THIS IS RELEVAN 

1632
01:10:44,816 --> 01:10:45,350
THERE'S AN ESSENTIAL ROLE 

1633
01:10:45,350 --> 01:10:48,653
BECAUSE YOU LOCALIZE.  AND 

1634
01:10:48,653 --> 01:10:50,355
INITIALLY, THIS SHOWED US IT'S 

1635
01:10:50,355 --> 01:10:54,226
REACHING A NEURON AND IT IS WHY 

1636
01:10:54,226 --> 01:10:56,762
THE SPECIFIC ACTIVITY OF THIS IS

1637
01:10:56,762 --> 01:10:58,897
FAILED.  SO YOU CAN SEE THIS 

1638
01:10:58,897 --> 01:11:02,234
TYPE OF MOUSE IN THE NEURONS ARE

1639
01:11:02,234 --> 01:11:05,904
NOT ABLE TO CONTROL.  WHILE AT 

1640
01:11:05,904 --> 01:11:08,340
LEAST AT THE FIRST GLANCE THE 

1641
01:11:08,340 --> 01:11:12,444
NEURONS SEEM TO BE PRESERVED SO 

1642
01:11:12,444 --> 01:11:14,012
INDICATING A FUNCTION SPECIFIC 

1643
01:11:14,012 --> 01:11:18,183
OF THE NEURONS COULD UNDERLIE 

1644
01:11:18,183 --> 01:11:21,453
THE BALANCE BETWEEN THE  THIS 

1645
01:11:21,453 --> 01:11:27,292
AND CAN CAUSE SEIZURES.  

1646
01:11:27,292 --> 01:11:29,094
THE POWS START TO APPEAR AROUND 

1647
01:11:29,094 --> 01:11:31,530
THE THIRD WEEK.  SO MICE START 

1648
01:11:31,530 --> 01:11:35,801
TO DIE.  AND LATER ON THEY ALSO 

1649
01:11:35,801 --> 01:11:42,774
START TO HAVE, APPEAR WITH 

1650
01:11:42,774 --> 01:11:48,547
ANXIETY AND THEY ARE 

1651
01:11:48,547 --> 01:11:52,818
HYPERACTIVE.  SO BUT FEW YEARS 

1652
01:11:52,818 --> 01:11:56,521
AGO AN IMPORTANT PAPER COME OUT 

1653
01:11:56,521 --> 01:11:58,757
DESCRIBING THAT WHAT IS 

1654
01:11:58,757 --> 01:12:01,793
CONSIDERED TO BE ALL MATTER OF 

1655
01:12:01,793 --> 01:12:05,564
DISEASE, THE NEURON FUNCTION IS 

1656
01:12:05,564 --> 01:12:08,867
TRANSIENT.  IT APPEARS IN THE 

1657
01:12:08,867 --> 01:12:12,938
ONSET OF DISEASE AND THIS HAS 

1658
01:12:12,938 --> 01:12:13,872
COMPLETELY CHANGED THE VIEW THAT

1659
01:12:13,872 --> 01:12:16,274
WE HAVE IN THE PATHOLOGY AND IT 

1660
01:12:16,274 --> 01:12:18,376
IS POSSIBLE SO PROBABLY TO 

1661
01:12:18,376 --> 01:12:22,347
RECRUIT INTO THE SEGMENT OR 

1662
01:12:22,347 --> 01:12:28,487
OTHER EDUCATION.  AND SO WHAT IS

1663
01:12:28,487 --> 01:12:30,989
IN THE FEN PHENOTYPES.  THERE IS

1664
01:12:30,989 --> 01:12:31,957
SOMETHING ELSE. 

1665
01:12:31,957 --> 01:12:35,327
AND THE LAB SHOWED THAT WHILE 

1666
01:12:35,327 --> 01:12:37,829
THE FIGHTING IS RECOVERED WHAT 

1667
01:12:37,829 --> 01:12:42,400
IS THERE IS THE PROPAGATION OF 

1668
01:12:42,400 --> 01:12:46,371
THE AX ON AND SO THERE IS MORE A

1669
01:12:46,371 --> 01:12:47,472
PROBLEM OF THE SUBMISSION INTO 

1670
01:12:47,472 --> 01:12:50,108
THE NEURONS.  AND THE OTHER 

1671
01:12:50,108 --> 01:12:54,880
SIDE, WHAT YOU OBSERVE, IS THAT 

1672
01:12:54,880 --> 01:12:57,849
THERE ARE SEQUENCES THAT ARE 

1673
01:12:57,849 --> 01:13:02,420
EXCITABLE.  AND ARE DESCRIBED 

1674
01:13:02,420 --> 01:13:06,925
AND THESE ARE COMING FROM THE 

1675
01:13:06,925 --> 01:13:11,730
CORTEX.  SO YOU HAVE THE 

1676
01:13:11,730 --> 01:13:13,298
CONDITION WHICH WE HAVE THE 

1677
01:13:13,298 --> 01:13:14,266
NEURON FUNCTION AT LEAST AT THE 

1678
01:13:14,266 --> 01:13:16,434
ONSET OF DISEASE AND LATER ON WE

1679
01:13:16,434 --> 01:13:18,370
HAVE THE COMPLETE CHANGED 

1680
01:13:18,370 --> 01:13:22,374
SITUATION AND SO IN THIS 

1681
01:13:22,374 --> 01:13:24,543
CONDITION PATIENTS WILL BE 

1682
01:13:24,543 --> 01:13:26,678
SUFFICIENT TO JUST INTRODUCE 

1683
01:13:26,678 --> 01:13:30,115
THIS AGAIN TO ACHIEVE.  AND YES,

1684
01:13:30,115 --> 01:13:31,216
THERE'LL BE A CRITICAL WINDOW 

1685
01:13:31,216 --> 01:13:35,120
FOR DELIVERY AND NOW WE HAVE THE

1686
01:13:35,120 --> 01:13:37,289
BEAUTIFUL REPRESENTATION SHOWING

1687
01:13:37,289 --> 01:13:42,394
THE BEAUTIFUL DATA GENE THERAPY.

1688
01:13:42,394 --> 01:13:45,897
THAT ACTUALLY WHEN WE STARTED 

1689
01:13:45,897 --> 01:13:47,566
THE QUESTION, THERE WERE OF 

1690
01:13:47,566 --> 01:13:50,201
COURSE MANY OTHER INTERESTS, 

1691
01:13:50,201 --> 01:13:53,605
MANY GROUPS WORKING ON GENE 

1692
01:13:53,605 --> 01:13:54,539
THERAPY STRATEGIES.  

1693
01:13:54,539 --> 01:13:57,175
ESSENTIALLY, ALL WITH THE TWO 

1694
01:13:57,175 --> 01:14:00,378
MAIN STRATEGIES POSSIBLE UP TO 

1695
01:14:00,378 --> 01:14:02,447
YESTERDAY I WOULD SAY WHEN THESE

1696
01:14:02,447 --> 01:14:06,551
WERE ALSO A WAY, A GOOD WAY TO 

1697
01:14:06,551 --> 01:14:08,486
GO.  SO THERE WERE ESSENTIALLY 

1698
01:14:08,486 --> 01:14:10,855
TO PLAN A NEW COPY OF THE GENE 

1699
01:14:10,855 --> 01:14:14,192
OR BOOSTING EXPRESSION TO MAKE 

1700
01:14:14,192 --> 01:14:16,628
IT -- PRODUCE WHAT IS REQUIRED 

1701
01:14:16,628 --> 01:14:20,131
TO MAKE NEURONS TO WORK AGAIN.  

1702
01:14:20,131 --> 01:14:23,602
AND SO TO OUR BEST IMPRESSION WE

1703
01:14:23,602 --> 01:14:26,371
THOUGHT WE COULD NOT DO JUST 

1704
01:14:26,371 --> 01:14:32,544
SIMPLY HAVE A GENE STRATEGY SO 

1705
01:14:32,544 --> 01:14:37,148
WE ARE CARRYING A SUBSET IN ONE 

1706
01:14:37,148 --> 01:14:41,019
GENE SO IT CAN HAVE THE AX ON 

1707
01:14:41,019 --> 01:14:44,556
AND SO THESE MICE WERE BORN BUT 

1708
01:14:44,556 --> 01:14:47,325
THEY CARRY THE SEQUENCE AND BY 

1709
01:14:47,325 --> 01:14:48,426
THE COMBINATION WE CAN STOP THIS

1710
01:14:48,426 --> 01:14:50,362
AND RESTORE A FUNCTIONAL ALLELE 

1711
01:14:50,362 --> 01:14:53,398
IN TIME DURING THE PROGRESSION 

1712
01:14:53,398 --> 01:14:56,001
OF DISEASE AND SO I MEAN, 

1713
01:14:56,001 --> 01:14:57,402
GETTING INFORMATION FOR GENE 

1714
01:14:57,402 --> 01:14:59,070
THERAPY DELIVERY.  AND SO I WANT

1715
01:14:59,070 --> 01:15:02,807
ALSO TO EXPRESS THE FACT THAT WE

1716
01:15:02,807 --> 01:15:06,778
ARE LIKELY MIMICKING A GENE 

1717
01:15:06,778 --> 01:15:09,080
THERAPY BASED ON THE MUTATION 

1718
01:15:09,080 --> 01:15:10,315
BECAUSE WE ARE RELYING ON THE 

1719
01:15:10,315 --> 01:15:13,385
SEQUENCE OF THE SAME GENE 

1720
01:15:13,385 --> 01:15:15,987
BECAUSE WE ARE JUST DEACTIVATING

1721
01:15:15,987 --> 01:15:18,923
THE GENE AND NOT -- CLARITY, FOR

1722
01:15:18,923 --> 01:15:23,461
EXAMPLE, IN THE PROMOTER.  SO 

1723
01:15:23,461 --> 01:15:27,866
HOW WE COULD ACHIEVE THE CONTROL

1724
01:15:27,866 --> 01:15:30,068
OF TIME FOR THE ACTIVATION.  WE 

1725
01:15:30,068 --> 01:15:32,303
CAN DO THIS IN OTHER WAYS.  BUT 

1726
01:15:32,303 --> 01:15:36,141
WE DECIDE TO DO THAT USING THE 

1727
01:15:36,141 --> 01:15:40,412
DELIVERY OF THE RECOME BY  -- 

1728
01:15:40,412 --> 01:15:44,549
RECOME BY NICE BUT WE USE THE 

1729
01:15:44,549 --> 01:15:46,351
VIRUS.  

1730
01:15:46,351 --> 01:15:47,919
BETWEEN THE SYSTEMICALLY 

1731
01:15:47,919 --> 01:15:50,955
CONSIDERING WHAT IS PRESENT.  

1732
01:15:50,955 --> 01:16:01,499
AND USE THE BRAIN EFFICIENCY.  

1733
01:16:02,634 --> 01:16:09,974
SO WE WE W RELEASE THIS AT C 2. 

1734
01:16:09,974 --> 01:16:13,078
SO WE STRESSED THAT OUR STRATEGY

1735
01:16:13,078 --> 01:16:15,146
WAS ABLE TO INCREASE AND RESTORE

1736
01:16:15,146 --> 01:16:17,282
THE LEVEL OF THE PROTEIN AND SO 

1737
01:16:17,282 --> 01:16:19,651
ESSENTIALLY WE SEE THAT OUR 

1738
01:16:19,651 --> 01:16:20,852
SUBSETS FIRST OF ALL WAS 

1739
01:16:20,852 --> 01:16:23,855
WORKING.  SO WITH MICE, WE WERE 

1740
01:16:23,855 --> 01:16:25,724
EXACTLY AT THE LEVEL OF THE 

1741
01:16:25,724 --> 01:16:28,460
PROTEIN.  AND IT WAS TRUE IN 

1742
01:16:28,460 --> 01:16:30,395
DIFFERENT BRAIN COMPARTMENTS IN 

1743
01:16:30,395 --> 01:16:33,598
THE CEREBELLUM WHILE WHEN YOU 

1744
01:16:33,598 --> 01:16:36,534
DELIVER, WE COULD ACHIEVE AGAIN 

1745
01:16:36,534 --> 01:16:38,269
THE LEVEL OF ONE IN THIS 

1746
01:16:38,269 --> 01:16:40,171
COMPARTMENT SO WE ARE REALLY 

1747
01:16:40,171 --> 01:16:43,141
RESTORING THE LEVEL OF THE 

1748
01:16:43,141 --> 01:16:45,276
PROTEIN.  AND SO GIVEN THIS IS 

1749
01:16:45,276 --> 01:16:48,446
WORKING PROPERLY WE CAN START 

1750
01:16:48,446 --> 01:16:51,816
OUR FUNCTIONAL PROPERTIES.  SO 

1751
01:16:51,816 --> 01:16:59,224
IN THIS THE MICE START TO DIE 

1752
01:16:59,224 --> 01:17:00,892
AND WE WERE CHECKING TO RECORD 

1753
01:17:00,892 --> 01:17:02,894
ABOUT THE ENZYME ASSESSING THE 

1754
01:17:02,894 --> 01:17:05,263
SEIZURES PHENOTYPE JUST IN THIS 

1755
01:17:05,263 --> 01:17:08,600
CASE BY THE OPTION AND WE COULD 

1756
01:17:08,600 --> 01:17:10,068
SEE ESSENTIALLY THAT WE WERE 

1757
01:17:10,068 --> 01:17:11,770
ABLE, WITH A SINGLE INJECTION WE

1758
01:17:11,770 --> 01:17:16,741
WERE ACTIVATING THE GENE.  WE 

1759
01:17:16,741 --> 01:17:19,744
COULD ACHIEVE THAT AND ALSO 

1760
01:17:19,744 --> 01:17:21,846
FURTHER IN THE SEIZURE BUT THIS 

1761
01:17:21,846 --> 01:17:23,648
WAS KIND OF EXPECTED BECAUSE WE 

1762
01:17:23,648 --> 01:17:25,750
WERE KIND OF FIXING THE GENE LOG

1763
01:17:25,750 --> 01:17:27,952
EVEN BEFORE THE GENE STARTS TO 

1764
01:17:27,952 --> 01:17:33,191
BE EXPRESSED BUT WHAT HAPPENS 

1765
01:17:33,191 --> 01:17:34,225
LATER?  THERE'S THE GENE 

1766
01:17:34,225 --> 01:17:42,433
THERAPY, IN THIS CASE, SO MICE 

1767
01:17:42,433 --> 01:17:49,107
WERE IN THE CHROMOSOME.  AND 

1768
01:17:49,107 --> 01:17:51,309
THEN AGAIN WE SEE A COMPLETE 

1769
01:17:51,309 --> 01:17:52,811
RESCUE IN OUR TEEN TYPE AND THE 

1770
01:17:52,811 --> 01:17:56,614
MICE WERE STILL DYING ALSO OF 

1771
01:17:56,614 --> 01:17:59,317
THE SPECIFIC POINTS.  AFTER GENE

1772
01:17:59,317 --> 01:18:02,387
THERAPY SO WHAT ABOUT THE 

1773
01:18:02,387 --> 01:18:06,391
SEIZURES?  SO, AGAIN, MICE IN 

1774
01:18:06,391 --> 01:18:14,065
WHICH EXCEED 45, AND MICE WERE 

1775
01:18:14,065 --> 01:18:17,702
PRETTY HAPPY IN THIS CASE WHICH 

1776
01:18:17,702 --> 01:18:20,839
IS MORE EFFORT IN PLANTED AND 

1777
01:18:20,839 --> 01:18:23,975
TWO IN THE DATA FROM THE CORTEX 

1778
01:18:23,975 --> 01:18:25,310
AND SO THESE MICE FOR A LONG 

1779
01:18:25,310 --> 01:18:27,011
TIME SO FOR TWO WEEKS AND WE 

1780
01:18:27,011 --> 01:18:32,016
COULD HAVE SERVED AT OUR CONSOLE

1781
01:18:32,016 --> 01:18:34,052
ANIMAL LIKE MODEL WHERE THE 

1782
01:18:34,052 --> 01:18:38,056
SEIZURES ALONG THE TWO WEEKS OF 

1783
01:18:38,056 --> 01:18:41,292
OBSERVATION SO YOU SEE IN THE 

1784
01:18:41,292 --> 01:18:42,360
VERTICAL LINE EACH MONTH AND THE

1785
01:18:42,360 --> 01:18:44,162
HORIZONTAL LINE YOU SEE THE 

1786
01:18:44,162 --> 01:18:45,830
SEIZURE THAT MICE HAD DURING THE

1787
01:18:45,830 --> 01:18:48,299
TWO WEEKS.  SO IT'S ANOTHER LOG 

1788
01:18:48,299 --> 01:18:51,769
LIKE THE SEIZURE DIARY.  

1789
01:18:51,769 --> 01:18:55,139
INSTEAD, WHEN -- IN MICE WE HAVE

1790
01:18:55,139 --> 01:18:57,642
ONCE THAT DEACTIVATED WE NEVER 

1791
01:18:57,642 --> 01:18:58,376
HAVE THIS DURING THE TWO WEEKS 

1792
01:18:58,376 --> 01:19:02,380
OF OBSERVATION.  I JUST WANTED 

1793
01:19:02,380 --> 01:19:05,083
TO PICK THAT AND ONCE THIS IS 

1794
01:19:05,083 --> 01:19:07,785
INCREASED WE TREAT THE MICE AND 

1795
01:19:07,785 --> 01:19:09,721
SUBJECT THEM TO THE SEIZURES AND

1796
01:19:09,721 --> 01:19:12,357
IF WE DIDN'T THE MICE HAVE THE 

1797
01:19:12,357 --> 01:19:16,194
SEIZURE IN THIS CASE.  ALL THE 

1798
01:19:16,194 --> 01:19:19,264
CONTROLLED MICE HAD A SEIZURE 

1799
01:19:19,264 --> 01:19:23,234
WHILE NONE OF THE MICE WERE 

1800
01:19:23,234 --> 01:19:25,570
DEACTIVATED WITH P30.  SO WE 

1801
01:19:25,570 --> 01:19:26,871
HAVE THAT WITH THE PHENOTYPE 

1802
01:19:26,871 --> 01:19:28,573
WHAT ABOUT THE REACTIVATION THAT

1803
01:19:28,573 --> 01:19:34,345
IS IMPORTANT ALSO FOR SUFFICIENT

1804
01:19:34,345 --> 01:19:36,147
RECOVERY.  SO WE HAVE THE MICE 

1805
01:19:36,147 --> 01:19:38,383
ACTIVITY IN OPEN SCALE SETS.  

1806
01:19:38,383 --> 01:19:42,954
AND THEY LOOK AT THE MICE.  SO 

1807
01:19:42,954 --> 01:19:45,857
THEY HAVE THIS COMPARED TO 

1808
01:19:45,857 --> 01:19:51,396
OFF-SITE ANIMALS WHILE MICE WERE

1809
01:19:51,396 --> 01:19:52,096
DEACTIV

1810
01:19:52,096 --> 01:19:54,532
DEACTIVATED.  AND THEY ALSO HAVE

1811
01:19:54,532 --> 01:19:58,403
THE SOCIAL SKILLS.  WE HAVE 30 

1812
01:19:58,403 --> 01:20:03,308
MICE WHICH HAD THE SKILLS WHILE 

1813
01:20:03,308 --> 01:20:13,851
OUR MICE.  AND WE HAVE THE CAN 

1814
01:20:17,121 --> 01:20:20,625
SEE THAT WHILE JUVENILE MICE 

1815
01:20:20,625 --> 01:20:24,529
MAKE MORE MISTAKES INTO 

1816
01:20:24,529 --> 01:20:27,665
NAVIGATING THE MAZE THE MICE 

1817
01:20:27,665 --> 01:20:32,603
THAT WERE DEACTIVATED ARE MORE 

1818
01:20:32,603 --> 01:20:34,005
PARTICULARLY IF YOU LOOK AT THE 

1819
01:20:34,005 --> 01:20:37,175
NUMBER OF THE CHOICE YOU DO SEE 

1820
01:20:37,175 --> 01:20:39,377
THAT THE MICE NEVER OVERCOME THE

1821
01:20:39,377 --> 01:20:42,113
LEVEL.  DURING THOSE DATASETS 

1822
01:20:42,113 --> 01:20:45,550
WHILE IN THE WILD TYPE THEY HAVE

1823
01:20:45,550 --> 01:20:50,822
THE TIME ALREADY AT THE FACTOR. 

1824
01:20:50,822 --> 01:20:53,891
SO WHAT ABOUT LATER ON?  

1825
01:20:53,891 --> 01:20:57,328
JUVENILE MICE CAN BE COMPARED TO

1826
01:20:57,328 --> 01:21:00,565
PATIENTS IN FEW YEARS AFTER 

1827
01:21:00,565 --> 01:21:02,567
DIAGNOSIS BUT WHAT ABOUT 

1828
01:21:02,567 --> 01:21:05,837
ADAPTATION SHOULD THEY BE 

1829
01:21:05,837 --> 01:21:07,772
INCLUDED IN CLINICAL TRIALS AND 

1830
01:21:07,772 --> 01:21:11,676
WE FIND THE WINDOW SO THAT WE 

1831
01:21:11,676 --> 01:21:15,079
COULD EFFICIENTLY AND WE PERFORM

1832
01:21:15,079 --> 01:21:18,383
A LATE OBSERVATION OF THIS GENE 

1833
01:21:18,383 --> 01:21:20,818
IN THE MICE AND SO IN THIS CASE 

1834
01:21:20,818 --> 01:21:23,688
WE COULD HAVE THE ANIMALS EVEN 

1835
01:21:23,688 --> 01:21:26,624
BEFORE ACTIVATION OF THE GENE 

1836
01:21:26,624 --> 01:21:30,862
AND RECORD THE ACTIVITIES AND 

1837
01:21:30,862 --> 01:21:33,331
SEE SEE THE MICE IN THIS PHASE 

1838
01:21:33,331 --> 01:21:34,999
OF ABILITIES AND MICE WERE 

1839
01:21:34,999 --> 01:21:37,301
UNDERLYING THEM.  AND, AGAIN, 

1840
01:21:37,301 --> 01:21:38,903
WHAT WE SAW WAS THAT THE 

1841
01:21:38,903 --> 01:21:41,172
CONTROLLED MICE CONTINUE TO HAVE

1842
01:21:41,172 --> 01:21:45,176
SEIZURE FOR 21 DAYS AT LEAST 

1843
01:21:45,176 --> 01:21:48,212
WHILE THE OTHER ONE HAVE A 

1844
01:21:48,212 --> 01:21:51,983
SEIZURE AROUND ONE WEEK AFTER 

1845
01:21:51,983 --> 01:21:53,151
THE THESE MICE CHALLENGE AGAIN 

1846
01:21:53,151 --> 01:21:57,955
WITH AN INCREASING IN BODY 

1847
01:21:57,955 --> 01:22:00,324
TEMPERATURE YOU CAN SEE THAT 

1848
01:22:00,324 --> 01:22:02,160
THE, THE SEIZURE DETERMINED THE 

1849
01:22:02,160 --> 01:22:04,929
USE WHEN THE BODY WAS BEING 

1850
01:22:04,929 --> 01:22:09,000
BROUGHT BACK TO THE FUTURE.  SO 

1851
01:22:09,000 --> 01:22:15,740
TO SUM UP, WE CAN TELL THAT WHAT

1852
01:22:15,740 --> 01:22:16,741
WE LEARNED IS WE COULD RESCUE 

1853
01:22:16,741 --> 01:22:23,748
THE SEIZURES AT BOTH THE 

1854
01:22:23,748 --> 01:22:27,051
ALTERATION.  AND SO THIS IS AN 

1855
01:22:27,051 --> 01:22:30,388
INDICATION ALSO OF COURSE FOR 

1856
01:22:30,388 --> 01:22:38,162
PATIENTS BECAUSE THESE MEAN THAT

1857
01:22:38,162 --> 01:22:39,897
AN OPTIMAL GENE THERAPY 

1858
01:22:39,897 --> 01:22:40,965
ADMINISTERED AFTER DIAGNOSIS CAN

1859
01:22:40,965 --> 01:22:43,234
MAKE A DIFFERENCE AND IMPROVE 

1860
01:22:43,234 --> 01:22:46,137
THE OUTCOME FOR BOTH SEIZURE AND

1861
01:22:46,137 --> 01:22:48,539
BEHAVIORAL ALTERATION.  WE GOT A

1862
01:22:48,539 --> 01:22:50,374
VERY GOOD START IN TERMS OF SE 

1863
01:22:50,374 --> 01:22:56,614
SURE RE -- SE SURE REDUCTION.  

1864
01:22:56,614 --> 01:23:00,585
AND CONSIDERING THE ROLE OF THE 

1865
01:23:00,585 --> 01:23:02,253
DEVELOPMENT WE HAVE THE PATIENTS

1866
01:23:02,253 --> 01:23:06,023
TO ENSURE OF THE PERIOD THAT A 

1867
01:23:06,023 --> 01:23:10,394
TYPICAL WINDOW DEVELOPMENT TO 

1868
01:23:10,394 --> 01:23:14,932
GET ADMINISTRATION OF THE 

1869
01:23:14,932 --> 01:23:17,201
PHENOTYPE AND THIS IS 

1870
01:23:17,201 --> 01:23:22,373
SPECIFICALLY FOR THE THERAPY.  

1871
01:23:22,373 --> 01:23:24,175
TO DO THAT, I'M SORRY THIS SLIDE

1872
01:23:24,175 --> 01:23:27,812
IS ALL MESSED UP, ESSENTIALLY, 

1873
01:23:27,812 --> 01:23:29,680
WE USE THE CONDITION NOT IN 

1874
01:23:29,680 --> 01:23:33,618
MOUSE MODEL IN THIS CASE SO WE 

1875
01:23:33,618 --> 01:23:35,686
HAVE THESE MOUSE IN WHICH IT CAN

1876
01:23:35,686 --> 01:23:38,222
BE INSERTED.  IN THIS CASE WITH 

1877
01:23:38,222 --> 01:23:46,397
A MOUSE EXPRESSING THE  THIS.  

1878
01:23:46,397 --> 01:23:53,538
AND ESSENTIALLY WE HAVE HAVE 

1879
01:23:53,538 --> 01:23:56,874
CONTROL IN TIME TO PRODUCE THE 

1880
01:23:56,874 --> 01:23:58,376
EFFICIENCY.  SO IT'S THE 

1881
01:23:58,376 --> 01:24:01,279
EXPERIMENT AS BEFORE AND SO WE 

1882
01:24:01,279 --> 01:24:02,380
WERE MAINTAINING THE LEVEL OF 

1883
01:24:02,380 --> 01:24:06,050
THE FUNCTION NUMBER ONE.  AND 

1884
01:24:06,050 --> 01:24:07,385
COMPARING, LOOKING AFTER THE 

1885
01:24:07,385 --> 01:24:08,619
PHENOTYPE OF THESE MICE AND 

1886
01:24:08,619 --> 01:24:10,454
COMPARING THAT TO MICE IN WHICH 

1887
01:24:10,454 --> 01:24:13,391
WE HAVE THE SUFFICIENCY THAT WAS

1888
01:24:13,391 --> 01:24:16,327
USED.  AND WE CONSIDER THAT IN 

1889
01:24:16,327 --> 01:24:18,396
OTHER MICE SO WHAT WE CAN TELL 

1890
01:24:18,396 --> 01:24:23,801
IS CLEAR IS THAT ALL THE MICE IS

1891
01:24:23,801 --> 01:24:26,971
NOT SUFFICIENT TO PREVENT 

1892
01:24:26,971 --> 01:24:28,806
SEIZURES.  IT'S NOT THE WINDOW 

1893
01:24:28,806 --> 01:24:31,809
OF DEVELOPMENT TO GET RID OF THE

1894
01:24:31,809 --> 01:24:34,979
SEIZURES.  AND ALSO WHEN THESE 

1895
01:24:34,979 --> 01:24:37,949
MICE WERE CHALLENGED THERE IS NO

1896
01:24:37,949 --> 01:24:40,651
DIFFERENCE IN TERMS OF THERMAL 

1897
01:24:40,651 --> 01:24:42,386
UP DUCTION SO THAT THE SEIZURE 

1898
01:24:42,386 --> 01:24:46,157
IS COMPATIBLE AND ALSO IN TERMS,

1899
01:24:46,157 --> 01:24:54,398
TOO, ALL THE MICE HAVE TO  DIE 

1900
01:24:54,398 --> 01:24:57,201
AND IF WE MERGE THIS NORMALIZING

1901
01:24:57,201 --> 01:25:00,638
WHEN THE TIME OF ADMINISTRATION 

1902
01:25:00,638 --> 01:25:06,244
WE DID SEE THAT IN ALL THESE AND

1903
01:25:06,244 --> 01:25:08,312
WHAT ABOUT BEHAVIOR IN THE 

1904
01:25:08,312 --> 01:25:11,949
SIGNAL OF MICE WERE INTERACTING 

1905
01:25:11,949 --> 01:25:18,489
SO THEY ALSO HAD THE SPECIAL 

1906
01:25:18,489 --> 01:25:20,358
FUNCTION.  THE OTHER THING THAT 

1907
01:25:20,358 --> 01:25:22,393
CAME INTO CONTACT.  SO 

1908
01:25:22,393 --> 01:25:26,597
ESSENTIALLY WE DO SEE THESE 

1909
01:25:26,597 --> 01:25:37,108
MICE, WE CONSIDER ARE TAKE MORE 

1910
01:25:37,108 --> 01:25:38,376
TIME TO REACH THE PLATFORM.  

1911
01:25:38,376 --> 01:25:41,646
THIS IS ONE TYPE.  WHAT -- SO 

1912
01:25:41,646 --> 01:25:43,848
MICE IN WHICH WE MAINTAIN A 

1913
01:25:43,848 --> 01:25:45,850
NORMAL LEVEL OF NUMBER ONE AND 

1914
01:25:45,850 --> 01:25:47,151
WE HAVE THE SUFFICIENCY, WE HAVE

1915
01:25:47,151 --> 01:25:50,221
THE PHENOTYPE.  SO IN THAT 

1916
01:25:50,221 --> 01:25:51,656
POSITION, THEY ARE LIKE MOST OF 

1917
01:25:51,656 --> 01:25:53,391
THE MICE WHILE IN THE REST OF 

1918
01:25:53,391 --> 01:25:55,526
THE STATE, THEY ARE MORE LIKELY 

1919
01:25:55,526 --> 01:25:57,995
ONE SIZE.  BUT IT DOES IMPRESS 

1920
01:25:57,995 --> 01:26:02,400
ME THAT MICE, WE PROTECT THE 

1921
01:26:02,400 --> 01:26:06,871
BRAIN AND IT IS RESCUED 

1922
01:26:06,871 --> 01:26:08,506
COMPLETELY BY THE PERFORMANCE IN

1923
01:26:08,506 --> 01:26:11,676
THIS TEST, SO, AGAIN, WHAT WE 

1924
01:26:11,676 --> 01:26:13,077
LEARNED FROM HERE IS THAT IN 

1925
01:26:13,077 --> 01:26:14,712
ORDER TO PROTECT THE BRAIN FROM 

1926
01:26:14,712 --> 01:26:18,316
SPECIFICALLY WHAT WE NEED TO 

1927
01:26:18,316 --> 01:26:22,253
HAVE THE LEVEL, NUMBER ONE, 

1928
01:26:22,253 --> 01:26:24,288
LIFELONG AND THIS GOES TO GET 

1929
01:26:24,288 --> 01:26:34,799
PROTECTION FROM SEIZURES AND 

1930
01:26:35,633 --> 01:26:36,600
ALSO THE PERFORMANCE IN THE 

1931
01:26:36,600 --> 01:26:41,639
TEST.  AND WHAT I SIGNATURE -- 

1932
01:26:41,639 --> 01:26:42,907
SUGGEST IS THERE PARTICULAR 

1933
01:26:42,907 --> 01:26:43,174
WINDOWS. 

1934
01:26:43,174 --> 01:26:46,243
AND FOR PARTICULAR GENES COMING 

1935
01:26:46,243 --> 01:26:48,045
OUT NOW WE SHOULD SET THIS 

1936
01:26:48,045 --> 01:26:49,613
POSSIBLY IN AN IDEAL WAY LIKE 

1937
01:26:49,613 --> 01:26:52,049
USING THE GENETIC MODEL IN ORDER

1938
01:26:52,049 --> 01:26:54,385
TO GET RID OF THE MEDIATION THAT

1939
01:26:54,385 --> 01:26:57,688
THE GENE THERAPIES MAY BE AND 

1940
01:26:57,688 --> 01:26:59,223
ALSO MAY BE MORE THE MESSAGE 

1941
01:26:59,223 --> 01:27:03,761
THAT THE GENE, RELATED TO THE 

1942
01:27:03,761 --> 01:27:07,832
POSSIBLE EPILEPTIC SYNDROME AND 

1943
01:27:07,832 --> 01:27:13,337
I AM FINISHED NOW.  AND 

1944
01:27:13,337 --> 01:27:13,971
ESSENTIALLY WILL SHOW YOU THE 

1945
01:27:13,971 --> 01:27:18,409
PLACE WHERE I COME FROM.  THIS 

1946
01:27:18,409 --> 01:27:21,679
IS MILAN AND THE TEAM WHICH I AM

1947
01:27:21,679 --> 01:27:22,980
WORKING WITH.  VERY FASCINATING 

1948
01:27:22,980 --> 01:27:25,015
WHAT THEY ARE DOING AND ALL THE 

1949
01:27:25,015 --> 01:27:26,384
PEOPLE WHICH CONTRIBUTED AND 

1950
01:27:26,384 --> 01:27:27,485
COLLABORATED TO THE WORK AND 

1951
01:27:27,485 --> 01:27:30,388
THANK YOU FOR THE ATTENTION.

1952
01:27:30,388 --> 01:27:37,928
>> AUDIENCE: (APPLAUSE).

1953
01:27:37,928 --> 01:27:41,532
>> AUDIENCE: BEAUTIFUL
WORK.  I 

1954
01:27:41,532 --> 01:27:42,433
WAS WONDERING IF YOU COULD 

1955
01:27:42,433 --> 01:27:44,368
COMMENT ON WHETHER YOU THOUGHT 

1956
01:27:44,368 --> 01:27:46,404
ALL CELL TYPES NEEDED TO BE 

1957
01:27:46,404 --> 01:27:49,540
CORRECTED THAT YOU'RE TARGETING 

1958
01:27:49,540 --> 01:27:51,909
WITH THIS?  IT LOOKS LIKE YOU 

1959
01:27:51,909 --> 01:27:55,012
USE A UBIQUITOUS PROMOTER OR 

1960
01:27:55,012 --> 01:27:56,881
WHETHER YOU THOUGHT ABOUT USING 

1961
01:27:56,881 --> 01:27:58,382
PREDRIVERS THAT HAVE DIFFERENT 

1962
01:27:58,382 --> 01:28:00,551
CELL TYPES? TELL US A LITTLE BIT

1963
01:28:00,551 --> 01:28:06,857
ABOUT HOW HUTMUCH DO WE REALLY 

1964
01:28:06,857 --> 01:28:07,091
NEED?  

1965
01:28:07,091 --> 01:28:08,259
>> GAIA: VERY GOOD
QUESTION AND 

1966
01:28:08,259 --> 01:28:09,894
ALSO, FOR THE FIRST EXPERIMENT, 

1967
01:28:09,894 --> 01:28:12,730
WHAT WE WERE TO DO WAS JUST 

1968
01:28:12,730 --> 01:28:16,267
TARGETING ALL THE CELLS AROUND. 

1969
01:28:16,267 --> 01:28:19,737
AND SO WE USE AND WE HAVE A 

1970
01:28:19,737 --> 01:28:23,073
PROMOTER IN THE EXPERIMENTS BUT 

1971
01:28:23,073 --> 01:28:25,209
WHAT IS REALLY IMPORTANT IS THAT

1972
01:28:25,209 --> 01:28:27,111
WE ARE RELYING ON THE EXPRESSION

1973
01:28:27,111 --> 01:28:29,280
OF THE GENE.  SO IT WILL BE IN 

1974
01:28:29,280 --> 01:28:30,848
ALL THE CELLS AND WE CORRECT THE

1975
01:28:30,848 --> 01:28:35,085
GENE LOSSES IN ALL THE CELLS 

1976
01:28:35,085 --> 01:28:37,188
THEN IT WILL STILL BE RELATED TO

1977
01:28:37,188 --> 01:28:38,722
WHAT IS THE REGION OF THE GENE. 

1978
01:28:38,722 --> 01:28:43,961
WHAT WE ARE DOING NOW IS ALSO 

1979
01:28:43,961 --> 01:28:47,565
MAKE SPECIAL CONTROL SO WE ARE 

1980
01:28:47,565 --> 01:28:49,500
ENTRUSTED WITH THE SPECIFIC CELL

1981
01:28:49,500 --> 01:28:54,305
TYPE PREDRIVER IN POSSIBLE WITH 

1982
01:28:54,305 --> 01:28:55,773
THE CONVERGENCE WITH THE NEURONS

1983
01:28:55,773 --> 01:29:00,044
AND WE DO SEE THAT EARLY IN THE 

1984
01:29:00,044 --> 01:29:04,114
DEVELOPMENT SO YOU TARGET THE 

1985
01:29:04,114 --> 01:29:06,884
NEURONS WITH A RECOVERY TIME OF 

1986
01:29:06,884 --> 01:29:08,486
PHENOTYPE BUT IT'S NOT CLEAR 

1987
01:29:08,486 --> 01:29:10,387
LATER ON SO IN THE PHASE OF THE 

1988
01:29:10,387 --> 01:29:11,121
DISEASE YOU SEE TARGETING ALL 

1989
01:29:11,121 --> 01:29:18,395
THE NEURONS IS NOT SIEVE.  SO 

1990
01:29:18,395 --> 01:29:23,067
YEAH THIS IS WHAT WE GET.

1991
01:29:23,067 --> 01:29:24,201
>> AUDIENCE: THANKS THAT
WAS 

1992
01:29:24,201 --> 01:29:25,102
BEAUTIFUL.  I HAVE THE OPPOSITE 

1993
01:29:25,102 --> 01:29:26,637
QUESTION IS IT ENOUGH TO TARGET 

1994
01:29:26,637 --> 01:29:28,005
ALL THE BRAIN AND I'M REFERRING 

1995
01:29:28,005 --> 01:29:31,876
IN PART TO LORI'S WORK AND ALSO 

1996
01:29:31,876 --> 01:29:35,045
WITH CARDIAC CONTRIBUTION TO NOT

1997
01:29:35,045 --> 01:29:38,249
JUST THE SEIZURES BUT THE SUDDEN

1998
01:29:38,249 --> 01:29:38,549
DEATH RISK 

1999
01:29:38,549 --> 01:29:42,253
>> GAIA: THERE ARE STUDIES

2000
01:29:42,253 --> 01:29:42,786
COMING.  HOW MUCH IS THE 

2001
01:29:42,786 --> 01:29:44,655
CONTRIBUTION LONG-TERM.  THERE 

2002
01:29:44,655 --> 01:29:48,092
ARE STUDIES IN INACTIVATING THE 

2003
01:29:48,092 --> 01:29:51,462
JEEP WAS STILL SUFFICIENT TO 

2004
01:29:51,462 --> 01:29:55,599
ACHIEVE A PHENOTYPE SO IT'S THE 

2005
01:29:55,599 --> 01:30:06,010
CONTRIBUTION TO THAT, YEAH.  SO

2006
01:30:06,010 --> 01:30:10,447
>> THANK YOU, GAIA.  I'D
LIKE 

2007
01:30:10,447 --> 01:30:12,750
THEM TO COME TO THE FRONT AND 

2008
01:30:12,750 --> 01:30:14,385
THEN WE'LL PUT GEMMA BACK ON, 

2009
01:30:14,385 --> 01:30:24,862
PLEASE.  DO WE SEE GEMMA?  

2010
01:30:37,041 --> 01:30:37,641
>> GEMMA: I HEAR YOU BUT I
DON'T

2011
01:30:37,641 --> 01:30:42,413
SEE ME.  

2012
01:30:42,413 --> 01:30:43,180
>> LORI: THERE SHE IS. 
OKAY.  

2013
01:30:43,180 --> 01:30:44,648
LET'S HAVE A PANEL DISCUSSION.  

2014
01:30:44,648 --> 01:30:50,387
GABBY.

2015
01:30:50,387 --> 01:30:52,990
>> AUDIENCE: HI, I'M
GABBY, SO 

2016
01:30:52,990 --> 01:30:53,591
GAY I CAN'T RECOLLECTS REALLY 

2017
01:30:53,591 --> 01:30:55,225
EXCITING WORK.  I HAVE A QUICK 

2018
01:30:55,225 --> 01:30:58,028
QUESTION ABOUT IS THERE, YOU 

2019
01:30:58,028 --> 01:30:59,330
KNOW, BECAUSE THERE'S SUCH A 

2020
01:30:59,330 --> 01:31:00,831
SPECTRUM IN A LOT OF THESE 

2021
01:31:00,831 --> 01:31:03,000
DISORDERS DOES THAT TIMEFRAME 

2022
01:31:03,000 --> 01:31:06,236
FOR INTERVENTION VARY BASED ON 

2023
01:31:06,236 --> 01:31:07,638
MUTATION-SPECIFIC?  IS THERE 

2024
01:31:07,638 --> 01:31:14,044
TIMEFRAMES THAT WILL VARY BASED 

2025
01:31:14,044 --> 01:31:14,678
ON THE DIFFERENT CHALLENGES THAT

2026
01:31:14,678 --> 01:31:22,853
ARISE?  

2027
01:31:22,853 --> 01:31:24,188
>> GAIA: I THINK IT'S
BASED ON A

2028
01:31:24,188 --> 01:31:26,390
GENE FUNCTION SO DEPENDING ON 

2029
01:31:26,390 --> 01:31:29,960
THE SEVERITY OF THE SEIZURES AND

2030
01:31:29,960 --> 01:31:32,062
ON THE CONTRIBUTION TO THE 

2031
01:31:32,062 --> 01:31:35,599
ELEMENT THAT EACH GENE MAY HAVE 

2032
01:31:35,599 --> 01:31:37,668
WE CAN GET VERY DIFFERENT KINDS.

2033
01:31:37,668 --> 01:31:38,669
SO WE CAN HAVE DIFFERENT 

2034
01:31:38,669 --> 01:31:42,006
DEPENDING ON THOSE TWO FACTORS. 

2035
01:31:42,006 --> 01:31:42,640
NOT THAT I SEE THE MUTATION BY 

2036
01:31:42,640 --> 01:31:48,579
ON THE GENE.

2037
01:31:48,579 --> 01:31:50,881
>> AUDIENCE: HI, MY
QUESTION FOR

2038
01:31:50,881 --> 01:31:53,350
ISABEL, INCREDIBLY EXCITING DATA

2039
01:31:53,350 --> 01:31:57,521
FROM THE TRIALS AND JUST A QUICK

2040
01:31:57,521 --> 01:31:59,657
QUESTION MAYBE IF YOU ACTUALLY 

2041
01:31:59,657 --> 01:32:01,792
COLLECTED DATA ON NATURAL 

2042
01:32:01,792 --> 01:32:03,394
PROCEDURE OR COGNITIVE FUNCTION 

2043
01:32:03,394 --> 01:32:05,763
BUT HAVE YOU THOUGHT ABOUT 

2044
01:32:05,763 --> 01:32:08,532
LOOKING FOR MOTOR FUNCTION LIKE 

2045
01:32:08,532 --> 01:32:11,335
GI EFFECT IN YOUR PATIENTS?  

2046
01:32:11,335 --> 01:32:13,537
>> GEMMA: YEP, CAN YOU
HEAR ME 

2047
01:32:13,537 --> 01:32:15,973
OKAY?  CAN YOU HEAR IN HELLO?  

2048
01:32:15,973 --> 01:32:18,075
YES.  YES, SO MOTOR FUNCTION, 

2049
01:32:18,075 --> 01:32:21,879
YES, FOR SURE.  SORRY, I'M 

2050
01:32:21,879 --> 01:32:23,414
CHEWING CANDY HERE.  YES.  WE'RE

2051
01:32:23,414 --> 01:32:25,849
LOOKING INTO THAT AND ACTUALLY 

2052
01:32:25,849 --> 01:32:29,887
THE -- WE'RE LOOKING IN ALSO IN 

2053
01:32:29,887 --> 01:32:31,355
CONVERSATIONS WITH THE FDA TO 

2054
01:32:31,355 --> 01:32:34,425
START USING VIDEO MONITORING ON 

2055
01:32:34,425 --> 01:32:36,794
THE MOTOR SKILLS AND STUFF LIKE 

2056
01:32:36,794 --> 01:32:38,162
THAT TO BE ABLE TO MEASURE, 

2057
01:32:38,162 --> 01:32:42,332
YEAH, THE DIFFERENT PHENOTYPE, 

2058
01:32:42,332 --> 01:32:47,571
YEP.

2059
01:32:47,571 --> 01:32:56,647
>> AUDIENCE: CAN I NOT 

2060
01:32:56,647 --> 01:32:59,016
COMPLIMENT THE ORGANIZERS ENOUGH

2061
01:32:59,016 --> 01:33:01,819
FOR THE PANEL.  LISTENING TO YOU

2062
01:33:01,819 --> 01:33:03,887
SPEAK, GEMMA HAS AN END-TO-END 

2063
01:33:03,887 --> 01:33:05,322
PIPELINE FOR DETERMINING WHAT 

2064
01:33:05,322 --> 01:33:08,325
THE MECHANISM OF ACTION OF A 

2065
01:33:08,325 --> 01:33:10,394
VARIANT IS.  AND WHETHER OR NOT 

2066
01:33:10,394 --> 01:33:11,929
IT CAN BE SENSIBLE.  GAIA IS 

2067
01:33:11,929 --> 01:33:14,398
DESCRIBING HOW TO FIGURE OUT 

2068
01:33:14,398 --> 01:33:17,835
WHEN TO TREAT THE DISEASE AND 

2069
01:33:17,835 --> 01:33:21,071
STOKE HAS THE SUBJECTS.  SO IN 

2070
01:33:21,071 --> 01:33:24,441
PRACTICAL TERMS WE'RE DOSING 

2071
01:33:24,441 --> 01:33:26,376
INDIVIDUAL CHILDREN WITH 

2072
01:33:26,376 --> 01:33:30,147
INDIVIDUAL ISSUES ONE BY ONE AND

2073
01:33:30,147 --> 01:33:31,081
THERE'S OTHERS DOING WHATEVER 

2074
01:33:31,081 --> 01:33:32,649
THEY WANT TO DO AND MY QUESTION 

2075
01:33:32,649 --> 01:33:34,785
TO YOU THREE, GIVEN THAT THIS IS

2076
01:33:34,785 --> 01:33:39,223
THE EASIEST, YOU CAN STILL DOSE,

2077
01:33:39,223 --> 01:33:40,624
YOU CAN'T UNEDIT A HUMAN BEING 

2078
01:33:40,624 --> 01:33:43,560
IS NOW THE TIME TO START WORK 

2079
01:33:43,560 --> 01:33:45,262
WITH FEDERAL SUPPORT, I'M SORRY,

2080
01:33:45,262 --> 01:33:50,367
AN OPEN ACCESS ASO COOKBOOK FOR 

2081
01:33:50,367 --> 01:33:52,002
EPILEPSY.  I MEAN INDIVIDUAL 

2082
01:33:52,002 --> 01:33:54,138
MUTATIONS, GEMMA CAN I START 

2083
01:33:54,138 --> 01:33:55,706
WITH YOU AND THEN MAYBE GAIA AND

2084
01:33:55,706 --> 01:34:02,379
ISABEL.  I'M NOT TRYING TO BREAK

2085
01:34:02,379 --> 01:34:05,048
STOKE'S BUSINESS MODEL BUT TO 

2086
01:34:05,048 --> 01:34:06,717
THE EXTENT THAT THERE CAN BE 

2087
01:34:06,717 --> 01:34:08,152
LEARNING THAT OTHER PEOPLE CAN 

2088
01:34:08,152 --> 01:34:09,620
START TO TAKE AWAY.  

2089
01:34:09,620 --> 01:34:12,222
>> GEMMA: THE ANSWER IS
YES AND 

2090
01:34:12,222 --> 01:34:14,191
LORI CAN BACK ME UP HERE THAT 

2091
01:34:14,191 --> 01:34:17,227
LITERALLY WE ARE THINKING ABOUT 

2092
01:34:17,227 --> 01:34:19,129
SOMETHING LIKE THIS IN 

2093
01:34:19,129 --> 01:34:20,764
SEPTEMBER, OCTOBER, THINKING 

2094
01:34:20,764 --> 01:34:23,467
ABOUT HOW TO DEVELOP PIPELINES 

2095
01:34:23,467 --> 01:34:25,035
TOWARDS ASOS FOR A VARIETY OF 

2096
01:34:25,035 --> 01:34:30,174
RARE EPILEPSIES.  SO -- AND KIND

2097
01:34:30,174 --> 01:34:36,146
OF INITIALLY SODIUM CHANNELS, I 

2098
01:34:36,146 --> 01:34:38,382
WANT TO SAY ARE EASIER BUT ARE 

2099
01:34:38,382 --> 01:34:40,517
EASIER AND SOME OF THE ION 

2100
01:34:40,517 --> 01:34:41,552
CHANNELS ARE MORE CHALLENGING.  

2101
01:34:41,552 --> 01:34:43,020
AT LEAST WITH THE ION CHANNELS 

2102
01:34:43,020 --> 01:34:45,589
WE HAVE A READOUT.  WE CAN LOOK 

2103
01:34:45,589 --> 01:34:47,224
AT CHANNEL FUNCTION, LIKE WE 

2104
01:34:47,224 --> 01:34:50,661
HAVE A GOOD GRASP ON HOW TO 

2105
01:34:50,661 --> 01:34:53,664
ASSAY VARIANT EFFECT AND WE HAVE

2106
01:34:53,664 --> 01:34:59,570
A GOOD GOOD ASSAY TO FIGURE OUT 

2107
01:34:59,570 --> 01:35:01,338
IF IT'S WORKING OR NOT AT LEAST 

2108
01:35:01,338 --> 01:35:03,841
IN PRECLINICAL MODELS BUT FOR 

2109
01:35:03,841 --> 01:35:06,343
THE OTHER EPILEPSY RELATED GENES

2110
01:35:06,343 --> 01:35:08,111
WE DON'T HAVE GOOD READOUTS AND 

2111
01:35:08,111 --> 01:35:09,713
THAT IS WHERE WE REALLY NEED TO 

2112
01:35:09,713 --> 01:35:12,449
BE FOCUSING AND SO, YEAH, LORI 

2113
01:35:12,449 --> 01:35:14,318
CAN ALSO JUMP IN HERE BUT THAT 

2114
01:35:14,318 --> 01:35:17,654
IS REALLY ONE OF THE GOALS OF 

2115
01:35:17,654 --> 01:35:20,123
OCTOBER TO WRITE AGRANT TOWARDS 

2116
01:35:20,123 --> 01:35:21,892
THIS AT LEAST WITH A VIEW IN THE

2117
01:35:21,892 --> 01:35:23,360
FUTURE TO TRANSLATE THAT. 

2118
01:35:23,360 --> 01:35:25,863
I WOULD LOVE TO PUT TOGETHER A 

2119
01:35:25,863 --> 01:35:26,930
BIG PLATFORM TO BE ABLE TO DO 

2120
01:35:26,930 --> 01:35:29,233
THIS IN A SYSTEMATIC WAY THAT 

2121
01:35:29,233 --> 01:35:31,702
LOTS OF GROUPS AREN'T 

2122
01:35:31,702 --> 01:35:33,203
REINVENTING THE WHEEL.  YES, I 

2123
01:35:33,203 --> 01:35:34,838
WOULD LOVE THIS IDEA AND TO 

2124
01:35:34,838 --> 01:35:38,375
STRATEGIZE ON HOW TO MAKE IT 

2125
01:35:38,375 --> 01:35:45,215
HAPPEN.  

2126
01:35:45,215 --> 01:35:46,783
>> LORI: COULD YOU COMMENT
ON 

2127
01:35:46,783 --> 01:35:48,485
WHAT ARE THE PITFALLS?

2128
01:35:48,485 --> 01:35:49,119
>> AUDIENCE: (SPEAKER FAR
FROM 

2129
01:35:49,119 --> 01:35:59,596
MIC).  TO ME THAT'S THE KEY 

2130
01:36:04,635 --> 01:36:06,370
QUESTION.  HOW MUCH (SPEAKER FAR

2131
01:36:06,370 --> 01:36:14,878
FROM MIC) 

2132
01:36:14,878 --> 01:36:18,382
>> GEMMA: WE PUBLISHED A
COUPLE 

2133
01:36:18,382 --> 01:36:20,517
PAPERS ALREADY ON THE CLINICAL 

2134
01:36:20,517 --> 01:36:22,319
DATA THAT WILL BE PUBLISHED AS 

2135
01:36:22,319 --> 01:36:26,323
WELL HOPEFULLY SOON.  WE DO LIKE

2136
01:36:26,323 --> 01:36:29,059
TO PUBLISH AND PRESENT DATA.  IN

2137
01:36:29,059 --> 01:36:31,128
TERMS OF THE -- DEVELOP A 

2138
01:36:31,128 --> 01:36:35,198
PIPELINE FOR THESE ASL 

2139
01:36:35,198 --> 01:36:38,201
DEVELOPMENT, SO IN ONE -- CAN --

2140
01:36:38,201 --> 01:36:42,439
THE TYPICAL -- OR THE BEST CASE 

2141
01:36:42,439 --> 01:36:46,610
SCENARIO FOR NF1 IS TECHNOLOGY. 

2142
01:36:46,610 --> 01:36:49,313
THAT IS WHERE EVERYTHING.  IT 

2143
01:36:49,313 --> 01:36:53,483
ALL STARTED.  SO I KNOW THAT THE

2144
01:36:53,483 --> 01:36:55,452
OTS WHICH IS THE SOCIETY WHICH I

2145
01:36:55,452 --> 01:36:57,254
USED TO BE ON THE BOARD UNTIL 

2146
01:36:57,254 --> 01:36:57,854
LAST YEAR WE PUT TOGETHER A 

2147
01:36:57,854 --> 01:37:06,096
GUIDELINES TO -- HOW TO APPROACH

2148
01:37:06,096 --> 01:37:08,165
NF1 AND IT IS EXTREMELY -- I 

2149
01:37:08,165 --> 01:37:09,933
THINK IT IS EXTREMELY POWERFUL 

2150
01:37:09,933 --> 01:37:13,904
AND 100% ON BOARD WITH THESE 

2151
01:37:13,904 --> 01:37:15,439
EFFORTS AND, YOU KNOW, AS A 

2152
01:37:15,439 --> 01:37:17,040
COMPANY, IT'S A DIFFERENT STORY,

2153
01:37:17,040 --> 01:37:19,776
BUT ME AS A SCIENTIST AND AS A 

2154
01:37:19,776 --> 01:37:23,347
PERSON I KNOW HOW TO USE THIS TO

2155
01:37:23,347 --> 01:37:26,717
MODULATE RNA PROCESSES I THINK 

2156
01:37:26,717 --> 01:37:29,086
THE POTENTIAL TO DEVELOP THIS 

2157
01:37:29,086 --> 01:37:34,324
USING THE NUCLEOTIDES IS 

2158
01:37:34,324 --> 01:37:35,592
ABSOLUTELY GREAT.  AND SO THERE 

2159
01:37:35,592 --> 01:37:38,061
ARE THESE ALREADY THAT THE OTS 

2160
01:37:38,061 --> 01:37:39,963
PUT TOGETHER TO HELP WITH THIS 

2161
01:37:39,963 --> 01:37:42,466
DEVELOPMENT AND I THINK THE -- 

2162
01:37:42,466 --> 01:37:50,407
NOW THE NF 1 CONNOISSSORTIUM IS 

2163
01:37:50,407 --> 01:37:52,209
TRYING TO BRING ALL THE DATA 

2164
01:37:52,209 --> 01:37:54,277
TOGETHER SO NEW INVESTIGATORS 

2165
01:37:54,277 --> 01:37:56,480
CAN LEARN FROM IT AND LEVERAGE 

2166
01:37:56,480 --> 01:37:58,415
ALL THE KNOWLEDGE THAT HAS BEEN 

2167
01:37:58,415 --> 01:37:59,449
DEVELOPED ALREADY.

2168
01:37:59,449 --> 01:38:00,083
>> AUDIENCE: YES A COUPLE
MORE 

2169
01:38:00,083 --> 01:38:04,654
QUESTIONS.  

2170
01:38:04,654 --> 01:38:06,223
>> LORI: I HAD A QUESTION
FOR 

2171
01:38:06,223 --> 01:38:09,726
YOU.  WHAT ARE THE PITFALLS.  

2172
01:38:09,726 --> 01:38:11,561
YOU HAD GREAT SUCCESS WITH THIS 

2173
01:38:11,561 --> 01:38:15,098
BUT NOT EVERYTHING HAS BEEN 

2174
01:38:15,098 --> 01:38:16,933
SUCCESSFUL.  ARE THERE -- HAPPEN

2175
01:38:16,933 --> 01:38:23,407
LOW INSIEVE VARIANTS THAT NOT 

2176
01:38:23,407 --> 01:38:23,940
WORKED 

2177
01:38:23,940 --> 01:38:25,375
>> ISABEL: IN TERMS OF 

2178
01:38:25,375 --> 01:38:27,077
UPREGULATION THERE'S DIFFERENT 

2179
01:38:27,077 --> 01:38:27,677
CONSIDERATIONS.  THERE'S ONE 

2180
01:38:27,677 --> 01:38:31,515
THING THAT GEMMA TOUCHED ON 

2181
01:38:31,515 --> 01:38:35,419
TODAY AND GEMMA AND I -- AND WE 

2182
01:38:35,419 --> 01:38:36,586
COLLABORATED ON THIS.  SOMETIMES

2183
01:38:36,586 --> 01:38:38,188
THE WAY A GENE IS REGULATED IS 

2184
01:38:38,188 --> 01:38:41,425
VERY COMPLICATED.  AND THERE ARE

2185
01:38:41,425 --> 01:38:45,095
OTHER FORCES THAT, YOU KNOW, 

2186
01:38:45,095 --> 01:38:46,963
MAKE -- AGAINST WHAT YOU'RE 

2187
01:38:46,963 --> 01:38:49,900
TRYING TO DO AND THAT IS GENE 

2188
01:38:49,900 --> 01:38:50,667
DEPENDENT AND WHAT YOU WERE 

2189
01:38:50,667 --> 01:38:51,868
SAYING ABOUT THE TIMING OF 

2190
01:38:51,868 --> 01:38:53,737
TREATMENT AND ALL THE THINGS A 

2191
01:38:53,737 --> 01:38:55,972
LOT OF IT IS THE BIOLOGY OF THE 

2192
01:38:55,972 --> 01:38:58,708
TARGET AND SO THERE IS THAT THAT

2193
01:38:58,708 --> 01:38:59,976
WE CAN FIND THOSE THAT MODULE 

2194
01:38:59,976 --> 01:39:02,145
AND AT THE END OF THE DAY WE MAY

2195
01:39:02,145 --> 01:39:04,081
NOT SEE THE UPREGULATION AND 

2196
01:39:04,081 --> 01:39:05,115
THAT'S BECAUSE THE -- THERE'S SO

2197
01:39:05,115 --> 01:39:07,551
MANY OTHER THINGS CONTRIBUTING 

2198
01:39:07,551 --> 01:39:08,685
TO THE REGULATION OF THAT 

2199
01:39:08,685 --> 01:39:11,621
PARTICULAR PROTEIN.  SO THAT IS 

2200
01:39:11,621 --> 01:39:15,792
SOMETHING WORTH THINKING -- CAN 

2201
01:39:15,792 --> 01:39:16,193
FOO

2202
01:39:16,193 --> 01:39:19,129
FALL APART.  THE SEQUENCE, AND 

2203
01:39:19,129 --> 01:39:20,764
THIS IS BACK TO ONE OF THE 

2204
01:39:20,764 --> 01:39:23,467
QUESTIONS I HAVE TODAY IS WHY 

2205
01:39:23,467 --> 01:39:25,001
THEY NEED TO HAVE SOME SIDE 

2206
01:39:25,001 --> 01:39:26,670
EFFECTS AND SOME DON'T AND WE 

2207
01:39:26,670 --> 01:39:28,939
SEE -- WE HAVE A TON OF -- 

2208
01:39:28,939 --> 01:39:30,540
THOUSANDS AND THOUSANDS OF DATA 

2209
01:39:30,540 --> 01:39:32,676
AND EVEN THOUGH THE CHEMISTRY 

2210
01:39:32,676 --> 01:39:34,344
MIGHT BE IDENTICAL, THERE IS A 

2211
01:39:34,344 --> 01:39:36,847
CLEAR EFFECT FROM THE SEQUENCE 

2212
01:39:36,847 --> 01:39:39,282
OF THIS AND SOME GENES HAPPEN TO

2213
01:39:39,282 --> 01:39:43,987
BE VERY GC RICH IT'S JUST THE 

2214
01:39:43,987 --> 01:39:45,589
NATURE OF THE GENE, THE PROTEIN 

2215
01:39:45,589 --> 01:39:48,625
THEY'RE CODING AND WHEN YOU HAVE

2216
01:39:48,625 --> 01:39:51,728
VERY GC REACH ASOS IT'S GOING TO

2217
01:39:51,728 --> 01:39:53,063
BE A PROBLEM THROUGHOUT THE 

2218
01:39:53,063 --> 01:39:55,298
DEVELOPMENT OF THAT TARGET.  OF 

2219
01:39:55,298 --> 01:39:57,100
THAT ASO AND THERE ARE A LOT OF 

2220
01:39:57,100 --> 01:39:58,401
THINGS WHEN IT COME TO BUILDING 

2221
01:39:58,401 --> 01:40:01,071
A PIPELINE TO TREAT DISEASES, NF

2222
01:40:01,071 --> 01:40:03,340
1, YOU KNOW, WHEN YOU 

2223
01:40:03,340 --> 01:40:04,307
MODULATING, SPLICING, YOU DON'T 

2224
01:40:04,307 --> 01:40:06,276
HAVE A LOT OF OPTIONS OF WHERE 

2225
01:40:06,276 --> 01:40:09,679
TO PUT YOUR ASO, THE REGULATORY 

2226
01:40:09,679 --> 01:40:10,614
SEQUENCES ARE WHERE THEY ARE AND

2227
01:40:10,614 --> 01:40:12,716
THE SEQUENCE IS WHAT IT IS.  

2228
01:40:12,716 --> 01:40:15,085
WHEN YOU'RE KNOCKING DOWN A GENE

2229
01:40:15,085 --> 01:40:16,386
YOU HAVE YOUR ENTIRE TRANSCRIPT 

2230
01:40:16,386 --> 01:40:19,489
AS AN OPTION SO THERE'S A LOT 

2231
01:40:19,489 --> 01:40:23,760
MORE THAT YOU CAN DO BY 

2232
01:40:23,760 --> 01:40:28,899
FORMATICALLY TO WEED OUT THE BAD

2233
01:40:28,899 --> 01:40:30,367
PLAYERS.  AND SO DEPENDS ON THAT

2234
01:40:30,367 --> 01:40:31,968
AND WHAT YOU'RE TYING TO DO.  

2235
01:40:31,968 --> 01:40:35,005
THE BIOLOGY OF THE GENE AND THE 

2236
01:40:35,005 --> 01:40:37,807
ASO SEQUENCE ITSELF THOSE ARE 

2237
01:40:37,807 --> 01:40:40,076
THE TWO PROBLEMS OR HURDLES THAT

2238
01:40:40,076 --> 01:40:43,380
SOMETIMES WE HAVE TO, YOU KNOW, 

2239
01:40:43,380 --> 01:40:45,515
OVERCOME WHEN DEVELOPING 

2240
01:40:45,515 --> 01:40:46,383
THERAPEUTICS.  

2241
01:40:46,383 --> 01:40:50,053
>> LORI: THANK YOU, THANK
YOU.  

2242
01:40:50,053 --> 01:40:51,955
HOW MANY ARE ONLINE?

2243
01:40:51,955 --> 01:40:53,356
>> AUDIENCE: WE HAVE ONE 

2244
01:40:53,356 --> 01:41:00,564
QUESTION FOR ISABEL.  FOR 

2245
01:41:00,564 --> 01:41:04,601
GEMMA'S POINT IS THIS SHARING 

2246
01:41:04,601 --> 01:41:10,373
VARIANCE DATA?  

2247
01:41:10,373 --> 01:41:11,007
>> ISABEL: PATIENTS THAT
COME 

2248
01:41:11,007 --> 01:41:14,377
ARE ALREADY GENOTYPES TO BEGIN 

2249
01:41:14,377 --> 01:41:16,046
WITH?  WE REPEAT IT AGAIN 

2250
01:41:16,046 --> 01:41:19,316
BECAUSE WE WANT TO MAKE SURE AND

2251
01:41:19,316 --> 01:41:25,021
CONFIRM FROM THE GENETIC 

2252
01:41:25,021 --> 01:41:27,424
PERSPECTIVE THAT PATIENTS HAVE 

2253
01:41:27,424 --> 01:41:30,393
THIS.  WE ALSO SPONSOR GENETICS 

2254
01:41:30,393 --> 01:41:34,264
SCREENING VIA WHAT'S CALLED, 

2255
01:41:34,264 --> 01:41:36,967
BEHIND THE SEIZURE BASICALLY 

2256
01:41:36,967 --> 01:41:39,603
CONSORTIUM WHERE ANY PATIENT 

2257
01:41:39,603 --> 01:41:42,439
THAT GOES INTO A PHYSICIAN'S 

2258
01:41:42,439 --> 01:41:44,674
OFFICE AND IN -- WITH AT LEAST 

2259
01:41:44,674 --> 01:41:46,476
ONE UNPROVOKED SEIZURE AND I 

2260
01:41:46,476 --> 01:41:48,478
BELIEVE UP TO EIGHT YEARS OF 

2261
01:41:48,478 --> 01:41:50,981
AGE, THEY GET FREE TESTING AND 

2262
01:41:50,981 --> 01:41:52,782
WE'RE NOT ONLY THE COMPANY 

2263
01:41:52,782 --> 01:41:54,417
SPONSORING THIS AND ALL THAT 

2264
01:41:54,417 --> 01:41:58,054
INFORMATION MEANS THAT, YOU 

2265
01:41:58,054 --> 01:41:59,289
KNOW, IT'S NOT OURS.  IT'S 

2266
01:41:59,289 --> 01:42:00,490
INFORMATION THAT WE CAN USE IT 

2267
01:42:00,490 --> 01:42:02,359
BUT IT'S ALSO INFORMATION THAT 

2268
01:42:02,359 --> 01:42:05,962
PHYSICIANS HAVE AND OTHERS ARE 

2269
01:42:05,962 --> 01:42:07,731
HAVING.  SO THE GENOTYPE, WE'RE 

2270
01:42:07,731 --> 01:42:10,367
NOT THE ONLY ONES, GENOTYPING 

2271
01:42:10,367 --> 01:42:12,435
THESE PATIENTS BUT THERE ARE 

2272
01:42:12,435 --> 01:42:14,371
PHYSICIANS THAT HAVE THIS 

2273
01:42:14,371 --> 01:42:18,575
INFORMATION AS WELL.  

2274
01:42:18,575 --> 01:42:19,609
>> LORI: LET'S TAKE ONE
MORE AND

2275
01:42:19,609 --> 01:42:21,278
THEN WE HAVE TO HAVE A BREAK, 

2276
01:42:21,278 --> 01:42:22,379
VICKY, RIGHT, WE HAVE TO BREAK, 

2277
01:42:22,379 --> 01:42:27,083
THANK YOU.  ONE MORE QUESTION.  

2278
01:42:27,083 --> 01:42:27,851
THANK YOU.

2279
01:42:27,851 --> 01:42:29,419
>> AUDIENCE: SO THIS
CONCEPT OF 

2280
01:42:29,419 --> 01:42:31,021
WHEN CAN THE ASSOCIATED 

2281
01:42:31,021 --> 01:42:32,689
COGNITIVE AND DEVELOPMENTAL 

2282
01:42:32,689 --> 01:42:34,491
PROBLEM BE ACTUALLY REVERSED.  I

2283
01:42:34,491 --> 01:42:36,359
THINK IS REALLY, REALLY AN 

2284
01:42:36,359 --> 01:42:37,927
IMPORTANT QUESTION AND I THINK 

2285
01:42:37,927 --> 01:42:40,730
IT'S IMPORTANT FOR US TO 

2286
01:42:40,730 --> 01:42:42,432
UNDERSTAND HOW WE'RE DOING THE 

2287
01:42:42,432 --> 01:42:46,202
READOUT FOR THAT ACROSS THIS 

2288
01:42:46,202 --> 01:42:49,673
DISORDER.  YOU PROTECT  

2289
01:42:49,673 --> 01:42:51,741
PRESENTED THE DATA BUT I WONDER 

2290
01:42:51,741 --> 01:42:53,410
IF YOU HAVE DATA ON THE 

2291
01:42:53,410 --> 01:42:56,012
PERFORMANCE MEASURES FOR THE FDA

2292
01:42:56,012 --> 01:43:01,151
TO USE TO MEASURE.  NOT AS A 

2293
01:43:01,151 --> 01:43:01,818
COMMISSION.  IT IS ADMINISTERED 

2294
01:43:01,818 --> 01:43:03,253
BY A CLINICIAN BUT THAT'S NOW 

2295
01:43:03,253 --> 01:43:06,222
THE FDA SEES IT AND THEY WON'T 

2296
01:43:06,222 --> 01:43:08,692
ACCEPT IT EXCEPT FOR AS A 

2297
01:43:08,692 --> 01:43:10,193
CONTROL TRIAL I'M WONDERING 

2298
01:43:10,193 --> 01:43:14,164
IF -- HAVE YOU BEEN USING ANY 

2299
01:43:14,164 --> 01:43:14,864
OBJECTIVE, YOU KNOW, 

2300
01:43:14,864 --> 01:43:18,101
PERFORM-BASED MEASURES LIKE THE 

2301
01:43:18,101 --> 01:43:20,904
IQ TEST OR ANYTHING LIKE THAT 

2302
01:43:20,904 --> 01:43:22,639
THIS AS WE GO INTO THIS IDEA 

2303
01:43:22,639 --> 01:43:26,543
THAT WE HAVE THE EARLY ONSET OF 

2304
01:43:26,543 --> 01:43:28,345
EPILEPSIES WE COME TO A WAY OF 

2305
01:43:28,345 --> 01:43:30,380
HOW ARE WE GOING TO GET THOSE 

2306
01:43:30,380 --> 01:43:32,048
HUMAN READOUTS BUT WE DON'T 

2307
01:43:32,048 --> 01:43:34,084
ACTUALLY KNOW THAT THE TIMEFRAME

2308
01:43:34,084 --> 01:43:36,586
FOR REVERSING THINGS IN THE 

2309
01:43:36,586 --> 01:43:37,854
MOUSE IS GOING TO CORRESPOND TO 

2310
01:43:37,854 --> 01:43:39,322
THE HUMANS.  THAT'S A QUESTION 

2311
01:43:39,322 --> 01:43:42,392
THAT WE HAVE TO ANSWER.  WE KNOW

2312
01:43:42,392 --> 01:43:44,694
IT PROBABLY DOESN'T BUT IN OTHER

2313
01:43:44,694 --> 01:43:45,428
DISORDERS WE HAVE TO ANSWER THAT

2314
01:43:45,428 --> 01:43:50,367
ONE BY ONE.  SO I'M JUST CURIOUS

2315
01:43:50,367 --> 01:43:53,703
IF OFF  YOU HAVE A MORE EXPANDED

2316
01:43:53,703 --> 01:43:54,371
OUTCOME.  

2317
01:43:54,371 --> 01:43:58,475
>> ISABEL: I KNOW WE USED
OTHER 

2318
01:43:58,475 --> 01:44:02,479
MEASUREMENTS OTHER THAN -- I'M 

2319
01:44:02,479 --> 01:44:04,514
NOT ON THE CLINICAL TEAM.  I 

2320
01:44:04,514 --> 01:44:06,282
DON'T KNOW FOR SURE.  I CAN FIND

2321
01:44:06,282 --> 01:44:09,352
THAT OUT FOR YOU.   IT'S A VERY 

2322
01:44:09,352 --> 01:44:12,255
GOOD QUESTION.  WHEN WE STARTED 

2323
01:44:12,255 --> 01:44:14,391
THE CLINICAL DEVELOPMENT 

2324
01:44:14,391 --> 01:44:15,859
SEIZURES WAS OF COURSE THE -- OF

2325
01:44:15,859 --> 01:44:19,162
COURSE THE PRIMARY BUT IT WAS 

2326
01:44:19,162 --> 01:44:22,365
EASY AND ALREADY APPROVED.  

2327
01:44:22,365 --> 01:44:24,901
ANYTHING COGNITIVE, WE HAD TO 

2328
01:44:24,901 --> 01:44:26,703
DEVELOP OURSELVES IN USING THE 

2329
01:44:26,703 --> 01:44:30,240
NATURAL HISTORY DATA HELPED A 

2330
01:44:30,240 --> 01:44:37,280
LOT.  IT HAD TO BE DESIGNED 

2331
01:44:37,280 --> 01:44:40,316
SPECIFICALLY.  NONE OF THE IQ 

2332
01:44:40,316 --> 01:44:43,653
TESTS TOOK INTO ACCOUNT THE 

2333
01:44:43,653 --> 01:44:46,055
DEVELOPMENTAL DELAY OF THESE 

2334
01:44:46,055 --> 01:44:48,558
PATIENTS, YOU KNOW, ARE PRESENT 

2335
01:44:48,558 --> 01:44:49,926
WITH AND SO IT -- THE FACT THAT 

2336
01:44:49,926 --> 01:44:53,396
WE DID SEE A CHANGE IN COGNITIVE

2337
01:44:53,396 --> 01:44:55,198
CHANGE IN COGNITIVE AND BEHAVIOR

2338
01:44:55,198 --> 01:44:57,901
AND ALSO BASED ON THE DATA, THAT

2339
01:44:57,901 --> 01:44:59,936
GAVE US A LOT OF, ALSO, YOU 

2340
01:44:59,936 --> 01:45:04,707
KNOW, HOPE.  THAT THINGS CAN BE 

2341
01:45:04,707 --> 01:45:07,510
CHANGED, YOU KNOW, EVEN DOWN THE

2342
01:45:07,510 --> 01:45:11,481
LINE AND SO NOW THAT OPENS UP 

2343
01:45:11,481 --> 01:45:13,283
MORE OPPORTUNITIES FOR OTHER 

2344
01:45:13,283 --> 01:45:15,318
DEVELOPMENT.  I THINK IT MAY NOT

2345
01:45:15,318 --> 01:45:19,589
BE EXACTLY THE SAME COGNITIVE 

2346
01:45:19,589 --> 01:45:21,057
TEST BUT THE FACT THAT THINGS 

2347
01:45:21,057 --> 01:45:22,759
CAN BE CHANGED POSTNATALLY AND 

2348
01:45:22,759 --> 01:45:26,362
AT THE COGNITIVE LEVEL OPENS UP 

2349
01:45:26,362 --> 01:45:31,167
A LOT OF DOORS TO NEURAL 

2350
01:45:31,167 --> 01:45:32,168
DISEASES AND THINGS THAT WE 

2351
01:45:32,168 --> 01:45:34,370
DIDN'T THINK OF BEFORE.

2352
01:45:34,370 --> 01:45:37,207
>> AUDIENCE: THIS IS A
HUGE 

2353
01:45:37,207 --> 01:45:40,176
PROBLEM THAT WE NEED TO DISCOVER

2354
01:45:40,176 --> 01:45:43,746
IN THE FIELD.  AND COVER ALL OF 

2355
01:45:43,746 --> 01:45:44,981
THESE RANGES.  

2356
01:45:44,981 --> 01:45:47,383
>> LORI: WE CAN TALK ABOUT
THIS 

2357
01:45:47,383 --> 01:45:49,085
ALL DAY BY WE HAVE TO END SO 

2358
01:45:49,085 --> 01:45:50,453
LET'S THANK OUR PANEL ONE MORE 

2359
01:45:50,453 --> 01:45:50,653
TIME.

2360
01:45:50,653 --> 01:45:54,157
>> AUDIENCE: (APPLAUSE).  

2361
01:45:54,157 --> 01:45:55,191
>> LORI: AND NOW WE HAVE A
BREAK

2362
01:45:55,191 --> 01:45:58,485
UNTIL 11:00.  

2363
01:46:29,086 --> 01:46:32,756
>> VICKY: OKAY, SO WE --
HAVE A 

2364
01:46:32,756 --> 01:46:34,558
SERIES OF SPEAKERS DURING THIS 

2365
01:46:34,558 --> 01:46:35,759
SESSION.  AND THESE ARE JUST 

2366
01:46:35,759 --> 01:46:37,327
SOME OF THE QUESTIONS THAT WE 

2367
01:46:37,327 --> 01:46:39,529
HOPE THAT THEY WILL ADDRESS.  SO

2368
01:46:39,529 --> 01:46:42,132
FIRST OF ALL IS A PERSON WITH A 

2369
01:46:42,132 --> 01:46:45,002
GENETIC CONDITION RECEIVING THE 

2370
01:46:45,002 --> 01:46:46,903
APPROPRIATE TREATMENT FOR THEIR 

2371
01:46:46,903 --> 01:46:48,672
DISEASE, DISORDER, GENE VARIANT 

2372
01:46:48,672 --> 01:46:49,940
AND THESE ISSUES HAVE BEEN 

2373
01:46:49,940 --> 01:46:52,242
RAISED IN SOME OF THE EARLIER 

2374
01:46:52,242 --> 01:46:53,777
SESSIONS BUT WE WILL REALLY 

2375
01:46:53,777 --> 01:46:55,512
FOCUS ON THIS AGAIN WHAT ARE 

2376
01:46:55,512 --> 01:46:58,615
CONSIDERATIONS A PARENT MUST 

2377
01:46:58,615 --> 01:46:59,249
CONSIDER WHEN WHETHER OR NOT 

2378
01:46:59,249 --> 01:47:01,184
THEY ENROLL THEIR CHILD IN A 

2379
01:47:01,184 --> 01:47:07,224
CLINICAL TRIAL WHAT ARE THE 

2380
01:47:07,224 --> 01:47:08,492
EXPERIENCES OF PARENTS AND 

2381
01:47:08,492 --> 01:47:10,160
CHILDREN WHO HAVE PARTICIPATED? 

2382
01:47:10,160 --> 01:47:11,962
WHY DO WE NEED TO UNDERSTAND THE

2383
01:47:11,962 --> 01:47:13,930
NATURAL HISTORY OF A DISEASE?  

2384
01:47:13,930 --> 01:47:18,001
IS REMOTE PHENOTYPING ESPECIALLY

2385
01:47:18,001 --> 01:47:19,536
FOR BEHAVIORAL AND COGNITIVE 

2386
01:47:19,536 --> 01:47:25,208
ISSUES AN OPTION FOR PEDIATRIC 

2387
01:47:25,208 --> 01:47:27,144
RESEARCH AN INTERVENTION.  WHAT 

2388
01:47:27,144 --> 01:47:29,179
ARE THE APPROPRIATE OUTCOME 

2389
01:47:29,179 --> 01:47:30,747
MEASURES FOR GIVEN CLINICAL 

2390
01:47:30,747 --> 01:47:33,317
TRIALS, GENETIC STRATEGY AND I 

2391
01:47:33,317 --> 01:47:35,118
APPRECIATE THE DISCUSSION OF 

2392
01:47:35,118 --> 01:47:38,588
HAVING SOME AGREEMENTS ON 

2393
01:47:38,588 --> 01:47:40,257
COGNITIVE, BEHAVIORAL PATH.  I 

2394
01:47:40,257 --> 01:47:41,692
THINK THAT SOUNDS LIKE ANOTHER 

2395
01:47:41,692 --> 01:47:44,828
WORKSHOP, STAY TUNED.  AND 

2396
01:47:44,828 --> 01:47:47,230
LASTLY, WHAT ARE -- I GUESS, NO,

2397
01:47:47,230 --> 01:47:49,099
SO WHAT ARE -- I ALREADY SAID 

2398
01:47:49,099 --> 01:47:51,601
THAT, DIDN'T I AND SO WHAT ARE 

2399
01:47:51,601 --> 01:47:52,969
THE ETHICAL CONSIDERATIONS OF 

2400
01:47:52,969 --> 01:47:53,970
THE LAST KIND OF THINGS, WHAT 

2401
01:47:53,970 --> 01:47:55,839
ARE THE ETHICAL CONSIDERATIONS 

2402
01:47:55,839 --> 01:48:00,277
FOR INVESTIGATORS WHO ARE 

2403
01:48:00,277 --> 01:48:01,878
PLANNING A CLINICAL TRIAL TO 

2404
01:48:01,878 --> 01:48:04,414
TREAT A NEUROLOGICAL DISORDER 

2405
01:48:04,414 --> 01:48:11,154
AND SPECIFICALLY EPILEPSY.  SO 

2406
01:48:11,154 --> 01:48:14,658
THE SPEAKER LINEUP THIS MORNING 

2407
01:48:14,658 --> 01:48:21,198
YOU'LL HEAR FROM DENNIS LAL, 

2408
01:48:21,198 --> 01:48:23,367
MARY ANN MESKIS COULD NOT BE 

2409
01:48:23,367 --> 01:48:25,669
HERE BECAUSE SHE'S RUNNING HER 

2410
01:48:25,669 --> 01:48:27,003
OWN CONFERENCE AT THE SAME TIME 

2411
01:48:27,003 --> 01:48:32,409
BUT HAS GRASCIOUSLY AGREED TO B 

2412
01:48:32,409 --> 01:48:36,380
ON ABOUT SPEAKING ABOUT TREATING

2413
01:48:36,380 --> 01:48:38,548
A GENETIC CONDITION AND TALKING 

2414
01:48:38,548 --> 01:48:43,120
ABOUT HOW BEING INVOLVED IN AN 

2415
01:48:43,120 --> 01:48:44,988
ADVOCACY GROUP, AND HAVING THEIR

2416
01:48:44,988 --> 01:48:46,523
OWN CHILDREN INVOLVED IN THE 

2417
01:48:46,523 --> 01:48:49,126
TRIAL AND THEN HEAR FROM MELANI 

2418
01:48:49,126 --> 01:48:51,628
WHO WILL TALK ABOUT INFORMED AND

2419
01:48:51,628 --> 01:48:53,130
EFFICIENT CLINICAL TRIALS DESIGN

2420
01:48:53,130 --> 01:48:55,632
USING NATURAL HISTORY DATA AND 

2421
01:48:55,632 --> 01:48:57,901
MODELING.  HEATHER WILL TALK 

2422
01:48:57,901 --> 01:48:59,069
ABOUT CONSIDERATIONS FOR REMOTE 

2423
01:48:59,069 --> 01:49:01,671
PHENOTYPING IN PEDIATRIC 

2424
01:49:01,671 --> 01:49:04,474
RESEARCH, LAINNY ROSS WILL WRAP 

2425
01:49:04,474 --> 01:49:07,144
UP THE SESSION FOR US REGARDING 

2426
01:49:07,144 --> 01:49:09,846
GENETIC STRATEGIES TO TREAT RARE

2427
01:49:09,846 --> 01:49:12,516
NEUROLOGICAL DISORDERS AND WE 

2428
01:49:12,516 --> 01:49:14,084
WILL BE JOINED BY ROSA WHO WILL 

2429
01:49:14,084 --> 01:49:17,687
HELP ANSWER, I HOPE, SOME 

2430
01:49:17,687 --> 01:49:19,189
REGULATORY ISSUES THAT HAVE COME

2431
01:49:19,189 --> 01:49:23,059
UP DURING THE COURSE OF THE 

2432
01:49:23,059 --> 01:49:25,095
WORKSHOP.  SO WITH THAT I AM 

2433
01:49:25,095 --> 01:49:27,664
GOING TO TURN IT OVER TO DENNIS 

2434
01:49:27,664 --> 01:49:30,100
LAL WHO IS AS THE UNIVERSITY OF 

2435
01:49:30,100 --> 01:49:32,969
TEXAS, HOUSTON TO TALK ABOUT 

2436
01:49:32,969 --> 01:49:36,873
ENHANCING GLOBAL RARE EPILEPSY 

2437
01:49:36,873 --> 01:49:47,150
CARE.  DENNIS?

2438
01:50:18,348 --> 01:50:19,749
>> I REALLY APPRECIATE TO
BE 

2439
01:50:19,749 --> 01:50:22,886
HERE.  THANK YOU SO MUCH FOR THE

2440
01:50:22,886 --> 01:50:25,255
INVITATION.  LIKE OFTEN I AM A 

2441
01:50:25,255 --> 01:50:26,423
LITTLE BIT DIFFERENT THAN MOST 

2442
01:50:26,423 --> 01:50:29,259
PEOPLE.  BUT I HOPE IT WILL BE 

2443
01:50:29,259 --> 01:50:31,995
ENTERTAINING AND SOMETHING FOR 

2444
01:50:31,995 --> 01:50:34,264
EVERYONE.  SO BEFORE I START 

2445
01:50:34,264 --> 01:50:35,832
WITH THE TALK I JUST WANT TO 

2446
01:50:35,832 --> 01:50:38,401
GIVE YOU SOME BACKGROUND WHERE 

2447
01:50:38,401 --> 01:50:41,371
I'M COMING FROM SO YOU HAVE AN 

2448
01:50:41,371 --> 01:50:42,906
UNDERSTANDING WHERE I'M GOING SO

2449
01:50:42,906 --> 01:50:46,576
MY LAB HAS BEEN INVOLVED I'M 

2450
01:50:46,576 --> 01:50:47,711
TRYING TO UNDERSTAND WHAT 

2451
01:50:47,711 --> 01:50:49,446
GENETIC BARRIERS DO ACROSS 

2452
01:50:49,446 --> 01:50:50,514
DISEASE AND WE ALWAYS TRY TO 

2453
01:50:50,514 --> 01:50:52,749
BRING IN THE BIOLOGY.  FOR 

2454
01:50:52,749 --> 01:50:53,850
EXAMPLE, I DON'T KNOW SO MUCH --

2455
01:50:53,850 --> 01:50:57,420
I DON'T REALLY LIKE MUCH THE, 

2456
01:50:57,420 --> 01:50:59,589
YOU KNOW, THE CRITERIA BECAUSE 

2457
01:50:59,589 --> 01:51:02,459
IT'S JUST A PROBABILITY BUT IF 

2458
01:51:02,459 --> 01:51:05,228
WE KNOW WHAT THE PROTEIN DOES IT

2459
01:51:05,228 --> 01:51:07,430
CAN GO TOWARDS A WORKING 

2460
01:51:07,430 --> 01:51:08,932
MECHANISM.  WE HAVE ALSO 

2461
01:51:08,932 --> 01:51:11,167
DEVELOPED ONLINE RESOURCES 

2462
01:51:11,167 --> 01:51:11,935
SPECIFICALLY FOR EPILEPSY TO 

2463
01:51:11,935 --> 01:51:14,437
UNDERSTAND WHY MUTATIONS ARE 

2464
01:51:14,437 --> 01:51:15,472
PATHOGENIC AND DEVELOP DIFFERENT

2465
01:51:15,472 --> 01:51:16,806
FRAMEWORKS FOR THAT AND WHERE WE

2466
01:51:16,806 --> 01:51:19,142
CAN HIGHLIGHT WHAT WE CALL 

2467
01:51:19,142 --> 01:51:20,477
ESSENTIAL REGIONS AND THEY ARE 

2468
01:51:20,477 --> 01:51:23,580
OFTEN CORRELATE WITH OTHER KNOWN

2469
01:51:23,580 --> 01:51:27,284
FUNCTIONAL MECHANISMS SO AND WE 

2470
01:51:27,284 --> 01:51:28,518
PROJECTED THOSE FOR MANY GENES 

2471
01:51:28,518 --> 01:51:30,453
AND DEVELOPED ONLINE TOOLS.  

2472
01:51:30,453 --> 01:51:32,122
THIS IS THE PATH WHEN I WAS 

2473
01:51:32,122 --> 01:51:34,291
YOUNG AND AMBITIOUS TO THINK 

2474
01:51:34,291 --> 01:51:36,626
THAT ONLINE TOOLS WOULD HELP TO 

2475
01:51:36,626 --> 01:51:38,461
IMPROVE CARE BUT STILL BELIEVING

2476
01:51:38,461 --> 01:51:43,033
THIS BUT I THINK WE KNENEED TO E

2477
01:51:43,033 --> 01:51:44,668
IN A DIFFERENT DIRECTION.  ONE 

2478
01:51:44,668 --> 01:51:47,103
IS TO DEVELOP ALGORITHMS TO 

2479
01:51:47,103 --> 01:51:48,605
ASSIST VARIANCE INTERPRETATION 

2480
01:51:48,605 --> 01:51:50,574
AND PARTICULARLY AGGREGATING 

2481
01:51:50,574 --> 01:51:52,475
INFORMATION FROM THE FUNCTIONAL 

2482
01:51:52,475 --> 01:51:55,579
EXPERIMENTS AND TRY TO HARNESS 

2483
01:51:55,579 --> 01:51:58,181
THE MANY EXPERIMENTS INTO A 

2484
01:51:58,181 --> 01:51:59,382
SYSTEM.  AND WE ARE REALLY 

2485
01:51:59,382 --> 01:52:01,918
ENGAGED IN WHEN IT COMES TO 

2486
01:52:01,918 --> 01:52:04,220
INFORMATICS TO UNDERSTAND WHY, 

2487
01:52:04,220 --> 01:52:07,123
SOME ALGORITHMS WORK BETTER AND 

2488
01:52:07,123 --> 01:52:09,159
WE HAVE STUDIES LIKE THIS ONE 

2489
01:52:09,159 --> 01:52:10,260
AND TRYING TO WORK OUT WHAT 

2490
01:52:10,260 --> 01:52:13,530
WORKS BEST AND THIS IS 

2491
01:52:13,530 --> 01:52:14,397
INCREDIBLY COMPLICATED WHERE 

2492
01:52:14,397 --> 01:52:19,636
WE'RE WORKING UNDER.  SO THERE'S

2493
01:52:19,636 --> 01:52:21,871
NOT TOO MUCH RELEVANCE ON WHAT I

2494
01:52:21,871 --> 01:52:23,573
WANT TO TALK ABOUT TODAY BUT 

2495
01:52:23,573 --> 01:52:25,542
OVER THE LAST TWO TO FOUR YEARS 

2496
01:52:25,542 --> 01:52:28,645
WE, REALLY WHAT I DO IS USELESS 

2497
01:52:28,645 --> 01:52:30,113
SO WE STARTED TO SHIFT A LITTLE 

2498
01:52:30,113 --> 01:52:33,550
BIT GEARS AND TO MOVE TOWARDS 

2499
01:52:33,550 --> 01:52:36,086
EDUCATION.  AND TRY TO REALLY 

2500
01:52:36,086 --> 01:52:40,724
WORK ON, BASED ON GUIDELINES 

2501
01:52:40,724 --> 01:52:43,159
THAT ARE THERE.  AND TO ENHANCE 

2502
01:52:43,159 --> 01:52:45,462
THEM AND TO MAX OUT WHAT ONE CAN

2503
01:52:45,462 --> 01:52:46,830
DO.  WHAT MANY PEOPLE DON'T KNOW

2504
01:52:46,830 --> 01:52:48,598
IS IF SOMEONE SAYS I CLASSIFY 

2505
01:52:48,598 --> 01:52:53,503
THE PATIENT BASED ON ACMG THAT 

2506
01:52:53,503 --> 01:52:55,138
CAN MEAN MANY DIFFERENT THINGS 

2507
01:52:55,138 --> 01:52:57,273
AND THERE'S NO OBJECTIVE MARKER 

2508
01:52:57,273 --> 01:52:59,676
FOR THAT SO SOME PEOPLE USE FIVE

2509
01:52:59,676 --> 01:53:01,244
CRITERIA AND SOME PEOPLE SPEND, 

2510
01:53:01,244 --> 01:53:04,381
LIKE A RESEARCH PAPER LEVEL ON 

2511
01:53:04,381 --> 01:53:07,617
USING THESE GUIDELINES TO 

2512
01:53:07,617 --> 01:53:09,619
CLASSIFY IT AND IT'S LEAD TO 

2513
01:53:09,619 --> 01:53:10,954
EXPERIMENTS SO WE GIVE A 

2514
01:53:10,954 --> 01:53:12,856
WORKSHOP.  OKAY, SO I HAVE A LOT

2515
01:53:12,856 --> 01:53:14,824
OF CONFLICTS TODAY WHICH BRING 

2516
01:53:14,824 --> 01:53:19,029
ME ALSO INTO THIS ROLE, WHY I AM

2517
01:53:19,029 --> 01:53:23,166
DOING THE RESEARCH AND I AM -- 

2518
01:53:23,166 --> 01:53:25,068
THE PROGRAMS I'M DEVELOPING 

2519
01:53:25,068 --> 01:53:27,003
TODAY, THEY ARE BASED ON THIS 

2520
01:53:27,003 --> 01:53:28,505
CONTEXT.  ON MANY OF THESE 

2521
01:53:28,505 --> 01:53:29,973
CONFLICTS WHICH YOU CAN SEE HERE

2522
01:53:29,973 --> 01:53:31,374
I'M SOMEHOW INVOLVED IN THE 

2523
01:53:31,374 --> 01:53:33,410
CLINICAL TRIAL MISS THE STUDY 

2524
01:53:33,410 --> 01:53:35,445
DESIGN IN TERMS OF ENROLLING THE

2525
01:53:35,445 --> 01:53:37,580
PATIENTS FROM THE GENETICS 

2526
01:53:37,580 --> 01:53:40,550
PERSPECTIVE SO HAVING THE 

2527
01:53:40,550 --> 01:53:41,317
COUNTERPART OF THE CLINICAL 

2528
01:53:41,317 --> 01:53:44,187
PERSPECTIVE PURELY FROM A 

2529
01:53:44,187 --> 01:53:44,854
MECHANISM PERSPECTIVE OR 

2530
01:53:44,854 --> 01:53:46,690
PATHOGEN PERSPECTIVE AND HAVING 

2531
01:53:46,690 --> 01:53:49,559
A SECONDARY OPINION.  OKAY, SO, 

2532
01:53:49,559 --> 01:53:52,262
YOU KNOW, LET'S DO THIS A LITTLE

2533
01:53:52,262 --> 01:53:56,332
MORE SPECIFIC, SO WHY DO WE NEED

2534
01:53:56,332 --> 01:53:58,735
TO FOCUS ON THE INTERPRETATION 

2535
01:53:58,735 --> 01:53:59,903
AND CLASSIFICATION.  IT'S AS 

2536
01:53:59,903 --> 01:54:01,504
SIMPLE AS THAT BECAUSE MOST OF 

2537
01:54:01,504 --> 01:54:04,908
OUR GENETIC TEST RESULTS CANNOT 

2538
01:54:04,908 --> 01:54:06,109
BE INTERPRETED TO A DEGREE THAT 

2539
01:54:06,109 --> 01:54:06,943
WE KNOW THE PATIENT HAS A 

2540
01:54:06,943 --> 01:54:08,244
DISEASE OR DOESN'T HAVE A 

2541
01:54:08,244 --> 01:54:10,547
DISEASE.  WE OFTEN OR MOST OF 

2542
01:54:10,547 --> 01:54:13,049
THE TIME HAVE THE VARIANTS OF 

2543
01:54:13,049 --> 01:54:14,451
SIGNIFICANCE WHICH IS WHAT GEMMA

2544
01:54:14,451 --> 01:54:17,620
MENTIONED THIS MORNING AND THIS 

2545
01:54:17,620 --> 01:54:19,622
IS A RECENT VISUALIZATION FROM 

2546
01:54:19,622 --> 01:54:21,057
THE PUBLICATION FROM OUR TEAM 

2547
01:54:21,057 --> 01:54:22,826
AND YOU CAN SEE THE MOST 

2548
01:54:22,826 --> 01:54:24,861
VARIANTS WHICH ARE CLINICALLY 

2549
01:54:24,861 --> 01:54:26,096
REPORTED ARE OF UNKNOWN 

2550
01:54:26,096 --> 01:54:28,198
SIGNIFICANCE EVEN IN THE BEST 

2551
01:54:28,198 --> 01:54:29,432
KNOWN EPILEPTIC GENE.  THAT'S 

2552
01:54:29,432 --> 01:54:31,601
ONE PROBLEM.  SO WITHOUT A 

2553
01:54:31,601 --> 01:54:32,769
DIAGNOSIS WE CANNOT ENROLL 

2554
01:54:32,769 --> 01:54:37,607
ANYONE OR SHOULD NOT.  AND YOU 

2555
01:54:37,607 --> 01:54:41,244
CANNOT GIVE THE FAMILY 

2556
01:54:41,244 --> 01:54:46,683
CONFIDENCE OR CLOSURE.  SO ON 

2557
01:54:46,683 --> 01:54:47,684
THE OTHER HAND WITHOUT A 

2558
01:54:47,684 --> 01:54:48,718
DIAGNOSIS.  DIAGNOSIS IS ONE 

2559
01:54:48,718 --> 01:54:50,687
PROBLEM BUT HAVING WORKED NOW IN

2560
01:54:50,687 --> 01:54:52,322
TWO HOSPITAL SYSTEMS IN THE U.S.

2561
01:54:52,322 --> 01:54:53,857
THE LAST TEN YEARS AND GIVING 

2562
01:54:53,857 --> 01:54:55,625
WORKSHOPS AND BEING INVOLVED, 

2563
01:54:55,625 --> 01:55:00,396
YOU KNOW, HAVING A PATHOGENIC 

2564
01:55:00,396 --> 01:55:02,332
VARIANT IN THE REPORT DOESN'T 

2565
01:55:02,332 --> 01:55:03,166
AUTOMATICALLY PRODUCE PATIENT 

2566
01:55:03,166 --> 01:55:05,602
CARE AND THERE ARE MANY ISSUES 

2567
01:55:05,602 --> 01:55:06,970
WITH THIS AND THIS IS 

2568
01:55:06,970 --> 01:55:08,304
COMPLICATED BUT THIS IS A 

2569
01:55:08,304 --> 01:55:10,540
PROBLEM THAT ALSO NEEDS TO BE 

2570
01:55:10,540 --> 01:55:11,207
SOLVED BECAUSE THERE'S SO MUCH 

2571
01:55:11,207 --> 01:55:14,410
KNOWLEDGE ALREADY THERE TODAY.  

2572
01:55:14,410 --> 01:55:19,215
SO WHAT -- WHAT MY YOUNG MIND 

2573
01:55:19,215 --> 01:55:23,987
THINKS ARE, INTEGRATIONAL, FOR 

2574
01:55:23,987 --> 01:55:26,422
BETTER INTERPRETATION WE CAN USE

2575
01:55:26,422 --> 01:55:29,092
THE EXPERT KNOWLEDGE BUT IT'S 

2576
01:55:29,092 --> 01:55:30,426
NOT DONE BECAUSE YOU CANNOT HAVE

2577
01:55:30,426 --> 01:55:33,396
ACCESS TO THE DATA OR HANDLE THE

2578
01:55:33,396 --> 01:55:34,197
DATA THAT'S THE PROBLEM AND 

2579
01:55:34,197 --> 01:55:36,833
TYPICALLY IF YOU WANT TO DO THE 

2580
01:55:36,833 --> 01:55:37,967
BEST INTERPRETATION POSSIBLE AND

2581
01:55:37,967 --> 01:55:40,403
CARE YOU NEED AN INTEGRATED TEAM

2582
01:55:40,403 --> 01:55:42,005
AND OFTEN, YOU KNOW, PEOPLE 

2583
01:55:42,005 --> 01:55:46,609
DON'T KNOW THAT THIS IS NEEDED 

2584
01:55:46,609 --> 01:55:47,544
THAT'S ALREADY PROBLEM MINUS ONE

2585
01:55:47,544 --> 01:55:49,579
AND EVEN IF YOU HAVE THE 

2586
01:55:49,579 --> 01:55:52,382
RESOURCES WHICH IS SUPER RARE, 

2587
01:55:52,382 --> 01:55:53,917
THEN IT'S ONLY FEW -- IT'S ONLY 

2588
01:55:53,917 --> 01:55:56,953
THERE FOR A FEW GENES.  AND 

2589
01:55:56,953 --> 01:55:58,087
OVERALL WE'RE TALKING ABOUT RARE

2590
01:55:58,087 --> 01:56:00,256
DISEASE AND WE'RE TALKING ABOUT 

2591
01:56:00,256 --> 01:56:03,159
FEW EXPERTS AND IT'S POSSIBLE 

2592
01:56:03,159 --> 01:56:04,327
THAT IT'S EVERY CENTER AND EVERY

2593
01:56:04,327 --> 01:56:06,763
HOSPITAL YOU HAVE AN EXPERT.  SO

2594
01:56:06,763 --> 01:56:09,632
WE NEED TO DEVELOP 

2595
01:56:09,632 --> 01:56:10,500
INFRASTRUCTURE WHERE EXPERT 

2596
01:56:10,500 --> 01:56:11,801
KNOWLEDGE COME TO EVERYONE NOT 

2597
01:56:11,801 --> 01:56:13,603
THE OTHER WAY AROUND BUT THE 

2598
01:56:13,603 --> 01:56:17,207
PATIENT HAS THE WORDS TO GET TO 

2599
01:56:17,207 --> 01:56:19,242
AN EXPERT.  NOT PEOPLE WHO 

2600
01:56:19,242 --> 01:56:20,443
SUFFER WITH A DISABILITY.  SO 

2601
01:56:20,443 --> 01:56:23,146
WHAT ARE THE ISSUES?  SO ONE OF 

2602
01:56:23,146 --> 01:56:25,782
THE ISSUES IS, YOU KNOW, WE ARE 

2603
01:56:25,782 --> 01:56:28,551
INCREDIBLY SUCCESSFUL IN 

2604
01:56:28,551 --> 01:56:30,620
IDENTIFYING EPILEPSY GENES.  SO 

2605
01:56:30,620 --> 01:56:34,824
THIS IS AMAZING.  BUT IT BRINGS 

2606
01:56:34,824 --> 01:56:38,795
A PROBLEM.  EVERY ONE OF THOSE 

2607
01:56:38,795 --> 01:56:40,830
GENES COUPLED WITH A DISORDER 

2608
01:56:40,830 --> 01:56:43,166
HAS IT OWN SPECTRUM, NEEDS, 

2609
01:56:43,166 --> 01:56:47,036
REFERRALS AND OWN SUPPORT.  SO 

2610
01:56:47,036 --> 01:56:48,538
THERE IS NO PROGRAM WHICH 

2611
01:56:48,538 --> 01:56:51,174
ENABLES YOU TO BE ON TOP OF THE 

2612
01:56:51,174 --> 01:56:52,942
GAME, SIMPLY IN HUMAN LEVEL NOT 

2613
01:56:52,942 --> 01:56:54,744
POSSIBLE.  SO IT'S A CHALLENGE. 

2614
01:56:54,744 --> 01:56:56,946
AND IT'S A CHALLENGE THAT IS 

2615
01:56:56,946 --> 01:56:58,948
INCREASING SO THE SECOND THING 

2616
01:56:58,948 --> 01:57:02,952
IS YOU NEED TO -- SO TO 

2617
01:57:02,952 --> 01:57:06,189
ILLUSTRATE A BIT FOR EVERY ONE 

2618
01:57:06,189 --> 01:57:09,392
OF THOSE GENES YOU NEED TO HAVE 

2619
01:57:09,392 --> 01:57:11,361
THIS FOR THE GENE ITSELF OR THE 

2620
01:57:11,361 --> 01:57:12,562
GENE NEED BUT YOU NEED TO HAVE 

2621
01:57:12,562 --> 01:57:14,597
THIS ACROSS AGE GROUPS.  IT'S 

2622
01:57:14,597 --> 01:57:16,366
VERY DIFFERENT THAN HOW THE 

2623
01:57:16,366 --> 01:57:19,369
DISEASE CAN PRESENT AND THE NEED

2624
01:57:19,369 --> 01:57:20,837
AND THE UNIT WHETHER IT'S A 

2625
01:57:20,837 --> 01:57:26,042
TEN-YEAR-OLD OR A 

2626
01:57:26,042 --> 01:57:26,976
FORTY-YEAR-OLD.  IT'S COMPLEX.  

2627
01:57:26,976 --> 01:57:31,147
EVEN WHEN WE TALK ABOUT THE GENE

2628
01:57:31,147 --> 01:57:32,849
WHERE A LOT OF RESEARCH IS GOING

2629
01:57:32,849 --> 01:57:34,817
IN WE NEED TO CONSIDER A LOT OF 

2630
01:57:34,817 --> 01:57:37,987
THINGS, YOU KNOW, IN TERMS OF 

2631
01:57:37,987 --> 01:57:40,456
CARE.  AND THESE DECISIONS ARE 

2632
01:57:40,456 --> 01:57:42,125
REALLY HARD.  SO, IN THE EXAMPLE

2633
01:57:42,125 --> 01:57:44,894
YOU CAN SEE THAT YOU HAVE A 

2634
01:57:44,894 --> 01:57:46,696
DISEASE WHICH IS DUE TO TOO MUCH

2635
01:57:46,696 --> 01:57:48,731
FUNCTIONING.  AND YOU HAVE A 

2636
01:57:48,731 --> 01:57:50,199
DISEASE WHICH IS DUE TO TOO LESS

2637
01:57:50,199 --> 01:57:53,836
OF A FUNCTION AND BOTH PRESENT 

2638
01:57:53,836 --> 01:57:55,939
IN THE QUALITY OF LIFE.  AND SO 

2639
01:57:55,939 --> 01:57:57,373
AT THIS POINT OFTEN THE 

2640
01:57:57,373 --> 01:57:58,875
REGRESSION IS NOT VISIBLE.  

2641
01:57:58,875 --> 01:58:01,177
RIGHT?  SO MOST CLINICIANS DON'T

2642
01:58:01,177 --> 01:58:03,846
SEE EVEN MORE THAN TEN PATIENTS 

2643
01:58:03,846 --> 01:58:05,481
IN THEIR CAREER.  EVEN AT LARGE 

2644
01:58:05,481 --> 01:58:08,618
CENTERS.  SO, YOU KNOW, WHEN WE 

2645
01:58:08,618 --> 01:58:10,853
MOVE IN DISEASE MODIFYING 

2646
01:58:10,853 --> 01:58:11,554
THERAPIES YOU NEED TO BE 

2647
01:58:11,554 --> 01:58:14,958
CAUTIOUS AND TO BE WELL AWARE.  

2648
01:58:14,958 --> 01:58:19,162
SO I DON'T SAY THIS BUT IT 

2649
01:58:19,162 --> 01:58:20,430
REQUIRES A LOT OF KNOWLEDGE ONLY

2650
01:58:20,430 --> 01:58:25,234
A FEW PEOPLE HAVE.  GIVING A 

2651
01:58:25,234 --> 01:58:27,170
REAL WORLD EXAMPLE NONE OF THIS 

2652
01:58:27,170 --> 01:58:30,206
IS RANDOMIZED CONTROL TRIALS.  

2653
01:58:30,206 --> 01:58:31,207
YOU HAVE THE LITERATURE FROM 

2654
01:58:31,207 --> 01:58:32,942
THOSE WHO ARE MEANINGFUL THAT 

2655
01:58:32,942 --> 01:58:35,278
CAN HELP YOUR PATIENTS.  WHERE 

2656
01:58:35,278 --> 01:58:40,583
IT WAS  SUGGESTED THAT THE 

2657
01:58:40,583 --> 01:58:42,418
SODIUM CHANNEL BLOCKERS.  

2658
01:58:42,418 --> 01:58:43,753
WHEREAS OTHERS IT SHOULD BE 

2659
01:58:43,753 --> 01:58:44,988
AVOIDED.  THERE'S A CERTAIN 

2660
01:58:44,988 --> 01:58:47,023
LEVEL OF RESEARCH KNOWLEDGE AND 

2661
01:58:47,023 --> 01:58:47,991
RESEARCH ABILITY TO READ THE 

2662
01:58:47,991 --> 01:58:49,592
RESEARCH AND THE TIME YOU ENEED 

2663
01:58:49,592 --> 01:58:52,295
TO HAVE TO INTEGRATE YOUR CARE. 

2664
01:58:52,295 --> 01:58:54,197
AND THEN THERE'S THE FDA 

2665
01:58:54,197 --> 01:58:55,598
APPROVAL.  THERE'S THINGS 

2666
01:58:55,598 --> 01:58:58,434
HAPPENING BUT IT CAN BE MAKE IT 

2667
01:58:58,434 --> 01:58:58,801
HOT. 

2668
01:58:58,801 --> 01:58:59,902
AND AT THE SAME TIME THERE'S 

2669
01:58:59,902 --> 01:59:00,503
CLINICAL TRIALS AND THERE'S 

2670
01:59:00,503 --> 01:59:01,537
DIFFERENT KINDS OF TECHNOLOGY 

2671
01:59:01,537 --> 01:59:02,171
WHICH IS BEAUTIFUL THAT WE CAN 

2672
01:59:02,171 --> 01:59:07,143
DO A LOT OF THINGS BUT IF YOU 

2673
01:59:07,143 --> 01:59:09,112
CONTEND YOUR PATIENTS IN TERMS 

2674
01:59:09,112 --> 01:59:11,180
OF SHOULD YOU DO IT IN YOU NEED 

2675
01:59:11,180 --> 01:59:13,583
TO HAVE A LOT OF KNOWLEDGE AND 

2676
01:59:13,583 --> 01:59:16,753
THIS IS INCREASING TREMENDOUSLY.

2677
01:59:16,753 --> 01:59:20,023
SO WHO HAS THAT?  SO TO 

2678
01:59:20,023 --> 01:59:21,824
ILLUSTRATE WHY GENETIC IS BETTER

2679
01:59:21,824 --> 01:59:24,193
THAN OTHER DOMAINS?  THIS IS 

2680
01:59:24,193 --> 01:59:28,064
WHAT IS HAPPENING AND 

2681
01:59:28,064 --> 01:59:28,965
PARTICULARLY IN THIS FIELD.  YOU

2682
01:59:28,965 --> 01:59:31,167
MIGHT BE THE WRITER'S MIND IN 

2683
01:59:31,167 --> 01:59:33,703
TERMS OF READING AN MRI AND YOU 

2684
01:59:33,703 --> 01:59:34,937
MIGHT BE STILL TODAY BUT KEEPING

2685
01:59:34,937 --> 01:59:37,607
UP WITH GENETICS THAT'S REALLY 

2686
01:59:37,607 --> 01:59:41,844
HOT, YOU NEED THE TIME.  TO GET 

2687
01:59:41,844 --> 01:59:43,513
THE GRANTS AND THAT WILL TAKE 

2688
01:59:43,513 --> 01:59:46,816
FOREVER.  FOR CLINICIANS IT'S A 

2689
01:59:46,816 --> 01:59:48,351
REALLY HARD CHALLENGE.  NOT ONLY

2690
01:59:48,351 --> 01:59:50,686
DO YOU NEED HAVE THE TUITION IF 

2691
01:59:50,686 --> 01:59:51,454
YOU WANT TO CARE FOR EVERYONE 

2692
01:59:51,454 --> 01:59:55,124
YOU NEED TO HAVE THE TUITION FOR

2693
01:59:55,124 --> 01:59:56,259
MANY GENES UNDERSTAND THE 

2694
01:59:56,259 --> 01:59:58,694
CLINICAL SPECTRUM ACROSS AN AGE 

2695
01:59:58,694 --> 02:00:00,763
RANGE IT'S AN INCREDIBLE HARD 

2696
02:00:00,763 --> 02:00:01,697
CHALLENGE TO PROVIDE THE BEST 

2697
02:00:01,697 --> 02:00:02,732
CARE POSSIBLE FOR A SINGLE 

2698
02:00:02,732 --> 02:00:05,935
PERSON SO YOU KNOW WHERE I'M 

2699
02:00:05,935 --> 02:00:07,870
GETTING SO, AND TO MAKE IT EVEN 

2700
02:00:07,870 --> 02:00:10,506
MORE COMPLICATED.  THIS IS, 

2701
02:00:10,506 --> 02:00:12,008
AGAIN, MIGHT BE COMPLETELY 

2702
02:00:12,008 --> 02:00:14,110
WRONG.  JUST THOUGHT ABOUT THIS.

2703
02:00:14,110 --> 02:00:16,512
SO WHAT WE PRESUME FOR THE NEXT 

2704
02:00:16,512 --> 02:00:17,480
GENERATION OF CHILDREN IS WE 

2705
02:00:17,480 --> 02:00:19,148
WANT TO PREVENT DISEASE.  RIGHT?

2706
02:00:19,148 --> 02:00:23,453
SO PREVENT MEANS WE WANT TO GO 

2707
02:00:23,453 --> 02:00:27,256
IN WITH, YOU KNOW, REALLY STRONG

2708
02:00:27,256 --> 02:00:31,594
ACTING THERAPY.  AS EARLY AS 

2709
02:00:31,594 --> 02:00:34,330
POSSIBLE BECAUSE WE'VE SEEN FROM

2710
02:00:34,330 --> 02:00:36,199
RESEARCH THERE'S THE BEST GAIN 

2711
02:00:36,199 --> 02:00:38,634
SO THIS MEANS THE CLINICAL 

2712
02:00:38,634 --> 02:00:39,602
TUITION YOU CAN BRING IN FOR 

2713
02:00:39,602 --> 02:00:43,139
PERSON WHO HAS NOT OR JUST IS 

2714
02:00:43,139 --> 02:00:45,274
ABOUT TO BE IN THE STAGE OF 

2715
02:00:45,274 --> 02:00:47,610
DISEASE.  BECOMES REALLY LOW SO 

2716
02:00:47,610 --> 02:00:48,711
ALL THE VARIANT INTERPRETATION 

2717
02:00:48,711 --> 02:00:50,980
IS REALLY MOVING TOWARDS 

2718
02:00:50,980 --> 02:00:55,952
GENETICS.  OKAY?  SO WE NEED TO 

2719
02:00:55,952 --> 02:00:57,787
BECOME BETTER AT THE SAME TIME 

2720
02:00:57,787 --> 02:00:59,922
WHEN WE LOOK AT OTHERS WE NEED 

2721
02:00:59,922 --> 02:01:02,191
TO FIGURE OUT MORE HOW -- OTHER 

2722
02:01:02,191 --> 02:01:05,761
FACTOR BEYOND GENETIC CONSIST 

2723
02:01:05,761 --> 02:01:08,865
MODIFY THE DISEASE PRESENTATION.

2724
02:01:08,865 --> 02:01:10,099
IS THERE AN OPPORTUNITIES WHERE 

2725
02:01:10,099 --> 02:01:12,535
THE PERSON SAYS AS A CHILD MIGHT

2726
02:01:12,535 --> 02:01:14,170
WORK IN AN ADULT OR HAS BEEN 

2727
02:01:14,170 --> 02:01:17,807
MODIFIED TO YEARS OF EXPOSURE TO

2728
02:01:17,807 --> 02:01:19,609
A DIFFERENT ONE.  THERE'S A LOT 

2729
02:01:19,609 --> 02:01:23,713
OF THINGS.  OFTEN PEOPLE TALK 

2730
02:01:23,713 --> 02:01:26,282
BACK ABOUT OTHER NEUROLOGISTS 

2731
02:01:26,282 --> 02:01:28,584
BUT COULD IT BE THAT CLEARCUT 

2732
02:01:28,584 --> 02:01:31,087
SYNDROME WHICH WE HAVE IN 

2733
02:01:31,087 --> 02:01:32,889
PEDIATRICS ARE AN ADULT VERSION 

2734
02:01:32,889 --> 02:01:34,590
ARE NOT SO MUCH CLEARCUT 

2735
02:01:34,590 --> 02:01:35,825
ANYMORE.  MAYBE THIS IS A 

2736
02:01:35,825 --> 02:01:38,127
DIFFERENT GROUP.  IT'S HARD TO 

2737
02:01:38,127 --> 02:01:39,328
INTEGRATE THIS INTO CARE.  SO, 

2738
02:01:39,328 --> 02:01:41,397
AND I FOCUS REALLY ON THE 

2739
02:01:41,397 --> 02:01:42,832
CLINICAL PART OF THE POINT 

2740
02:01:42,832 --> 02:01:44,667
BECAUSE I GUESS WE HAVE MORE 

2741
02:01:44,667 --> 02:01:45,401
NEUROLOGISTS LISTENING THAN 

2742
02:01:45,401 --> 02:01:48,905
GENETICISTS BUT WE HAVE A LOT OF

2743
02:01:48,905 --> 02:01:51,140
CHALLENGES IN MEDICAL GENETICS 

2744
02:01:51,140 --> 02:01:55,111
AND PARTICULARLY FOR THE 

2745
02:01:55,111 --> 02:01:58,080
CLASSIFICATION PROBLEM.  SO THE 

2746
02:01:58,080 --> 02:02:01,617
GOOD THING IS IT'S MORE 

2747
02:02:01,617 --> 02:02:02,885
STANDARDIZED AND GETTING BETTER 

2748
02:02:02,885 --> 02:02:05,721
THAN EVER AND AT A RAPID PACE 

2749
02:02:05,721 --> 02:02:08,191
BUT THERE'S SO MANY RULES.  IT'S

2750
02:02:08,191 --> 02:02:09,792
A BIG COMPUTATIONAL CHALLENGE 

2751
02:02:09,792 --> 02:02:11,427
AND HARD TO KEEP UP THERE.  A 

2752
02:02:11,427 --> 02:02:12,728
PATIENT WHO HAS THIS YESTERDAY 

2753
02:02:12,728 --> 02:02:15,898
MIGHT HAVE TOMORROW, A NEW 

2754
02:02:15,898 --> 02:02:17,600
RELEASE, HAVE BARRIERS.  SO 

2755
02:02:17,600 --> 02:02:19,936
IT'S, YOU KNOW, IT'S A -- 

2756
02:02:19,936 --> 02:02:20,937
OVERWHELMING AMOUNT OF 

2757
02:02:20,937 --> 02:02:22,905
INFORMATION WHICH NEEDS TO BE 

2758
02:02:22,905 --> 02:02:24,574
INCORPORATED IN ORDER TO PROVIDE

2759
02:02:24,574 --> 02:02:27,410
THE BEST CARE POSSIBLE.  SO THE 

2760
02:02:27,410 --> 02:02:28,678
BUSINESS ADMINISTRATION, WE'RE 

2761
02:02:28,678 --> 02:02:30,780
LIVING IN AN AGE WHERE WE HAVE 

2762
02:02:30,780 --> 02:02:31,380
INFORMATION OVERLOAD AND WE 

2763
02:02:31,380 --> 02:02:34,550
DON'T YET HAVE THE SUPPORT WHICH

2764
02:02:34,550 --> 02:02:36,752
ARE CLINICAL GRADE AND HAVE BEEN

2765
02:02:36,752 --> 02:02:39,155
VETTED FDA APPROVAL.  IT WILL 

2766
02:02:39,155 --> 02:02:39,922
HAPPEN FOR SURE BUT AT THE 

2767
02:02:39,922 --> 02:02:43,059
MOMENT WE DON'T.  SO WHAT TO DO,

2768
02:02:43,059 --> 02:02:46,462
RIGHT?  AND OUR RESEARCH, WE ARE

2769
02:02:46,462 --> 02:02:49,632
EXPLORING DIFFERENT TYPES OF 

2770
02:02:49,632 --> 02:02:52,868
APPROACHES TO, YOU KNOW, DEAL 

2771
02:02:52,868 --> 02:02:54,904
WITH THE PROBLEM, ALL AT A VERY 

2772
02:02:54,904 --> 02:02:56,872
EARLY STAGE, FOR EXAMPLE HERE WE

2773
02:02:56,872 --> 02:02:58,874
TOOK FROM 10 MILLION PEOPLE, ALL

2774
02:02:58,874 --> 02:03:00,509
THE MEDICAL HEALTH RECORDS, 

2775
02:03:00,509 --> 02:03:03,746
EVERY ENCOUNTER AND HAVE THE 

2776
02:03:03,746 --> 02:03:11,187
TERMS AND SUPPLEMENT IT WITH THE

2777
02:03:11,187 --> 02:03:14,290
GENETIC DIAGNOSIS.  AND THEN 

2778
02:03:14,290 --> 02:03:16,259
LOOKED AT THE TRAJECTORY.  HOW 

2779
02:03:16,259 --> 02:03:17,860
MANY ENCOUNTERS THEY HAVE.  YOU 

2780
02:03:17,860 --> 02:03:19,996
CAN SEE THAT THE GENETIC 

2781
02:03:19,996 --> 02:03:21,497
EPILEPSIES HAVE WAY MORE 

2782
02:03:21,497 --> 02:03:23,733
ENCOUNTERS AS A WHOLE AND THEY 

2783
02:03:23,733 --> 02:03:25,768
HAVE THE MOST ENCOUNTERS PER 

2784
02:03:25,768 --> 02:03:27,770
PHYSICIAN A PERIOD WHICH IS 

2785
02:03:27,770 --> 02:03:30,373
REALLY HARD FOR MANY FAMILIES.  

2786
02:03:30,373 --> 02:03:34,310
WE SEE ALSO LIKE STRONG SIGNS OF

2787
02:03:34,310 --> 02:03:35,945
INFECTION.  AND SO ON.  SO YOU 

2788
02:03:35,945 --> 02:03:38,414
CAN DO THIS KIND OF WORK WHERE 

2789
02:03:38,414 --> 02:03:40,283
YOU TAKE NON CLINIC -- 

2790
02:03:40,283 --> 02:03:43,619
NON-RESEARCH DATA AND TRY TO 

2791
02:03:43,619 --> 02:03:45,421
INCORPORATE IT INTO STRONG 

2792
02:03:45,421 --> 02:03:46,989
HEALTH ASSISTANCE AND 

2793
02:03:46,989 --> 02:03:48,624
INCORPORATE -- DO RESEARCH ON 

2794
02:03:48,624 --> 02:03:50,693
THE FUTURE.  BUT YOU KNOW THE 

2795
02:03:50,693 --> 02:03:51,794
PEOPLE.  SO THIS IS THE THING 

2796
02:03:51,794 --> 02:03:55,131
THAT WE'RE BUILDING AT THE 

2797
02:03:55,131 --> 02:03:57,233
MOMENT WHERE WE TRY TO 

2798
02:03:57,233 --> 02:03:58,267
INCORPORATE THE DATA COMBINED 

2799
02:03:58,267 --> 02:04:04,674
WITH THE ALGORITHMS FROM THE 

2800
02:04:04,674 --> 02:04:08,277
RESEARCH WORLD TO THEN DO DAILY 

2801
02:04:08,277 --> 02:04:09,779
UPDATING INTERPRETATION BECAUSE 

2802
02:04:09,779 --> 02:04:12,581
THE PHENOTYPE IS IMPORTANT WITH 

2803
02:04:12,581 --> 02:04:15,017
THE GENOTYPE.  HOWEVER, YOU 

2804
02:04:15,017 --> 02:04:18,587
DON'T HAVE ALWAYS AN EXPERT AND 

2805
02:04:18,587 --> 02:04:23,859
YOU CAN'T EXPECT THE RESOURCES. 

2806
02:04:23,859 --> 02:04:25,294
SO THIS WILL BE IMPLEMENTING.  

2807
02:04:25,294 --> 02:04:28,597
SO WE HAVE THE SUPPORTS TO PUT 

2808
02:04:28,597 --> 02:04:30,466
IN A CONFLICT WHERE YOU CAN 

2809
02:04:30,466 --> 02:04:32,101
ENTER A VARIANT AND YOU WILL SEE

2810
02:04:32,101 --> 02:04:35,838
THE MRN.  SO THE PATIENT WILL 

2811
02:04:35,838 --> 02:04:37,873
IDENTIFY THIS.  SO LONG STORY 

2812
02:04:37,873 --> 02:04:44,914
SHORT, WE LOOK AT FOR EXAMPLE 

2813
02:04:44,914 --> 02:04:46,782
THIS.  AND WE LOOK AT THE TEST 

2814
02:04:46,782 --> 02:04:49,518
RESULTS FOR PEOPLE WITH EPILEPSY

2815
02:04:49,518 --> 02:04:51,887
AND YOUNG AND OLD.  AND ROUND 

2816
02:04:51,887 --> 02:04:55,157
ABOUT 5.8% OF TESTS WE NEEDED TO

2817
02:04:55,157 --> 02:04:56,325
RECLASSIFY.  SO, YOU KNOW, THIS 

2818
02:04:56,325 --> 02:04:59,161
IS NOT SURPRISING, RIGHT?  SO 

2819
02:04:59,161 --> 02:05:01,931
THE MORE YOU GO BACK THE MORE 

2820
02:05:01,931 --> 02:05:05,601
YOU HAVE TO RECLASSIFY THAT'S 

2821
02:05:05,601 --> 02:05:07,636
WHY IT'S IMPORTANT TO REEVALUATE

2822
02:05:07,636 --> 02:05:09,171
EVERY TWO YEARS.  SO YOU CAN SEE

2823
02:05:09,171 --> 02:05:11,507
HOW THINGS CHANGE IN THE FEW 

2824
02:05:11,507 --> 02:05:13,476
TERMS ALSO THAT YOU KNOW THINGS 

2825
02:05:13,476 --> 02:05:16,512
CAN BE LIKELY BENIGN HAPPENS 

2826
02:05:16,512 --> 02:05:19,982
SUPER RARELY AND ONLY IN OLDER 

2827
02:05:19,982 --> 02:05:23,986
REPORTS.  SO YOU NEED TO CONTACT

2828
02:05:23,986 --> 02:05:25,588
YOUR PATIENTS VERY CAREFULLY SO 

2829
02:05:25,588 --> 02:05:28,290
IT'S NOT SET IN STONE BUT THIS 

2830
02:05:28,290 --> 02:05:30,960
IS ONLY HERE.  THIS IS OKAY BUT 

2831
02:05:30,960 --> 02:05:32,528
YOU WANT TO HELP ON THE GLOBAL 

2832
02:05:32,528 --> 02:05:37,633
SCALE AND THERE ARE MANY, YOU 

2833
02:05:37,633 --> 02:05:44,039
KNOW SH, MANY RESOURCES.  AND W 

2834
02:05:44,039 --> 02:05:45,808
HAVE THIS FROM THREE OR FOUR 

2835
02:05:45,808 --> 02:05:47,176
YEARS AGO.  I THINK THERE WAS 

2836
02:05:47,176 --> 02:05:50,913
ONE PUBLICATION ON THIS.  AND SO

2837
02:05:50,913 --> 02:05:56,385
THIS IS THE LARGEST RESOURCE FOR

2838
02:05:56,385 --> 02:06:03,092
MONOGENIC EXPERT CREATED GLOBAL 

2839
02:06:03,092 --> 02:06:04,827
LY.  WE HAVE ONE HUNDRED 

2840
02:06:04,827 --> 02:06:05,961
THOUSAND PATIENTS.  SOME OF THIS

2841
02:06:05,961 --> 02:06:08,197
IS IN THE PROBLEM AND SOME OF 

2842
02:06:08,197 --> 02:06:10,566
THIS IS THE INVESTIGATORS.  WE 

2843
02:06:10,566 --> 02:06:11,700
HAVE THE FUNCTIONAL DATA HERE 

2844
02:06:11,700 --> 02:06:19,175
AND OTHER THINGS.  HERE NOW YOU 

2845
02:06:19,175 --> 02:06:21,977
HAVE THE EDUCATIONAL RESOURCES. 

2846
02:06:21,977 --> 02:06:24,480
AND ALL THE DATA THAT EXPLORE 

2847
02:06:24,480 --> 02:06:27,149
MEDICAL RESEARCH AND WE HAVE 

2848
02:06:27,149 --> 02:06:29,418
DEVELOPED A LOT OF TOOLS FOR 

2849
02:06:29,418 --> 02:06:30,986
RESEARCH THAT LOOK LIKE THIS.  

2850
02:06:30,986 --> 02:06:33,522
YOU CAN LOOK AT THE STRUCTURE 

2851
02:06:33,522 --> 02:06:35,958
AND IF THE VARIANT -- IT'S A 

2852
02:06:35,958 --> 02:06:38,260
FUNCTION OR THE PATIENT HAD 

2853
02:06:38,260 --> 02:06:40,062
SEIZURES OR AUTISM OR WHATEVER. 

2854
02:06:40,062 --> 02:06:48,471
THIS IS NEW.  SO THIS WE 

2855
02:06:48,471 --> 02:06:49,805
RELEASED THIS TWO DAYS AGO OR 

2856
02:06:49,805 --> 02:06:52,575
THREE DAYS AGO.  SO THIS IS 

2857
02:06:52,575 --> 02:06:55,077
WORTH LOOKING AT.  SO HERE'S AN 

2858
02:06:55,077 --> 02:06:59,148
EXAMPLE FOR THE PORTAL.  SO THE 

2859
02:06:59,148 --> 02:07:01,083
MDA RECEPTOR GENE WHERE I DON'T 

2860
02:07:01,083 --> 02:07:02,318
KNOW THROUGH THE ANALYSIS PART 

2861
02:07:02,318 --> 02:07:05,855
WHERE WE INCLUDED THE LATEST 

2862
02:07:05,855 --> 02:07:09,625
VERSE OF THE FIGURE AND THE 

2863
02:07:09,625 --> 02:07:11,193
LATEST ONE IS GOING TO BE 

2864
02:07:11,193 --> 02:07:11,727
PUBLISHED THIS YEAR. 

2865
02:07:11,727 --> 02:07:14,330
AND HERE WE INCLUDED INFORMATION

2866
02:07:14,330 --> 02:07:16,932
FROM THE VARIANT INTERPRETATION 

2867
02:07:16,932 --> 02:07:19,134
GROUP.  SO WHERE THIS RESOURCE 

2868
02:07:19,134 --> 02:07:21,270
HAS KNOWN THE LARGEST FUNCTIONAL

2869
02:07:21,270 --> 02:07:23,339
DATASET WHICH WAS SPECIFICALLY 

2870
02:07:23,339 --> 02:07:25,174
LOOKED AT BASED ON VERY 

2871
02:07:25,174 --> 02:07:29,078
CONSERVATIVE ESTIMATES BY THE 

2872
02:07:29,078 --> 02:07:31,113
EXPERTS IN THIS CASE.  

2873
02:07:31,113 --> 02:07:33,449
INTEGRATED FOR CLINICAL 

2874
02:07:33,449 --> 02:07:34,717
INTERPRETATION.  AND THEN WE 

2875
02:07:34,717 --> 02:07:37,553
HAVE THE LARGEST PATIENT COHORT 

2876
02:07:37,553 --> 02:07:39,555
HERE ALL EXPERT CURATED.  

2877
02:07:39,555 --> 02:07:41,524
EVERYBODY HAS LOOKED AT THIS AND

2878
02:07:41,524 --> 02:07:44,426
WE HAVE ALL THE LATEST 

2879
02:07:44,426 --> 02:07:45,895
BIOINFORMATICS.  WE HAVE THE 

2880
02:07:45,895 --> 02:07:47,563
GENERAL DATABASE FOR VARIOUS 

2881
02:07:47,563 --> 02:07:51,600
POPULATION OF THE UK BIOBANK, 

2882
02:07:51,600 --> 02:07:54,470
AND, YEAH, AND THIS YOU CAN 

2883
02:07:54,470 --> 02:07:55,204
ACCESS AUTOMATICALLY, YOU CAN 

2884
02:07:55,204 --> 02:07:58,173
TYPE IN THE BARRIERS AND THEN --

2885
02:07:58,173 --> 02:08:00,509
WHICH YOU KNOW GIVE AS AN 

2886
02:08:00,509 --> 02:08:04,647
EXPERT.  IF YOU KNOW BETTER 

2887
02:08:04,647 --> 02:08:08,450
OVERRIDE NOW ON ALL THE FIGURES 

2888
02:08:08,450 --> 02:08:09,118
SO THIS IS FOR THE GENERAL 

2889
02:08:09,118 --> 02:08:12,454
COUNSEL.  IF YOU THINK, FOR 

2890
02:08:12,454 --> 02:08:20,796
EXAMPLE, THE FULL FREQUENCY IS 

2891
02:08:20,796 --> 02:08:23,465
WHATEVER AND FOUR TIMES IS NOT 

2892
02:08:23,465 --> 02:08:25,734
FREQUENT ENOUGH OR TOO FREQUENT 

2893
02:08:25,734 --> 02:08:27,603
BECAUSE THE PATIENT HAS A 

2894
02:08:27,603 --> 02:08:28,203
DIFFERENT PHENOTYPE YOU CAN 

2895
02:08:28,203 --> 02:08:30,105
DERIVE THAT AS WELL.  YOU CAN 

2896
02:08:30,105 --> 02:08:33,309
LOOK UP BASICALLY ALL THE 

2897
02:08:33,309 --> 02:08:35,644
RESOURCES FOR THE VARIOUS 

2898
02:08:35,644 --> 02:08:36,679
INTERPRETATIONS AND THEN YOU CAN

2899
02:08:36,679 --> 02:08:38,280
SEE THE PATIENTS WHICH ARE 

2900
02:08:38,280 --> 02:08:39,915
SUBMITTED IN OUR DATABASE.  YOU 

2901
02:08:39,915 --> 02:08:41,383
CAN GET THE BASIC IDENTIFIED 

2902
02:08:41,383 --> 02:08:43,018
INFORMATION AND THEN YOU CAN NOW

2903
02:08:43,018 --> 02:08:45,387
MODIFY ALL THE CRITERIA WHICH 

2904
02:08:45,387 --> 02:08:47,856
HAVE BEEN BY DEFAULT BEEN USED. 

2905
02:08:47,856 --> 02:08:55,164
FOR EXAMPLE, YOU CAN CHANGE THE 

2906
02:08:55,164 --> 02:08:57,566
INHERITANCE AND CHANGE THE 

2907
02:08:57,566 --> 02:09:00,302
CRITERIA HERE AT THE BOTTOM.  SO

2908
02:09:00,302 --> 02:09:03,606
LOOKING FOR THE GENETIC 

2909
02:09:03,606 --> 02:09:05,674
COUNSELOR OR PEOPLE WHO DO ON A 

2910
02:09:05,674 --> 02:09:08,177
RESEARCH BASIS AND VARY IN 

2911
02:09:08,177 --> 02:09:09,945
CLASSIFICATION.  YOU CAN CHANGE 

2912
02:09:09,945 --> 02:09:10,579
ALL THE CLASSIFICATION HOW YOU 

2913
02:09:10,579 --> 02:09:13,649
WANT AND YOU ALWAYS HAVE THE 

2914
02:09:13,649 --> 02:09:17,886
BEST DATA THERE IS.  SO IT'S 

2915
02:09:17,886 --> 02:09:20,422
IMPORTANT TO BRING THIS HUMAN 

2916
02:09:20,422 --> 02:09:22,458
EXPERT KNOWLEDGE IN.  SO YOU CAN

2917
02:09:22,458 --> 02:09:25,060
CONSIDER ALL THE EFFECTS OF 

2918
02:09:25,060 --> 02:09:27,162
WHICH MIGHT BE RELEVANT FOR THAT

2919
02:09:27,162 --> 02:09:29,398
VARIANT OR PATIENT IN THAT VERY 

2920
02:09:29,398 --> 02:09:34,703
MOMENT.  AND HOWEVER YOU CAN 

2921
02:09:34,703 --> 02:09:35,537
INTEGRATE

2922
02:09:35,537 --> 02:09:36,071
INTEGRATE.  THERE'S THE 

2923
02:09:36,071 --> 02:09:37,139
POPULATION DATA AND THE NORMAL 

2924
02:09:37,139 --> 02:09:40,643
FREQUENCY SO, AGAIN, HERE'S THE 

2925
02:09:40,643 --> 02:09:41,744
PATIENT DATA WHICH WAS 

2926
02:09:41,744 --> 02:09:43,846
AUTOMATICALLY HERE APPLIED AND 

2927
02:09:43,846 --> 02:09:45,848
HERE'S THE ALGORITHM YOU'LL SEE 

2928
02:09:45,848 --> 02:09:46,782
IN GREEN THE PATIENT VARIES IN 

2929
02:09:46,782 --> 02:09:49,251
THE MIDDLE AND IN RED, THE 

2930
02:09:49,251 --> 02:09:51,553
REGISTRY DATA SO THE LARGEST 

2931
02:09:51,553 --> 02:09:52,655
DATASET THERE IS AND YOU CAN GET

2932
02:09:52,655 --> 02:09:55,824
AN INTUITION IF YOU'RE A PATIENT

2933
02:09:55,824 --> 02:09:57,226
OF INTEREST IT'S BEHAVING MORE 

2934
02:09:57,226 --> 02:10:01,063
LIKE THE POPULATION ONE.  THE 

2935
02:10:01,063 --> 02:10:03,165
COMPUTE MUTATION, IF YOU HAVE A 

2936
02:10:03,165 --> 02:10:06,101
PROTEIN STRUCTURE IF OFF LOT OF 

2937
02:10:06,101 --> 02:10:09,104
PATIENT VARIANTS IN THE REGION 

2938
02:10:09,104 --> 02:10:13,942
AND WE HAVE THE FUNCTION AND THE

2939
02:10:13,942 --> 02:10:15,744
DATA.  THAT'S THE BEAUTY ABOUT 

2940
02:10:15,744 --> 02:10:16,712
THIS.  BECAUSE OF TIME I AM 

2941
02:10:16,712 --> 02:10:18,013
GOING TO MOVE A LITTLE BIT 

2942
02:10:18,013 --> 02:10:23,018
AHEAD.  JUST CHECK IT OUT.  IT'S

2943
02:10:23,018 --> 02:10:26,055
PUBLICLY AVAILABLE FOR EVERYONE.

2944
02:10:26,055 --> 02:10:31,193
OKAY.  AND ALTHOUGH ONLY ONE HAS

2945
02:10:31,193 --> 02:10:33,696
BEEN PUBLISHED WE HAVE 150 DAILY

2946
02:10:33,696 --> 02:10:35,264
USERS AND WE ARE STARTING NEXT 

2947
02:10:35,264 --> 02:10:39,902
WEEK A STUDY WHERE WE WILL CHECK

2948
02:10:39,902 --> 02:10:42,705
THE PERFORMANCE STUDY OVER THIS 

2949
02:10:42,705 --> 02:10:44,573
BUT IN GENERAL IF YOU HAVE THE 

2950
02:10:44,573 --> 02:10:46,575
COUNSEL AND YOU HAVE THE GENES, 

2951
02:10:46,575 --> 02:10:48,310
YOU CAN DO SOMETHING WITH THE 

2952
02:10:48,310 --> 02:10:49,978
BEST DATASET THERE IS WHICH YOU 

2953
02:10:49,978 --> 02:10:51,980
CANNOT GET BY THE WAY AND WE 

2954
02:10:51,980 --> 02:10:53,882
HAVE THE CLASSIFICATION IN FIVE 

2955
02:10:53,882 --> 02:10:54,917
MINUTES WHICH OTHERWISE WOULD 

2956
02:10:54,917 --> 02:10:58,287
TAKE YOU FOUR HOURS OR SO AND 

2957
02:10:58,287 --> 02:11:01,423
YOU NOT HAVE THE AMOUNT OF DATA 

2958
02:11:01,423 --> 02:11:02,925
LIKE THERE IS IN THIS PORTAL AND

2959
02:11:02,925 --> 02:11:05,360
WE NEED IT TRANSLATED IN 

2960
02:11:05,360 --> 02:11:06,462
MULTIPLE LANGUAGE WHICH WE 

2961
02:11:06,462 --> 02:11:09,231
HAVEN'T DONE YET BECAUSE WE NEED

2962
02:11:09,231 --> 02:11:10,799
FUNDING.  SO, YOU KNOW, ONE PART

2963
02:11:10,799 --> 02:11:14,436
OF, YOU KNOW, MOVING FORWARD IS 

2964
02:11:14,436 --> 02:11:16,171
DEFINITELY, YOU KNOW, GETTING 

2965
02:11:16,171 --> 02:11:17,272
DATA ORGANIZED, BRINGING IT TO 

2966
02:11:17,272 --> 02:11:20,576
THE SAME PLACE, MAKING IT 

2967
02:11:20,576 --> 02:11:21,243
ACCEPTABLE FOR EVERYONE AND ONCE

2968
02:11:21,243 --> 02:11:22,544
YOU HAVE THIS YOU CAN DO QUITE A

2969
02:11:22,544 --> 02:11:25,314
BIT OF RESEARCH WITH THIS DATA 

2970
02:11:25,314 --> 02:11:27,549
ONCE IT'S TOGETHER.  THERE'S TO 

2971
02:11:27,549 --> 02:11:29,685
REASON WHY YOU SHOULDN'T COMBINE

2972
02:11:29,685 --> 02:11:31,653
IT.  AND SO IF YOU HAVE THE 

2973
02:11:31,653 --> 02:11:33,355
SOURCES AGAIN, IT ENABLES PEOPLE

2974
02:11:33,355 --> 02:11:34,923
WHO CANNOT DO PROTEIN STRUCTURE 

2975
02:11:34,923 --> 02:11:36,258
ON THAT THING SO THE VARIANCE IS

2976
02:11:36,258 --> 02:11:38,594
ON THE STRUCTURE AND WITH SOME 

2977
02:11:38,594 --> 02:11:40,129
GOOD CLINICAL QUESTIONS ON THE 

2978
02:11:40,129 --> 02:11:43,098
VARIANT TYPES AND THIS IS, YOU 

2979
02:11:43,098 --> 02:11:44,166
KNOW, YOU BASICALLY CHANGE THE 

2980
02:11:44,166 --> 02:11:47,136
GAME BEFORE IT'S ONLY, YOU KNOW,

2981
02:11:47,136 --> 02:11:48,971
DATA ANALYSIS ONLY FOR THOSE WHO

2982
02:11:48,971 --> 02:11:52,141
REALLY LIKE DATA BUT AT THE 

2983
02:11:52,141 --> 02:11:54,843
MOMENT YOU DEVELOP USER 

2984
02:11:54,843 --> 02:11:56,745
RESOURCES AND ENABLE SCIENTISTS,

2985
02:11:56,745 --> 02:11:58,247
PARENTS WHO CARE ABOUT THEIR 

2986
02:11:58,247 --> 02:11:59,715
CHILDREN TO LEARN ABOUT THE DATA

2987
02:11:59,715 --> 02:12:00,315
THERE IS AND EXPLORE A LITTLE 

2988
02:12:00,315 --> 02:12:03,185
BIT AND SO I THINK THE MORE 

2989
02:12:03,185 --> 02:12:05,387
PEOPLE HAVE THE CAPACITY TO 

2990
02:12:05,387 --> 02:12:06,989
ACCESS DATA AND USE THE 

2991
02:12:06,989 --> 02:12:08,757
RESOURCES, THEN, YOU KNOW, WE 

2992
02:12:08,757 --> 02:12:11,527
CAN, YOU KNOW, GET GREATER 

2993
02:12:11,527 --> 02:12:15,097
COVERAGE.  OKAY, SO HERE'S AN 

2994
02:12:15,097 --> 02:12:18,233
EXAMPLE, ONCE WE HAVE ALL THE 

2995
02:12:18,233 --> 02:12:22,271
DATA THE GENE TOGETHER, WE HAVE 

2996
02:12:22,271 --> 02:12:24,039
A THOUSAND PEOPLE WHERE WE HAVE 

2997
02:12:24,039 --> 02:12:26,675
INFORMATION IF THEY EITHER HAVE 

2998
02:12:26,675 --> 02:12:29,578
THE CAPACITIES, THE MINOR 

2999
02:12:29,578 --> 02:12:32,347
EPILEPSY OR THE SYNDROME AND IF 

3000
02:12:32,347 --> 02:12:37,119
THEY HAVE THE GENOTYPE AND  

3001
02:12:37,119 --> 02:12:40,355
PHENOTYPE WHERE THERE'S SPECIFIC

3002
02:12:40,355 --> 02:12:46,528
REGIONS.  AND WHAT WE NOTICE IS 

3003
02:12:46,528 --> 02:12:47,496
THERE'S A GREAT DIFFERENCE 

3004
02:12:47,496 --> 02:12:50,566
BETWEEN DISEASES.  IT WAS WAY 

3005
02:12:50,566 --> 02:12:52,367
MORE WIDE.  IF YOU READ THE 

3006
02:12:52,367 --> 02:12:54,436
LITERATURE YOU GET IT OUT BUT WE

3007
02:12:54,436 --> 02:12:56,071
SEE IT SUDDENLY ONLY CLEARCUT 

3008
02:12:56,071 --> 02:12:57,272
WHEN YOU LOOK AT THE DATA AND 

3009
02:12:57,272 --> 02:13:01,643
THEN WE THOUGHT, HEY, MAYBE 

3010
02:13:01,643 --> 02:13:06,148
THAT'S ALSO YJEANEGENETIC AND T 

3011
02:13:06,148 --> 02:13:07,549
THINGS APPARENTLY DON'T HAVE AN 

3012
02:13:07,549 --> 02:13:09,351
INTERACTION AFFECT AND WE PUT IT

3013
02:13:09,351 --> 02:13:12,187
TOGETHER UNDER A SIMPLE TOOL.  

3014
02:13:12,187 --> 02:13:17,192
AND SO THIS TOOL HAS NOT BEEN 

3015
02:13:17,192 --> 02:13:18,560
TESTED BLINDED TWICE AND I WANT 

3016
02:13:18,560 --> 02:13:20,929
TO PUSH REALLY THAT ONE OF THE 

3017
02:13:20,929 --> 02:13:24,266
BLIND COHORTS WAS REALLY AT THE 

3018
02:13:24,266 --> 02:13:27,135
HIGHEST LEVEL TO THE RESEARCH 

3019
02:13:27,135 --> 02:13:29,137
AND WE WERE NINE OUT OF TEN 

3020
02:13:29,137 --> 02:13:30,439
TIMES CORRECT JUST FOR THE 

3021
02:13:30,439 --> 02:13:31,740
SEIZURE ONSET AND GENETIC 

3022
02:13:31,740 --> 02:13:33,408
VARIANCE.  SO THIS IS SOMETHING 

3023
02:13:33,408 --> 02:13:35,577
WHERE I AM REALLY CONSIDERING 

3024
02:13:35,577 --> 02:13:39,147
ENHANCING WITH A COUPLE MORE 

3025
02:13:39,147 --> 02:13:40,649
ITEMS AND DOING CLINICAL TRIAL. 

3026
02:13:40,649 --> 02:13:43,151
THIS IS REALLY OUTSTANDING IN 

3027
02:13:43,151 --> 02:13:48,090
TERMS OF ALL EPILEPSY RESEARCH. 

3028
02:13:48,090 --> 02:13:51,159
OKAY, SO AND THE MOST IMPORTANT 

3029
02:13:51,159 --> 02:13:53,629
THING HERE IS FOR GENE THERAPY. 

3030
02:13:53,629 --> 02:13:55,230
SO THIS IS THE SEIZURE ONSET AND

3031
02:13:55,230 --> 02:13:57,599
GENETIC TEST RESULTS SO WHAT 

3032
02:13:57,599 --> 02:13:58,600
ELSE CAN WE DO IN ONCE YOU HAVE 

3033
02:13:58,600 --> 02:14:00,769
A LOT OF DATA TOGETHER SUDDENLY 

3034
02:14:00,769 --> 02:14:03,772
YOU SEE PATTERNS WHICH YOU NEVER

3035
02:14:03,772 --> 02:14:04,740
WOULD BE -- THOUGHT THAT YOU 

3036
02:14:04,740 --> 02:14:09,311
COULD SEE THEM.  SO THIS IS JUST

3037
02:14:09,311 --> 02:14:13,248
A BIG PUSH THAT WE HAVE TO HAVE 

3038
02:14:13,248 --> 02:14:16,885
ONE MASTER.  DUE TO PREDICTION 

3039
02:14:16,885 --> 02:14:17,986
MODELS WE HAVE THIS.  AND WE HAD

3040
02:14:17,986 --> 02:14:19,488
AN INTERESTING THING TO USE FOR 

3041
02:14:19,488 --> 02:14:21,089
OUR PREDICTION MODELS FOR 

3042
02:14:21,089 --> 02:14:29,298
EXAMPLE, YOU SEE HERE IF THE 

3043
02:14:29,298 --> 02:14:30,599
PERCENTAGE OF PEOPLE.  AND YOU 

3044
02:14:30,599 --> 02:14:33,602
HAVE DIFFERENT GROUPS HERE.  

3045
02:14:33,602 --> 02:14:35,137
THIS IS IS VERY SIMILAR TO THIS 

3046
02:14:35,137 --> 02:14:37,873
ONE.  AND WALK AS WELL AND 

3047
02:14:37,873 --> 02:14:39,841
SIMILAR TO WHAT THIS IS IN THAT 

3048
02:14:39,841 --> 02:14:42,477
GROUP.  BUT IF WE LOOK NOW AT 

3049
02:14:42,477 --> 02:14:46,281
USED WORDS OR COMBINED WORDS 

3050
02:14:46,281 --> 02:14:46,882
SUDDENLY VERSION IT WURNT SO 

3051
02:14:46,882 --> 02:14:48,317
WELL SO YOU GET THESE ACROSS THE

3052
02:14:48,317 --> 02:14:50,085
DIFFERENT FIFTEEN TYPES AND YOU 

3053
02:14:50,085 --> 02:14:52,020
CAN UNDERSTAND NOW A LITTLE BIT 

3054
02:14:52,020 --> 02:14:53,855
MOREOVER THE DISEASE PROGRESSION

3055
02:14:53,855 --> 02:14:55,190
AND YOU CAN EVEN THINK ABOUT 

3056
02:14:55,190 --> 02:15:00,095
BASKET TRUCKS, IF YOU WANT TO 

3057
02:15:00,095 --> 02:15:04,066
SOMETHING VERY CHEAP AND 

3058
02:15:04,066 --> 02:15:06,268
EFFICIENT YOU WANT TO LOOK 

3059
02:15:06,268 --> 02:15:06,868
AROUND ONE YEAR TO ONE AND A 

3060
02:15:06,868 --> 02:15:08,804
HALF YEAR YOU GET A LOT OF 

3061
02:15:08,804 --> 02:15:11,974
CHANGE HERE.  WHEREAS YOU DID 

3062
02:15:11,974 --> 02:15:14,409
NOT -- YOU SEE LESS CHANGE IN 

3063
02:15:14,409 --> 02:15:15,610
THE OTHER GRIPES.  YOU CAN SEE 

3064
02:15:15,610 --> 02:15:17,312
WHAT YOU WOULD LIKE TO PUT 

3065
02:15:17,312 --> 02:15:19,147
TOGETHER.  SO YOU CAN ALSO LOOK 

3066
02:15:19,147 --> 02:15:22,250
AT WRITING COMMUNICATIONS SO 

3067
02:15:22,250 --> 02:15:24,219
HERE, FOR EXAMPLE, UNAFFECTED 

3068
02:15:24,219 --> 02:15:26,321
CHILDREN, SO THE SIBLINGS OR THE

3069
02:15:26,321 --> 02:15:31,159
PEOPLE WITH AUTISMIC SEE THERE 

3070
02:15:31,159 --> 02:15:33,295
AND YOU SEE HOW IT ALREADY 

3071
02:15:33,295 --> 02:15:34,429
STARTED TO DEVIATE FROM HERE AND

3072
02:15:34,429 --> 02:15:36,531
YOU CAN SEE IN THE DIFFERENT 

3073
02:15:36,531 --> 02:15:39,134
GENETIC DISORDERS YOU CAN 

3074
02:15:39,134 --> 02:15:42,204
PREDICT THE FUNCTIONS AS BEFORE.

3075
02:15:42,204 --> 02:15:46,041
I OFTEN HERE COMMUNICATION IS 

3076
02:15:46,041 --> 02:15:48,110
THE BIG BUCKET WHERE IT'S HARD 

3077
02:15:48,110 --> 02:15:49,678
TO SEPARATE AND WHERE THERE ARE 

3078
02:15:49,678 --> 02:15:50,812
CHALLENGES IN IDENTIFYING END 

3079
02:15:50,812 --> 02:15:52,748
POINTS WHICH ARE CLINICALLY 

3080
02:15:52,748 --> 02:15:55,250
USED.  AND, FOR EXAMPLE, I HAVE 

3081
02:15:55,250 --> 02:15:58,186
A LARGE PATHOLOGIST IN MY TEAM 

3082
02:15:58,186 --> 02:16:01,356
WHO SAID WHY DON'T WE BREAK 

3083
02:16:01,356 --> 02:16:04,059
LANGUAGE DOWN AND SEE IF THERE'S

3084
02:16:04,059 --> 02:16:05,227
DIFFERENT ANSWERS.  LOOK IF WE 

3085
02:16:05,227 --> 02:16:08,830
LOOK AT DIFFICULTY TO ANSWERING 

3086
02:16:08,830 --> 02:16:09,798
QUESTIONS, EFFICIENCY.  SO YOU 

3087
02:16:09,798 --> 02:16:13,235
SEE A LOT OF THEM ARE OVERLAP 

3088
02:16:13,235 --> 02:16:15,303
AND THESE ARE AT LEAST 50 

3089
02:16:15,303 --> 02:16:16,471
PATIENTS SO IT'S RATHER GOOD 

3090
02:16:16,471 --> 02:16:18,640
DATA BUT IF YOU LOOK AT AUDITORY

3091
02:16:18,640 --> 02:16:20,275
PROCESSING AND SPEECH AND 

3092
02:16:20,275 --> 02:16:21,576
MOVEMENT THEY SUDDENLY SPREAD 

3093
02:16:21,576 --> 02:16:23,145
OUT.  ALL THE INFORMATION WHICH 

3094
02:16:23,145 --> 02:16:27,783
YOU CAN E  USE FOR PREDICTION 

3095
02:16:27,783 --> 02:16:28,050
MODELING. 

3096
02:16:28,050 --> 02:16:31,620
THIS IS ALL YOU KNOW,  POPULAR 

3097
02:16:31,620 --> 02:16:32,854
BECAUSE DATA IS TOGETHER. 

3098
02:16:32,854 --> 02:16:34,990
HERE'S ANOTHER EXAMPLE IF YOU 

3099
02:16:34,990 --> 02:16:37,692
ARE A PARENT OF A CHILD WITH 

3100
02:16:37,692 --> 02:16:39,861
THIS.  DOES YOUR CHILD HAVE AN 

3101
02:16:39,861 --> 02:16:43,532
EYE CONDITION?  IF THEY DO, MOST

3102
02:16:43,532 --> 02:16:46,034
WILL SAY YES.  HOWEVER FOR TRAN 

3103
02:16:46,034 --> 02:16:49,237
INDICATED THEY WILL SAY NO.  THE

3104
02:16:49,237 --> 02:16:50,105
INTERESTING THING IS THIS IS ONE

3105
02:16:50,105 --> 02:16:52,207
VERSION TO LOOK AT THIS. 

3106
02:16:52,207 --> 02:16:52,908
BUT YOU CAN ALSO ADD WHEN YOU 

3107
02:16:52,908 --> 02:16:56,278
HAVE THESE RESOURCES, WHEN, FOR 

3108
02:16:56,278 --> 02:16:58,547
EXAMPLE, DO THE -- SO FOR THOSE 

3109
02:16:58,547 --> 02:17:01,683
WHO HAVE AN EYE CONDITION WHEN 

3110
02:17:01,683 --> 02:17:03,151
DO YOU, YOU KNOW -- WHEN DID IT 

3111
02:17:03,151 --> 02:17:05,620
START AND YOU CAN SEE, FOR 

3112
02:17:05,620 --> 02:17:10,292
EXAMPLE, NOT ONLY DO THEY HAVE 

3113
02:17:10,292 --> 02:17:11,426
MORE BUT THEY HAVE IT EARLIER SO

3114
02:17:11,426 --> 02:17:14,029
YOU CAN COMBINE ALL OF THESE AND

3115
02:17:14,029 --> 02:17:16,465
DEVELOP EYE RHYTHMS.  THEY 

3116
02:17:16,465 --> 02:17:17,165
HAVEN'T DONE THIS YET BUT 

3117
02:17:17,165 --> 02:17:20,168
THEY'RE WORKING ON IT.  MY LAST 

3118
02:17:20,168 --> 02:17:22,104
PART TO CLOSE OUT WHY I BELIEVE 

3119
02:17:22,104 --> 02:17:24,206
THIS IS A RESOURCE THAT IS NOT 

3120
02:17:24,206 --> 02:17:26,475
ONLY RELEVANT FOR INCLUSION OF 

3121
02:17:26,475 --> 02:17:28,710
CLINICAL TRIALS AND INCLUDING 

3122
02:17:28,710 --> 02:17:31,146
PEOPLE IN THE RIGHT CARE BUT AND

3123
02:17:31,146 --> 02:17:34,216
RESEARCH BUT ALSO FOR THE 

3124
02:17:34,216 --> 02:17:35,250
CLINICAL TRIAL AND THIS IS WHERE

3125
02:17:35,250 --> 02:17:37,052
I'M MOST INTERESTED.  IMAGINE WE

3126
02:17:37,052 --> 02:17:38,920
HAVE AN APPROVED DRUG AND THE 

3127
02:17:38,920 --> 02:17:41,923
CLINICAL TRIAL WAS DESIGNED LIKE

3128
02:17:41,923 --> 02:17:43,692
THIS.  YOU KNOW CHILDREN AND WE 

3129
02:17:43,692 --> 02:17:46,795
HAVE FOR CERTAIN REASONS HAVE TO

3130
02:17:46,795 --> 02:17:50,932
REMOVE PEOPLE WHO HAD SURGERY.  

3131
02:17:50,932 --> 02:17:52,601
THESE ARE YOUR END POINTS.  

3132
02:17:52,601 --> 02:17:55,036
THAT'S A REAL SCENARIO, I GUESS,

3133
02:17:55,036 --> 02:17:58,206
RIGHT?  IMAGINE THE DRUG IS 

3134
02:17:58,206 --> 02:17:59,441
APPROVED.  YOU HAVE SO MUCH MORE

3135
02:17:59,441 --> 02:18:02,577
QUESTIONS, WHAT ARE THE ADVERSE 

3136
02:18:02,577 --> 02:18:04,613
EFFECTS, SHORT-TERM?  LONG-TERM?

3137
02:18:04,613 --> 02:18:09,317
SINL EVERYONE -- SUDDENLY 

3138
02:18:09,317 --> 02:18:10,519
EVERYONE HAS A RANK. 

3139
02:18:10,519 --> 02:18:12,721
WE NEED TO HAVE DATA FLOWING TO 

3140
02:18:12,721 --> 02:18:14,289
SEE THIS.  SO, YOU KNOW, ALSO WE

3141
02:18:14,289 --> 02:18:16,424
NEED TO FIGURE OUT HOW DO WE 

3142
02:18:16,424 --> 02:18:17,626
MEASURE WHAT TYPICAL AND 

3143
02:18:17,626 --> 02:18:20,395
ATYPICAL BUT WE NEED TO HAVE A 

3144
02:18:20,395 --> 02:18:22,297
NATURAL HISTORY RUNNING ALREADY 

3145
02:18:22,297 --> 02:18:24,299
AND THE DATA NEEDS TO BE THERE. 

3146
02:18:24,299 --> 02:18:25,734
JUST GO ON AND IN PARALLEL WE 

3147
02:18:25,734 --> 02:18:29,237
HAVE TO LABEL THOSE INDIVIDUALS 

3148
02:18:29,237 --> 02:18:30,906
AND SEE IF THERE'S DEVIATIONS 

3149
02:18:30,906 --> 02:18:34,042
ACROSS THOUSANDS OF PHENOTYPES. 

3150
02:18:34,042 --> 02:18:37,712
OTHERS FROM HIGH GRADE.  SO, YOU

3151
02:18:37,712 --> 02:18:40,448
KNOW, YOU KNOW, THE QUESTION IS 

3152
02:18:40,448 --> 02:18:42,150
WILL THE DRUG WORK IN OTHER 

3153
02:18:42,150 --> 02:18:45,153
PATIENTS?  OLDER ONES?  WHAT IS 

3154
02:18:45,153 --> 02:18:46,755
THE END POINT THERE?  OTHER 

3155
02:18:46,755 --> 02:18:48,723
RESOURCES MIGHT GIVE YOU SOME 

3156
02:18:48,723 --> 02:18:50,792
IDEAS, YOU KNOW?  AND BROADER 

3157
02:18:50,792 --> 02:18:52,661
PATIENT POPULATION.  YOU KNOW, 

3158
02:18:52,661 --> 02:18:54,496
YOU KNOW, THESE WHO HAVE BEEN 

3159
02:18:54,496 --> 02:18:55,030
EXCLUDED RIGHT FROM THE 

3160
02:18:55,030 --> 02:18:58,166
BEGINNING AND SO ON AND SO 

3161
02:18:58,166 --> 02:19:00,268
FORTH.  BEFORE I READ THE 

3162
02:19:00,268 --> 02:19:01,736
STUDIES, OVER THE NEXT TWENTY 

3163
02:19:01,736 --> 02:19:05,407
YEARS LET'S PUT IT TOGETHER AND 

3164
02:19:05,407 --> 02:19:15,951
DO LIKE RETROSPECTIVE RESEARCH. 

3165
02:19:19,754 --> 02:19:21,590
WHICH IS THE NEXT GENE WHERE 

3166
02:19:21,590 --> 02:19:24,960
THIS WILL BE TESTED IN?  THERE'S

3167
02:19:24,960 --> 02:19:26,761
THE PATHWAY SET UP AND YOU CAN 

3168
02:19:26,761 --> 02:19:29,264
ADD YOUR BIOLOGY, THIS IS THE 

3169
02:19:29,264 --> 02:19:31,132
NEXT GENE WHICH SHOULD -- THE 

3170
02:19:31,132 --> 02:19:35,270
DRUG SHOULD BE TESTED IN BUT YOU

3171
02:19:35,270 --> 02:19:37,706
COULD ARGUE THE PHENOTYPE.  THEY

3172
02:19:37,706 --> 02:19:39,074
HAVE THE SAME COMPUTATION AND 

3173
02:19:39,074 --> 02:19:41,109
THE END POINT WORKED THE SAME.  

3174
02:19:41,109 --> 02:19:42,277
LET'S LOOK AT THIS.  THEY ARE ON

3175
02:19:42,277 --> 02:19:44,579
THE SAME PATHWAY AND THE 

3176
02:19:44,579 --> 02:19:45,447
CLINICAL INTERPRETATION IS THE 

3177
02:19:45,447 --> 02:19:46,615
SAME LET'S GO IN THERE WITH THE 

3178
02:19:46,615 --> 02:19:54,623
NEW DRUG AND GET IT APPROVED 

3179
02:19:54,623 --> 02:19:56,291
THERE BUT WE CANNOT MAKE THE 

3180
02:19:56,291 --> 02:19:57,726
SAME DECISION FOR THIS I CLOSE 

3181
02:19:57,726 --> 02:19:58,793
AND THANK YOU SO MUCH FOR GIVING

3182
02:19:58,793 --> 02:20:00,061
ME THE OPPORTUNITY TO SPEAK.

3183
02:20:00,061 --> 02:20:10,505
>> AUDIENCE: (APPLAUSE).

3184
02:20:19,381 --> 02:20:20,148
>> AUDIENCE: I JUST WANT
TO MAKE

3185
02:20:20,148 --> 02:20:22,217
ONE COMMENT ABOUT THE UTILITY, 

3186
02:20:22,217 --> 02:20:24,152
THE IMPORTANCE OF WHAT YOU'RE 

3187
02:20:24,152 --> 02:20:27,422
DOING.  AND JUST SHARE WITH YOU 

3188
02:20:27,422 --> 02:20:28,923
THAT THE FIRST PATIENT, 

3189
02:20:28,923 --> 02:20:31,426
COMMERCIAL PATIENT WHO IS GOING 

3190
02:20:31,426 --> 02:20:36,064
TO BE TREATED, CAN BE TREAT AT 

3191
02:20:36,064 --> 02:20:41,903
MOUNT SINAI IN BOSTON.  THE 

3192
02:20:41,903 --> 02:20:42,637
INSURANCE COMPANY HAD TO RELEASE

3193
02:20:42,637 --> 02:20:46,708
THE VECTOR, AGREE, PATIENT HAD 

3194
02:20:46,708 --> 02:20:49,644
ONE PATHOGENIC ALLELE AND ONE 

3195
02:20:49,644 --> 02:20:51,112
VARIETY OF UNKNOWN SIGNIFICANCE 

3196
02:20:51,112 --> 02:20:55,150
ON THE OTHER ALLELE, INSURANCE 

3197
02:20:55,150 --> 02:21:01,690
COMPANY RREFUSED TO RELEASE.  

3198
02:21:01,690 --> 02:21:05,427
THEY FOUND A PATIENT WHO WAS 

3199
02:21:05,427 --> 02:21:06,761
HOMOZYGOUS AND WAS CLINICALLY 

3200
02:21:06,761 --> 02:21:08,163
AFFECTED THEREFORE THEY RELEASED

3201
02:21:08,163 --> 02:21:09,931
IT.  ONCE YOU DO HAVE THE DRUG 

3202
02:21:09,931 --> 02:21:18,573
THIS IS ALSO VERY IMPORTANT.

3203
02:21:18,573 --> 02:21:19,474
>> AUDIENCE: I HAVE A
BASIC 

3204
02:21:19,474 --> 02:21:22,477
QUESTION FROM THE CLINICAL 

3205
02:21:22,477 --> 02:21:27,148
PERSPECTIVE.  WHICH IS -- OH, A 

3206
02:21:27,148 --> 02:21:30,085
BASIC QUESTION FROM THE CLINICAL

3207
02:21:30,085 --> 02:21:31,186
PERSPECTIVE WHICH I ACTUALLY 

3208
02:21:31,186 --> 02:21:34,689
MEANT TO ASK GEMMA EARLIER BUT I

3209
02:21:34,689 --> 02:21:36,725
THINK I CAN ASK YOU AS WELL WITH

3210
02:21:36,725 --> 02:21:39,127
ALL OF THE CHANGES OVER TIME AND

3211
02:21:39,127 --> 02:21:41,229
HOW WE ARE CLASSIFYING VARIANTS 

3212
02:21:41,229 --> 02:21:43,698
AS DATA FUNCTION VERSUS LOSS OF 

3213
02:21:43,698 --> 02:21:44,966
FUNCTION AND IT'S THE SAME 

3214
02:21:44,966 --> 02:21:48,236
VARIANT WE'VE BEEN WORKING ON 

3215
02:21:48,236 --> 02:21:50,372
FOR YEARS AS LONG AS SOMETHING 

3216
02:21:50,372 --> 02:21:51,906
CHANGES IT'S EITHER GAINED OR 

3217
02:21:51,906 --> 02:21:53,475
MIXED OR SOMETHING CHANGES.  IS 

3218
02:21:53,475 --> 02:21:56,711
THERE ANY WAY TO HAVE SOME 

3219
02:21:56,711 --> 02:21:58,780
OVERSIGHT?  THESE WERE 

3220
02:21:58,780 --> 02:22:00,882
CLINICIANS WHILE WE'RE WAITING 

3221
02:22:00,882 --> 02:22:04,219
FOR ALL OF THOSE GENES THERAPIES

3222
02:22:04,219 --> 02:22:05,620
WHILE WE TRY TO LOOK AT OUR 

3223
02:22:05,620 --> 02:22:07,122
BASIC MEDICATION.  I WILL GIVE 

3224
02:22:07,122 --> 02:22:11,159
AN EXAMPLE FROM THE SDM 2A WHICH

3225
02:22:11,159 --> 02:22:13,962
SOME OF THE -- ALL OF THE TRIALS

3226
02:22:13,962 --> 02:22:16,798
ACTUALLY HAVE BEEN RELYING ON A 

3227
02:22:16,798 --> 02:22:17,699
COMBINATION OF THE CLINICAL 

3228
02:22:17,699 --> 02:22:19,701
PHENOTYPES AND THE GENOTYPE IN 

3229
02:22:19,701 --> 02:22:23,805
ORDER TO LEARN WHETHER WE ARE 

3230
02:22:23,805 --> 02:22:24,973
GOING TO BE USING -- WE ARE 

3231
02:22:24,973 --> 02:22:27,075
GOING TO BE CALLING THE 

3232
02:22:27,075 --> 02:22:27,909
INVESTIGATIVE FUNCTION BUT THEN 

3233
02:22:27,909 --> 02:22:31,112
WITH THE NEW PAPER THAT JUST 

3234
02:22:31,112 --> 02:22:37,685
CAME OUT, FROM AL GEORGE'S LAB, 

3235
02:22:37,685 --> 02:22:39,154
SOME OF THESE WERE ANOTHER 

3236
02:22:39,154 --> 02:22:40,588
FUNCTION HOW DO WE LOOK AT THAT.

3237
02:22:40,588 --> 02:22:43,992
HOW DO WE READ A PAPER NOW AND 

3238
02:22:43,992 --> 02:22:47,128
DECIDE WHETHER THIS IS WHAT WE 

3239
02:22:47,128 --> 02:22:51,299
SHOULD CALL IT OR NOT?

3240
02:22:51,299 --> 02:22:53,835
>> DENNIS: I CANNOT ANSWER
THIS 

3241
02:22:53,835 --> 02:22:56,171
BECAUSE IT IS VERY COMPLICATED 

3242
02:22:56,171 --> 02:22:57,906
AND EVERY GENE IS DIFFERENT.  I 

3243
02:22:57,906 --> 02:22:59,974
CAN ALWAYS COMPARE TO EPILEPSY 

3244
02:22:59,974 --> 02:23:03,378
SURGERY.  PEOPLE DO HAVE AN 

3245
02:23:03,378 --> 02:23:04,579
INTEGRATIVE TEAM TYPICALLY WHERE

3246
02:23:04,579 --> 02:23:05,814
MANY DIFFERENT PERSPECTIVES ARE 

3247
02:23:05,814 --> 02:23:08,316
SHARED.  AT THE END, THE 

3248
02:23:08,316 --> 02:23:09,617
CLINICIAN TAKES ON THE 

3249
02:23:09,617 --> 02:23:11,119
RESPONSIBILITY AND DOCUMENTS 

3250
02:23:11,119 --> 02:23:13,455
AND, YOU KNOW, VERY THOROUGHLY 

3251
02:23:13,455 --> 02:23:15,123
WHAT THE REASONS WHERE THERE'S 

3252
02:23:15,123 --> 02:23:18,893
THE DECISION.  AND THE -- YOU 

3253
02:23:18,893 --> 02:23:21,596
CAN DO THIS IN YOUR OWN CENTER 

3254
02:23:21,596 --> 02:23:22,530
BUT YOU CAN ALSO SEEK 

3255
02:23:22,530 --> 02:23:24,332
COLLEAGUE'S OPINION TO ENHANCE 

3256
02:23:24,332 --> 02:23:26,468
YOUR OWN CURRENT ASSESSMENT AND 

3257
02:23:26,468 --> 02:23:27,735
IT'S A LITTLE BIT ALL OVER THE 

3258
02:23:27,735 --> 02:23:30,638
PLACE LIKE THIS, RIGHT?  AND 

3259
02:23:30,638 --> 02:23:32,040
THERE'S NO STANDARD.  SO I THINK

3260
02:23:32,040 --> 02:23:35,410
THE FIRST STEP WE HAD FOR THE 

3261
02:23:35,410 --> 02:23:37,512
RECEPTOR IS THAT THERE WAS A 

3262
02:23:37,512 --> 02:23:39,848
PAPER LAST YEAR PUBLISHED BY 

3263
02:23:39,848 --> 02:23:42,517
STEVE AND ALSO A LITTLE BIT OF 

3264
02:23:42,517 --> 02:23:43,718
US.  BUT TINY WHERE THE TITLE 

3265
02:23:43,718 --> 02:23:45,320
WAS THIS IS HOW YOU CLASSIFY 

3266
02:23:45,320 --> 02:23:48,723
GAIN AND LOSS OF FUNCTION IN THE

3267
02:23:48,723 --> 02:23:50,925
RECEPTORS.  AND SO THIS IS NOT 

3268
02:23:50,925 --> 02:23:52,794
EXISTING FOR THE SODIUM 

3269
02:23:52,794 --> 02:23:55,129
CHANNELS.  AND IN THE SODIUM 

3270
02:23:55,129 --> 02:23:56,030
CHANNELS WE ARE POINTING AT MORE

3271
02:23:56,030 --> 02:23:58,266
THE PROBLEM AND NO ONE AT THE 

3272
02:23:58,266 --> 02:23:59,634
MOMENT IS REALLY COMFORTABLE TO 

3273
02:23:59,634 --> 02:24:03,137
SAY THIS IS -- INSTEAD OF ASSAYS

3274
02:24:03,137 --> 02:24:05,573
AND THE SET OF, YOU KNOW, YEAH 

3275
02:24:05,573 --> 02:24:06,941
SO, WE NEED -- THAT'S PRACTICE 

3276
02:24:06,941 --> 02:24:09,410
GUIDELINES FOR THE MOLECULAR 

3277
02:24:09,410 --> 02:24:10,912
PART AS WELL AS THE CLINICAL 

3278
02:24:10,912 --> 02:24:12,313
PART AND THERE SHOULD BE A 

3279
02:24:12,313 --> 02:24:13,715
DATABASE BECAUSE THEN YOU CAN 

3280
02:24:13,715 --> 02:24:15,850
INTEGRATE IT INTO COMPUTATIONAL 

3281
02:24:15,850 --> 02:24:18,086
SLOPE.  SO OTHER THAN THAT, IT'S

3282
02:24:18,086 --> 02:24:19,153
ALWAYS TOO QUIET IF SOMEONE IS 

3283
02:24:19,153 --> 02:24:22,056
MAKING A SEARCH AND THE SEARCH 

3284
02:24:22,056 --> 02:24:23,958
CAN BE HIGH QUALITY BUT CAN ALSO

3285
02:24:23,958 --> 02:24:25,693
BE A FIVE MINUTE SEARCH WHILE 

3286
02:24:25,693 --> 02:24:28,463
DOING AN OPEN CHART, RIGHT?  SO 

3287
02:24:28,463 --> 02:24:29,797
WE NEED TO ORGANIZE.  THAT'S -- 

3288
02:24:29,797 --> 02:24:33,735
I AM REPEATING MYSELF BUT 

3289
02:24:33,735 --> 02:24:44,279
THERE'S NO CLEAR SOLUTION.  SNAD

3290
02:24:44,846 --> 02:24:45,113
TH

3291
02:24:45,113 --> 02:24:45,313
.

3292
02:24:45,313 --> 02:24:46,114
>> AUDIENCE: THIS WORK IS
REALLY

3293
02:24:46,114 --> 02:24:47,949
GROUND BREAKING AND APPRECIATED.

3294
02:24:47,949 --> 02:24:51,920
SINCE YOU'RE USING DOLLY AND 

3295
02:24:51,920 --> 02:24:53,454
YOU'RE USING NATURAL LANGUAGE 

3296
02:24:53,454 --> 02:24:55,490
PROCESSING CAN YOU EXPAND MORE 

3297
02:24:55,490 --> 02:24:56,724
ON THE ROLE THAT AI IS GOING TO 

3298
02:24:56,724 --> 02:24:58,593
BE PLACED IN ALL OF THIS?

3299
02:24:58,593 --> 02:24:59,994
BECAUSE I HEARD YOU SAY THAT WE 

3300
02:24:59,994 --> 02:25:03,131
NEED TO HAVE A WORKFORCE OF 

3301
02:25:03,131 --> 02:25:05,033
CLINICAL GENETICISTS AND 

3302
02:25:05,033 --> 02:25:07,735
COUNSELORS.  TO ENABLE THIS TO 

3303
02:25:07,735 --> 02:25:10,038
BE AVAILABLE TO SOCIETY.  I'M 

3304
02:25:10,038 --> 02:25:12,974
NOT SO SURE THAT THAT'S EVEN 

3305
02:25:12,974 --> 02:25:15,176
FEASIBLE.  SO CAN YOU -- I KNOW 

3306
02:25:15,176 --> 02:25:17,779
YOU'VE THOUGHT A LOT ABOUT THIS.

3307
02:25:17,779 --> 02:25:24,352
CAN YOU EXPAND THE ROLE OF AI?

3308
02:25:24,352 --> 02:25:26,921
>> DENNIS: PERSONAL
OPINION, CAN

3309
02:25:26,921 --> 02:25:33,695
BE COMPLETELY WRONG.  SO I THINK

3310
02:25:33,695 --> 02:25:35,630
AUBS AI IS MORE IMPORTANT FOR 

3311
02:25:35,630 --> 02:25:37,599
COMMON DISEASE. 

3312
02:25:37,599 --> 02:25:38,166
TYPICALLY THE CLINICAL 

3313
02:25:38,166 --> 02:25:39,934
EXPRESSION IS VERY WRONG AND 

3314
02:25:39,934 --> 02:25:42,303
IT'S RARE WHICH IS WHY PEOPLE 

3315
02:25:42,303 --> 02:25:43,137
DON'T RECOGNIZE IT BUT I HAVE 

3316
02:25:43,137 --> 02:25:44,906
THOSE WHO HAVE ACCESS TO A LOT 

3317
02:25:44,906 --> 02:25:48,109
OF DATA AND PATTERNS CLEARLY.  

3318
02:25:48,109 --> 02:25:51,145
THE EVIDENCE REQUIRES THAT WE 

3319
02:25:51,145 --> 02:25:53,615
HAVE A RECORD CLEARLY INDICATING

3320
02:25:53,615 --> 02:25:54,449
WHO HAS WHICH DISEASE WHICH IS A

3321
02:25:54,449 --> 02:25:58,486
BIG PROBLEM AT THE MOMENT.  SO I

3322
02:25:58,486 --> 02:26:01,222
THINK IF YOU COMBINE HIGH 

3323
02:26:01,222 --> 02:26:02,156
QUALITY DATABASES AND HEALTH 

3324
02:26:02,156 --> 02:26:05,660
RECORDS WHICH ARE WELL TAKEN 

3325
02:26:05,660 --> 02:26:09,230
CARE OF, YOU CAN DEVELOP THE 

3326
02:26:09,230 --> 02:26:11,466
CHATGPT STYLE OF REPORT SYSTEMS 

3327
02:26:11,466 --> 02:26:14,168
WHICH BEAT CLINICIANS AND 

3328
02:26:14,168 --> 02:26:16,771
RECOGNIZE A GENETIC DISEASE VERY

3329
02:26:16,771 --> 02:26:19,941
PAST BECAUSE HARDLY ANYONE HAS 

3330
02:26:19,941 --> 02:26:21,175
SEEN IN THEIR CAREER MORE THAN 

3331
02:26:21,175 --> 02:26:23,011
TEN PATIENTS.  SO YOU CANNOT BE 

3332
02:26:23,011 --> 02:26:24,412
AN EXPERT ON THOUSANDS.  SO 

3333
02:26:24,412 --> 02:26:26,814
THERE'S A LOT OF OPPORTUNITY BUT

3334
02:26:26,814 --> 02:26:28,916
THE PATH TOWARDS BRINGING THE 

3335
02:26:28,916 --> 02:26:31,285
DATA TOGETHER, HAVING EXPERT 

3336
02:26:31,285 --> 02:26:33,788
CURATION AND HAVE THE RIGHT 

3337
02:26:33,788 --> 02:26:34,956
MECHANISM IN PLACE TO BENCHMARK,

3338
02:26:34,956 --> 02:26:38,559
THERE'S NO AGREEMENT ON HOW TO 

3339
02:26:38,559 --> 02:26:42,530
IDENTIFY THIS RIGHT?  AND THIS 

3340
02:26:42,530 --> 02:26:43,731
IS TYPICALLY WHEN YOU LOOK AT 

3341
02:26:43,731 --> 02:26:48,102
THE RESEARCH.  IT'S BECAUSE IT 

3342
02:26:48,102 --> 02:26:51,472
IS WHAT IT IS.  AND I WOULD 

3343
02:26:51,472 --> 02:26:53,508
DEFINITELY ADVOCATE TO GO TO THE

3344
02:26:53,508 --> 02:26:54,709
SPACE AND GIVE THE RESEARCH IF 

3345
02:26:54,709 --> 02:26:56,511
PEOPLE NEED THE RESEARCH AND 

3346
02:26:56,511 --> 02:26:58,613
HAVE THE CLINICAL COMPONENT, THE

3347
02:26:58,613 --> 02:27:00,782
CURATION, AS WELL AS THE AI PATH

3348
02:27:00,782 --> 02:27:02,750
AT THE END AS WELL.  I THINK 

3349
02:27:02,750 --> 02:27:03,985
IT'S DEFINITELY THE WAY TO GO.  

3350
02:27:03,985 --> 02:27:06,254
WE NEED TO BRING KNOWLEDGE TO 

3351
02:27:06,254 --> 02:27:09,924
THE DOCTOR AND NOT THE DECISION,

3352
02:27:09,924 --> 02:27:12,060
KNOWLEDGE AND THEN THE 

3353
02:27:12,060 --> 02:27:13,561
INDIVIDUAL CAN TAKE KNOWLEDGE 

3354
02:27:13,561 --> 02:27:17,031
BASED ON WHAT IS MEANINGFUL AND 

3355
02:27:17,031 --> 02:27:23,137
WHAT IS NOT.

3356
02:27:23,137 --> 02:27:27,141
>> AUDIENCE: I HAVE A
COMMENT 

3357
02:27:27,141 --> 02:27:32,480
AND A CHALLENGE.  I AM PART OF A

3358
02:27:32,480 --> 02:27:37,719
COLLABORATION OF 140.  I AM FROM

3359
02:27:37,719 --> 02:27:39,887
AN EPILEPSY COORDINATION AND WE 

3360
02:27:39,887 --> 02:27:42,990
GIVE ACCESS OF COMMUNICATION, 

3361
02:27:42,990 --> 02:27:45,293
RESEARCH, GRANTS, MONEY, MY HOPE

3362
02:27:45,293 --> 02:27:48,096
IS THE YOU'LL CHECK IT OUT.  I 

3363
02:27:48,096 --> 02:27:49,697
WANT TO COMMEND DR. LAL WHO HAS 

3364
02:27:49,697 --> 02:27:52,033
SPENT A LOT OF TIME WORKING WITH

3365
02:27:52,033 --> 02:27:53,901
OUR NETWORK AND DID SOME PRELIM 

3366
02:27:53,901 --> 02:27:55,703
FAIR ANALYSIS IN ADVANCE OF THE 

3367
02:27:55,703 --> 02:27:57,171
CONFERENCE THAT WE HAD LAST YEAR

3368
02:27:57,171 --> 02:27:59,407
AT THE AMERICAN EPILEPSY SOCIETY

3369
02:27:59,407 --> 02:28:00,842
TO REALLY THINK STRATEGICALLY 

3370
02:28:00,842 --> 02:28:02,744
ABOUT NEW AND INNOVATIVE WAYS 

3371
02:28:02,744 --> 02:28:06,180
THAT WE CAN CLUSTER ACROSS THESE

3372
02:28:06,180 --> 02:28:09,150
TWO PIECES.  FIRST THANK YOU TO 

3373
02:28:09,150 --> 02:28:11,152
DR. LAL FOR THAT WORK AND THE 

3374
02:28:11,152 --> 02:28:13,721
CHALLENGE HERE, I'M A LAYPERSON 

3375
02:28:13,721 --> 02:28:15,857
SO NOT A SCIENTIST BUT MY 

3376
02:28:15,857 --> 02:28:17,925
TAKEAWAY FROM A LOT OF THIS 

3377
02:28:17,925 --> 02:28:20,094
CONFLICT SO FAR IS THIS 

3378
02:28:20,094 --> 02:28:22,930
DISCUSSION ABOUT MECHANISM, WHAT

3379
02:28:22,930 --> 02:28:25,733
COMMUNITY DISORDERS, CAN'T BE 

3380
02:28:25,733 --> 02:28:28,302
ADDRESSED ONE AT A TIME, WE NEED

3381
02:28:28,302 --> 02:28:30,271
TO BE THOUGHTFUL IN WHAT WE 

3382
02:28:30,271 --> 02:28:33,374
DEVELOP, SO HOW DO WE AS A 

3383
02:28:33,374 --> 02:28:34,776
COMMUNITY MARRY AN ANALYSIS LIKE

3384
02:28:34,776 --> 02:28:37,044
WHAT DR. LAL HAS DONE LOOKING AT

3385
02:28:37,044 --> 02:28:38,412
THESE DISORDERS WITH THE 

3386
02:28:38,412 --> 02:28:39,747
PLATFORMS THAT WE'RE DISCUSSING 

3387
02:28:39,747 --> 02:28:41,516
TO ADVANCE AND I JUST WANT TO 

3388
02:28:41,516 --> 02:28:43,050
THANK EVERYBODY IN THIS ROOM AND

3389
02:28:43,050 --> 02:28:46,154
ONLINE FOR THINKING ABOUT THAT. 

3390
02:28:46,154 --> 02:28:54,228
THERE ARE A LOT OF CAREGIVERS 

3391
02:28:54,228 --> 02:28:57,431
AND ADVOCATES THAT CARE 

3392
02:28:57,431 --> 02:28:59,901
PASSIONATELY TO TRY TO FUND THIS

3393
02:28:59,901 --> 02:29:04,472
WORK ONE AT A TIME AND WE'RE 

3394
02:29:04,472 --> 02:29:06,474
LOOKING TO YOU TO HELP US DO 

3395
02:29:06,474 --> 02:29:07,909
THIS MORE SYSTEMATICALLY WITH 

3396
02:29:07,909 --> 02:29:09,777
THE INFRASTRUCTURE AND TAKE 

3397
02:29:09,777 --> 02:29:12,280
ADVANTAGE OF WHAT EXISTS OR WHAT

3398
02:29:12,280 --> 02:29:19,153
WE CAN DEVELOP DOWN THE ROAD.  

3399
02:29:19,153 --> 02:29:29,363
THANK YOU.  

3400
02:29:35,002 --> 02:29:37,839
>> VICKY: THANK YOU,
DENNIS.

3401
02:29:37,839 --> 02:29:39,540
>> AUDIENCE: (APPLAUSE).  

3402
02:29:39,540 --> 02:29:40,975
>> VICKY: SO DO WE HAVE
MARY ANN

3403
02:29:40,975 --> 02:29:43,778
ON LINE?  

3404
02:29:43,778 --> 02:29:54,188
>> MARY: I AM HERE, VICKY.

3405
02:29:54,188 --> 02:29:55,189
>> VICKY: I SEE YOU. 
SORRY 

3406
02:29:55,189 --> 02:29:57,325
WE'RE RUNNING A LITTLE LATE.  I 

3407
02:29:57,325 --> 02:29:58,426
KNEW YOU'RE RUNNING YOUR 

3408
02:29:58,426 --> 02:30:01,596
CONFERENCE.  MARY ANN MESKIS IS 

3409
02:30:01,596 --> 02:30:03,297
THE EXECUTIVE DIRECTOR OF THE 

3410
02:30:03,297 --> 02:30:05,333
DRAVET SYNDROME FOUNDATION AND 

3411
02:30:05,333 --> 02:30:07,735
WILL TALK ABOUT IT BECOMING A 

3412
02:30:07,735 --> 02:30:11,172
TREATABLE GENETIC CONDITION, 

3413
02:30:11,172 --> 02:30:19,614
THANK YOU.  

3414
02:30:19,614 --> 02:30:20,915
>> MARY: THANK YOU.  TODAY
I 

3415
02:30:20,915 --> 02:30:23,150
WILL SPEAKING ABOUT THE 

3416
02:30:23,150 --> 02:30:24,252
CONTRIBUTIONS OUR ORGANIZATION 

3417
02:30:24,252 --> 02:30:27,521
HAS MADE TO ADVANCE US TO THE 

3418
02:30:27,521 --> 02:30:29,824
STAGE, THE OBSTACLES WE 

3419
02:30:29,824 --> 02:30:33,294
ENCOUNTER WHEN CONSIDERING 

3420
02:30:33,294 --> 02:30:34,195
UPCOMING TREATMENT OPTIONS AND 

3421
02:30:34,195 --> 02:30:38,165
THE TREATMENTS THAT WE 

3422
02:30:38,165 --> 02:30:48,843
ANTICIPATE OUR ROLE -- OKAY.  

3423
02:30:48,843 --> 02:30:53,447
AND SO ASCROLLINGS (SPEAKING AT 

3424
02:30:53,447 --> 02:30:56,217
ONCE) AS WE GET CLOSER TO 

3425
02:30:56,217 --> 02:30:57,485
BECOMING A TREATABLE GENETIC 

3426
02:30:57,485 --> 02:30:58,653
CONDITION I WILL BE SPEAKING 

3427
02:30:58,653 --> 02:31:03,524
ABOUT THE CONTRIBUTIONS AS 

3428
02:31:03,524 --> 02:31:05,526
ORGANIZATION HAS MADE.  THE 

3429
02:31:05,526 --> 02:31:07,128
OBSTACLES WE MAY ENCOUNTER AND 

3430
02:31:07,128 --> 02:31:09,797
THE PERSISTING CHALLENGES POST 

3431
02:31:09,797 --> 02:31:11,165
COMMERCIALIZATION ALONG WITH 

3432
02:31:11,165 --> 02:31:13,367
WHAT WE ANTICIPATE OUR ROLE WILL

3433
02:31:13,367 --> 02:31:17,038
BE IN SUPPORTING FAMILIES I AM 

3434
02:31:17,038 --> 02:31:18,239
MARY ANN MESKIS I WAS A FOUNDING

3435
02:31:18,239 --> 02:31:20,474
MEMBER IN 2009 AND CURRENTLY 

3436
02:31:20,474 --> 02:31:22,643
SERVE AS THE EXECUTIVE DIRECTOR.

3437
02:31:22,643 --> 02:31:23,978
OUR MISSION IS VERY IMPORTANT TO

3438
02:31:23,978 --> 02:31:26,113
ME BECAUSE MY YOUNGEST SON 

3439
02:31:26,113 --> 02:31:30,084
ELLIOT, EXCUSE ME, WHO IS NOW 24

3440
02:31:30,084 --> 02:31:32,887
YEARS OLD HAS DRAVET SYNDROME.  

3441
02:31:32,887 --> 02:31:39,126
FOR THOSE UNFAMILIAR, IT IS AN 

3442
02:31:39,126 --> 02:31:43,130
EPILEPTIC ENCEPHALOPATHY THAT 

3443
02:31:43,130 --> 02:31:45,299
MANIFESTS.  YOU ALL, I AM SO 

3444
02:31:45,299 --> 02:31:50,104
SORRY, I THINK I SEPTEMBER -- 

3445
02:31:50,104 --> 02:31:50,738
SENT OVER THE WRONG VERSION OF 

3446
02:31:50,738 --> 02:31:59,146
THIS. -- SENT OVER 

3447
02:31:59,146 --> 02:32:01,749
THE WRONG VERSION OF THIS.  IF 

3448
02:32:01,749 --> 02:32:03,150
YOU WANT TO GIVE ME TEN MINUTES 

3449
02:32:03,150 --> 02:32:07,121
TO FIND THE RIGHT VERSION AND 

3450
02:32:07,121 --> 02:32:17,365
SEND IT OVER.

3451
02:32:23,070 --> 02:32:24,038
>> IF YOU HAVE YOUR
PRESENTATION

3452
02:32:24,038 --> 02:32:25,172
YOU CAN SHARE IT FROM YOUR 

3453
02:32:25,172 --> 02:32:26,273
COMPUTER AND WE CAN GO FROM 

3454
02:32:26,273 --> 02:32:30,344
THERE.  

3455
02:32:30,344 --> 02:32:31,746
>> MARY: PERFECT.  LET ME
PULL 

3456
02:32:31,746 --> 02:32:34,782
IT UP FOR YOUR REALLY QUICK.

3457
02:32:34,782 --> 02:32:36,984
>> AWESOME.  LOVE THE
PAINTING 

3458
02:32:36,984 --> 02:32:37,752
IN THE BACKGROUND.  

3459
02:32:37,752 --> 02:32:39,120
>> MARY: THANK YOU, I'M IN
A 

3460
02:32:39,120 --> 02:32:42,123
HOTEL.  LET'S SEE.  IT'S THIS 

3461
02:32:42,123 --> 02:32:43,758
ONE.  SO HOW SHOULD I SHARE THIS

3462
02:32:43,758 --> 02:32:54,335
WITH YOU?  WHAT IS THE BEST WAY 

3463
02:32:54,335 --> 02:32:57,605
ON MY SCREEN?

3464
02:32:57,605 --> 02:33:08,049
>> (FIXING PRESENTATION).

3465
02:35:40,901 --> 02:35:43,771
>> IF WE BREAK FOR LUNCH
NOW CAN

3466
02:35:43,771 --> 02:35:45,039
YOU DO IT LATER 

3467
02:35:45,039 --> 02:35:45,906
>> I WILL FIND IT AND SEND
IT 

3468
02:35:45,906 --> 02:35:47,875
OVER.

3469
02:35:47,875 --> 02:35:51,145
>> SO CAN YOU BE BACK ON
AT 1 

3470
02:35:51,145 --> 02:35:51,512
O'CLOCK EASTERN?

3471
02:35:51,512 --> 02:35:52,746
>> ABSOLUTELY.

3472
02:35:52,746 --> 02:35:55,149
>> OKAY, THANKS SO MUCH. 
ALL 

3473
02:35:55,149 --> 02:35:56,183
RIGHT, SO LET'S BREAK FOR LUNCH 

3474
02:35:56,183 --> 02:35:58,986
AND WE'LL TAKE MARY ANN AFTER.  

3475
02:35:58,986 --> 02:36:01,922
THANK YOU.  BE BACK AT ONE 

3476
02:36:01,922 --> 02:36:02,523
O'CLOCK.  

3477
02:36:02,523 --> 02:36:04,258
>> MARY: OKAY WHEN I SEND
THAT 

3478
02:36:04,258 --> 02:36:10,795
OVER WHO SHOULD THAT GO TO. . . 

3479
02:36:19,806 --> 02:36:20,874
WE'LL SHORTEN THE PANEL 

3480
02:36:20,874 --> 02:36:21,842
DISCUSSION AFTER THE SESSION AND

3481
02:36:21,842 --> 02:36:25,746
SHORTEN THE WRAP UP AT THE END 

3482
02:36:25,746 --> 02:36:27,581
BUT OUR GOAL IS TO GET YOU OUT 

3483
02:36:27,581 --> 02:36:30,217
BY 3:00 BECAUSE I KNOW SEVERAL 

3484
02:36:30,217 --> 02:36:31,652
PEOPLE HAVE FLIGHTS.

3485
02:36:31,652 --> 02:36:33,553
WITH THAT I'LL INTRODUCE MARY 

3486
02:36:33,553 --> 02:36:35,722
ANN AGAIN AND WHAT SHE'S GOING 

3487
02:36:35,722 --> 02:36:37,090
TO TALK AND I'LL CHANGE HER 

3488
02:36:37,090 --> 02:36:38,959
SLIDES FOR HER SO TAKE IT AWAY.

3489
02:36:38,959 --> 02:36:40,227
>> THANKS, VICKI.

3490
02:36:40,227 --> 02:36:41,495
I APPRECIATE YOU HAVING ME SPEAK

3491
02:36:41,495 --> 02:36:44,131
TODAY AND LET ME SERVE AS THE 

3492
02:36:44,131 --> 02:36:45,265
POSTER CHILD AS SOMEONE WHO 

3493
02:36:45,265 --> 02:36:47,134
SHOULD NOT TRY TO RECORD THEIR 

3494
02:36:47,134 --> 02:36:48,468
SESSION WHILE SICK AND THREE 

3495
02:36:48,468 --> 02:36:52,305
DAYS BEFORE THEIR CONFERENCE.

3496
02:36:52,305 --> 02:36:58,245
SO IT'S GREAT TO SEE EVERYONE.

3497
02:36:58,245 --> 02:37:00,447
I'M MARY ANN MESKIS AND SERVE AS

3498
02:37:00,447 --> 02:37:02,482
THE EXECUTIVE DIRECTOR OF OUR 

3499
02:37:02,482 --> 02:37:03,383
ORGANIZATION.

3500
02:37:03,383 --> 02:37:05,886
I HAVE A 24-YEAR-OLD SON WITH 

3501
02:37:05,886 --> 02:37:07,054
GERVAIS SYNDROME AND HAVE BEEN 

3502
02:37:07,054 --> 02:37:09,289
IN THIS NOW OVER TWO DECADES.

3503
02:37:09,289 --> 02:37:11,124
IT'S BEEN VERY EXCITING TO SEE 

3504
02:37:11,124 --> 02:37:12,092
THE PROGRESS OUR COMMUNITY HAS 

3505
02:37:12,092 --> 02:37:20,233
MADE AND TODAY I'M HERE TO TALK 

3506
02:37:20,233 --> 02:37:22,035
ABOUT ABOUT WHAT IT'S BEEN LIKE 

3507
02:37:22,035 --> 02:37:23,437
TO MAKE THIS A TREATABLE 

3508
02:37:23,437 --> 02:37:24,171
CONDITION.

3509
02:37:24,171 --> 02:37:25,939
I WANT TO TALK ABOUT 

3510
02:37:25,939 --> 02:37:27,507
CONTRIBUTIONS OUR ORGANIZATION 

3511
02:37:27,507 --> 02:37:30,110
HAS MADE TO THIS AND WHAT WE 

3512
02:37:30,110 --> 02:37:31,578
HELPED WITH WORKING WITH BIO 

3513
02:37:31,578 --> 02:37:36,950
TECH IN HELPING IN RECRUITMENT 

3514
02:37:36,950 --> 02:37:39,352
FOR CUTTING EDGE TRIALS AND 

3515
02:37:39,352 --> 02:37:42,322
OBSTACLES IN CONSIDERATION 

3516
02:37:42,322 --> 02:37:44,057
THERAPIES AND WHAT WE'LL SEE 

3517
02:37:44,057 --> 02:37:46,226
WILL BE PERSISTING CHALLENGES 

3518
02:37:46,226 --> 02:37:48,562
POST COMMERCIALIZATION WITH ROLE

3519
02:37:48,562 --> 02:37:49,963
OUR ADVOCACY GROUP WILL LIKELY 

3520
02:37:49,963 --> 02:37:55,435
CONTINUE TO PROVIDE IN 

3521
02:37:55,435 --> 02:37:58,672
SUPPORTING FAMILIES.

3522
02:37:58,672 --> 02:38:09,149
SO WHAT ISD -- SO PHOR OUR 

3523
02:38:12,352 --> 02:38:13,954
PATIENTS IT'S NOT JUST 

3524
02:38:13,954 --> 02:38:24,498
SIGNIFICANT SEIZURES OR MULTIPLE

3525
02:38:25,966 --> 02:38:28,135
SEIZURES AND ACROSS THE SPECTRUM

3526
02:38:28,135 --> 02:38:32,572
OF DED HE IS AND IMPACTS THE 

3527
02:38:32,572 --> 02:38:35,108
PATIENTS AND CAREGIVERS AND 

3528
02:38:35,108 --> 02:38:35,375
FAMILIES.

3529
02:38:35,375 --> 02:38:36,143
IT'S CLASSIFIED AS A RARE 

3530
02:38:36,143 --> 02:38:36,376
DISEASE.

3531
02:38:36,376 --> 02:38:40,013
WE HAVE AN ESTIMATED INCIDENT 

3532
02:38:40,013 --> 02:38:50,690
RATE OF APPROXIMATELY 1 IN 15, 

3533
02:38:53,026 --> 02:38:56,797
700 AND SHOW INSUFFICIENT IN 

3534
02:38:56,797 --> 02:38:57,998
GENES AND WITH THE COMORBIDITIES

3535
02:38:57,998 --> 02:39:04,871
THE PATIENTS HAVE UP TO 25% TO 

3536
02:39:04,871 --> 02:39:06,807
20% MORTALITY RATE WITH 50% 

3537
02:39:06,807 --> 02:39:10,911
BEING ATTRIBUTED TO SUDEP AND 

3538
02:39:10,911 --> 02:39:21,454
PROLONGS SIEZURE RELATED DEATHS 

3539
02:39:23,890 --> 02:39:25,725
AND OUR CHILDREN ARE ALWAYS 

3540
02:39:25,725 --> 02:39:30,230
EXPERIENCING CHALLENGES AND OUR 

3541
02:39:30,230 --> 02:39:32,299
FAMILIES PUT THEIR CHILDREN TO 

3542
02:39:32,299 --> 02:39:35,569
BED AT NIGHT AND DON'T KNOW IF 

3543
02:39:35,569 --> 02:39:36,937
THEY'LL WAKE UP AND FRAMES THE 

3544
02:39:36,937 --> 02:39:44,277
URGENCY FOR NEW AND BETTER 

3545
02:39:44,277 --> 02:39:45,178
TREATMENTS.

3546
02:39:45,178 --> 02:39:48,348
WHEN WE LOOK AT TREATMENTS FOR 

3547
02:39:48,348 --> 02:39:49,883
SEIZURES AND OVER ALL QUALITY OF

3548
02:39:49,883 --> 02:39:52,385
LIFE IT'S GIVEN HOPE AND 

3549
02:39:52,385 --> 02:40:02,929
OPTIMISMD OUR FAMILIES ARE TIRED

3550
02:40:04,798 --> 02:40:07,133
OF THEIR CHIRP BEING A GUINEA 

3551
02:40:07,133 --> 02:40:09,135
PIG AND HAVE A SUBPAR QUALITY OF

3552
02:40:09,135 --> 02:40:11,238
LIFE AND THE FAMILIES ARE 

3553
02:40:11,238 --> 02:40:12,405
EXHAUSTED FROM THE CONSTANT CARE

3554
02:40:12,405 --> 02:40:13,607
REQUIRED IN ORDER TO TAKE CARE 

3555
02:40:13,607 --> 02:40:24,084
OF THEIR LOVED ONE PROPERLY.

3556
02:40:27,020 --> 02:40:29,456
YOU WHEN WE FOUNDED OUR 

3557
02:40:29,456 --> 02:40:31,057
ORGANIZATION WE THOUGHT OF WAYS 

3558
02:40:31,057 --> 02:40:32,425
WE COULD BE A CONVENER WITHIN 

3559
02:40:32,425 --> 02:40:33,326
THE FIELD.

3560
02:40:33,326 --> 02:40:34,895
WE ACTIVELY SOUGHT OUT THE 

3561
02:40:34,895 --> 02:40:36,830
RESEARCHERS OR CLINICIANS THAT 

3562
02:40:36,830 --> 02:40:38,331
WE KNEW THAT WERE SEEING THESE 

3563
02:40:38,331 --> 02:40:38,598
PATIENTS.

3564
02:40:38,598 --> 02:40:40,567
MANY OF THEM ARE NOW PART OF OUR

3565
02:40:40,567 --> 02:40:41,902
SCIENTIFIC AND MEDICAL ADVISORY 

3566
02:40:41,902 --> 02:40:43,169
BOARD AND FELT THOSE ARE THE 

3567
02:40:43,169 --> 02:40:45,338
INDIVIDUALS WE NEEDED TO TALK TO

3568
02:40:45,338 --> 02:40:47,107
TO HELP US UNDERSTAND WHAT OUR 

3569
02:40:47,107 --> 02:40:48,441
FUTURE PRIORITIES AND FOCUS 

3570
02:40:48,441 --> 02:40:50,777
AREAS SHOULD BE.

3571
02:40:50,777 --> 02:40:52,312
THROUGH OUR FUNDFAISING EFFORTS 

3572
02:40:52,312 --> 02:40:55,949
WE'VE BEEN ABLE TO HAVE A ROBUST

3573
02:40:55,949 --> 02:40:58,218
PROGRAM AND EXCITED AS OF LAST 

3574
02:40:58,218 --> 02:41:00,854
YEAR 2023 WE HAD BEEN ABLE TO 

3575
02:41:00,854 --> 02:41:03,890
PROVIDE $9.1 MILLION IN SEED 

3576
02:41:03,890 --> 02:41:05,191
GRANTS AND THAT'S OVER A 15 YEAR

3577
02:41:05,191 --> 02:41:07,127
TIME PERIOD AND ALLOWED US TO 

3578
02:41:07,127 --> 02:41:09,095
RECOGNIZE OR TO LOOK AT THE GAPS

3579
02:41:09,095 --> 02:41:11,164
IN THE FIELD AND MAKE SURE WE'RE

3580
02:41:11,164 --> 02:41:12,299
SUPPORTING THE MOST VITAL 

3581
02:41:12,299 --> 02:41:18,538
RESEARCH INITIATIVES.

3582
02:41:18,538 --> 02:41:20,407
IN ADDITION WE DO A ROUNDTABLE 

3583
02:41:20,407 --> 02:41:25,545
WITH OUR SCIENTIFIC ADVISORY 

3584
02:41:25,545 --> 02:41:27,447
CO-CHAIRS FOR KEY OPINION 

3585
02:41:27,447 --> 02:41:29,516
LEADERS, RESEARCHERS AND EVEN 

3586
02:41:29,516 --> 02:41:32,786
INDUSTRY MEMBERS WITH A FOCUS ON

3587
02:41:32,786 --> 02:41:35,588
OUR DISEASE STATE AND GIVES US A

3588
02:41:35,588 --> 02:41:37,457
FORUM TO TALK ABOUT THE 

3589
02:41:37,457 --> 02:41:39,659
ADVANCEMENTS, WHAT ARE PROGRESS 

3590
02:41:39,659 --> 02:41:41,328
AND WHAT ARE OTHER PRIORITIES 

3591
02:41:41,328 --> 02:41:45,065
NOT BEING MET AND AS IT A NICE 

3592
02:41:45,065 --> 02:41:47,167
BAROMETER TO TAKE BACK TO OUR 

3593
02:41:47,167 --> 02:41:48,935
BOARD OF DIRECTORS SO SAY THIS 

3594
02:41:48,935 --> 02:41:51,671
IS WHAT WE INTO HE HAD TO FOCUS 

3595
02:41:51,671 --> 02:41:51,838
ON.

3596
02:41:51,838 --> 02:41:53,440
IT'S BEEN INSTRUCTIONAL IN 

3597
02:41:53,440 --> 02:41:56,276
SHAPING OUR RESEARCH ROAD MAP 

3598
02:41:56,276 --> 02:41:59,779
AND GUIDING OUR FUNDING 

3599
02:41:59,779 --> 02:42:00,280
DECISIONS.

3600
02:42:00,280 --> 02:42:02,315
WE RECOGNIZE NONE OF THIS COULD 

3601
02:42:02,315 --> 02:42:05,752
HAPPEN WITHOUT OUR PATIENTS AND 

3602
02:42:05,752 --> 02:42:07,554
EDUCATE OUR FAMILIES AND MAKE 

3603
02:42:07,554 --> 02:42:08,722
THEM UNDERSTAND HOW IMPORTANT IT

3604
02:42:08,722 --> 02:42:10,190
IS TO SHARE THE PATIENT 

3605
02:42:10,190 --> 02:42:13,593
EXPERIENCE SO THOSE LIVING ON A 

3606
02:42:13,593 --> 02:42:14,427
DAILY BASIS CAN UNDERSTAND HOW 

3607
02:42:14,427 --> 02:42:16,296
MANY UNMET NEEDS ARE IN OUR 

3608
02:42:16,296 --> 02:42:26,473
COMMUNITY.

3609
02:42:36,850 --> 02:42:40,286
WE HAVE A PATHWAY TO COMMUNICATE

3610
02:42:40,286 --> 02:42:50,430
INFORMATION OUT TO THEM.

3611
02:42:50,430 --> 02:42:52,198
 EARLY ON WE THOUGHT WE COULD 

3612
02:42:52,198 --> 02:42:54,300
IDENTIFY WHAT EXISTING RESOURCES

3613
02:42:54,300 --> 02:42:57,070
ARE OUT THERE AND THINK WHAT 

3614
02:42:57,070 --> 02:42:58,772
AREAS WE COULD CURRENTLY TRY TO 

3615
02:42:58,772 --> 02:43:00,540
TACKLE AS WELL AS WHAT WE THESED

3616
02:43:00,540 --> 02:43:02,242
TO DO THREE, FOUR, FIVE YEARS 

3617
02:43:02,242 --> 02:43:02,942
DOWN THE LINE.

3618
02:43:02,942 --> 02:43:04,277
WE'VE BEEN FORTUNATE BECAUSE 

3619
02:43:04,277 --> 02:43:05,512
THERE HAVE BEEN GREAT 

3620
02:43:05,512 --> 02:43:06,913
INDIVIDUALS WORKING IN OUR FIELD

3621
02:43:06,913 --> 02:43:10,917
PRIOR TO DSF COMING TO FRUITION 

3622
02:43:10,917 --> 02:43:11,451
IN 2009.

3623
02:43:11,451 --> 02:43:13,553
THERE WERE THINGS IN PLACE AND 

3624
02:43:13,553 --> 02:43:15,188
WE TRIED TO LEVERAGE THOSE AND 

3625
02:43:15,188 --> 02:43:16,790
WORK THROUGH A COMBINATION OF 

3626
02:43:16,790 --> 02:43:18,825
RESEARCH FUNDING, STRATEGIC 

3627
02:43:18,825 --> 02:43:19,492
PARTNERSHIPS AND DIRECT ACTION 

3628
02:43:19,492 --> 02:43:23,863
TO TRY TO ADDRESS THE GAPS AND 

3629
02:43:23,863 --> 02:43:25,598
MAKE OUR DISEASE STATE EASY FOR 

3630
02:43:25,598 --> 02:43:26,666
ANYONE TO RESEARCH OR LOOK AT 

3631
02:43:26,666 --> 02:43:27,934
DRUG DEVELOPMENT FOR.

3632
02:43:27,934 --> 02:43:32,505
WE SECURED AN ICD10 COHORT 

3633
02:43:32,505 --> 02:43:34,274
DISEASE STATE AND THERE'S THREE 

3634
02:43:34,274 --> 02:43:36,242
AND HAVE A PATIENT FOCUSSED DRUG

3635
02:43:36,242 --> 02:43:37,343
DEVELOPMENT MEETING WITH FDA IN 

3636
02:43:37,343 --> 02:43:39,345
2022 AND CONTINUE TO LOOK AND 

3637
02:43:39,345 --> 02:43:43,550
SEE WHAT ARE ANY TOOLS MISSING 

3638
02:43:43,550 --> 02:43:44,851
WE CAN OFFER TO MAKE PROGRESS 

3639
02:43:44,851 --> 02:43:46,886
FASTER IN OUR FIELD.

3640
02:43:46,886 --> 02:43:48,788
THANKS TO THE COLLABORATIVE 

3641
02:43:48,788 --> 02:43:54,227
EFFORT OF NOT JUST DSF BUT THIS 

3642
02:43:54,227 --> 02:43:55,762
ENTIRE COMMUNITY WE HAVE A 

3643
02:43:55,762 --> 02:44:00,366
WEALTH OF RESOURCES DEDICATED TO

3644
02:44:00,366 --> 02:44:03,636
RESEARCH IN DRAVET SYNDROME AND 

3645
02:44:03,636 --> 02:44:08,374
THE RESOURCES HAVE HELPED US 

3646
02:44:08,374 --> 02:44:09,809
ALLOWING DRUG DEVELOPERS IN EACH

3647
02:44:09,809 --> 02:44:12,312
PHASE OF THE DEVELOPMENT AND 

3648
02:44:12,312 --> 02:44:17,550
HAVE BEEN SURPRISED WHEN WE HAD 

3649
02:44:17,550 --> 02:44:19,719
PHARMACEUTICAL COMPANIES COME TO

3650
02:44:19,719 --> 02:44:23,523
US AND PUT THEM IN TOUCH WITH 

3651
02:44:23,523 --> 02:44:24,090
TOP RESEARCHERS MADE IT A 

3652
02:44:24,090 --> 02:44:30,230
DISEASE TO TARGET.

3653
02:44:30,230 --> 02:44:33,933
HERE YOU SEE PART OF OUR 

3654
02:44:33,933 --> 02:44:34,968
STRATEGIC APPROACH TO MAXIMIZING

3655
02:44:34,968 --> 02:44:39,372
OUR RESOURCES WAS LOOKING AT 

3656
02:44:39,372 --> 02:44:42,709
WHAT GRANTS ARE OUT WE CAN COVER

3657
02:44:42,709 --> 02:44:44,277
AND IT COVERS 65 GRANTS IN THE 

3658
02:44:44,277 --> 02:44:46,246
PAST 15 YEARS.

3659
02:44:46,246 --> 02:44:49,048
WE FELT IF WE WERE STRATEGIC NOT

3660
02:44:49,048 --> 02:44:50,550
ONLY COULD WE BRING ADDITIONAL 

3661
02:44:50,550 --> 02:44:52,318
RESEARCHERS TO OUR FIELD THEN 

3662
02:44:52,318 --> 02:44:54,320
GIVE THEM THE CRUCIAL SUPPORT, 

3663
02:44:54,320 --> 02:44:55,722
HELP THEM COLLECT THE INITIAL 

3664
02:44:55,722 --> 02:44:57,957
DATA THEY NEEDED TO GO ON AND 

3665
02:44:57,957 --> 02:44:59,459
SECURE LARGER FUNDING AND HAVE 

3666
02:44:59,459 --> 02:45:01,628
BEEN PLEASED TO SEE IT PLAYED 

3667
02:45:01,628 --> 02:45:04,364
OUT LIKE WE HOPED.

3668
02:45:04,364 --> 02:45:08,067
THE $9 MILLION RESULTED IN AN 

3669
02:45:08,067 --> 02:45:09,402
ADDITIONAL $23 MILLION IN NIH 

3670
02:45:09,402 --> 02:45:11,938
LEVEL FUNDING GOING TO 

3671
02:45:11,938 --> 02:45:13,406
RESEARCHERS WORKING SPECIFICALLY

3672
02:45:13,406 --> 02:45:18,411
IN DRAVET'S SYNDROME.

3673
02:45:18,411 --> 02:45:20,380
IT'S BEEN A HUGE BOON TO OUR 

3674
02:45:20,380 --> 02:45:21,848
COMMUNITY BECAUSE IT'S DIFFICULT

3675
02:45:21,848 --> 02:45:25,685
FOR OUR FAMILIES TO FUND RAISE 

3676
02:45:25,685 --> 02:45:27,153
SO IT'S BEEN MOTIVATED FOR THEM.

3677
02:45:27,153 --> 02:45:29,989
IN ADDITION WE'VE BEEN FORTUNATE

3678
02:45:29,989 --> 02:45:32,025
OVER 75% OF THESE GRANTS HAVE 

3679
02:45:32,025 --> 02:45:35,094
LED TO PUBLICATIONS AND THAT'S 

3680
02:45:35,094 --> 02:45:37,497
HELPED TO EXPAND AND DEEPEN OUR 

3681
02:45:37,497 --> 02:45:38,932
UNDERSTANDING OF DRAVET'S 

3682
02:45:38,932 --> 02:45:39,666
SYNDROME WHICH HAS BEEN HELPFUL 

3683
02:45:39,666 --> 02:45:43,703
AS WELL.

3684
02:45:43,703 --> 02:45:46,306
I WOULD LIKE TO THINK EVERYONE 

3685
02:45:46,306 --> 02:45:48,308
HERE UNDERSTANDS THE ROLE OF 

3686
02:45:48,308 --> 02:45:49,943
PATIENT ADVOCACY GROUPS IN 

3687
02:45:49,943 --> 02:45:50,510
CLINICAL TRIALS AND THEIR 

3688
02:45:50,510 --> 02:45:51,444
IMPORTANCE BUT OF COURSE I'M 

3689
02:45:51,444 --> 02:45:53,813
GOING TO TALK ABOUT IT.

3690
02:45:53,813 --> 02:45:55,982
WE CAN'T HAVE ANY OF THESE 

3691
02:45:55,982 --> 02:45:57,050
ADVANCEMENTS WITHOUT OUR 

3692
02:45:57,050 --> 02:45:57,317
PATIENTS.

3693
02:45:57,317 --> 02:46:01,454
SO THESE GROUPS PLAY SUCH A 

3694
02:46:01,454 --> 02:46:02,422
CRUCIAL ROLE IN CLINICAL TRIALS 

3695
02:46:02,422 --> 02:46:04,390
ENSURING WE'RE THINKING WHAT THE

3696
02:46:04,390 --> 02:46:06,259
PATIENT NEEDS AND PERSPECTIVES 

3697
02:46:06,259 --> 02:46:08,628
ARE THAT WILL BE INTERGRAL TO 

3698
02:46:08,628 --> 02:46:10,363
THE DEVELOPMENT OF NEW 

3699
02:46:10,363 --> 02:46:10,630
THERAPIES.

3700
02:46:10,630 --> 02:46:17,670
THE NIH ESTIMATES 5% FOR RARE 

3701
02:46:17,670 --> 02:46:20,039
DISEASES WILL BE APPROVED AND 

3702
02:46:20,039 --> 02:46:21,975
WE'RE FORTUNATE SINCE 2018 OUR 

3703
02:46:21,975 --> 02:46:23,243
PATIENT COMMUNITY HAS HAD THREE 

3704
02:46:23,243 --> 02:46:26,713
NEW DRUGS COME TO APPROVAL WITH 

3705
02:46:26,713 --> 02:46:28,481
INDICATIONS FOR DRAVET'S 

3706
02:46:28,481 --> 02:46:30,783
SYNDROME TARGETED ON SEIZURE 

3707
02:46:30,783 --> 02:46:32,018
REDUCTION AND HELPED SOME 

3708
02:46:32,018 --> 02:46:33,319
PATIENTS IN OUR COMMUNITY BUT 

3709
02:46:33,319 --> 02:46:35,054
UNFORTUNATELY WE'RE STILL IN A 

3710
02:46:35,054 --> 02:46:37,890
POSITION AS MANY DEEs NOT EVERY 

3711
02:46:37,890 --> 02:46:40,093
TREATMENT HAS THE SAME EFFICACY 

3712
02:46:40,093 --> 02:46:41,694
LEVEL FOR EVERY PATIENT.

3713
02:46:41,694 --> 02:46:43,329
SO THERE ARE PATIENTS TRULY 

3714
02:46:43,329 --> 02:46:44,430
SUFFERING, HAVE NO TYPE OF 

3715
02:46:44,430 --> 02:46:46,332
SEIZURE CONTROL AND WE STILL 

3716
02:46:46,332 --> 02:46:49,335
HAVE A LOT OF UNMET NEEDS EVEN 

3717
02:46:49,335 --> 02:46:50,770
WITH THESE THREE NEW DRUGS.

3718
02:46:50,770 --> 02:46:53,740
WE ALSO WANT TO THINK ABOUT IS 

3719
02:46:53,740 --> 02:46:56,075
THERE A POSSIBILITY OF WAYS TO 

3720
02:46:56,075 --> 02:47:05,852
SLOW DOWN THE PROGRESSION OR 

3721
02:47:05,852 --> 02:47:08,121
POSSIBLY REVERSAL OF DISEASE AND

3722
02:47:08,121 --> 02:47:08,788
EXCITING TO SEE SOME TREATMENT 

3723
02:47:08,788 --> 02:47:10,857
COME TO CLINICAL TRIAL AND WANT 

3724
02:47:10,857 --> 02:47:11,791
OUR PATIENT COMMUNITY UNITED AND

3725
02:47:11,791 --> 02:47:13,493
HAVE EVERYTHING THEY NEED AT 

3726
02:47:13,493 --> 02:47:14,160
HAND TO MAKE DECISION TO 

3727
02:47:14,160 --> 02:47:18,531
PARTICIPATE IN CLINICAL TRIALS.

3728
02:47:18,531 --> 02:47:21,267
 WE'RE ALWAYS WORKING TO 

3729
02:47:21,267 --> 02:47:23,069
AWARENESS OF DRAVET'S SYNDROME 

3730
02:47:23,069 --> 02:47:26,005
AND CONNECT FAMILIES IN OUR 

3731
02:47:26,005 --> 02:47:27,540
ORGANIZATION AND ALSO MAKE SURE 

3732
02:47:27,540 --> 02:47:28,274
THEY'RE AWAY OF TRIAL 

3733
02:47:28,274 --> 02:47:28,908
OPPORTUNITIES THERE.

3734
02:47:28,908 --> 02:47:30,810
WE DO THIS THROUGH THINGS LIKE 

3735
02:47:30,810 --> 02:47:33,680
OUR WEBSITE, NEWSLETTER, SOCIAL 

3736
02:47:33,680 --> 02:47:36,015
MEDIA CHANNELS.

3737
02:47:36,015 --> 02:47:39,252
WE HAVE FAMILIES THE OPPORTUNITY

3738
02:47:39,252 --> 02:47:42,221
TO LET US KNOW IF THEY'D LIKE TO

3739
02:47:42,221 --> 02:47:46,693
BE AVAILABLE TO SHARE THEIR 

3740
02:47:46,693 --> 02:47:47,927
INPUT ON TRIAL DESIGNS OR 

3741
02:47:47,927 --> 02:47:49,562
ANYTHING TO HELP THE DRUG 

3742
02:47:49,562 --> 02:47:50,530
COMPANIES UNDERSTAND WHAT WOULD 

3743
02:47:50,530 --> 02:47:52,532
BE MOST HELPFUL IN TRIAL DESIGN 

3744
02:47:52,532 --> 02:47:53,800
AND WHAT OUR PATIENTS WANT.

3745
02:47:53,800 --> 02:47:55,635
AT THE END OF THE DAY WE WANT 

3746
02:47:55,635 --> 02:47:56,235
THE DRUGS TO SUCCEED.

3747
02:47:56,235 --> 02:47:58,237
WE'RE MORE THAN HAPPY TO SHARE 

3748
02:47:58,237 --> 02:48:00,073
WHATEVER INFORMATION WE CAN TO 

3749
02:48:00,073 --> 02:48:02,375
MAKE THAT HAPPEN.

3750
02:48:02,375 --> 02:48:03,776
WE'VE DONE THING SUCH AS 

3751
02:48:03,776 --> 02:48:05,011
REPRESENTING OUR COMMUNITY AS A 

3752
02:48:05,011 --> 02:48:07,246
WHOLE BY ENGAGING IN 

3753
02:48:07,246 --> 02:48:09,115
CONVERSATIONS WITH THE FDA 

3754
02:48:09,115 --> 02:48:10,750
INCLUDING OUR EXTERNALLY LED 

3755
02:48:10,750 --> 02:48:11,984
DRUG DEVELOPMENT MEETING AND TRY

3756
02:48:11,984 --> 02:48:14,721
TO WORK TO EDUCATE AND FOSTER 

3757
02:48:14,721 --> 02:48:15,955
TRUST WITHIN OUR COMMUNITY.

3758
02:48:15,955 --> 02:48:17,557
I THINK WHEN YOU'RE TALKING 

3759
02:48:17,557 --> 02:48:19,792
ABOUT A DISEASE LIKE THIS WHERE 

3760
02:48:19,792 --> 02:48:21,828
OUR PATIENTS ARE ON MULTIPLE 

3761
02:48:21,828 --> 02:48:23,563
DRUG EVERY DAY AND STILL NOT 

3762
02:48:23,563 --> 02:48:25,765
GETTING GOOD RESULTS.

3763
02:48:25,765 --> 02:48:27,600
THERE CAN BE A PERCEPTION OF 

3764
02:48:27,600 --> 02:48:29,168
FRUSTRATION ON THE CAREGIVER'S 

3765
02:48:29,168 --> 02:48:30,370
PART BECAUSE THEY THINK THE DRUG

3766
02:48:30,370 --> 02:48:31,938
COMPANIES ARE JUST MAKING MONEY 

3767
02:48:31,938 --> 02:48:33,906
OFF MY CHILD AND NO ONE CARES 

3768
02:48:33,906 --> 02:48:35,508
THEY'RE SUFFERING WHILE WE KNOW 

3769
02:48:35,508 --> 02:48:36,275
THAT'S NOT TRUE.

3770
02:48:36,275 --> 02:48:38,511
WHEN YOU'RE IN THE DEPTHS OF 

3771
02:48:38,511 --> 02:48:41,247
THAT AND DESPERATE AND SAD THAT 

3772
02:48:41,247 --> 02:48:42,548
CAN HAP EN.

3773
02:48:42,548 --> 02:48:44,283
WE TRY TO REMIND PARENTS AND 

3774
02:48:44,283 --> 02:48:48,321
CAREGIVERS THIS IS ALL OF US 

3775
02:48:48,321 --> 02:48:49,489
TOGETHER SO IF THINGS AREN'T 

3776
02:48:49,489 --> 02:48:51,424
WORKING WE HAVE TO SPEAK UP AND 

3777
02:48:51,424 --> 02:48:52,558
SHARE THE PATIENT EXPERIENCE AND

3778
02:48:52,558 --> 02:48:53,760
HAVE TO BE WILLING TO 

3779
02:48:53,760 --> 02:48:54,694
PARTICIPATE IN CLINICAL TRIALS 

3780
02:48:54,694 --> 02:48:57,363
OR NOTHING WILL GO FORWARD.

3781
02:48:57,363 --> 02:49:01,167
AND WE TRY TO ON A REGULAR BASIS

3782
02:49:01,167 --> 02:49:02,869
BY EDUCATING OUR COMMUNITY 

3783
02:49:02,869 --> 02:49:05,037
MEMBERS WITH NEW COMMUNITY 

3784
02:49:05,037 --> 02:49:06,072
MEMBERS JOINING OR PARENTS THAT 

3785
02:49:06,072 --> 02:49:08,841
MAY HAVE MISSED THE MESSAGE AND 

3786
02:49:08,841 --> 02:49:12,345
IT'S AN ONGOING EDUCATION WE 

3787
02:49:12,345 --> 02:49:20,153
OFFER THE COMMUNITY.

3788
02:49:20,153 --> 02:49:28,294
 SO FOR THOSE NOT FAMILIAR WITH 

3789
02:49:28,294 --> 02:49:34,634
STOKE THERAPEUTIC STK001 THEY 

3790
02:49:34,634 --> 02:49:37,703
HAVE TARGETED AUGMENTATION OF 

3791
02:49:37,703 --> 02:49:38,905
NUCLEAR GENE OUTPUT AND INCREASE

3792
02:49:38,905 --> 02:49:40,673
INCREASING OUTPUT FROM HEALTHY 

3793
02:49:40,673 --> 02:49:45,011
GENES AND COMPENSATING FOR THE 

3794
02:49:45,011 --> 02:49:46,612
NON-FUNCTIONING COPY OF THE GENE

3795
02:49:46,612 --> 02:49:52,151
AND THIS IS AN ADEAL -- IDEAL 

3796
02:49:52,151 --> 02:49:55,188
AND ASOs ARE HELPING INCREASE 

3797
02:49:55,188 --> 02:49:57,457
THE PROTEIN PRODUCTION FROM THE 

3798
02:49:57,457 --> 02:49:59,292
HEALTHY COPY OF THIS GENE AND 

3799
02:49:59,292 --> 02:50:03,062
HOPING WHEN IT'S RESTORED YOU 

3800
02:50:03,062 --> 02:50:05,965
MAY SEE A SLOWING OR COMPLETELY 

3801
02:50:05,965 --> 02:50:08,267
STOP IN THE DISEASE PROGRESSION.

3802
02:50:08,267 --> 02:50:13,005
THIS NOVEL APPROACH ALLOWED THEM

3803
02:50:13,005 --> 02:50:15,041
TO -- WE'RE HOPING THIS WILL 

3804
02:50:15,041 --> 02:50:17,477
ALLOW THEM TO PURSUE DISEASE 

3805
02:50:17,477 --> 02:50:18,744
MODIFYING TREATMENT FOR MULTIPLE

3806
02:50:18,744 --> 02:50:20,012
SEVERE DISEASES BUT WERE EXCITED

3807
02:50:20,012 --> 02:50:21,614
WHEN I THEY CAME TO US AND SAID 

3808
02:50:21,614 --> 02:50:23,549
THEIR GOAL WAS TO DEVELOP THAT 

3809
02:50:23,549 --> 02:50:26,786
FIRST DISEASE MODIFYING THERAPY 

3810
02:50:26,786 --> 02:50:30,389
TO ADDRESS THE GENETIC CAUSE OF 

3811
02:50:30,389 --> 02:50:32,391
DRAVET'S SYNDROME AND YOU CAN 

3812
02:50:32,391 --> 02:50:35,328
IMAGINE THE EXCITEMENT IN OUR 

3813
02:50:35,328 --> 02:50:35,595
COMMUNITY.

3814
02:50:35,595 --> 02:50:40,566
THE MONARCH STUDY WAS THEIR 

3815
02:50:40,566 --> 02:50:45,538
PHASE I/II STUDY AND ESTABLISHED

3816
02:50:45,538 --> 02:50:52,578
TOLERABILITY OF STK001 AND AN 

3817
02:50:52,578 --> 02:50:53,145
ANTI-SEIZURE TREATMENT.

3818
02:50:53,145 --> 02:50:54,413
IT'S IMPORTANT TO TALK ABOUT THE

3819
02:50:54,413 --> 02:50:55,281
PROCESS OF THE PATIENT AND 

3820
02:50:55,281 --> 02:51:00,419
FAMILIES HAVE TO GO THROUGH.

3821
02:51:00,419 --> 02:51:03,689
STK001 IS DELIVERED VIA A NEEDLE

3822
02:51:03,689 --> 02:51:05,358
INTO THE SPINE.

3823
02:51:05,358 --> 02:51:07,693
THOUGH OUR COMMUNITY IS PRETTY 

3824
02:51:07,693 --> 02:51:09,395
SAVVY WHEN IT COMES TO CLINICAL 

3825
02:51:09,395 --> 02:51:10,196
TRIALS THIS IS DIFFICULT THAN 

3826
02:51:10,196 --> 02:51:11,831
WHAT WE'RE USED TO AND MORE 

3827
02:51:11,831 --> 02:51:13,132
PAINFUL THAN A TYPICAL SHOT OR 

3828
02:51:13,132 --> 02:51:14,667
ASKING A CHILD TO SWALLOW A 

3829
02:51:14,667 --> 02:51:15,468
PILL.

3830
02:51:15,468 --> 02:51:18,137
PARTICIPANTS HAVE TO GIVE CSF 

3831
02:51:18,137 --> 02:51:22,341
FLUID SAMPLES THROUGHOUT VIA 

3832
02:51:22,341 --> 02:51:26,479
LUMBAR PUNCTURES AND THERE'S 

3833
02:51:26,479 --> 02:51:26,979
OFFICE VISITS AND THREE 

3834
02:51:26,979 --> 02:51:29,582
INTRATHECAL INJECTIONS AND FIVE 

3835
02:51:29,582 --> 02:51:30,016
CSS COLLECTIONS.

3836
02:51:30,016 --> 02:51:32,285
WHEN YOU BREAK IT DOWN IT'S A 

3837
02:51:32,285 --> 02:51:34,320
PRETTY SIGNIFICANT ASK FOR OUR 

3838
02:51:34,320 --> 02:51:34,987
PATIENTS PARTICULARLY SINCE MOST

3839
02:51:34,987 --> 02:51:39,025
OF OUR PATIENTS HAVE TO TRAVEL 

3840
02:51:39,025 --> 02:51:41,227
LONG DISTANCE TO SEE A 

3841
02:51:41,227 --> 02:51:42,528
SPECIALIST AND THEY WOULD BE 

3842
02:51:42,528 --> 02:51:43,596
CONDUCTING THE TRIALS.

3843
02:51:43,596 --> 02:51:45,197
I HOPE YOU UNDERSTAND THAT LEVEL

3844
02:51:45,197 --> 02:51:47,567
OF INVASIVENESS AND THE 

3845
02:51:47,567 --> 02:51:48,301
COMMITMENT TO PARTICIPATE.

3846
02:51:48,301 --> 02:51:50,937
I THINK IT HELPS TO FRAME UP THE

3847
02:51:50,937 --> 02:51:52,104
DESPERATION OF OUR COMMUNITY 

3848
02:51:52,104 --> 02:51:53,506
THAT THE TREATMENTS THAT ARE OUT

3849
02:51:53,506 --> 02:51:55,408
THERE ARE NOT GOOD ENOUGH AND WE

3850
02:51:55,408 --> 02:51:56,075
NEED BETTER.

3851
02:51:56,075 --> 02:51:58,377
THE PATIENTS THAT WERE IN 

3852
02:51:58,377 --> 02:52:00,279
MONARCH FOLLOWING THAT WHO MET 

3853
02:52:00,279 --> 02:52:04,283
THE STUDY CRITERIA DID CONTINUE 

3854
02:52:04,283 --> 02:52:07,753
ON IN AN ONGOING OPEN LABEL 

3855
02:52:07,753 --> 02:52:08,087
EXTENSION.

3856
02:52:08,087 --> 02:52:10,323
WE'RE AWAITING NEWS ON STOKE AND

3857
02:52:10,323 --> 02:52:13,392
WHEN THEY'LL ME OF ON TO PHASE 

3858
02:52:13,392 --> 02:52:16,028
III WHICH WE ANTICIPATE THEY'VE 

3859
02:52:16,028 --> 02:52:19,031
NOT MADE A COMMITMENT BUT WE 

3860
02:52:19,031 --> 02:52:26,639
THINK SOME TIME IN 2025.

3861
02:52:26,639 --> 02:52:28,274
WE'VE BEEN FORTUNATE TO HAVE THE

3862
02:52:28,274 --> 02:52:29,275
DISEASES COME TO MARKET AND PART

3863
02:52:29,275 --> 02:52:30,610
OF OUR SUCCESS IS NOT ONLY 

3864
02:52:30,610 --> 02:52:35,781
SETTING UP THE STRUCTURE 

3865
02:52:35,781 --> 02:52:36,449
BENEFICIAL TO THE COMPANIES BUT 

3866
02:52:36,449 --> 02:52:41,454
HAVE HIGH STANDARDS.

3867
02:52:41,454 --> 02:52:42,922
IF SOMEONE IS ASKING OUR PATIENT

3868
02:52:42,922 --> 02:52:44,690
COMMUNITY TO PUT FORTH THEIR 

3869
02:52:44,690 --> 02:52:49,495
CHILD THERE NEEDS TO BE A 

3870
02:52:49,495 --> 02:52:50,396
RECIPROCAL EXCHANGE.

3871
02:52:50,396 --> 02:52:52,264
WE WANT YOU TO LEARN FROM US 

3872
02:52:52,264 --> 02:52:53,599
BECAUSE AT THE END OF THE DAY WE

3873
02:52:53,599 --> 02:52:58,104
WANT THE NEW TREATMENTS.

3874
02:52:58,104 --> 02:52:59,639
WHAT'S BEEN BENEFICIAL WITH US 

3875
02:52:59,639 --> 02:53:01,474
WITH STOKE THERAPEUTICS IS THEY 

3876
02:53:01,474 --> 02:53:04,477
ENGAGED WITH US EVEN BEFORE THEY

3877
02:53:04,477 --> 02:53:05,578
DECIDED WHAT THEIR TARGET WOULD 

3878
02:53:05,578 --> 02:53:07,513
BE AND IT'S BEEN A POSITIVE 

3879
02:53:07,513 --> 02:53:08,414
EXPERIENCE FOR US.

3880
02:53:08,414 --> 02:53:10,816
THEY'VE DEMONSTRATED A GENUINE 

3881
02:53:10,816 --> 02:53:12,284
INTEREST IN OUR COMMUNITY, THEY 

3882
02:53:12,284 --> 02:53:14,487
WANT TO KNOW THE NEEDS AND 

3883
02:53:14,487 --> 02:53:15,354
PRIORITIES OF OUR PATIENT 

3884
02:53:15,354 --> 02:53:16,689
COMMUNITY AND LOOKED FOR INPUT 

3885
02:53:16,689 --> 02:53:18,357
ON TRIAL DESIGN NOT JUST FROM 

3886
02:53:18,357 --> 02:53:22,728
OUR IMMEDIATE STAFF BUT TALKED 

3887
02:53:22,728 --> 02:53:24,063
TO THE BROADER COMMUNITY AND 

3888
02:53:24,063 --> 02:53:26,632
WERE ALWAYS OPEN AND RECEPTIVE 

3889
02:53:26,632 --> 02:53:31,504
ANYTHING WE SAID WOULD NOT WORK.

3890
02:53:31,504 --> 02:53:33,839
WE FEEL FORTUNATE WE'VE BEEN 

3891
02:53:33,839 --> 02:53:35,441
ABLE TO WORK WITH A COMPANY IN 

3892
02:53:35,441 --> 02:53:36,175
THIS WAY.

3893
02:53:36,175 --> 02:53:37,710
IT GAVE US A HEAD START BECAUSE 

3894
02:53:37,710 --> 02:53:39,545
AGAIN IT'S A NEW TYPE OF 

3895
02:53:39,545 --> 02:53:39,779
THERAPY.

3896
02:53:39,779 --> 02:53:42,381
WHAT DID WE NEED TO DO TO 

3897
02:53:42,381 --> 02:53:43,482
PROACTIVELY EDUCATE OUR 

3898
02:53:43,482 --> 02:53:45,618
COMMUNITY AND START TO ADDRESS 

3899
02:53:45,618 --> 02:53:51,023
THE QUESTIONS WE ANTICIPATED 

3900
02:53:51,023 --> 02:53:56,429
WOULD COME TO THE TOP AS WELL AS

3901
02:53:56,429 --> 02:53:57,797
CONCERNS OUR EDUCATIONAL 

3902
02:53:57,797 --> 02:53:59,065
OPPORTUNITIES TO HELP PEOPLE 

3903
02:53:59,065 --> 02:54:03,369
UNDERSTAND WHAT THEY'D BE PA

3904
02:54:03,369 --> 02:54:10,309
PART -- PARTICIPATING IN AND 

3905
02:54:10,309 --> 02:54:13,012
THERE'S A SHARED DESIRE TO SEE 

3906
02:54:13,012 --> 02:54:14,080
THE TRIALS SUCCEED.

3907
02:54:14,080 --> 02:54:16,215
FOR COMPANIES HESITANT IN 

3908
02:54:16,215 --> 02:54:16,982
ENGAGING WITH PATIENT GROUPS IT 

3909
02:54:16,982 --> 02:54:17,750
SHOULD BE YOUR FIRST STOP.

3910
02:54:17,750 --> 02:54:20,052
WE WANT TO MAKE SURE YOU DESIGN 

3911
02:54:20,052 --> 02:54:24,490
THE TRIAL OUR PATIENTS ARE GOING

3912
02:54:24,490 --> 02:54:26,158
TO BE INTERESTED IN SO THAT 

3913
02:54:26,158 --> 02:54:27,560
THERE'S NO IMPEDIMENT WHETHER 

3914
02:54:27,560 --> 02:54:28,794
RECRUITMENT OR INTEREST.

3915
02:54:28,794 --> 02:54:32,264
IT'S IMPORTANT TO HAVE THOSE 

3916
02:54:32,264 --> 02:54:35,234
EARLY DISCUSSIONS.

3917
02:54:35,234 --> 02:54:37,169
AGAIN BECAUSE WE'RE TALKING 

3918
02:54:37,169 --> 02:54:41,407
ABOUT THIS NEW MORE INVASIVE 

3919
02:54:41,407 --> 02:54:44,276
TREATMENT I WENT TO OUR PARENT 

3920
02:54:44,276 --> 02:54:46,345
SUPPORT GROUP ON FACEBOOK AND 

3921
02:54:46,345 --> 02:54:48,314
ASKED PARENTS IF THEY'D MIND 

3922
02:54:48,314 --> 02:54:50,416
SHARING THEIR TRIAL EXPERIENCE 

3923
02:54:50,416 --> 02:54:52,618
TO HELP SHED LIGHT ON WHY THIS 

3924
02:54:52,618 --> 02:54:54,253
IS SUCH A BIG ASK ON OUR 

3925
02:54:54,253 --> 02:54:57,022
FAMILIES ON THE MONARCH STUDY.

3926
02:54:57,022 --> 02:54:58,824
WE HAVE AN OBLIGATION BEYOND NOT

3927
02:54:58,824 --> 02:55:02,495
JUST ENSURING SAFETY OF PATIENTS

3928
02:55:02,495 --> 02:55:03,529
DURING CLINICAL TRIALS BUT WHAT 

3929
02:55:03,529 --> 02:55:05,531
ELSE CAN WE DO TO HELP ALLEVIATE

3930
02:55:05,531 --> 02:55:06,999
THE BURDEN.

3931
02:55:06,999 --> 02:55:09,435
I HAVE A SERIOUSLY ILL CHILD IF 

3932
02:55:09,435 --> 02:55:13,038
YOU ASK THEM TO COME ACROSS THE 

3933
02:55:13,038 --> 02:55:14,440
COUNTRY THERE'S A LOT OF TRAVEL 

3934
02:55:14,440 --> 02:55:15,574
INVOLVED AND MOVING PIECES THAT 

3935
02:55:15,574 --> 02:55:18,677
MAKE IT HARD FOR FAMILIES TO 

3936
02:55:18,677 --> 02:55:19,011
PARTICIPATE.

3937
02:55:19,011 --> 02:55:21,580
I ASKED FOR PARTICIPANTS WHO 

3938
02:55:21,580 --> 02:55:22,815
RESPONDED BACK IF THEY'D BE 

3939
02:55:22,815 --> 02:55:28,554
WILLING TO SHARE RESPONSES TO 

3940
02:55:28,554 --> 02:55:30,856
INQUIR

3941
02:55:30,856 --> 02:55:32,291
INQUIRIES THAT WE HEAR TIME AND 

3942
02:55:32,291 --> 02:55:34,927
AGAIN FROM OTHERS IN THE TRIAL 

3943
02:55:34,927 --> 02:55:37,229
BECAUSE WE ANTICIPATE THERE WILL

3944
02:55:37,229 --> 02:55:39,098
LIKELY BE OTHER TRIALS DOWN THE 

3945
02:55:39,098 --> 02:55:42,401
PIPELINE WITH SIMILAR INVASIVE 

3946
02:55:42,401 --> 02:55:43,035
TREATMENT PROTOCOL AND WANT 

3947
02:55:43,035 --> 02:55:44,904
FAMILIES TO THINK ABOUT THAT AND

3948
02:55:44,904 --> 02:55:47,439
FIND THEIR COMFORT ZONE.

3949
02:55:47,439 --> 02:55:50,209
I WAS HOPING THE NEXT SLIDES 

3950
02:55:50,209 --> 02:55:51,677
HELP UNDER SCORE THE CRUCIAL 

3951
02:55:51,677 --> 02:55:53,546
CONSIDERATIONS AS WE MAKE 

3952
02:55:53,546 --> 02:55:55,447
PROGRESS TOWARDS THESE 

3953
02:55:55,447 --> 02:55:56,015
TRANSFORMATIVE TREATMENTS.

3954
02:55:56,015 --> 02:55:58,884
WHEN I ASK WHY A CAREGIVER 

3955
02:55:58,884 --> 02:56:00,286
DECIDED TO HAVE THEIR IT CHILD 

3956
02:56:00,286 --> 02:56:03,088
PARTICIPATE IN THE TRIAL I THINK

3957
02:56:03,088 --> 02:56:05,357
THE ANSWERS HIGHLIGHTED THE 

3958
02:56:05,357 --> 02:56:07,026
BURDEN AND LACK OF OPTIONS.

3959
02:56:07,026 --> 02:56:09,562
THE FAMILIES MENTIONED WANTING 

3960
02:56:09,562 --> 02:56:10,663
TO INCREASE THE OVERALL-QUALITY 

3961
02:56:10,663 --> 02:56:12,398
OF LIFE FOR THEIR CHILD AND FELT

3962
02:56:12,398 --> 02:56:15,034
THEY DIDN'T HAVE OTHER OPTIONS 

3963
02:56:15,034 --> 02:56:19,338
OR CHOICE THIS IS WILL ALL THAT 

3964
02:56:19,338 --> 02:56:20,906
WAS FOR AVAILABLE FOR THEM.

3965
02:56:20,906 --> 02:56:23,509
HERE YOU SEE QUOTES FROM 

3966
02:56:23,509 --> 02:56:25,611
FAMILIES WHEN I ASK WHAT TOP 

3967
02:56:25,611 --> 02:56:27,012
CONCERNS WERE AROUND CHILD 

3968
02:56:27,012 --> 02:56:27,379
PARTICIPATION.

3969
02:56:27,379 --> 02:56:33,152
THOUGH WE'RE TALKING ABOUT 

3970
02:56:33,152 --> 02:56:35,487
PRETTY INVASIVE MEASURES 

3971
02:56:35,487 --> 02:56:38,824
FAMILIES ARE STILL WILLING TO 

3972
02:56:38,824 --> 02:56:41,894
CONSIDER THEM AND HAIRING THE 

3973
02:56:41,894 --> 02:56:43,429
PROTOCOL DOESN'T MAKE THEM SAY 

3974
02:56:43,429 --> 02:56:47,933
YES OR NO BUT LOOKING AT HOW 

3975
02:56:47,933 --> 02:56:49,735
MUCH SUFFERING THEIR CHILD HAS 

3976
02:56:49,735 --> 02:56:51,070
AND IN PARTICULAR REGARDING 

3977
02:56:51,070 --> 02:56:54,240
THEIR PARTICIPATION IN STK001 I 

3978
02:56:54,240 --> 02:56:59,111
THINK YOU CAN SEE IT'S EF 

3979
02:56:59,111 --> 02:57:00,713
DEPARTMENT THEY'RE WILLING TO 

3980
02:57:00,713 --> 02:57:01,680
THINK ABOUT IT AND MOST ARE 

3981
02:57:01,680 --> 02:57:04,216
WILLING TO MOVE FORWARD WITH IT 

3982
02:57:04,216 --> 02:57:04,950
THOUGH THERE'S A LOT OF OUT 

3983
02:57:04,950 --> 02:57:09,355
THERE FOR THEM TO BE CONCERNED 

3984
02:57:09,355 --> 02:57:13,225
ABOUT NOT JUST UP TRIAL FOR THE 

3985
02:57:13,225 --> 02:57:14,827
INVASIVENESS OF THE 

3986
02:57:14,827 --> 02:57:15,194
ADMINISTRATION.

3987
02:57:15,194 --> 02:57:17,429
THERE'S AN EMOTIONAL AND 

3988
02:57:17,429 --> 02:57:20,366
PHYSICAL STRAIN AND RIGHT NOW 

3989
02:57:20,366 --> 02:57:21,834
UNFORESEEN LONG-TERM HEALTH 

3990
02:57:21,834 --> 02:57:22,835
IMPLICATIONS WE DON'T KNOW ABOUT

3991
02:57:22,835 --> 02:57:24,270
SO IT'S A BIG LEAP OF FAITH 

3992
02:57:24,270 --> 02:57:31,777
WE'RE ASKING THEM TO MAKE.

3993
02:57:31,777 --> 02:57:38,317
WHEN I ASK ABOUT THINGS THAT MAY

3994
02:57:38,317 --> 02:57:41,053
HAVE AFFECTED THEIR WILL 

3995
02:57:41,053 --> 02:57:41,754
PARTICIPATION AND THIS WOULD 

3996
02:57:41,754 --> 02:57:44,723
MAKE IT EASIER FOR FAMILIES.

3997
02:57:44,723 --> 02:57:46,425
CONDUCTING CLINICAL TRIAL FOR A 

3998
02:57:46,425 --> 02:57:48,327
RARE DISEASE HAS UNIQUE 

3999
02:57:48,327 --> 02:57:51,597
CHALLENGES LUKE I'D MENTIONED, 

4000
02:57:51,597 --> 02:57:53,365
TRAVELLING TO CARE TO TOP 

4001
02:57:53,365 --> 02:57:56,635
CLINICIANS OFTEN THE WILL TOP 

4002
02:57:56,635 --> 02:57:58,404
INVESTIGATORS IN THE TRIALS IS A

4003
02:57:58,404 --> 02:57:59,905
HEAVY BURDEN AND NOW WE'RE 

4004
02:57:59,905 --> 02:58:02,308
ASKING THEM TO DO EIGHT, NINE, 

4005
02:58:02,308 --> 02:58:03,542
10 VISITS IN A YEAR.

4006
02:58:03,542 --> 02:58:05,811
WE HAVE TO BE THOUGHTFUL AND 

4007
02:58:05,811 --> 02:58:07,479
EXPLORE EVERY OPPORTUNITY TO 

4008
02:58:07,479 --> 02:58:09,081
REDUCE THE BURDEN ON PATIENTS 

4009
02:58:09,081 --> 02:58:11,050
AND THEIR FAMILIES.

4010
02:58:11,050 --> 02:58:15,587
THESE CAN BE THINGS LIKE 

4011
02:58:15,587 --> 02:58:17,723
TELEHEALTH IS THERE ADDITIONAL 

4012
02:58:17,723 --> 02:58:23,362
TESTING LOCALLY THAN TRAVELLING 

4013
02:58:23,362 --> 02:58:25,164
AND WE HAVE TO BE CREATIVE.

4014
02:58:25,164 --> 02:58:26,332
AS WE'RE TALKING ABOUT NEW 

4015
02:58:26,332 --> 02:58:30,436
TREATMENTS WE HAVE TO REALIZE 

4016
02:58:30,436 --> 02:58:31,270
SOME THINGS THAT WORKED FOR 

4017
02:58:31,270 --> 02:58:33,205
TRIALS IN THE PAST IT WILL BE 

4018
02:58:33,205 --> 02:58:34,807
MORE DIFFICULT IN THE SITUATION 

4019
02:58:34,807 --> 02:58:36,709
AND WE HAVE TO BE FLEXIBLE AND 

4020
02:58:36,709 --> 02:58:38,711
DO WHAT'S RIGHT FOR THE PATIENT 

4021
02:58:38,711 --> 02:58:39,044
FAMILIES.

4022
02:58:39,044 --> 02:58:40,412
WE OWE THAT TO THEM.

4023
02:58:40,412 --> 02:58:43,549
AND HEALTH DISPARITIES WILL 

4024
02:58:43,549 --> 02:58:48,253
PRESENT ANOTHER LAYER OF 

4025
02:58:48,253 --> 02:58:48,554
COMPLEXITY.

4026
02:58:48,554 --> 02:58:51,256
THE FAMILIES PARTICIPATED AND 

4027
02:58:51,256 --> 02:58:54,960
NOT JUST STK001 HAVE A CERTAIN 

4028
02:58:54,960 --> 02:58:57,529
LEVEL OF PRIVILEGE TO BE ABLE TO

4029
02:58:57,529 --> 02:58:59,131
PARTICIPATE AND WE NEED TO 

4030
02:58:59,131 --> 02:59:00,265
ADDRESS THE BROADER SYSTEMIC 

4031
02:59:00,265 --> 02:59:02,167
ISSUES TO MAKE SURE WE HAVE 

4032
02:59:02,167 --> 02:59:03,202
EQUITABLE ACCESS.

4033
02:59:03,202 --> 02:59:06,472
I WOULD HATE TO THINK THERE WILL

4034
02:59:06,472 --> 02:59:08,273
BE A LIFE CHANGING MEDICINE AND 

4035
02:59:08,273 --> 02:59:10,409
THEY WON'T BE ABLE TO ACCESS IT 

4036
02:59:10,409 --> 02:59:15,748
BECAUSE OF THAT.

4037
02:59:15,748 --> 02:59:17,116
HERE'S WHERE WE ASK ABOUT FUTURE

4038
02:59:17,116 --> 02:59:18,117
TRIAL PARTICIPATION.

4039
02:59:18,117 --> 02:59:20,953
THIS IS BECOMING SCARY BECAUSE 

4040
02:59:20,953 --> 02:59:24,223
IF WE FOLLOW THE STANDARD 

4041
02:59:24,223 --> 02:59:29,128
PROTOCOL WITH THE FDA LIKELY 

4042
02:59:29,128 --> 02:59:30,996
WE'LL HAVE TO -- SORRY, I WENT 

4043
02:59:30,996 --> 02:59:32,264
OFF TOPIC.

4044
02:59:32,264 --> 02:59:34,433
SO WE KNOW WHEN OUR FAMILIES 

4045
02:59:34,433 --> 02:59:37,403
TRAVEL IF WE CAN PREVENT THESE 

4046
02:59:37,403 --> 02:59:38,971
PROLONGED STAYS OVERNIGHT 

4047
02:59:38,971 --> 02:59:40,072
AFFECTING NOT ONLY HAVING THE 

4048
02:59:40,072 --> 02:59:42,207
PATIENT THERE AND TRYING TO KEEP

4049
02:59:42,207 --> 02:59:44,343
THEM ENTERTAINED OUTSIDE THEIR 

4050
02:59:44,343 --> 02:59:46,612
HOME ENVIRONMENT BUT IT AFFECTS 

4051
02:59:46,612 --> 02:59:49,782
CARE CAN GIVER WORK SCHEDULES 

4052
02:59:49,782 --> 02:59:55,521
AND SIBLINGS' SCHEDULES.

4053
02:59:55,521 --> 02:59:57,589
AND FAMILIES ARE CHALLENGED WHEN

4054
02:59:57,589 --> 02:59:58,924
THEY'RE OUT OF THEIR HOME 

4055
02:59:58,924 --> 02:59:59,892
ENVIRONMENT OR IF THEY HAVE TO 

4056
02:59:59,892 --> 03:00:00,926
FAST FOR A PERIOD OF TIME.

4057
03:00:00,926 --> 03:00:03,228
WE NEED TO THINK HOW TO MAKE 

4058
03:00:03,228 --> 03:00:04,396
THIS EASIER FOR OUR PATIENT 

4059
03:00:04,396 --> 03:00:09,668
FAMILIES GOING FORWARD.

4060
03:00:09,668 --> 03:00:11,503
AND THIS IS A LOT BUT I THINK WE

4061
03:00:11,503 --> 03:00:16,175
ALSO NEED TO THINK ABOUT IF 

4062
03:00:16,175 --> 03:00:16,909
THERE ARE PLACEBO ARMS IN THESE 

4063
03:00:16,909 --> 03:00:18,744
TRIALS AGAIN IT'S NOT TAKING A 

4064
03:00:18,744 --> 03:00:19,378
PILL.

4065
03:00:19,378 --> 03:00:21,013
WE'RE ASKING FOR PRETTY INVASIVE

4066
03:00:21,013 --> 03:00:22,614
THINGS TO BE DONE WITH THE 

4067
03:00:22,614 --> 03:00:23,782
POTENTIAL YOUR CHILD IS NOT 

4068
03:00:23,782 --> 03:00:24,850
GETTING THE MEDICATION.

4069
03:00:24,850 --> 03:00:26,685
IT'S BEEN A CONVERSATION GOING 

4070
03:00:26,685 --> 03:00:27,886
ON IN OUR COMMUNITY.

4071
03:00:27,886 --> 03:00:30,989
YOU CAN SEE WE HAVE PEOPLE FROM 

4072
03:00:30,989 --> 03:00:32,558
THE QUOTES ON BOTH SIDES THAT 

4073
03:00:32,558 --> 03:00:35,561
WOULD NOT PARTICIPATE BECAUSE 

4074
03:00:35,561 --> 03:00:37,129
THEY FEEL THEY'RE ALREADY 

4075
03:00:37,129 --> 03:00:37,963
PUTTING THE PATIENT SO MUCH AND 

4076
03:00:37,963 --> 03:00:39,064
OTHERS ARE WILLING TO GO THROUGH

4077
03:00:39,064 --> 03:00:40,265
IT TO GET MEDICATION BECAUSE OF 

4078
03:00:40,265 --> 03:00:41,467
THE QUALITY OF LIFE FOR THEIR 

4079
03:00:41,467 --> 03:00:47,606
CHILD IS SO TERRIBLE.

4080
03:00:47,606 --> 03:00:50,776
WE HAVE TO THINK ABOUT THIS AND 

4081
03:00:50,776 --> 03:00:52,277
NOT EXPLOIT A CAREGIVER'S 

4082
03:00:52,277 --> 03:00:55,948
DESPERATION AND WHAT ARE THE 

4083
03:00:55,948 --> 03:00:56,548
ETHICAL IMPLICATIONS OF THE 

4084
03:00:56,548 --> 03:00:58,383
TRIAL DESIGN AND REMAIN 

4085
03:00:58,383 --> 03:00:59,985
ALIGNMENT WITH THE FDA 

4086
03:00:59,985 --> 03:01:01,720
EXPECTATIONS BUT IS THERE AN 

4087
03:01:01,720 --> 03:01:03,956
OPPORTUNITY TO WORK WITH PATIENT

4088
03:01:03,956 --> 03:01:04,857
ADVOCACY GROUPS TO BETTER 

4089
03:01:04,857 --> 03:01:06,258
UNDERSTAND THE CHALLENGES FOR 

4090
03:01:06,258 --> 03:01:07,793
OUR COMMUNITY AND PHARMACEUTICAL

4091
03:01:07,793 --> 03:01:09,394
COMPANIES AND WE CONSIDER ARE WE

4092
03:01:09,394 --> 03:01:10,963
ABLE TO APPROACH THIS IN A 

4093
03:01:10,963 --> 03:01:12,464
DIFFERENT WAY TO ACCOMMODATE THE

4094
03:01:12,464 --> 03:01:13,799
NEW TREATMENTS.

4095
03:01:13,799 --> 03:01:15,734
THIS COULD INVOLVE REFRAMING 

4096
03:01:15,734 --> 03:01:18,203
PREVIOUS STANDARDS TO MAKE IT 

4097
03:01:18,203 --> 03:01:19,805
EASIER FOR PATIENT 

4098
03:01:19,805 --> 03:01:20,339
PARTICIPATION.

4099
03:01:20,339 --> 03:01:24,276
CAN WE USE NATURAL HISTORY DATA 

4100
03:01:24,276 --> 03:01:26,478
OR KNOWN DISEASE RISK IN THE 

4101
03:01:26,478 --> 03:01:28,413
REASSESSMENT INSTEAD OF PLACEBO 

4102
03:01:28,413 --> 03:01:28,714
GROUPS?

4103
03:01:28,714 --> 03:01:31,350
WHEN WE TALK ABOUT SCIENTIFIC 

4104
03:01:31,350 --> 03:01:32,351
INTEGRITY IT NEEDS TO BE 

4105
03:01:32,351 --> 03:01:34,453
BALANCED WITH TO THE BURDEN 

4106
03:01:34,453 --> 03:01:35,220
WE'RE PUTTING ON THE CAREGIVERS 

4107
03:01:35,220 --> 03:01:39,291
AND PATIENTS.

4108
03:01:39,291 --> 03:01:40,792
AND A COUPLE CONSIDERATIONS.

4109
03:01:40,792 --> 03:01:43,662
I KNOW I'M OVER TIME I'LL SKIM 

4110
03:01:43,662 --> 03:01:44,496
THROUGH THESE QUICK.

4111
03:01:44,496 --> 03:01:45,831
OUR GROUPS STILL NEED TO DO OUR 

4112
03:01:45,831 --> 03:01:46,165
PART.

4113
03:01:46,165 --> 03:01:48,333
SO WE NEED TO WORK ON DOING 

4114
03:01:48,333 --> 03:01:52,404
EARLY DIAGNOSIS, MAKING SURE OUR

4115
03:01:52,404 --> 03:01:55,607
PATIENTS GET ACCESS TO CARE AND 

4116
03:01:55,607 --> 03:01:56,542
ADDRESSING THE IT WILL PAYER 

4117
03:01:56,542 --> 03:01:58,310
ISSUES WHEN WE TALK ABOUT NEW 

4118
03:01:58,310 --> 03:01:59,411
TREATMENTS AND WE DON'T 

4119
03:01:59,411 --> 03:02:00,045
UNDERSTAND WHAT THE RESPONSE 

4120
03:02:00,045 --> 03:02:01,446
WILL BE FOR PAYERS.

4121
03:02:01,446 --> 03:02:02,147
THAT'S SOMETHING HIGH ON OUR 

4122
03:02:02,147 --> 03:02:11,890
PRIORITY LIST.

4123
03:02:11,890 --> 03:02:15,027
THOUGH THE TREATMENTS ARE 

4124
03:02:15,027 --> 03:02:16,195
EXCITING THERE'LL BE CRUCIAL 

4125
03:02:16,195 --> 03:02:17,429
SUPPORT FOR FAMILIES BECAUSE NOT

4126
03:02:17,429 --> 03:02:19,064
EVERY PATIENT WILL RESPOND 

4127
03:02:19,064 --> 03:02:20,933
OPTIMALLY AND SOME MAY STILL 

4128
03:02:20,933 --> 03:02:22,334
EXPERIENCE DISEASE BURDEN IF 

4129
03:02:22,334 --> 03:02:23,068
THEY DO RESPOND.

4130
03:02:23,068 --> 03:02:26,205
WE NEED TO BE THINKING ABOUT 

4131
03:02:26,205 --> 03:02:28,006
THIS, ACKNOWLEDGING THE 

4132
03:02:28,006 --> 03:02:29,474
POTENTIAL OUTCOME AND ENSURING 

4133
03:02:29,474 --> 03:02:31,176
WE HAVE CONTINUAL SUPPORT 

4134
03:02:31,176 --> 03:02:32,277
SERVICES AVAILABLE TO HELP OUR 

4135
03:02:32,277 --> 03:02:34,580
COMMUNITY REGARDLESS OF WHERE 

4136
03:02:34,580 --> 03:02:35,214
THEY ARE THROUGHOUT THEIR 

4137
03:02:35,214 --> 03:02:40,953
TREATMENT JOURNEY.

4138
03:02:40,953 --> 03:02:51,463
HAPPY TO ANSWER ANY QUESTIONS.

4139
03:02:57,436 --> 03:02:58,437
>> THANK YOU, MARY ANN.

4140
03:02:58,437 --> 03:03:06,545
MANY DOES ANYONE HAVE ONE QUICK 

4141
03:03:06,545 --> 03:03:06,812
QUESTION.

4142
03:03:06,812 --> 03:03:07,446
OKAY, THANK YOU FOR JOINING US.

4143
03:03:07,446 --> 03:03:09,581
>> THANK YOU.

4144
03:03:09,581 --> 03:03:14,353
SO MOVING ON THE NEXT SPEAKER IS

4145
03:03:14,353 --> 03:03:16,722
MELANIE QUINTANA FROM BERRY 

4146
03:03:16,722 --> 03:03:20,959
CONSULTANTS WHO IS GOING TO TALK

4147
03:03:20,959 --> 03:03:22,894
ABOUT INFORMED AND EFFICIENT 

4148
03:03:22,894 --> 03:03:23,462
CLINICAL TRIAL DESIGN USING 

4149
03:03:23,462 --> 03:03:33,739
NATURAL HISTORY.

4150
03:03:38,043 --> 03:03:41,046
>> THANK YOU ALL FOR
INVITING ME

4151
03:03:41,046 --> 03:03:44,116
TO TALK TODAY AND I'M GOING TO 

4152
03:03:44,116 --> 03:03:45,851
SWITCH GEARS AND TALK ABOUT WILL

4153
03:03:45,851 --> 03:03:46,852
STATISTICAL SCIENCE AND HOPE TO 

4154
03:03:46,852 --> 03:03:47,786
EXCITE YOU WITH STATISTICS AFTER

4155
03:03:47,786 --> 03:03:51,123
LUNCH.

4156
03:03:51,123 --> 03:03:53,959
IN PARTICULAR I'M GOING TO TALK 

4157
03:03:53,959 --> 03:03:57,162
BASED ON MY EXPERIENCE IN 

4158
03:03:57,162 --> 03:03:58,130
DESIGNING CLINICAL TRIALS FOR 

4159
03:03:58,130 --> 03:03:59,564
RARE GENETIC DISEASES.

4160
03:03:59,564 --> 03:04:01,933
OFTEN MANY OF THESE ARE IN 

4161
03:04:01,933 --> 03:04:03,635
ADULTS BUT SOME IN PEDIATRICS AS

4162
03:04:03,635 --> 03:04:03,969
WELL.

4163
03:04:03,969 --> 03:04:05,404
TWO CASE STUDIES I WANT TO TALK 

4164
03:04:05,404 --> 03:04:08,640
ABOUT IS DESIGNING CLINICAL 

4165
03:04:08,640 --> 03:04:10,842
TRIALS IN FAMILIAL FRONTAL 

4166
03:04:10,842 --> 03:04:14,713
TEMPORAL DEMENTIA MOST ARE 

4167
03:04:14,713 --> 03:04:15,647
FAMILIAR WITH AND ALSO 

4168
03:04:15,647 --> 03:04:18,016
EXPERIENCE IN DEVELOPING A 

4169
03:04:18,016 --> 03:04:19,751
CLINICAL TRIAL FOR A DISEASE 

4170
03:04:19,751 --> 03:04:22,454
CALLED GNE MYOPATHY.

4171
03:04:22,454 --> 03:04:26,091
A RARE GENETIC MUSCLE DISEASE.

4172
03:04:26,091 --> 03:04:27,492
SOME COMMON THEMES FOR THE 

4173
03:04:27,492 --> 03:04:28,393
COMPLEXITIES IN DESIGNING 

4174
03:04:28,393 --> 03:04:29,928
CLINICAL TRIALS FOR RARE 

4175
03:04:29,928 --> 03:04:33,065
DISEASES AS ALL OF YOU ARE AWARE

4176
03:04:33,065 --> 03:04:35,834
THERE'S A GREAT AMOUNT OF 

4177
03:04:35,834 --> 03:04:38,270
HETEROGENEITY IN PROGRESSION AND

4178
03:04:38,270 --> 03:04:40,272
DIFFERENT END POINTS TEND TO BE 

4179
03:04:40,272 --> 03:04:41,640
AFFECTED AT DIFFERENT STAGES IN 

4180
03:04:41,640 --> 03:04:44,076
THE DISEASE AND COMMON SOLUTIONS

4181
03:04:44,076 --> 03:04:52,284
TO THIS IS TO WILL ENROLL ONE 

4182
03:04:52,284 --> 03:04:54,619
HOMOGENOUS SUBSET AND BOTH ARE 

4183
03:04:54,619 --> 03:04:56,254
NOT IDEAL IN THE RARE DISEASE 

4184
03:04:56,254 --> 03:04:57,656
SETTING FOR GENE THERAPIES.

4185
03:04:57,656 --> 03:05:00,092
WE DON'T WANT TO MAKE A RARE 

4186
03:05:00,092 --> 03:05:01,693
DISEASE BY MORE RARE BY ONLY 

4187
03:05:01,693 --> 03:05:04,262
ENROLLING A SUBSET AND OFTEN 

4188
03:05:04,262 --> 03:05:05,464
TIMES THE SAMPLE SIZE NEEDED IS 

4189
03:05:05,464 --> 03:05:09,568
NOT FEASIBLE.

4190
03:05:09,568 --> 03:05:11,670
SO SOME SOLUTIONS I'LL TALK 

4191
03:05:11,670 --> 03:05:12,604
ABOUT THAT WERE COMMON BETWEEN 

4192
03:05:12,604 --> 03:05:15,941
THE TWO TYPES OF DISEASES WHEN 

4193
03:05:15,941 --> 03:05:16,908
WE WERE DESIGNING CLINICAL 

4194
03:05:16,908 --> 03:05:19,644
TRIALS ARE A, NATURAL HISTORY 

4195
03:05:19,644 --> 03:05:23,081
DATA AND DEVELOPING DISEASE 

4196
03:05:23,081 --> 03:05:24,182
PROGRESSION MODEL WITHIN THE 

4197
03:05:24,182 --> 03:05:26,351
NATURAL DATA TO KNOW WHAT YOU'RE

4198
03:05:26,351 --> 03:05:27,486
WORKING WITH.

4199
03:05:27,486 --> 03:05:29,621
KNOW IF THE DESIGN YOU'RE 

4200
03:05:29,621 --> 03:05:30,622
PROPOSING IS POWERED.

4201
03:05:30,622 --> 03:05:33,091
WHAT ARE THE RIGHT END POINTS, 

4202
03:05:33,091 --> 03:05:36,161
HOW DO THEY MEET AND SYNERGY 

4203
03:05:36,161 --> 03:05:38,630
WITH ONE ANOTHER AND NATURAL 

4204
03:05:38,630 --> 03:05:39,998
HISTORY IS INVALUABLE IN 

4205
03:05:39,998 --> 03:05:41,233
DESIGNING CLINICAL TRIAL FOR 

4206
03:05:41,233 --> 03:05:41,566
RARE DISEASE.

4207
03:05:41,566 --> 03:05:45,437
THE OTHER COMMON THEME IS MORE 

4208
03:05:45,437 --> 03:05:45,971
INNOVATIVE DESIGN.

4209
03:05:45,971 --> 03:05:47,639
MORE POWERFUL ANALYSIS METHODS 

4210
03:05:47,639 --> 03:05:49,908
THAT MAKE USE OF ALL THE DATA 

4211
03:05:49,908 --> 03:05:51,910
AVAILABLE AND COLLECTED THROUGH 

4212
03:05:51,910 --> 03:05:54,212
THE CLINICAL TRIAL USING 

4213
03:05:54,212 --> 03:05:55,213
ADAPTIVE DESIGN TO STOP EARLY 

4214
03:05:55,213 --> 03:05:57,783
FOR SUCCESS OR FUTILITY AND ALSO

4215
03:05:57,783 --> 03:06:07,492
MAKE USE OF OTHER DATA SOURCES 

4216
03:06:07,492 --> 03:06:09,361
OR DOING WILL PLATFORM TRIALS 

4217
03:06:09,361 --> 03:06:11,196
WHERE YOU CAN BORROW INFORMATION

4218
03:06:11,196 --> 03:06:12,197
ACROSS DIFFERENT INTERVENTIONS 

4219
03:06:12,197 --> 03:06:16,001
THAT ARE BEING TESTED.

4220
03:06:16,001 --> 03:06:17,836
I'M GOING TALK VERY SPECIFICALLY

4221
03:06:17,836 --> 03:06:22,808
ABOUT MY WORK IN DEVELOPING 

4222
03:06:22,808 --> 03:06:24,843
CLINICAL TRIALS FOR FAMILIAL 

4223
03:06:24,843 --> 03:06:25,010
FTD.

4224
03:06:25,010 --> 03:06:30,949
I WAS UNFORTUNATE ENOUGH TO WORK

4225
03:06:30,949 --> 03:06:31,683
WITH COLLABORATORS WITH A 

4226
03:06:31,683 --> 03:06:37,122
NATURAL HISTORY STUDY AND 

4227
03:06:37,122 --> 03:06:38,290
COLLABORATORS IN EUROPE WITH THE

4228
03:06:38,290 --> 03:06:40,892
IT GENFI STUDY AND PUT THEM 

4229
03:06:40,892 --> 03:06:44,262
TOGETHER TO HAVE A WEALTH OF 

4230
03:06:44,262 --> 03:06:46,965
INFORMATION ON FAMILIAL FTD.

4231
03:06:46,965 --> 03:06:49,768
WE HAVE INFORMATION ON THREE 

4232
03:06:49,768 --> 03:06:54,306
GENETIC MUTATIONS, C9, GRN AND 

4233
03:06:54,306 --> 03:06:57,609
MAPT AND HEALTHY CONTROLS IN 

4234
03:06:57,609 --> 03:06:57,843
YELLOW.

4235
03:06:57,843 --> 03:06:59,077
ALONG WITH THE END POINTS.

4236
03:06:59,077 --> 03:07:02,481
WE HAVE WHAT TENDS TO BE THE 

4237
03:07:02,481 --> 03:07:05,250
PRIMARY CLINIC OUTCOME MEASURE 

4238
03:07:05,250 --> 03:07:10,422
WHICH IS THE FTDRDR AND WE HAVE 

4239
03:07:10,422 --> 03:07:12,891
DIFFERENT IT NEUROPSYCH MEASURES

4240
03:07:12,891 --> 03:07:15,794
AND MRI MEASURES AND FLUID 

4241
03:07:15,794 --> 03:07:16,428
BIOMARKERS AND WE HAVE PRIOR 

4242
03:07:16,428 --> 03:07:18,663
YEARS OF ONSET.

4243
03:07:18,663 --> 03:07:21,399
OUR PRIOR BELIEF WHEN SOMEONE 

4244
03:07:21,399 --> 03:07:24,369
WILL HAVE CLINICAL ONSET OR WHEN

4245
03:07:24,369 --> 03:07:25,537
THEY DID.

4246
03:07:25,537 --> 03:07:28,340
IF SOMEONE STARTED OR HAD 

4247
03:07:28,340 --> 03:07:31,076
SYMPTOMS IT'S BASICALLY WHEN THE

4248
03:07:31,076 --> 03:07:33,545
PATIENT RECALLS THEIR FIRST 

4249
03:07:33,545 --> 03:07:33,778
SYMPTOM.

4250
03:07:33,778 --> 03:07:35,380
IT NOT THE AVERAGE AGE OF ONSET 

4251
03:07:35,380 --> 03:07:36,648
FOR THAT MUTATION.

4252
03:07:36,648 --> 03:07:42,120
HERE'S SOME THOUGHTS OF SOME 

4253
03:07:42,120 --> 03:07:44,256
DATA WE HAVE AND THE END POINTS 

4254
03:07:44,256 --> 03:07:46,157
FOR ALL THE MUTATIONS AT 

4255
03:07:46,157 --> 03:07:47,192
CLINICAL ONSET.

4256
03:07:47,192 --> 03:07:49,861
WE HAVE THIS RAPID PROGRESSION 

4257
03:07:49,861 --> 03:07:53,231
IN THE END POINT.

4258
03:07:53,231 --> 03:07:58,370
BELOW THAT IS NFL YOU SEE THE 

4259
03:07:58,370 --> 03:08:02,307
SMALL INCREASE IN AGING THAT IS 

4260
03:08:02,307 --> 03:08:04,209
NORMAL AND THE RAPID INCREASE 

4261
03:08:04,209 --> 03:08:08,079
SIMILAR TO CLINICAL ONSET.

4262
03:08:08,079 --> 03:08:10,715
SO OUR GOAL OF DISEASE 

4263
03:08:10,715 --> 03:08:12,250
PROGRESSION MODELLING IS TO TWO 

4264
03:08:12,250 --> 03:08:12,751
DO THINGS.

4265
03:08:12,751 --> 03:08:15,353
ONE IS TO TAKE ALL THE 

4266
03:08:15,353 --> 03:08:16,087
INDIVIDUAL SNAPSHOTS OF THE 

4267
03:08:16,087 --> 03:08:19,190
DISEASE FROM ALL OF THE 

4268
03:08:19,190 --> 03:08:21,826
DIFFERENT PARTICIPANT AND TAKE 

4269
03:08:21,826 --> 03:08:23,128
THE PUZZLE AND PUT THE PIECES 

4270
03:08:23,128 --> 03:08:24,529
TOGETHER TO ALIGN THEM ALL IN 

4271
03:08:24,529 --> 03:08:27,699
WHAT WE CALL DISEASE AGE OR 

4272
03:08:27,699 --> 03:08:29,367
DISEASE STAGE AND ONCE ALIGNED 

4273
03:08:29,367 --> 03:08:31,403
PUT THEM TOGETHER AND CAN 

4274
03:08:31,403 --> 03:08:33,405
ESTIMATE HOW THE END POINTS MOVE

4275
03:08:33,405 --> 03:08:34,906
IN RELATION TO ONE ANOTHER.

4276
03:08:34,906 --> 03:08:39,311
ON THE TOP IT YOU CAN NOW WE'VE 

4277
03:08:39,311 --> 03:08:42,747
ALIGNED PEOPLE BASED ON OUR 

4278
03:08:42,747 --> 03:08:43,515
POSTERIOR WILL ESTIMATE IN WHERE

4279
03:08:43,515 --> 03:08:45,383
THEY ARE IN THEIR DISEASE AND 

4280
03:08:45,383 --> 03:08:50,455
SEE A MORE CLEAN PATTERN OF 

4281
03:08:50,455 --> 03:08:53,191
PROGRESSION THE MUTATION 

4282
03:08:53,191 --> 03:08:55,727
CARRIERS TEND TO PROGRESS 

4283
03:08:55,727 --> 03:08:58,396
RAPIDLY AND C9 AFTER BUT THE 

4284
03:08:58,396 --> 03:09:00,165
BOTTOM PICTURE GOT A LITTLE BIT 

4285
03:09:00,165 --> 03:09:02,100
MESSED UP BUT THIS IS ALSO THE 

4286
03:09:02,100 --> 03:09:03,001
PICTURE OF NFL.

4287
03:09:03,001 --> 03:09:08,807
YOU CAN SEE THE MOST RAPID 

4288
03:09:08,807 --> 03:09:12,277
INCREASE IN THE GRN PARTICIPANTS

4289
03:09:12,277 --> 03:09:20,719
AND THE OTHER PIECE.

4290
03:09:20,719 --> 03:09:26,291
AND ESTIMATING THE SURVEYS SHOWS

4291
03:09:26,291 --> 03:09:28,193
END POINTS TO UNDERSTAND HOW 

4292
03:09:28,193 --> 03:09:31,563
THEY MOVE IN SYNERGY AND WHAT 

4293
03:09:31,563 --> 03:09:35,834
END POINTS MAY START TO LOOK 

4294
03:09:35,834 --> 03:09:37,035
ABNORMAL IN THE DISEASE COURSE 

4295
03:09:37,035 --> 03:09:38,503
BEFORE CLINICAL SYSTEMS AND WITH

4296
03:09:38,503 --> 03:09:42,207
THE GRN PARTICIPANTS NFL STARTS 

4297
03:09:42,207 --> 03:09:51,750
TO RISE EVEN 10 YEARS PRIOR TO 

4298
03:09:51,750 --> 03:09:53,952
CLINICAL ONSET AND THE FRONTAL 

4299
03:09:53,952 --> 03:09:56,921
REGION AND GRN AND THE C9 

4300
03:09:56,921 --> 03:09:59,290
PICTURES ARE SIMILAR TO NFL AND 

4301
03:09:59,290 --> 03:10:01,860
MRI START TO LOOK ABNORMAL EVEN 

4302
03:10:01,860 --> 03:10:04,663
20 YEARS PRIOR TO CLINICAL 

4303
03:10:04,663 --> 03:10:04,863
ONSET.

4304
03:10:04,863 --> 03:10:08,500
WITH MAPT YOU DON'T SEE THE NFL 

4305
03:10:08,500 --> 03:10:10,669
RISE AS MUCH PRIOR TO ONSET BUT 

4306
03:10:10,669 --> 03:10:13,371
TEND TO SEE THE NPL REGION IN 

4307
03:10:13,371 --> 03:10:13,938
PARTICULAR START TO ATROPHY 

4308
03:10:13,938 --> 03:10:18,643
EARLY ON.

4309
03:10:18,643 --> 03:10:20,412
SO GREAT A GREAT PUBLICATION OUT

4310
03:10:20,412 --> 03:10:22,247
IN NATURE TALKING ABOUT THE 

4311
03:10:22,247 --> 03:10:23,848
DISEASE PROGRESSION MODELS.

4312
03:10:23,848 --> 03:10:26,951
I ENCOURAGE YOU TO READ THAT IF 

4313
03:10:26,951 --> 03:10:27,952
YOU'RE INTERESTED.

4314
03:10:27,952 --> 03:10:30,822
WHAT I WANT TO TALK ABOUT MORE 

4315
03:10:30,822 --> 03:10:34,592
IS HOW WE USE THE PROGRESSION 

4316
03:10:34,592 --> 03:10:35,794
MODELS TO DESIGN MORE CLINICAL 

4317
03:10:35,794 --> 03:10:36,661
TRIALS IN THREE WAYS.

4318
03:10:36,661 --> 03:10:39,798
ONE IS TO USE THE MODELS OR 

4319
03:10:39,798 --> 03:10:44,002
CONCEPT OF DISEASE STAGING TO 

4320
03:10:44,002 --> 03:10:45,937
LOOK AT INDIVIDUALS LIKELY TO 

4321
03:10:45,937 --> 03:10:47,138
PROGRESS OVER THE COURSE OF THE 

4322
03:10:47,138 --> 03:10:47,372
DISEASE.

4323
03:10:47,372 --> 03:10:50,842
WE CAN USE THE MODELS TO DO 

4324
03:10:50,842 --> 03:10:52,277
REALISTIC MODEL BASED SIMULATION

4325
03:10:52,277 --> 03:10:54,479
TO UNDERSTAND THE OPERATING 

4326
03:10:54,479 --> 03:10:56,181
CHARACTERISTICS OF OUR PROPOSED 

4327
03:10:56,181 --> 03:10:57,649
CLINICAL TRIAL AND FINALLY USING

4328
03:10:57,649 --> 03:10:59,818
THEM OR THE MODELLING FRAMEWORK 

4329
03:10:59,818 --> 03:11:00,351
TO DEVELOP MORE POWERFUL 

4330
03:11:00,351 --> 03:11:03,655
ANALYSIS TOOLS.

4331
03:11:03,655 --> 03:11:05,957
SO FIRST FOR USING AS A TARGETED

4332
03:11:05,957 --> 03:11:08,259
ENROLLMENT TOOL AS I THINK MOST 

4333
03:11:08,259 --> 03:11:10,161
ARE FAMILIAR AND WE TALKED A 

4334
03:11:10,161 --> 03:11:13,098
LITTLE BIT ABOUT TODAY EARLIER 

4335
03:11:13,098 --> 03:11:14,866
ON IT'S IMPORTANT TO FIND THE 

4336
03:11:14,866 --> 03:11:15,934
ENROLLMENT CRITERIA.

4337
03:11:15,934 --> 03:11:18,937
IF WE ENROLL INDIVIDUALS TOO 

4338
03:11:18,937 --> 03:11:21,005
EARLY BEFORE THEY START TO 

4339
03:11:21,005 --> 03:11:22,373
CLINICALLY MANIFEST WE WOULD 

4340
03:11:22,373 --> 03:11:24,642
HAVE NO POWER OR TOO LATE THE 

4341
03:11:24,642 --> 03:11:26,044
TREATMENTS MAY NOT BE AS 

4342
03:11:26,044 --> 03:11:26,311
EFFECTIVE.

4343
03:11:26,311 --> 03:11:29,180
WE WANT TO TRY TO ENROLL 

4344
03:11:29,180 --> 03:11:30,648
PARTICIPANTS IN THE SWEET SPOT 

4345
03:11:30,648 --> 03:11:33,852
WHERE MAYBE WE BELIEVE THEY'LL 

4346
03:11:33,852 --> 03:11:34,753
PROGRESS ON CLINICAL END POINTS 

4347
03:11:34,753 --> 03:11:36,254
DURING THE COURSE OF THE TRIAL 

4348
03:11:36,254 --> 03:11:43,461
BUT WELL LIKELY STILL BENEFIT.

4349
03:11:43,461 --> 03:11:47,632
AND WE CAN TAKE OBSERVED VALUES 

4350
03:11:47,632 --> 03:11:50,835
ON DIFFERENT MEASURES WHEN A 

4351
03:11:50,835 --> 03:11:53,037
PATIENT WALKS IN THE DOOR.

4352
03:11:53,037 --> 03:11:57,208
SAY A PATIENT HAS GRN MUTATION 

4353
03:11:57,208 --> 03:12:01,045
AND HAVE NO EVIDENCE OF CLINICAL

4354
03:12:01,045 --> 03:12:04,482
SYMPTOM AND THEIR MLI FRONTAL 

4355
03:12:04,482 --> 03:12:07,752
REGION IS ATROPHIED.

4356
03:12:07,752 --> 03:12:10,488
THEIR NFL IS TWO STANDARD 

4357
03:12:10,488 --> 03:12:11,990
DEVIATIONS ABOVE CONTROL AND 

4358
03:12:11,990 --> 03:12:13,258
TAKE THAT TOGETHER WITH WHAT WE 

4359
03:12:13,258 --> 03:12:15,827
KNOW ABOUT THE DISEASE AND 

4360
03:12:15,827 --> 03:12:17,428
LEARNED ABOUT THE DISEASE IN THE

4361
03:12:17,428 --> 03:12:19,497
PROGRESSION MODEL TO TRY TO 

4362
03:12:19,497 --> 03:12:20,265
ESTIMATE WHERE WE THINK THE 

4363
03:12:20,265 --> 03:12:22,400
PARTICIPANT IS IN TERMS OF THEIR

4364
03:12:22,400 --> 03:12:23,935
DISEASE SPECTRUM.

4365
03:12:23,935 --> 03:12:26,337
HERE'S THAT DATA THE BIG DOTS 

4366
03:12:26,337 --> 03:12:28,373
ARE THE BASELINE VALUES THAT I 

4367
03:12:28,373 --> 03:12:30,809
MENTIONED AND SO WE CAN JUST USE

4368
03:12:30,809 --> 03:12:33,478
THOSE BASELINE VALUES OR VALUES 

4369
03:12:33,478 --> 03:12:35,446
AT SCREENING TO TRY TO SEE WHERE

4370
03:12:35,446 --> 03:12:36,247
THEY FIT IN THE CURVE.

4371
03:12:36,247 --> 03:12:41,085
SO THIS IS AN EXAMPLE OF AN 

4372
03:12:41,085 --> 03:12:42,287
INDIVIDUAL WHERE.

4373
03:12:42,287 --> 03:12:44,255
WE WOULD PREDICT TWO YEARS FROM 

4374
03:12:44,255 --> 03:12:47,625
CLINICAL ONSET AND WHAT WE CAN 

4375
03:12:47,625 --> 03:12:51,996
THEN OBSERVE THEREAFTER IS THEY 

4376
03:12:51,996 --> 03:12:53,898
STILL REMAIN WITH NO CLINICAL 

4377
03:12:53,898 --> 03:12:55,333
ONSET UP TO THREE YEARS AFTER 

4378
03:12:55,333 --> 03:12:56,367
BASELINE AND THEN START TO 

4379
03:12:56,367 --> 03:13:01,539
ELEVATE THEREAFTER.

4380
03:13:01,539 --> 03:13:03,675
THIS IS ANOTHER EXAMPLE OF 

4381
03:13:03,675 --> 03:13:08,680
ANOTHER DRN PARTICIPANT AND NFL 

4382
03:13:08,680 --> 03:13:11,850
AND MRI IN THE FRONTAL TEMPORAL 

4383
03:13:11,850 --> 03:13:12,083
REGION.

4384
03:13:12,083 --> 03:13:14,085
NO EVIDENCE OF CLINICAL SYMPTOMS

4385
03:13:14,085 --> 03:13:15,653
AND MODELLING WOULD PREDICT 

4386
03:13:15,653 --> 03:13:18,723
THEY'RE A YEAR POST ONSET BUT 

4387
03:13:18,723 --> 03:13:19,290
HAVEN'T OBSERVED CLINICAL 

4388
03:13:19,290 --> 03:13:24,529
SYMPTOMS YET AND YOU CAN SEE 

4389
03:13:24,529 --> 03:13:27,799
AFTER BASELINE THE BLACK LINE 

4390
03:13:27,799 --> 03:13:29,601
AND BOXES PROGRESS QUITE RAPIDLY

4391
03:13:29,601 --> 03:13:33,004
OVER THE NEXT COUPLE YEARS.

4392
03:13:33,004 --> 03:13:35,273
SO THE ABILITY AT BASELINE OR 

4393
03:13:35,273 --> 03:13:37,942
SCREENING TO ESTIMATE WHERE WE 

4394
03:13:37,942 --> 03:13:39,110
BELIEVE A PARTICIPANT IS WITH 

4395
03:13:39,110 --> 03:13:40,845
RELATION TO ONSET COULD ALLOW US

4396
03:13:40,845 --> 03:13:46,784
TO ACTUALLY BROADEN OUR 

4397
03:13:46,784 --> 03:13:48,319
ENROLLMENT CRITERIA AND IT'S 

4398
03:13:48,319 --> 03:13:53,191
COMMON TO ENROLL POPULATIONS 

4399
03:13:53,191 --> 03:13:55,226
PRESYMPTOMATIC WITH AN A GLOBAL 

4400
03:13:55,226 --> 03:13:58,463
.5 OR CDR GLOBAL OF 1 

4401
03:13:58,463 --> 03:14:02,033
SYMPTOMATIC AND WHAT YOU CAN SEE

4402
03:14:02,033 --> 03:14:03,134
IS THE PROGRESSION RATES 

4403
03:14:03,134 --> 03:14:05,503
THEREAFTER FOR THOSE 

4404
03:14:05,503 --> 03:14:06,170
INDIVIDUALS.

4405
03:14:06,170 --> 03:14:08,806
CRD GLOBAL .5 IS A PROGNOSTIC OF

4406
03:14:08,806 --> 03:14:09,707
FUTURE PROGRESSION.

4407
03:14:09,707 --> 03:14:11,876
SOME INDIVIDUALS DO NOT GO ON TO

4408
03:14:11,876 --> 03:14:13,878
PROGRESS AND SOME INDIVIDUALS 

4409
03:14:13,878 --> 03:14:16,047
PROGRESS QUITE RAPIDLY SIMILAR 

4410
03:14:16,047 --> 03:14:19,183
TO THE CDR GLOBAL 1.

4411
03:14:19,183 --> 03:14:22,487
SO BY USING THIS WILL WILL WILL 

4412
03:14:22,487 --> 03:14:23,988
CONTEXT ESTIMATED AT SCREENING 

4413
03:14:23,988 --> 03:14:26,457
WE CAN BROADEN THAT ENROLLMENT 

4414
03:14:26,457 --> 03:14:29,360
CRITERIA AND ENROLL INDIVIDUALS 

4415
03:14:29,360 --> 03:14:31,796
WHO HAVE A CDR GLOBAL VALUE OF 0

4416
03:14:31,796 --> 03:14:34,232
BUT PREDICTED TO HAVE ONSET 

4417
03:14:34,232 --> 03:14:35,800
WITHIN 3 YEARS.

4418
03:14:35,800 --> 03:14:38,369
YOU CAN SEE THIS GROUP LOOKED 

4419
03:14:38,369 --> 03:14:41,973
SIMILAR TO THE CDR GLOBAL .5 

4420
03:14:41,973 --> 03:14:43,775
GROUP AS A PROGNOSTIC FOR FUTURE

4421
03:14:43,775 --> 03:14:51,549
PROGRESSION AND SLIGHTLY BETTER 

4422
03:14:51,549 --> 03:14:56,220
AND WE GET A HIGHER PROPORTION 

4423
03:14:56,220 --> 03:14:56,721
TO PROGRESS THEREAFTER.

4424
03:14:56,721 --> 03:15:00,258
SO THAT'S A WAY TO SORT OF USE 

4425
03:15:00,258 --> 03:15:03,828
THE DISEASE AGE OR PROGRESSION 

4426
03:15:03,828 --> 03:15:07,632
MODEL TO BROADEN ENROLLMENT 

4427
03:15:07,632 --> 03:15:08,299
CRITERIA AND FOCUS ON 

4428
03:15:08,299 --> 03:15:11,369
INDIVIDUALS LIKELY TO PROGRESS.

4429
03:15:11,369 --> 03:15:13,237
THE SECOND AREA WE USE THE 

4430
03:15:13,237 --> 03:15:15,807
MODELS IS FOR CLINICAL TRIAL 

4431
03:15:15,807 --> 03:15:16,908
SIMULATION.

4432
03:15:16,908 --> 03:15:18,609
EVERY CLINICAL TRIAL THAT WE 

4433
03:15:18,609 --> 03:15:20,979
DESIGN WE USE SIMULATION.

4434
03:15:20,979 --> 03:15:23,281
JUST LIKE AN AIRPLANE PILOT 

4435
03:15:23,281 --> 03:15:25,583
WOULD NOT FLY HIS FIRST FLIGHT 

4436
03:15:25,583 --> 03:15:27,318
WITHOUT SIMULATING THOUSANDS OF 

4437
03:15:27,318 --> 03:15:31,022
FLIGHTS BEFORE HAND, WE WOULD 

4438
03:15:31,022 --> 03:15:33,958
NOT DO A CLINICAL TRIAL WITHOUT 

4439
03:15:33,958 --> 03:15:34,892
SIMULATING THOUSANDS OF CLINICAL

4440
03:15:34,892 --> 03:15:35,994
TRIALS BEFORE HAND.

4441
03:15:35,994 --> 03:15:37,829
THIS INVOLVED SOME MECHANISM TO 

4442
03:15:37,829 --> 03:15:40,698
GENERATE REALISTIC PATIENT-LEVEL

4443
03:15:40,698 --> 03:15:44,268
DATA TO SOME SORT OF MODEL OR 

4444
03:15:44,268 --> 03:15:47,572
ASSUMPTION TO TAKE IT AND 

4445
03:15:47,572 --> 03:15:49,974
SIMULATE DATA AND RUN THE 

4446
03:15:49,974 --> 03:15:52,143
PROPOSED ANALYSIS WITH THE DATA 

4447
03:15:52,143 --> 03:15:54,379
AND SIMULATED AFFECTS THOUSANDS 

4448
03:15:54,379 --> 03:15:55,780
OF TIMES UNDER DIFFERENT 

4449
03:15:55,780 --> 03:15:56,948
ASSUMPTION TO UNDERSTAND THE 

4450
03:15:56,948 --> 03:15:58,416
OPERATING CHARACTERISTICS.

4451
03:15:58,416 --> 03:16:01,486
AS AN EXAMPLE OR ILLUSTRATION, 

4452
03:16:01,486 --> 03:16:03,488
WE CAN TAKE THE DISEASE 

4453
03:16:03,488 --> 03:16:06,357
PROGRESSION MODELS FOR 

4454
03:16:06,357 --> 03:16:09,227
PARTICIPANTS AND USE THOSE TO 

4455
03:16:09,227 --> 03:16:11,295
SIMULATE DATA LIKE I HAVE 

4456
03:16:11,295 --> 03:16:15,233
PICTURED HERE ON THE RIGHT.

4457
03:16:15,233 --> 03:16:19,637
AND WE CAN USE THE CONCEPT OF 

4458
03:16:19,637 --> 03:16:21,873
DISEASE IT STATE AND NOW AND 

4459
03:16:21,873 --> 03:16:27,011
VARIABLE AND UNOBSERVED.

4460
03:16:27,011 --> 03:16:29,547
AND SAY A PARTICIPANT WALKS IN 

4461
03:16:29,547 --> 03:16:30,748
THE DOOR AND SIMULATE THEY'RE A 

4462
03:16:30,748 --> 03:16:31,716
YEAR PRIOR TO ONSET.

4463
03:16:31,716 --> 03:16:36,554
ON THE LEFT YOU CAN SEE OVER THE

4464
03:16:36,554 --> 03:16:38,056
NEXT YEAR AND A HALF WE ESTIMATE

4465
03:16:38,056 --> 03:16:42,160
THEY'LL FALL ON THE BLACK CURVE 

4466
03:16:42,160 --> 03:16:45,730
HIGHLIGHTED AND SAMPLE AROUND 

4467
03:16:45,730 --> 03:16:47,298
WITH VARIABILITY AROUND WHAT WE 

4468
03:16:47,298 --> 03:16:49,133
ESTIMATED IT TO BE AND WHAT YOU 

4469
03:16:49,133 --> 03:16:51,302
OBSERVED FOR THE PARTICIPANT IS 

4470
03:16:51,302 --> 03:16:53,271
THE TRAJECTORY WE HAVE IN THE 

4471
03:16:53,271 --> 03:16:56,274
MIDDLE.

4472
03:16:56,274 --> 03:16:57,475
THEY'RE PROGRESSION OVER THE 

4473
03:16:57,475 --> 03:16:59,343
COURSE OF THE TRIAL AND DO IT 

4474
03:16:59,343 --> 03:17:00,845
FOR SIMULATING TREATED 

4475
03:17:00,845 --> 03:17:01,345
PARTICIPANTS.

4476
03:17:01,345 --> 03:17:04,515
SAY WE RANDOMLY SAMPLE A 

4477
03:17:04,515 --> 03:17:05,550
SUBJECT.

4478
03:17:05,550 --> 03:17:08,252
THERE ARE DISEASE AGENTS CLOSE 

4479
03:17:08,252 --> 03:17:09,454
TO TWO YEARS POST ONSET.

4480
03:17:09,454 --> 03:17:11,456
IF THEY WERE NOT TREATED WE 

4481
03:17:11,456 --> 03:17:12,690
WOULD THINK THEY WOULD LOOK LIKE

4482
03:17:12,690 --> 03:17:14,959
THE GRAY LINE BUT NOW WE'RE 

4483
03:17:14,959 --> 03:17:16,761
APPLYING A TREATMENT AFFECT SAY 

4484
03:17:16,761 --> 03:17:19,063
30% AND FOLLOW THE BLUE LINE.

4485
03:17:19,063 --> 03:17:21,699
SO WE CAN SIMULATE AROUND THE 

4486
03:17:21,699 --> 03:17:23,901
BLUE LINE WITH WILL MEASUREMENT 

4487
03:17:23,901 --> 03:17:25,670
ERROR AND RECORD WHAT WOULD BE 

4488
03:17:25,670 --> 03:17:27,405
OBSERVED IN THE CLINICAL TRIAL.

4489
03:17:27,405 --> 03:17:32,810
WE CAN DO THIS HOWEVER, MANY 

4490
03:17:32,810 --> 03:17:34,946
TIMES FOR HOWEVER MANY PATIENTS 

4491
03:17:34,946 --> 03:17:45,123
YOU PLAN TO ONREL -- ENROLL IN 

4492
03:17:45,123 --> 03:17:46,924
THE CLINICAL TRIALS AND CAN TAKE

4493
03:17:46,924 --> 03:17:51,129
THIS DATA SET THROUGH OUR 

4494
03:17:51,129 --> 03:17:52,163
PROPOSED ANALYSIS METHOD WITH 

4495
03:17:52,163 --> 03:17:54,031
ASSUMPTIONS AND WHAT WE SEE WHEN

4496
03:17:54,031 --> 03:17:56,601
WE DO THE REALISTIC CLINICAL 

4497
03:17:56,601 --> 03:18:01,405
TRIAL SIMULATIONS OFTEN TIMES IN

4498
03:18:01,405 --> 03:18:02,607
RARE DISEASE WE ARE VERY UNDER 

4499
03:18:02,607 --> 03:18:04,208
POWERED FOR A TRIAL THAT IS 

4500
03:18:04,208 --> 03:18:04,442
USEFUL.

4501
03:18:04,442 --> 03:18:09,380
THIS WAS AN EXAMPLE OF A 

4502
03:18:09,380 --> 03:18:12,250
PROPOSED CLINICAL TRIAL AND A 

4503
03:18:12,250 --> 03:18:13,951
RANDOMIZED CLINICAL TRIAL WITH 

4504
03:18:13,951 --> 03:18:16,521
75 PARTICIPANTS, 2:1 

4505
03:18:16,521 --> 03:18:18,322
RANDOMIZATION FOLLOWED FOR A 

4506
03:18:18,322 --> 03:18:25,596
YEAR AND A HALF AND WE FOUND FOR

4507
03:18:25,596 --> 03:18:31,435
CLINICALLY MEANINGFUL STATISTICS

4508
03:18:31,435 --> 03:18:32,937
WE'RE UNDERPOWERED.

4509
03:18:32,937 --> 03:18:34,939
THIS IS OUR LAST PIECE TO BE 

4510
03:18:34,939 --> 03:18:36,107
INNOVATIVE AND EFFICIENT AND 

4511
03:18:36,107 --> 03:18:37,808
USING ALL THE DATA AT HAND.

4512
03:18:37,808 --> 03:18:41,679
GOING BACK TO THIS IDEA OF 

4513
03:18:41,679 --> 03:18:43,147
DISEASE STAGING, IT'S SOMETHING 

4514
03:18:43,147 --> 03:18:45,449
THAT WE CAN DO AND USE ALMOST AS

4515
03:18:45,449 --> 03:18:50,755
A CO-VARIATE AND WE KNOW MORE 

4516
03:18:50,755 --> 03:18:51,789
THAN YOU OBSERVE ON THE PICTURE 

4517
03:18:51,789 --> 03:18:52,690
ON THE LEFT.

4518
03:18:52,690 --> 03:18:55,860
WE CAN TRY TO IT WILL PREDICT 

4519
03:18:55,860 --> 03:18:57,495
WHERE THIS BLUE PARTICIPANT IS 

4520
03:18:57,495 --> 03:18:59,430
IN THEIR DISEASE COURSE AND CAN 

4521
03:18:59,430 --> 03:19:01,832
DO THAT WITH MANY OUTCOME 

4522
03:19:01,832 --> 03:19:02,099
MEASURES.

4523
03:19:02,099 --> 03:19:06,470
WE MIGHT KNOW THE NFL AND BRAIN 

4524
03:19:06,470 --> 03:19:08,039
IMAGING AND TRY TO ESTIMATE 

4525
03:19:08,039 --> 03:19:09,407
WHERE THEY ARE IN THEIR DISEASE 

4526
03:19:09,407 --> 03:19:09,640
COURSE.

4527
03:19:09,640 --> 03:19:13,277
NOW WHEN WE DO THAT, WHEN WE 

4528
03:19:13,277 --> 03:19:15,680
ADDRESS BY DISEASE STAGE WE CAN 

4529
03:19:15,680 --> 03:19:18,015
EXPLAIN THE HETEROGENEITY IN THE

4530
03:19:18,015 --> 03:19:20,651
DATA AND SEE A MUCH CLEARER 

4531
03:19:20,651 --> 03:19:24,255
PATTERN IN THE CONTROL DATA AND 

4532
03:19:24,255 --> 03:19:26,958
SEE WILL VERY CLEARLY THAT THIS 

4533
03:19:26,958 --> 03:19:27,825
TREATED PARTICIPANT PROGRESSES 

4534
03:19:27,825 --> 03:19:30,061
MUCH LESS THAN WHAT YOU WOULD 

4535
03:19:30,061 --> 03:19:36,267
EXPECT FOR THE SIMILAR CONTROL 

4536
03:19:36,267 --> 03:19:37,435
COUNTERPART.

4537
03:19:37,435 --> 03:19:38,436
TAKING THE CONCEPT OF DISEASE 

4538
03:19:38,436 --> 03:19:40,705
STAGING AS A VARIABLE TO ALIGN 

4539
03:19:40,705 --> 03:19:43,307
OUR PARTICIPANTS TO EXPLAIN THE 

4540
03:19:43,307 --> 03:19:44,942
HETEROGENEITY IN THE DATA AND 

4541
03:19:44,942 --> 03:19:46,377
SEE A CLEARER PICTURE IF THE 

4542
03:19:46,377 --> 03:19:56,821
TREATMENT WORKING OR NOT.

4543
03:20:04,729 --> 03:20:06,897
 HERE WE'RE EXPLAINING WHY WE 

4544
03:20:06,897 --> 03:20:11,802
THINK WE DIDN'T OBSERVE ANY 

4545
03:20:11,802 --> 03:20:15,106
CHANGES IN THIS ONE.

4546
03:20:15,106 --> 03:20:16,974
AND WE SLOWED PROGRESSION IN 

4547
03:20:16,974 --> 03:20:19,377
THIS PARTICIPANT.

4548
03:20:19,377 --> 03:20:25,082
JUST BY DOING THIS SLIGHTLY 

4549
03:20:25,082 --> 03:20:27,785
INNOVATIVE METHOD YOU CAN GO TO 

4550
03:20:27,785 --> 03:20:29,186
OVER 80% POWER IN YOUR CLINICAL 

4551
03:20:29,186 --> 03:20:29,487
TRIALS.

4552
03:20:29,487 --> 03:20:31,789
I'M NOT SAYING GO HOME AND USE 

4553
03:20:31,789 --> 03:20:33,257
THE EXACT METHOD BUT WE'RE 

4554
03:20:33,257 --> 03:20:38,596
TRYING TO SAY BE THOUGHTFUL 

4555
03:20:38,596 --> 03:20:42,733
ABOUT THE ANALYSIS  METHOD YOU 

4556
03:20:42,733 --> 03:20:45,136
USE AND DATA AT HAND AND 

4557
03:20:45,136 --> 03:20:46,604
ACCOUNTING FOR INDIVIDUALS CAN 

4558
03:20:46,604 --> 03:20:48,272
GIVE YOU MORE POWER TO DETECT 

4559
03:20:48,272 --> 03:20:48,973
THE TREATMENT EFFECT.

4560
03:20:48,973 --> 03:20:51,442
THIS COMES WITH A WORD OF 

4561
03:20:51,442 --> 03:20:51,676
CAUTION.

4562
03:20:51,676 --> 03:20:52,977
YOU SHOULD UNDERSTAND THE 

4563
03:20:52,977 --> 03:20:55,946
ASSUMPTIONS GOING IN TO THOSE 

4564
03:20:55,946 --> 03:20:57,081
ANALYSES METHODS.

4565
03:20:57,081 --> 03:20:59,016
FOR INSTANCE, THIS ASSUMPTION IN

4566
03:20:59,016 --> 03:21:02,219
THIS ANALYSIS METHOD WE HAVE 

4567
03:21:02,219 --> 03:21:04,555
THIS COMMON SWELLING AND DISEASE

4568
03:21:04,555 --> 03:21:05,923
PROGRESSION OVER TIME AND COMMON

4569
03:21:05,923 --> 03:21:08,159
ACROSS ALL INDIVIDUALS 

4570
03:21:08,159 --> 03:21:09,860
INDEPENDENT OF DISEASE STAGE BUT

4571
03:21:09,860 --> 03:21:12,830
GOING BACK TO TREATING TOO LATE 

4572
03:21:12,830 --> 03:21:14,999
WHAT IF THE INDIVIDUALS FURTHER 

4573
03:21:14,999 --> 03:21:17,101
FROM ONSET THE TREATMENT DOESN'T

4574
03:21:17,101 --> 03:21:18,636
WORK AS WELL.

4575
03:21:18,636 --> 03:21:20,271
WHAT IF WE DON'T SEE AS MUCH 

4576
03:21:20,271 --> 03:21:22,239
SLOWING IN THOSE INDIVIDUAL?

4577
03:21:22,239 --> 03:21:26,010
WE DID SIMULATIONS AND BASICALLY

4578
03:21:26,010 --> 03:21:28,012
AS YOU TAKEAWAY THE INDIVIDUALS 

4579
03:21:28,012 --> 03:21:29,747
ADDING TO THE EFFECT BECAUSE 

4580
03:21:29,747 --> 03:21:32,249
THAT'S THE BIGGEST DIFFERENCE WE

4581
03:21:32,249 --> 03:21:35,119
CAN SEE, YOU START TO LOSE 

4582
03:21:35,119 --> 03:21:35,319
POWER.

4583
03:21:35,319 --> 03:21:37,455
FOR INSTANCE IF THERE'S NO 

4584
03:21:37,455 --> 03:21:39,623
BENEFIT IN INDIVIDUALS WHO ARE 

4585
03:21:39,623 --> 03:21:42,360
FOUR YEARS PAST ONSET WE'RE NOW 

4586
03:21:42,360 --> 03:21:43,928
MAJOR UNDER POWERED AGAIN AND 

4587
03:21:43,928 --> 03:21:45,363
NEED TO GO BACK TO THE DRAWING 

4588
03:21:45,363 --> 03:21:45,563
BOARD.

4589
03:21:45,563 --> 03:21:46,964
IT'S EXTREMELY IMPORTANT YOU 

4590
03:21:46,964 --> 03:21:47,998
UNDERSTAND THE ASSUMPTIONS THAT 

4591
03:21:47,998 --> 03:21:50,201
GO INTO THE MODEL AND 

4592
03:21:50,201 --> 03:21:51,302
SENSITIVITY OF THE POWER 

4593
03:21:51,302 --> 03:21:52,269
CALCULATIONS TO THOSE 

4594
03:21:52,269 --> 03:21:55,606
ASSUMPTIONS.

4595
03:21:55,606 --> 03:21:57,708
YOU CAN GO BACK TO THE DRAWING 

4596
03:21:57,708 --> 03:21:59,176
BOARD AND CAN APPLY THE DISEASE 

4597
03:21:59,176 --> 03:22:01,579
AGE CRITERIA ON THE OTHER SIDE 

4598
03:22:01,579 --> 03:22:04,682
TOO SAYING WE WANT TO ENROLL 

4599
03:22:04,682 --> 03:22:06,617
THOSE WITHIN FOUR YEARS PAST 

4600
03:22:06,617 --> 03:22:08,386
ONSET TO GET MORE POWER OR YOU 

4601
03:22:08,386 --> 03:22:10,621
MIGHT SAY OKAY BECAUSE WE DON'T 

4602
03:22:10,621 --> 03:22:13,157
BELIEVE IT WORKS AS STRONGLY IN 

4603
03:22:13,157 --> 03:22:15,259
THOSE FAR FROM ONSET MAYBE WE 

4604
03:22:15,259 --> 03:22:17,495
NEED DO A TWO OR THREE YEAR 

4605
03:22:17,495 --> 03:22:19,964
STUDY BUT YOU CAN BE WELL 

4606
03:22:19,964 --> 03:22:20,664
INFORMED OF WHAT YOU'RE TRUE 

4607
03:22:20,664 --> 03:22:27,238
POWER OF YOUR STUDY IS.

4608
03:22:27,238 --> 03:22:29,240
IN SUMMARY THIS MAY NOT FIT 

4609
03:22:29,240 --> 03:22:34,612
EVERYONE'S EXACT NEEDS BUT THE 

4610
03:22:34,612 --> 03:22:38,849
MESSAGE IS THAT NATURAL HISTORY 

4611
03:22:38,849 --> 03:22:42,820
STUDIES AND DISEASE PROGRESSION 

4612
03:22:42,820 --> 03:22:43,921
MODELLING IS IMPORTANT WHERE 

4613
03:22:43,921 --> 03:22:46,457
EVERY PATIENT MATTERS SO MUCH.

4614
03:22:46,457 --> 03:22:48,793
WE COULDN'T DO THIS WITHOUT DATA

4615
03:22:48,793 --> 03:22:50,761
SHARING IN A COMPETITIVE SPACE 

4616
03:22:50,761 --> 03:22:51,595
SO EVERYONE NEEDS TO SHARE THEIR

4617
03:22:51,595 --> 03:22:54,598
DATA IN A PRECOMPETITIVE SPACE 

4618
03:22:54,598 --> 03:22:55,866
TO LEARN AS MUCH AS POSSIBLE.

4619
03:22:55,866 --> 03:22:57,601
IT'S IMPORTANT IN RARE DISEASE 

4620
03:22:57,601 --> 03:23:01,405
WE'RE ABLE TO BE MORE CREATIVE 

4621
03:23:01,405 --> 03:23:03,073
AND THINK MORE THOUGHTFULLY HOW 

4622
03:23:03,073 --> 03:23:03,774
WE ANALYZE OUR DATA.

4623
03:23:03,774 --> 03:23:05,876
WHAT THAT MEANS IS YOU'LL HAVE 

4624
03:23:05,876 --> 03:23:09,246
TO INVEST IN THE INNOVATION UP 

4625
03:23:09,246 --> 03:23:09,447
FRONT.

4626
03:23:09,447 --> 03:23:10,414
CAN'T GIVE YOUR STATISTICIAN A 

4627
03:23:10,414 --> 03:23:13,651
DAY TO GIVE YOU A SAMPLE SIZE 

4628
03:23:13,651 --> 03:23:14,018
CALCULATION.

4629
03:23:14,018 --> 03:23:15,953
A LOT OF THE WORK TAKES YEARS SO

4630
03:23:15,953 --> 03:23:18,322
INVEST THE TIME AND INNOVATION 

4631
03:23:18,322 --> 03:23:20,090
UP FRONT AND IT SPEAK WITH 

4632
03:23:20,090 --> 03:23:22,359
PARTNERS EARLY AND OFTEN.

4633
03:23:22,359 --> 03:23:24,428
INNOVATIVE APPROACHES MAY BE NEW

4634
03:23:24,428 --> 03:23:26,063
TO DIFFERENT PEOPLE.

4635
03:23:26,063 --> 03:23:27,465
MAY BE NEW TO REGULATORY BUT YOU

4636
03:23:27,465 --> 03:23:30,768
CAN SHOW IN SIMULATIONS AND GET 

4637
03:23:30,768 --> 03:23:32,803
COMFORTABLE WITH IT OVER TIME.

4638
03:23:32,803 --> 03:23:34,872
AND I'LL LEAVE YOU WITH THESE 

4639
03:23:34,872 --> 03:23:40,244
LAST COUPLE REFERENCES JUST ON 

4640
03:23:40,244 --> 03:23:46,650
DISEASE PROGRESSION AND 

4641
03:23:46,650 --> 03:23:48,285
MODELLING AND HAPPY TO TAKE 

4642
03:23:48,285 --> 03:23:58,462
QUESTIONS.

4643
03:24:09,974 --> 03:24:11,642
>> OUR NEXT SPEAKER IS
HEATHER 

4644
03:24:11,642 --> 03:24:16,213
HAZLETT FROM THE UNIVERSITY OF 

4645
03:24:16,213 --> 03:24:25,923
NORTH CAROLINA TO TALK ABOUT -- 

4646
03:24:25,923 --> 03:24:27,458
SO WE'RE IN THE FINAL STRETCH.

4647
03:24:27,458 --> 03:24:30,327
THANK YOU TO RICK VICKY AND THE 

4648
03:24:30,327 --> 03:24:31,729
WORKSHOP ORGANIZERS AND I FEEL 

4649
03:24:31,729 --> 03:24:33,430
LIKE I'VE LEARNED SO MUCH 

4650
03:24:33,430 --> 03:24:36,100
PROBABLY MORE THAN I'LL LET YOU 

4651
03:24:36,100 --> 03:24:37,401
LEARN BY MY SPEAKING HERE TODAY 

4652
03:24:37,401 --> 03:24:40,738
BUT I'LL TALK ABOUT REMOTE 

4653
03:24:40,738 --> 03:24:50,948
PHENOTYPING.

4654
03:24:59,323 --> 03:25:01,091
 TECHNICAL DIFFICULTIES I'M A 

4655
03:25:01,091 --> 03:25:06,931
FAST SPEAKER SO I'LL CATCH US UP

4656
03:25:06,931 --> 03:25:09,967
ON TIME.

4657
03:25:09,967 --> 03:25:15,039
REMOTE PHENOTYPING CAN MEAN 

4658
03:25:15,039 --> 03:25:24,048
DIFFERENT THINGS AND  WANTED TO 

4659
03:25:24,048 --> 03:25:25,416
LIST WHAT PEOPLE INCLUDE 

4660
03:25:25,416 --> 03:25:27,184
SOMETHING TO DO WITH THEIR 

4661
03:25:27,184 --> 03:25:28,085
COMPUTER ON THEIR PHONE OR 

4662
03:25:28,085 --> 03:25:31,255
CALLING OR VISITING THEIR HOME 

4663
03:25:31,255 --> 03:25:33,223
AND CONSIDER THE REMOTE WAY TO 

4664
03:25:33,223 --> 03:25:35,492
PHENOTYPE AND THE TELEASSESSMENT

4665
03:25:35,492 --> 03:25:40,531
THAT'S BECOME MORE POPULAR IN 

4666
03:25:40,531 --> 03:25:40,864
RECENT YEARS.

4667
03:25:40,864 --> 03:25:44,635
FINALLY WEARABLES ARE 

4668
03:25:44,635 --> 03:25:45,402
CONSIDERABLE PHENOTYPING.

4669
03:25:45,402 --> 03:25:46,637
THANKS WILL TO COVID I THINK A 

4670
03:25:46,637 --> 03:25:50,307
LOT OF US IN RESEARCH HAD TO 

4671
03:25:50,307 --> 03:25:53,344
LEARN ABOUT REMOTE PHENOTYPING 

4672
03:25:53,344 --> 03:25:55,312
BECAUSE COVID SHUT EVERYTHING 

4673
03:25:55,312 --> 03:25:55,512
DOWN.

4674
03:25:55,512 --> 03:25:56,680
FROM OUR RESEARCH PERSPECTIVE WE

4675
03:25:56,680 --> 03:25:58,048
NEEDED FAMILIES TO COME AND SEE 

4676
03:25:58,048 --> 03:26:00,284
US AND HAD TO WORK AROUND WHAT 

4677
03:26:00,284 --> 03:26:02,653
HAPPENED WHEN WE COULDN'T SEE 

4678
03:26:02,653 --> 03:26:03,821
FAMILIES, WE COULDN'T BRING THEM

4679
03:26:03,821 --> 03:26:05,789
TO OUR CENTER, WHAT COULD WE DO 

4680
03:26:05,789 --> 03:26:07,691
TO GET DATA FROM THEM EVEN 

4681
03:26:07,691 --> 03:26:08,926
REMOTELY.

4682
03:26:08,926 --> 03:26:11,962
SO WE HAD TO LOOK AND INSTITUTE 

4683
03:26:11,962 --> 03:26:13,731
A LOT OF DIFFERENT NEW 

4684
03:26:13,731 --> 03:26:14,064
METHODOLOGIES.

4685
03:26:14,064 --> 03:26:16,066
WHAT WE FOUND WHEN WE TRIED TO 

4686
03:26:16,066 --> 03:26:18,802
DO THAT WAS THERE ARE 

4687
03:26:18,802 --> 03:26:19,136
LIMITATIONS.

4688
03:26:19,136 --> 03:26:21,372
THERE'S JUST NOT A WORLD OF 

4689
03:26:21,372 --> 03:26:23,407
THINGS TO CHOOSE FROM BUT WHEN 

4690
03:26:23,407 --> 03:26:26,243
YOU DEAL WITH PEDIATRIC 

4691
03:26:26,243 --> 03:26:26,844
POPULATIONS IT'S HARD.

4692
03:26:26,844 --> 03:26:30,414
THERE ARE BENEFITS.

4693
03:26:30,414 --> 03:26:32,082
IT DOES TO OUR ADVANTAGE THINK 

4694
03:26:32,082 --> 03:26:36,220
ABOUT HOW TO DO THIS IN A GOOD 

4695
03:26:36,220 --> 03:26:38,088
WAY BECAUSE YOU'RE ABLE TO REACH

4696
03:26:38,088 --> 03:26:39,056
A BROADER RESEARCH GEOGRAPHIC 

4697
03:26:39,056 --> 03:26:42,693
AREA FOR YOUR STUDIES.

4698
03:26:42,693 --> 03:26:43,727
IT DOES AS IT MARY ANN MENTIONED

4699
03:26:43,727 --> 03:26:46,997
CREATE BURDEN ON FAMILIES.

4700
03:26:46,997 --> 03:26:48,832
THEY DON'T HAVE TO TRAVEL TO 

4701
03:26:48,832 --> 03:26:51,402
YOUR CENTER AND CAN INCLUDE MORE

4702
03:26:51,402 --> 03:26:52,670
RARE DISEASE POPULATIONS THAT 

4703
03:26:52,670 --> 03:26:56,240
ARE LOCATED AND SPREAD ACROSS 

4704
03:26:56,240 --> 03:27:05,349
THE COUNTRY.

4705
03:27:05,349 --> 03:27:11,288
IT CAN INCLUDE NON-ENGLISH 

4706
03:27:11,288 --> 03:27:16,160
POPULATIONS BECAUSE MORE 

4707
03:27:16,160 --> 03:27:16,827
MEASURES ARE SUITED FOR SPANISH 

4708
03:27:16,827 --> 03:27:18,162
AND CLINICAL TRIALS.

4709
03:27:18,162 --> 03:27:20,931
IT DOES EXPAND YOUR MONEY.

4710
03:27:20,931 --> 03:27:25,869
IT CAN BE DONE ON A BROAD SCALE 

4711
03:27:25,869 --> 03:27:27,538
AND IT'S VERY MUCH SUITED FOR 

4712
03:27:27,538 --> 03:27:31,075
THAT REASON, GENETIC STUDIES, 

4713
03:27:31,075 --> 03:27:34,712
CLINICAL TRIALS, ASSESSMENT 

4714
03:27:34,712 --> 03:27:35,345
REPOSITORIES AND MORE EFFICIENT.

4715
03:27:35,345 --> 03:27:37,715
SO IT ALSO ALLOWS FOR A LOT OF 

4716
03:27:37,715 --> 03:27:39,383
CROSS-SITE COLLABORATIONS.

4717
03:27:39,383 --> 03:27:41,952
WE HAVE INDIVIDUALS IN OUR 

4718
03:27:41,952 --> 03:27:44,354
NETWORK ACROSS THE U.S. AND 

4719
03:27:44,354 --> 03:27:46,423
COLLABORATORS ARE ALL ACROSS THE

4720
03:27:46,423 --> 03:27:46,590
U.S.

4721
03:27:46,590 --> 03:27:49,493
THAT REMOTE ASSESSMENT, REMOTE 

4722
03:27:49,493 --> 03:27:50,928
DATA GATHERING AND PHENOTYPING 

4723
03:27:50,928 --> 03:27:55,132
ALLOWS US TO DO THIS AND I PUT 

4724
03:27:55,132 --> 03:27:57,735
THIS AS A BEE IN THE BONNET FOR 

4725
03:27:57,735 --> 03:27:59,470
SOME TRAINEES AND INVESTIGATORS,

4726
03:27:59,470 --> 03:28:01,205
IT CREATES A LOT TO DO BECAUSE 

4727
03:28:01,205 --> 03:28:04,108
AGAIN AS I MENTIONED, THERE'S 

4728
03:28:04,108 --> 03:28:06,477
NOT EVERYTHING AVAILABLE AND 

4729
03:28:06,477 --> 03:28:07,111
EVERYTHING THAT IS AVAILABLE 

4730
03:28:07,111 --> 03:28:08,779
HASN'T NECESSARILY BEEN USED IN 

4731
03:28:08,779 --> 03:28:09,980
THIS WAY.

4732
03:28:09,980 --> 03:28:12,983
SO JUST BECAUSE YOU'RE USING AN 

4733
03:28:12,983 --> 03:28:15,319
INSTRUMENT THAT THEN GIVEN IN A 

4734
03:28:15,319 --> 03:28:17,154
CLINIC 100 TIMES OVER AND WE 

4735
03:28:17,154 --> 03:28:19,456
WANT TO JUST NOW SEND IT TO A 

4736
03:28:19,456 --> 03:28:21,024
FAMILY AND CONVERT IT TO RED CAP

4737
03:28:21,024 --> 03:28:22,726
A FORM THEY COMPLETE ON THEIR 

4738
03:28:22,726 --> 03:28:24,294
COMPUTER, THAT MAY WORK 

4739
03:28:24,294 --> 03:28:25,929
DIFFERENTLY THAN WHAT YOU THINK 

4740
03:28:25,929 --> 03:28:26,897
IT DOES.

4741
03:28:26,897 --> 03:28:29,333
THERE'S A GREAT WEALTH OF DATA 

4742
03:28:29,333 --> 03:28:32,269
FOR PEOPLE TO LOOK AT AND THINK 

4743
03:28:32,269 --> 03:28:34,538
ABOUT THE VALIDITY QUESTIONS.

4744
03:28:34,538 --> 03:28:36,907
SO THERE ARE SOME CONSIDERATIONS

4745
03:28:36,907 --> 03:28:39,643
AND AGAIN I'M NOT GOING TO HAVE 

4746
03:28:39,643 --> 03:28:43,547
THE ANSWER OF LIKE HERE'S YOUR 

4747
03:28:43,547 --> 03:28:44,148
REMOTE BATTERY BUT GIVE AN 

4748
03:28:44,148 --> 03:28:46,316
EXAMPLE AND CONSIDERATIONS OF 

4749
03:28:46,316 --> 03:28:47,851
PEOPLE THINKING THINK ABOUT HOW 

4750
03:28:47,851 --> 03:28:50,487
TO DO THIS AND WHAT TO THINK 

4751
03:28:50,487 --> 03:28:50,888
ABOUT.

4752
03:28:50,888 --> 03:28:53,724
THE FIRST AREA YOU NEED TO THINK

4753
03:28:53,724 --> 03:28:56,360
ABOUT IS THE AGE RANGE.

4754
03:28:56,360 --> 03:28:58,729
THERE ARE LIMITATIONS 

4755
03:28:58,729 --> 03:29:00,531
PARTICULARLY FOR PEDIATRIC 

4756
03:29:00,531 --> 03:29:02,499
POPULATIONS ON THE TYPE OF DATA 

4757
03:29:02,499 --> 03:29:06,236
YOU CAN GATHER.

4758
03:29:06,236 --> 03:29:08,172
ESPECIALLY IF IT'S PERFORMANCE 

4759
03:29:08,172 --> 03:29:08,372
BASED.

4760
03:29:08,372 --> 03:29:10,707
THE YOUNGER THE CHILD THE MORE 

4761
03:29:10,707 --> 03:29:13,677
YOU'LL DEAL WITH A PARENT OR 

4762
03:29:13,677 --> 03:29:16,280
CAREGIVER REPORT VERSUS DIRECT 

4763
03:29:16,280 --> 03:29:17,748
OBSERVATIONS AND NEED TO THINK 

4764
03:29:17,748 --> 03:29:20,284
ABOUT THE DOMAINS AND SOME ARE 

4765
03:29:20,284 --> 03:29:21,552
MORE SUITED TO REMOTE DATA 

4766
03:29:21,552 --> 03:29:22,486
GATHERING THAN OTHERS.

4767
03:29:22,486 --> 03:29:24,955
ON THAT LIST IS COGNITIVE AND 

4768
03:29:24,955 --> 03:29:28,058
THAT IS AS A PSYCHOLOGIST THE 

4769
03:29:28,058 --> 03:29:28,559
HARDEST ONE.

4770
03:29:28,559 --> 03:29:32,296
I THINK WE'VE HAD THE BIGGEST 

4771
03:29:32,296 --> 03:29:33,497
STRUGGLE HOW TO DEVELOP 

4772
03:29:33,497 --> 03:29:34,965
COGNITIVE OR DEVELOPMENTAL LEVEL

4773
03:29:34,965 --> 03:29:36,133
REMOTELY IS CHALLENGING.

4774
03:29:36,133 --> 03:29:37,868
ALSO WHETHER YOU NEED TO HAVE A 

4775
03:29:37,868 --> 03:29:41,205
MEASURE REPEATED ACROSS MULTIPLE

4776
03:29:41,205 --> 03:29:43,607
TIME POINTS AND COLLECT 

4777
03:29:43,607 --> 03:29:46,109
CROSS-SECTIONAL OR LONGITUDINAL 

4778
03:29:46,109 --> 03:29:48,846
DATA AS YOU'RE TRACKING 

4779
03:29:48,846 --> 03:29:49,146
OUTCOMES.

4780
03:29:49,146 --> 03:29:50,380
AND WHETHER YOU'RE SATISFIED 

4781
03:29:50,380 --> 03:29:51,982
WITH THE OBSERVATION OR IT CAN 

4782
03:29:51,982 --> 03:29:54,418
BE A CAREGIVER REPORT.

4783
03:29:54,418 --> 03:29:56,286
THOSE ARE ALL CONSIDERATIONS.

4784
03:29:56,286 --> 03:29:56,954
THERE'S MORE.

4785
03:29:56,954 --> 03:29:58,655
THERE ARE SOME THINGS OFF THE 

4786
03:29:58,655 --> 03:29:59,489
SHELF.

4787
03:29:59,489 --> 03:30:00,390
THERE ARE THINGS YOU CAN 

4788
03:30:00,390 --> 03:30:03,994
PURCHASE THAT ARE OUT THERE YOU 

4789
03:30:03,994 --> 03:30:08,232
CAN USE.

4790
03:30:08,232 --> 03:30:14,438
PRIMARILY QUESTIONNAIRES AND 

4791
03:30:14,438 --> 03:30:19,576
EXPERIMENTAL MEASURES AND WILL 

4792
03:30:19,576 --> 03:30:22,713
IT WILL MEASURES AND YOU HAVE TO

4793
03:30:22,713 --> 03:30:24,514
BE CAREFUL WHEN YOU'RE GETTING 

4794
03:30:24,514 --> 03:30:26,617
OFF THE SHELF INSTRUMENTS YOU'RE

4795
03:30:26,617 --> 03:30:28,285
PAYING ATTENTION TO THE 

4796
03:30:28,285 --> 03:30:29,486
LICENSING AND PURCHASING OFTEN 

4797
03:30:29,486 --> 03:30:32,289
INVOLVED AND THAT GETS TO THE 

4798
03:30:32,289 --> 03:30:39,763
NEXT THING WHICH IS COST.

4799
03:30:39,763 --> 03:30:43,033
PER EACH COST OR A SCORING 

4800
03:30:43,033 --> 03:30:44,735
PROGRAM YOU NEED TO PURCHASE AND

4801
03:30:44,735 --> 03:30:46,904
SOME PERSONNEL COSTS.

4802
03:30:46,904 --> 03:30:47,738
THESE WILL NEED TO BE DELIVERED 

4803
03:30:47,738 --> 03:30:48,872
IN SOME WAY.

4804
03:30:48,872 --> 03:30:50,741
YOU CAN'T QUITE TAKE THE HUMAN 

4805
03:30:50,741 --> 03:30:52,009
OUT OF THE EQUATION.

4806
03:30:52,009 --> 03:30:54,278
SOMEBODY NEEDS TO E-MAIL 

4807
03:30:54,278 --> 03:30:56,280
SOMETHING OR SET UP A VISIT.

4808
03:30:56,280 --> 03:31:00,284
DO THAT TELEVISIT AND WHAT LEVEL

4809
03:31:00,284 --> 03:31:01,685
OF EXPERTISE DO YOU NEED THAT 

4810
03:31:01,685 --> 03:31:03,754
PERSON TO HAVE TO BE A LICENSED 

4811
03:31:03,754 --> 03:31:05,122
CLINICIAN OR RESEARCH ASSISTANT.

4812
03:31:05,122 --> 03:31:06,990
THAT IS ALL COSTLY.

4813
03:31:06,990 --> 03:31:09,026
YOU WANT TO THINK ABOUT AND AS I

4814
03:31:09,026 --> 03:31:11,328
MENTIONED BEFORE BUT WANT TO 

4815
03:31:11,328 --> 03:31:14,131
REPEAT HERE, SPANISH SPEAKING 

4816
03:31:14,131 --> 03:31:17,134
MEASURES AND OTHER LANGUAGES TOO

4817
03:31:17,134 --> 03:31:18,235
CREATES AN ADDITIONAL LEVEL OF 

4818
03:31:18,235 --> 03:31:18,535
COMPLEXITY.

4819
03:31:18,535 --> 03:31:22,239
YOU HAVE TO BE ABLE TO 

4820
03:31:22,239 --> 03:31:24,007
ADMINISTER THOSE MEASURES AND 

4821
03:31:24,007 --> 03:31:26,276
INSTRUMENTS IN THAT LANGUAGE OF 

4822
03:31:26,276 --> 03:31:29,112
INTEREST OR HAVE SOME TRANSLATED

4823
03:31:29,112 --> 03:31:29,579
MATERIALS.

4824
03:31:29,579 --> 03:31:30,147
THOSE THINGS ARE ALSO MORE 

4825
03:31:30,147 --> 03:31:34,318
EXPENSIVE.

4826
03:31:34,318 --> 03:31:35,719
THIS IS WHERE I'LL SHOW AN 

4827
03:31:35,719 --> 03:31:38,655
EXAMPLE.

4828
03:31:38,655 --> 03:31:40,290
I'M TALKING ABOUT THIS REGISTRY 

4829
03:31:40,290 --> 03:31:43,927
THE BRAIN GENE REGISTRY WITH A 

4830
03:31:43,927 --> 03:31:46,964
JOINTLY FUNDED PROJECT, THE 

4831
03:31:46,964 --> 03:31:48,298
INTELLECTUAL DISABILITIES 

4832
03:31:48,298 --> 03:31:48,966
RESEARCH CENTERS.

4833
03:31:48,966 --> 03:31:51,568
THERE WERE A NUMBER FUNDED TO 

4834
03:31:51,568 --> 03:31:54,037
POOL RESOURCES THINKING ABOUT 

4835
03:31:54,037 --> 03:31:56,273
HOW TO COLLECT DATA AND MAKE A 

4836
03:31:56,273 --> 03:31:59,309
REGISTRY FOR INDIVIDUALS THAT 

4837
03:31:59,309 --> 03:32:00,844
HAVE RARE GENES ASSOCIATED WITH 

4838
03:32:00,844 --> 03:32:02,546
BRAIN DEVELOPMENT.

4839
03:32:02,546 --> 03:32:04,748
THERE WERE THREE AIMS.

4840
03:32:04,748 --> 03:32:06,950
ASSOCIATED AGE AIM 1 THE 

4841
03:32:06,950 --> 03:32:07,651
PHENOTYPING.

4842
03:32:07,651 --> 03:32:09,286
WE HAD A GROUP IN BOSTON HELPING

4843
03:32:09,286 --> 03:32:11,922
WITH THE CURATION.

4844
03:32:11,922 --> 03:32:15,092
THESE ARE RARE GENES THEY NEEDED

4845
03:32:15,092 --> 03:32:16,560
TO THINK ABOUT CURATION AND 

4846
03:32:16,560 --> 03:32:17,761
WHAT'S KNOWN AND HOW THEY WERE 

4847
03:32:17,761 --> 03:32:19,863
ON THE LIST OF GENES WE 

4848
03:32:19,863 --> 03:32:20,130
INCLUDED.

4849
03:32:20,130 --> 03:32:22,499
AND THE REGISTRY NEEDS TO BE 

4850
03:32:22,499 --> 03:32:22,733
CREATED.

4851
03:32:22,733 --> 03:32:24,301
THAT WAS AN INFRASTRUCTURE 

4852
03:32:24,301 --> 03:32:26,370
BUILDING THAT HAPPENED AT WASH 

4853
03:32:26,370 --> 03:32:27,437
U.

4854
03:32:27,437 --> 03:32:28,672
WILL AND I'LL TELL YOU A LITTLE 

4855
03:32:28,672 --> 03:32:35,145
BIT ABOUT WHAT WE DID.

4856
03:32:35,145 --> 03:32:37,481
THE RATIONALE WAS POWER IN 

4857
03:32:37,481 --> 03:32:37,814
NUMBERS.

4858
03:32:37,814 --> 03:32:40,784
WE NEEDED THE CENTERS LOOKING 

4859
03:32:40,784 --> 03:32:42,686
FOR THESE RARE GENES TO GET 

4860
03:32:42,686 --> 03:32:48,191
ENOUGH OF A SAMPLE OR COHORT SO 

4861
03:32:48,191 --> 03:32:48,725
ADVOC

4862
03:32:48,725 --> 03:32:49,393
INVESTIGATORS COULD LOOK AT THEM

4863
03:32:49,393 --> 03:32:51,194
AND THERE'S HUNDREDS OF GENE 

4864
03:32:51,194 --> 03:32:52,396
ASSOCIATED WITH NEURAL 

4865
03:32:52,396 --> 03:32:53,430
DEVELOPMENT AND MAYBE A CENTER 

4866
03:32:53,430 --> 03:32:54,698
WOULD SEE ONE OR TWO.

4867
03:32:54,698 --> 03:32:57,801
YOU NEED MORE PEOPLE LOOKING.

4868
03:32:57,801 --> 03:32:58,869
THAT SMALL SAMPLE SIZE CREATES A

4869
03:32:58,869 --> 03:33:01,204
CHALLENGE FOR RESEARCH.

4870
03:33:01,204 --> 03:33:05,609
SO THESE ARE THE CENTERS THAT 

4871
03:33:05,609 --> 03:33:07,477
WERE INVOLVED IN THE BRAIN GENE 

4872
03:33:07,477 --> 03:33:08,278
REGISTRY WE'RE IN THE TAIL END 

4873
03:33:08,278 --> 03:33:12,649
IN THE TRIPLE ENROLLMENT RIGHT 

4874
03:33:12,649 --> 03:33:13,150
NOW.

4875
03:33:13,150 --> 03:33:16,286
WE WERE PRETTY SUCCESSFUL IN 

4876
03:33:16,286 --> 03:33:17,654
GETTING THE 13 CENTER TO 

4877
03:33:17,654 --> 03:33:18,422
CONTRIBUTE DATA AND WHAT WAS 

4878
03:33:18,422 --> 03:33:19,823
INVOLVED AND THEY NEEDED TO LOOK

4879
03:33:19,823 --> 03:33:21,858
FOR PATIENTS THAT HAD SOME OF 

4880
03:33:21,858 --> 03:33:24,261
THESE GENES WE HAD ON OUR LIST.

4881
03:33:24,261 --> 03:33:26,196
THEY HAD TO ENROLL THESE 

4882
03:33:26,196 --> 03:33:26,463
PATIENTS.

4883
03:33:26,463 --> 03:33:28,765
THEY HAD TO COLLECT THEIR 

4884
03:33:28,765 --> 03:33:31,101
E.H.R., ELECTRONIC HEALTH 

4885
03:33:31,101 --> 03:33:34,671
RECORDS, PRIMARILY GENETIC TEST 

4886
03:33:34,671 --> 03:33:35,972
REPORTS AND CONDUCTED 

4887
03:33:35,972 --> 03:33:37,607
PHENOTYPING WITH THEM.

4888
03:33:37,607 --> 03:33:39,142
NOW WE HAVE WILL 621 

4889
03:33:39,142 --> 03:33:45,015
PARTICIPANTS IN THE REGISTRY.

4890
03:33:45,015 --> 03:33:55,392
THERE'S A CLOUD-BASED DATA 

4891
03:33:55,392 --> 03:33:57,627
HOLDING AND IF YOU LOOK HAT 

4892
03:33:57,627 --> 03:34:00,063
GENES 1-20 PER GROUP IN THE GENE

4893
03:34:00,063 --> 03:34:01,431
AND ENROLLMENT STILL HAPPENING 

4894
03:34:01,431 --> 03:34:04,835
BUT AT A TRICKLE LEVEL BECAUSE 

4895
03:34:04,835 --> 03:34:06,369
WE'RE IN THE STAGES OF 

4896
03:34:06,369 --> 03:34:07,838
REFUNDING -- HOPING TO BE 

4897
03:34:07,838 --> 03:34:08,171
REFUNDED.

4898
03:34:08,171 --> 03:34:10,140
YOU CAN SEE MORE HERE.

4899
03:34:10,140 --> 03:34:11,741
THERE'S A QR CODE TO TAKE US TO 

4900
03:34:11,741 --> 03:34:13,410
OUR WEBSITE.

4901
03:34:13,410 --> 03:34:16,413
IT IS A REG IS GEARED TO BE A 

4902
03:34:16,413 --> 03:34:18,849
RESOURCE SO THERE'S A WAY TO GET

4903
03:34:18,849 --> 03:34:20,150
ACCESS TO THE DATA.

4904
03:34:20,150 --> 03:34:22,319
YOU CAN FIND IT HERE.

4905
03:34:22,319 --> 03:34:24,888
WE RECENTLY PUBLISHED A PAPER TO

4906
03:34:24,888 --> 03:34:25,989
TELL YOU MORE ABOUT THE 

4907
03:34:25,989 --> 03:34:29,926
DEMOGRAPHIC OF THE PATIENTS IN 

4908
03:34:29,926 --> 03:34:30,427
THE DATABASE.

4909
03:34:30,427 --> 03:34:32,362
THIS WAS PUBLISHED THIS YEAR BUT

4910
03:34:32,362 --> 03:34:33,363
CAN'T REMEMBER HOW MANY SUBJECTS

4911
03:34:33,363 --> 03:34:38,068
WERE IN IT BUT IT'S NOT ALL THE 

4912
03:34:38,068 --> 03:34:41,104
SUBJECTS THAT WERE STATED BUT 

4913
03:34:41,104 --> 03:34:43,140
GIVES A PRETTY GOOD SNAPSHOT OF 

4914
03:34:43,140 --> 03:34:43,540
THE DEMOGRAPHICS.

4915
03:34:43,540 --> 03:34:45,609
I'M GOING TO TALK ABOUT WHAT I 

4916
03:34:45,609 --> 03:34:47,010
LOVE WHICH IS THE PHENOTYPING.

4917
03:34:47,010 --> 03:34:47,644
THIS IS AIM 1.

4918
03:34:47,644 --> 03:34:49,613
I WANTED TO LET YOU HEAR A 

4919
03:34:49,613 --> 03:34:51,715
LITTLE BIT ABOUT THE DEVELOPMENT

4920
03:34:51,715 --> 03:34:56,486
OF THE PHENOTYPING BATTERY.

4921
03:34:56,486 --> 03:35:01,291
WE CREATED THIS BATLY THE RAPID 

4922
03:35:01,291 --> 03:35:02,392
NEUROBEHAVIORAL ASSESSMENT 

4923
03:35:02,392 --> 03:35:04,361
PROTOCOL AND JOHN CONSTANTINO 

4924
03:35:04,361 --> 03:35:05,996
WAS THE OTHER P.I. AND HAD BIG 

4925
03:35:05,996 --> 03:35:08,298
IDEAS ON WHAT NEEDED TO HAPPEN 

4926
03:35:08,298 --> 03:35:11,234
WITH THE BATTERY AND PROTOCOL 

4927
03:35:11,234 --> 03:35:13,003
AND WANTED IT TO BE STANDARDIZED

4928
03:35:13,003 --> 03:35:15,238
AND LOOKED AT DOMAINS IMPORTANT 

4929
03:35:15,238 --> 03:35:16,706
TO INTELLECTUAL DISABILITY AND 

4930
03:35:16,706 --> 03:35:18,208
ACROSS A BROAD AGE RANGE AND 

4931
03:35:18,208 --> 03:35:19,409
WANTED TO BE ABLE TO SEE 

4932
03:35:19,409 --> 03:35:20,277
ANYBODY.

4933
03:35:20,277 --> 03:35:21,878
HE WANTED IT TO BE FREE WHICH I 

4934
03:35:21,878 --> 03:35:24,781
HAD TO SAY, LOOK, I DON'T KNOW 

4935
03:35:24,781 --> 03:35:26,283
THAT'S POSSIBLE BUT WE'LL MAKE 

4936
03:35:26,283 --> 03:35:29,386
IT AS CHEAP AS POSSIBLE AND LOOK

4937
03:35:29,386 --> 03:35:32,022
FOR NORMED OR THINGS AVAILABLE 

4938
03:35:32,022 --> 03:35:32,923
AT LOW COST.

4939
03:35:32,923 --> 03:35:34,291
HE WANTED IT TO BE SOMETHING 

4940
03:35:34,291 --> 03:35:38,862
THAT COULD BE EASILY 

4941
03:35:38,862 --> 03:35:40,397
ADMINISTERED BY WILL CLAIMS 

4942
03:35:40,397 --> 03:35:44,267
PEOPLE BUT NOT WILL Ph.D. LEVEL 

4943
03:35:44,267 --> 03:35:45,535
PERSON AND WHEN COVID HAPPENED 

4944
03:35:45,535 --> 03:35:48,838
THAT ALL ADDED TO THE MIX OF 

4945
03:35:48,838 --> 03:35:49,072
REMOTE.

4946
03:35:49,072 --> 03:35:50,574
SO REMOTE ADMINISTRATION FOR ALL

4947
03:35:50,574 --> 03:35:50,774
THIS.

4948
03:35:50,774 --> 03:35:53,710
THAT WAS A BIG ASK.

4949
03:35:53,710 --> 03:35:57,247
THEE ARE DOMAINS WE WERE HOPING 

4950
03:35:57,247 --> 03:35:57,581
TO TAP.

4951
03:35:57,581 --> 03:36:00,317
IT'S AN ABBREVIATED BATTERY.

4952
03:36:00,317 --> 03:36:02,852
IT'S NOT SUPPOSED TO BE THE 

4953
03:36:02,852 --> 03:36:04,854
BIGGEST MOST ROBUST PICTURE OF 

4954
03:36:04,854 --> 03:36:05,121
PATIENTS.

4955
03:36:05,121 --> 03:36:06,089
IT'S A SNAPSHOT ACROSS THESE 

4956
03:36:06,089 --> 03:36:09,960
DOMAINS.

4957
03:36:09,960 --> 03:36:12,562
THE IDEA WILL WOULD SERVE AS A 

4958
03:36:12,562 --> 03:36:15,665
JUMPING OFF PLACE FOR STUDY AND 

4959
03:36:15,665 --> 03:36:16,032
INVESTIGATIONS.

4960
03:36:16,032 --> 03:36:17,000
THESE ARE THE TOOLS AND MEASURES

4961
03:36:17,000 --> 03:36:19,569
THAT ARE INCLUDED IN THE BATTERY

4962
03:36:19,569 --> 03:36:22,105
AND YOU CAN SEE HERE THE THINGS 

4963
03:36:22,105 --> 03:36:24,274
YOU RECOGNIZE BUT A COMBINATION 

4964
03:36:24,274 --> 03:36:29,145
OF QUESTIONNAIRES, OFF THE SHELF

4965
03:36:29,145 --> 03:36:32,282
THINGS AND A FEW ADAPTED OR 

4966
03:36:32,282 --> 03:36:41,258
ADMINISTERED VIA 

4967
03:36:41,258 --> 03:36:42,292
TELEOBSERVATELE 

4968
03:36:42,292 --> 03:36:43,126
OBSERVAHEALTH 

4969
03:36:43,126 --> 03:36:43,793
OBSERVATIONS AND WE USED IT WILL

4970
03:36:43,793 --> 03:36:45,462
AND ADAPTED AND GOT PERMISSION 

4971
03:36:45,462 --> 03:36:52,269
FROM THE PUBLISHER TO ADAPT ONE 

4972
03:36:52,269 --> 03:36:55,705
SUB SCALE OF THE SHIPLEY A 

4973
03:36:55,705 --> 03:37:00,176
NON-VERBAL REASONING TASK TO 

4974
03:37:00,176 --> 03:37:01,244
ADMINISTER THROUGH TELEHEALTH 

4975
03:37:01,244 --> 03:37:02,279
WITH A SHARED SCREEN.

4976
03:37:02,279 --> 03:37:04,381
WE GOT PERMISSION BUT IT'S NOT 

4977
03:37:04,381 --> 03:37:06,216
GOING TO WORK FOR EVERYBODY.

4978
03:37:06,216 --> 03:37:08,885
WE ALSO USED A PARENT REPORT 

4979
03:37:08,885 --> 03:37:13,790
PROFILE FOR THOSE SITUATIONS.

4980
03:37:16,092 --> 03:37:18,595
 SO WE TRIED FOR A DIRECT 

4981
03:37:18,595 --> 03:37:20,297
OBSERVATION BUT COULDN'T WENT 

4982
03:37:20,297 --> 03:37:26,303
WITH ALTERNATIVES AND THIS IS A 

4983
03:37:26,303 --> 03:37:28,104
LAUNDRY LIST OF THINGS WE WERE 

4984
03:37:28,104 --> 03:37:28,405
COLLECTING.

4985
03:37:28,405 --> 03:37:30,507
IT'S KIND OF BROKEN DOWN INTO 

4986
03:37:30,507 --> 03:37:31,107
TWO SECTIONS.

4987
03:37:31,107 --> 03:37:33,977
A SECTION WHERE WE HAVE 

4988
03:37:33,977 --> 03:37:34,544
QUESTIONNAIRES AND REPORTS.

4989
03:37:34,544 --> 03:37:36,680
WE HAVE CONVERTED ALL OF THOSE 

4990
03:37:36,680 --> 03:37:39,683
INSTRUMENTS WHERE WE NEEDED TO 

4991
03:37:39,683 --> 03:37:41,051
WITH PUBLISHER PERMISSION TO RED

4992
03:37:41,051 --> 03:37:44,888
CAP FORM TO E-MAIL TO FAMILIES.

4993
03:37:44,888 --> 03:37:47,390
SO WE HAD TO CODE THAT AND DID 

4994
03:37:47,390 --> 03:37:50,160
AND ON THE BACK END WE HAD TO 

4995
03:37:50,160 --> 03:37:52,062
CODE THE SCORING FOR THOSE 

4996
03:37:52,062 --> 03:37:52,262
FORMS.

4997
03:37:52,262 --> 03:37:53,263
SO FORMS GET SCORED.

4998
03:37:53,263 --> 03:37:55,131
WE HAD TO DO BOTH OF THOSE 

4999
03:37:55,131 --> 03:37:58,034
THINGS BUT THOSE HAVE BEEN DONE 

5000
03:37:58,034 --> 03:37:59,536
AND THEN HAVE A TELEHEALTH 

5001
03:37:59,536 --> 03:37:59,736
VISIT.

5002
03:37:59,736 --> 03:38:01,905
IT DEPENDS ON HOW MUCH TIME WE 

5003
03:38:01,905 --> 03:38:02,772
NEED BUT INCLUDES THIS 

5004
03:38:02,772 --> 03:38:06,309
ACCOUNTING SCREEN IF WE NEED TO 

5005
03:38:06,309 --> 03:38:07,043
DO IT.

5006
03:38:07,043 --> 03:38:08,278
AN AUTISM OBSERVATIONAL SCREEN 

5007
03:38:08,278 --> 03:38:11,681
AND SOME SCREENERS WE CREATED TO

5008
03:38:11,681 --> 03:38:15,785
LOOK FOR MORPHOLOGY AND 

5009
03:38:15,785 --> 03:38:18,722
NEUROLOGICAL SCREEN.

5010
03:38:18,722 --> 03:38:22,359
IT'S ABOUT 30 TO 60 MINUTE 

5011
03:38:22,359 --> 03:38:23,693
BATTERY OF TELEHEALTH AND THE 

5012
03:38:23,693 --> 03:38:25,595
REST IS REMOTELY ADMINISTERED 

5013
03:38:25,595 --> 03:38:29,833
QUESTIONNAIRES.

5014
03:38:29,833 --> 03:38:31,668
WE ALSO ON THE SLIDE I USUALLY 

5015
03:38:31,668 --> 03:38:35,505
HAVE A PICTURE OF A PLANE AS 

5016
03:38:35,505 --> 03:38:37,540
WE'RE TRYING TO BUILD IT AND 

5017
03:38:37,540 --> 03:38:39,642
IT'S IMPORTANT BECAUSE THE OFF 

5018
03:38:39,642 --> 03:38:43,079
THE SHELF THINGS WEREN'T USED IN

5019
03:38:43,079 --> 03:38:45,081
THE WAYS AND WANTED TO MAKE SURE

5020
03:38:45,081 --> 03:38:48,118
WE WOULD VALIDATE WHAT WE WERE 

5021
03:38:48,118 --> 03:38:50,553
COLLECTING TO MATCH UP IT WITH 

5022
03:38:50,553 --> 03:38:52,455
GOLD STANDARD DIAGNOSTIC DATA.

5023
03:38:52,455 --> 03:38:58,194
WE DID IT IN AN ACTIVE WAY AND 

5024
03:38:58,194 --> 03:39:01,598
WHAT WE REALIZED WE NEEDED WAS 

5025
03:39:01,598 --> 03:39:02,966
MAPPING TOOLS.

5026
03:39:02,966 --> 03:39:07,437
AND SO WE TOOK THE -- THIS IS 

5027
03:39:07,437 --> 03:39:12,041
PARTLY BECAUSE THE GENOME -- THE

5028
03:39:12,041 --> 03:39:16,579
GENE CURATION SAID WE NEED 

5029
03:39:16,579 --> 03:39:17,847
EVERYTHING IN TERMINOLOGY AND 

5030
03:39:17,847 --> 03:39:19,015
THAT WILL HELP WITH THE GENE 

5031
03:39:19,015 --> 03:39:21,818
CREATION.

5032
03:39:21,818 --> 03:39:25,522
WE HAD TO TAKE THE PHENOTYPING 

5033
03:39:25,522 --> 03:39:31,194
DATA AND MAP IT TO HPO TERMS AND

5034
03:39:31,194 --> 03:39:32,429
HELPS WITH THE VALIDATION 

5035
03:39:32,429 --> 03:39:32,662
PURPOSE.

5036
03:39:32,662 --> 03:39:35,732
SO WE DID NOT DO ALL 13,000 

5037
03:39:35,732 --> 03:39:36,099
TERMS.

5038
03:39:36,099 --> 03:39:37,167
THERE'S A LOT OF HPO TERMS.

5039
03:39:37,167 --> 03:39:38,902
WE SAID YOU HAVE TO GIVE US YOUR

5040
03:39:38,902 --> 03:39:39,469
LAUNDRY LIST.

5041
03:39:39,469 --> 03:39:40,370
SO THEY DID.

5042
03:39:40,370 --> 03:39:42,038
I DON'T EXPECT YOU TO READ THIS 

5043
03:39:42,038 --> 03:39:43,306
BUT THEY PICKED OUT THE TERMS 

5044
03:39:43,306 --> 03:39:46,342
AND SAID PLEASE LOOK FOR THESE.

5045
03:39:46,342 --> 03:39:49,612
THEY'RE PRIMARILY ASSOCIATED 

5046
03:39:49,612 --> 03:39:52,515
WITH INTELLECTUAL DISABILITY AND

5047
03:39:52,515 --> 03:39:54,350
DEVELOPMENT DELAY AND ADHD AND 

5048
03:39:54,350 --> 03:39:55,685
THEY SAID HERE'S WHAT WE'D LIKE 

5049
03:39:55,685 --> 03:39:56,486
YOU TO DO.

5050
03:39:56,486 --> 03:39:59,589
SO WE MAPPED OUT THE 30 OR SO 

5051
03:39:59,589 --> 03:40:00,824
HPO TERMS AND TOOK OUR 

5052
03:40:00,824 --> 03:40:02,459
PHENOTYPING DATA AND CONVERTED 

5053
03:40:02,459 --> 03:40:06,429
THEM WITH AN ALGORITHM INTO THE 

5054
03:40:06,429 --> 03:40:06,629
TERMS.

5055
03:40:06,629 --> 03:40:10,467
I DON'T HAVE IT HERE BUT WE DID 

5056
03:40:10,467 --> 03:40:13,870
A LOT OF QC WITH IT AND HAVE 

5057
03:40:13,870 --> 03:40:15,238
100% MAPPING SUCCESS.

5058
03:40:15,238 --> 03:40:17,474
THAT WE WERE PLEASED ABOUT AFTER

5059
03:40:17,474 --> 03:40:21,211
THE QC AND NOW WHEN WE GO INTO 

5060
03:40:21,211 --> 03:40:22,979
OUR DATABASE YOU CAN GENERATE A 

5061
03:40:22,979 --> 03:40:24,481
REPORT THAT SAYS TELL ME FROM 

5062
03:40:24,481 --> 03:40:28,952
THE PATIENTS WHAT ARE THE HPO 

5063
03:40:28,952 --> 03:40:29,152
TERMS.

5064
03:40:29,152 --> 03:40:32,288
IT DIDN'T TELL YOU WHAT THEY'RE 

5065
03:40:32,288 --> 03:40:34,958
ASSOCIATED WITH AND IT'S 

5066
03:40:34,958 --> 03:40:35,492
PROBABLY THERE.

5067
03:40:35,492 --> 03:40:37,660
SO THEN WE USED THOSE TERMS TO 

5068
03:40:37,660 --> 03:40:39,329
THINK ABOUT OUR VALIDATION FOR 

5069
03:40:39,329 --> 03:40:40,263
THE PHENOTYPING.

5070
03:40:40,263 --> 03:40:46,102
AND WHAT WE NEEDED FOR THAT WAS 

5071
03:40:46,102 --> 03:40:48,304
GOLD STANDARD CLINICAL REPORT 

5072
03:40:48,304 --> 03:40:50,273
AND SAY THE CHILD HAS A 

5073
03:40:50,273 --> 03:40:51,241
COGNITIVE MEASURE.

5074
03:40:51,241 --> 03:40:55,111
THEY GOT A CLINICAL DIAGNOSIS OF

5075
03:40:55,111 --> 03:41:00,450
AUTISM AND IDD.

5076
03:41:00,450 --> 03:41:04,654
GOOD OUR RNAP DATA FALL IN LINE 

5077
03:41:04,654 --> 03:41:07,824
WITH THEIR CLINICALLY OBSERVED 

5078
03:41:07,824 --> 03:41:10,527
GOLD STANDARD REPORTING?

5079
03:41:10,527 --> 03:41:12,495
WE'VE HAD TO DO A LOT OF DATA 

5080
03:41:12,495 --> 03:41:12,762
CLEANING.

5081
03:41:12,762 --> 03:41:15,365
THE 13 CENTERS THAT WERE 

5082
03:41:15,365 --> 03:41:20,537
COLLECTING DATA FOR US, THEIR 

5083
03:41:20,537 --> 03:41:23,339
MISSION WAS TO COLLECT THE DATA 

5084
03:41:23,339 --> 03:41:24,674
FOR THE PROJECT AND GOLD 

5085
03:41:24,674 --> 03:41:25,074
STANDARD REPORTS.

5086
03:41:25,074 --> 03:41:27,310
WHEN YOU DIG INTO THE GOLD 

5087
03:41:27,310 --> 03:41:29,479
STANDARD REPORT SOMETIMES IT WAS

5088
03:41:29,479 --> 03:41:31,614
THE SCHOOL IP THAT DIDN'T REALLY

5089
03:41:31,614 --> 03:41:32,415
MENTION ANYTHING ABOUT THE 

5090
03:41:32,415 --> 03:41:33,917
CLINICAL DIAGNOSIS OR HOW IT GOT

5091
03:41:33,917 --> 03:41:34,117
THERE.

5092
03:41:34,117 --> 03:41:36,019
JUST HAD MORE ACADEMIC MATERIAL 

5093
03:41:36,019 --> 03:41:41,558
OR SOMETIMES JUST A CLINIC NOTE 

5094
03:41:41,558 --> 03:41:46,529
AND DIDN'T REALLY DESCRIBE WHAT 

5095
03:41:46,529 --> 03:41:48,231
WAS USED AND SOME DATA WE HAD TO

5096
03:41:48,231 --> 03:41:51,935
CLEAN OR REMOVE AND IT'S BEEN A 

5097
03:41:51,935 --> 03:41:55,338
LENGTHY PROCESS AND HAVE DONE 

5098
03:41:55,338 --> 03:41:57,707
EXTRACTION FROM THE E.H.R. AND 

5099
03:41:57,707 --> 03:41:58,274
CLINICAL RECORDS AND DATA 

5100
03:41:58,274 --> 03:41:59,042
CLEANING AND WE JUST FINISHED 

5101
03:41:59,042 --> 03:42:08,017
THIS SPRING.

5102
03:42:08,017 --> 03:42:09,953
I LOOKED AT THE DATA AND LOOK 

5103
03:42:09,953 --> 03:42:16,526
LIKE IT GOOD CONCURRENT VALIDITY

5104
03:42:16,526 --> 03:42:19,529
WITH MORE SEVERE CASES YOU MAY 

5105
03:42:19,529 --> 03:42:21,564
CONSIDER STRAIGHTFORWARD AND LOW

5106
03:42:21,564 --> 03:42:22,932
FUNCTIONING.

5107
03:42:22,932 --> 03:42:25,168
WHEN THE DATA SAID THERE'S AN 

5108
03:42:25,168 --> 03:42:25,768
INTELLECTUAL DISABILITY THE 

5109
03:42:25,768 --> 03:42:28,271
SUBJECT AND CLINICAL REPORT HAS 

5110
03:42:28,271 --> 03:42:30,106
A CLEAR CASE OF INTELLECTUAL 

5111
03:42:30,106 --> 03:42:30,406
DISABILITY.

5112
03:42:30,406 --> 03:42:33,343
IT WORKED PRETTY WELL FOR THOSE.

5113
03:42:33,343 --> 03:42:40,216
IT DID NOT WORK PRETTY WELL AND 

5114
03:42:40,216 --> 03:42:50,727
AGAIN THIS IS PRELIMINARY BUT 

5115
03:42:52,261 --> 03:42:55,298
WE'LL NEED TO GET AN ADDITIONAL 

5116
03:42:55,298 --> 03:42:57,667
REPORTER BECAUSE THE 

5117
03:42:57,667 --> 03:42:59,402
SELF-REPORTING DIDN'T WORK WELL 

5118
03:42:59,402 --> 03:43:00,903
AND IF PEOPLE DIDN'T COMPLETE 

5119
03:43:00,903 --> 03:43:02,105
THINGS OR COMPLETE THEIR 

5120
03:43:02,105 --> 03:43:07,043
INFORMATION AND THE MISSING DATA

5121
03:43:07,043 --> 03:43:16,185
PROBLEM LOOKING TO SEE IF THE.

5122
03:43:16,185 --> 03:43:19,522
RNA

5123
03:43:19,522 --> 03:43:20,223
RNAPA AGREES WITH THE DIAGNOSTIC

5124
03:43:20,223 --> 03:43:23,159
REPORT AND WANT TO DO WITH 

5125
03:43:23,159 --> 03:43:26,496
ADDITIONAL HPO TERMS AND STARTED

5126
03:43:26,496 --> 03:43:29,298
WITH THE WILL AUTISM RELATED 

5127
03:43:29,298 --> 03:43:34,437
TERMS AND WHAT THE COLLABORATORS

5128
03:43:34,437 --> 03:43:38,408
WERE SO EAGER TO SEE AND HAVE 

5129
03:43:38,408 --> 03:43:39,475
ADHD AND THINGS OF HIGH INTEREST

5130
03:43:39,475 --> 03:43:40,943
AND THAT IS ALSO GOING TO BE ON 

5131
03:43:40,943 --> 03:43:51,120
OUR LIST.

5132
03:43:56,025 --> 03:44:00,263
AND SOME USE A MACHINE LEARNING 

5133
03:44:00,263 --> 03:44:07,503
ARLING -- ALGORITHM AND WHAT 

5134
03:44:07,503 --> 03:44:10,840
I'LL DESCRIBE WHEN YOU LOOK IN 

5135
03:44:10,840 --> 03:44:13,776
THE E.H.R. YOU CAN GO OFF ON AN 

5136
03:44:13,776 --> 03:44:16,045
ERRONEOUS PATH AND SEE A PERSON 

5137
03:44:16,045 --> 03:44:17,747
MAY HAVE A DIAGNOSIS OF AUTISM 

5138
03:44:17,747 --> 03:44:19,982
BUT WHEN YOU DIG IN THE RECORD 

5139
03:44:19,982 --> 03:44:22,151
IT'S BECAUSE THEY WENT TO A 

5140
03:44:22,151 --> 03:44:23,720
CLINIC AND PEOPLE THOUGHT THEY 

5141
03:44:23,720 --> 03:44:26,355
HAD AUTISM AND NEVER GOT A 

5142
03:44:26,355 --> 03:44:27,423
DIAGNOSIS BUT IT STUCK IN THE 

5143
03:44:27,423 --> 03:44:29,125
E.H.R. AND WHEN YOU DO AN 

5144
03:44:29,125 --> 03:44:29,659
EXTRACTION IT PULLS UP AS 

5145
03:44:29,659 --> 03:44:39,802
AUTISM.

5146
03:44:45,508 --> 03:44:48,244
WE'RE TRYING TO GET MORE DATA 

5147
03:44:48,244 --> 03:44:50,313
THAT'S RELIABLE.

5148
03:44:50,313 --> 03:44:51,914
I DIDN'T TALK A LOT ABOUT 

5149
03:44:51,914 --> 03:44:53,950
SPANISH BUT WE'RE DOING ALL THE 

5150
03:44:53,950 --> 03:44:55,084
SAME THING FOR OUR 

5151
03:44:55,084 --> 03:45:00,022
SPANISH-SPEAKING PARTICIPANTS.

5152
03:45:00,022 --> 03:45:01,858
ALONG THE WAY WE HAD 

5153
03:45:01,858 --> 03:45:03,860
INVESTIGATORS SAY WHAT ABOUT 

5154
03:45:03,860 --> 03:45:04,260
SPANISH?

5155
03:45:04,260 --> 03:45:06,229
WE HIRED PEOPLE TO DO THE 

5156
03:45:06,229 --> 03:45:07,697
TELEHEALTH IN SPANISH AND 

5157
03:45:07,697 --> 03:45:08,464
COLLECTED THE DATA.

5158
03:45:08,464 --> 03:45:17,974
THAT'S ALSO ON OUR LAUNDRY LIST.

5159
03:45:17,974 --> 03:45:21,711
SO THERE'S PROS AND CONS WITH 

5160
03:45:21,711 --> 03:45:22,979
THESE PHENOTYPING AND WE CAN 

5161
03:45:22,979 --> 03:45:24,714
ANTICIPATE THE PROS.

5162
03:45:24,714 --> 03:45:25,515
IT'S COST EFFICIENT AND CAN DO 

5163
03:45:25,515 --> 03:45:30,019
BIG NUMBERS.

5164
03:45:30,019 --> 03:45:32,288
YOU CAN SEE PATIENTS IN THE 

5165
03:45:32,288 --> 03:45:33,489
COMFORT OF THEIR HOMES AND THERE

5166
03:45:33,489 --> 03:45:34,991
ARE SOME CONS AND THEY'RE NOT 

5167
03:45:34,991 --> 03:45:45,101
SMALL.

5168
03:45:47,937 --> 03:45:52,708
TELEHEALTH REQUIRES IT DEVICES 

5169
03:45:52,708 --> 03:45:55,211
AND MANY FAMILIES WHEN YOU SAY 

5170
03:45:55,211 --> 03:46:00,149
CAN YOU DO A TELEHEA HEAHEALTH  

5171
03:46:00,149 --> 03:46:03,219
THEY LOOK AT THEIR PHONE AND SAY

5172
03:46:03,219 --> 03:46:03,586
YES.

5173
03:46:03,586 --> 03:46:11,027
SOME TOOLS REQUIRE A BIG SCREEN 

5174
03:46:11,027 --> 03:46:13,629
SO WHEN YOU ASK IF THEY HAVE THE

5175
03:46:13,629 --> 03:46:15,364
TECHNOLOGY MAYBE THEY DO AND 

5176
03:46:15,364 --> 03:46:16,098
MAYBE THEY DON'T.

5177
03:46:16,098 --> 03:46:17,700
I HAVE COLLEAGUES THAT SHIP A 

5178
03:46:17,700 --> 03:46:20,536
LAPTOP TO FAMILIES TO DO THE 

5179
03:46:20,536 --> 03:46:22,839
ASSESSMENT AND THEN SHIP IT 

5180
03:46:22,839 --> 03:46:23,039
BACK.

5181
03:46:23,039 --> 03:46:24,373
THE INTERNET CONNECTIVITY IS 

5182
03:46:24,373 --> 03:46:26,409
ALSO A PROBLEM FOR THE 

5183
03:46:26,409 --> 03:46:26,676
TELEVISIT.

5184
03:46:26,676 --> 03:46:30,012
NOT SO MUCH THE QUESTIONNAIRES 

5185
03:46:30,012 --> 03:46:36,319
BUT THE TELEHEALTH VISIT THE 

5186
03:46:36,319 --> 03:46:44,293
INTERNET CAN BE CHOPPY AND YOU 

5187
03:46:44,293 --> 03:46:50,166
NEED A PRETTY GOOD INTERNET 

5188
03:46:50,166 --> 03:46:57,206
CONNECTION.

5189
03:46:57,206 --> 03:46:58,941
A PAPER TALKS ABOUT THE COMPUTER

5190
03:46:58,941 --> 03:47:03,012
ADMINISTERED BATTERY AND A PAPER

5191
03:47:03,012 --> 03:47:13,556
TALKED ABOUT MEASURE ON UNSU

5192
03:47:14,824 --> 03:47:15,124
UNSUPERADVISED.

5193
03:47:15,124 --> 03:47:17,894
IF YOU CAN IMAGINE WHEN YOU'RE 

5194
03:47:17,894 --> 03:47:20,263
AT HOME MAYBE YOU'RE FEELING 

5195
03:47:20,263 --> 03:47:23,599
UNDER THE GUN TO DO IT QUICKLY 

5196
03:47:23,599 --> 03:47:25,368
AND UNCONTROLLED.

5197
03:47:25,368 --> 03:47:30,873
WE HAVE MANY VIDEOS OF SIBLING 

5198
03:47:30,873 --> 03:47:33,376
RUNNING IN THE BACKGROUND AND 

5199
03:47:33,376 --> 03:47:34,543
DON'T KNOW WHAT WILL HAPPEN IN 

5200
03:47:34,543 --> 03:47:38,481
THE BACKGROUND THAT MAY AFFECT 

5201
03:47:38,481 --> 03:47:39,348
THE TELEHEALTH ASSESSMENT.

5202
03:47:39,348 --> 03:47:49,892
THOSE ARE THE CONS BUT 

5203
03:47:50,426 --> 03:48:00,836
TELEHEALTH IS HERE TO STAY.

5204
03:48:05,841 --> 03:48:07,710
AND THE NIH IS WORKING IN THIS 

5205
03:48:07,710 --> 03:48:09,445
EFFORT AND THERE'S NEW THINGS 

5206
03:48:09,445 --> 03:48:11,047
AND NEW THINGS ARE BEING 

5207
03:48:11,047 --> 03:48:12,148
VALIDATED AS WE SPEAK IN TERMS 

5208
03:48:12,148 --> 03:48:19,455
OF ASSESSMENTS CONDUCTED AND 

5209
03:48:19,455 --> 03:48:20,489
EVALUATED VIA TELEHEALTH.

5210
03:48:20,489 --> 03:48:22,992
I THINK IT'S THE WAY OF THIS 

5211
03:48:22,992 --> 03:48:26,162
FUTURE AND CLINICAL TRIALS IS 

5212
03:48:26,162 --> 03:48:27,997
WELL SUITED TO THINK OF HOW TO 

5213
03:48:27,997 --> 03:48:28,965
IMPLEMENT MEASURES TO DECREASE 

5214
03:48:28,965 --> 03:48:33,369
THE BURDEN OF COMING IN MULTIPLE

5215
03:48:33,369 --> 03:48:34,537
TIMES TO A SITE.

5216
03:48:34,537 --> 03:48:36,272
I'M GOING TO JUST STOP HERE AND 

5217
03:48:36,272 --> 03:48:38,841
ACKNOWLEDGE THE FUNDING FOR OUR 

5218
03:48:38,841 --> 03:48:49,251
BRIDGING REGISTRY TEAM.

5219
03:48:50,152 --> 03:48:52,288
AND I WANT TO THANK OUR FUNDERS.

5220
03:48:52,288 --> 03:49:02,465
THANK YOU.

5221
03:49:07,770 --> 03:49:08,304
>> THANK YOU.

5222
03:49:08,304 --> 03:49:09,305
I DON'T KNOW.

5223
03:49:09,305 --> 03:49:14,010
>> QUESTION.

5224
03:49:14,010 --> 03:49:16,278
>> WHY CAN'T YOU DO
PATIENT 

5225
03:49:16,278 --> 03:49:18,180
RETURN OUTCOME RESULTS?

5226
03:49:18,180 --> 03:49:20,583
>> WHAT DO WE DO OR WHAT
DO I 

5227
03:49:20,583 --> 03:49:21,450
THINK WE SHOULD DO.

5228
03:49:21,450 --> 03:49:23,753
>> WHAT ARE YOU DOING?

5229
03:49:23,753 --> 03:49:27,656
>> SO WE DID FEEL IT WAS 

5230
03:49:27,656 --> 03:49:29,859
IMPORTANT TO GIVE BACK FEEDBACK 

5231
03:49:29,859 --> 03:49:31,360
RESULTS BUT DIDN'T WANT TO GIVE 

5232
03:49:31,360 --> 03:49:35,765
BACK THE INFORMATION FROM ALL 

5233
03:49:35,765 --> 03:49:37,433
THE EXPERIMENTAL MEASURES.

5234
03:49:37,433 --> 03:49:40,269
WE HAD A BIG DEBATE AND INCLUDED

5235
03:49:40,269 --> 03:49:42,571
DATA INCLUDED IN OUR BATTERY AND

5236
03:49:42,571 --> 03:49:43,105
DATA FROM THE DEVELOPMENT 

5237
03:49:43,105 --> 03:49:48,644
ASSESSMENT.

5238
03:49:48,644 --> 03:49:50,246
WHETHER THE SHIPLEY BECAUSE 

5239
03:49:50,246 --> 03:49:52,181
THOSE ARE STANDARDIZED SCORES WE

5240
03:49:52,181 --> 03:49:53,516
THOUGHT MANY FAMILIES MIGHT LIKE

5241
03:49:53,516 --> 03:49:55,718
TO GIVE TO THEIR SCHOOL SYSTEM 

5242
03:49:55,718 --> 03:49:58,020
FOR EXAMPLE OR THEIR CLINICIANS.

5243
03:49:58,020 --> 03:50:01,157
THOSE WERE THE PRIMARY -- ALSO 

5244
03:50:01,157 --> 03:50:04,160
THE CBPL OF THINGS WE ADMINISTER

5245
03:50:04,160 --> 03:50:06,262
SO WE GIVE THAT OUTPUT AS WELL.

5246
03:50:06,262 --> 03:50:10,966
IT'S A VERY ABBREVIATED FEEDBACK

5247
03:50:10,966 --> 03:50:18,874
REPORT WE GIVE.

5248
03:50:18,874 --> 03:50:20,509
>> I APPRECIATE THE
PRESENTATION

5249
03:50:20,509 --> 03:50:26,582
AS WELL AS EMPHASIZING AS PART 

5250
03:50:26,582 --> 03:50:27,616
OF THE PROGRAM BECAUSE TO ME 

5251
03:50:27,616 --> 03:50:30,252
IT'S BEEN A MAJOR OBSTACLE IN 

5252
03:50:30,252 --> 03:50:33,656
OUR ABILITY TO DO LARGE SCALE 

5253
03:50:33,656 --> 03:50:39,295
EPILEPSY CLINICAL WORK AND 

5254
03:50:39,295 --> 03:50:41,864
OBSERVATIONAL TRIALS I'M SURE 

5255
03:50:41,864 --> 03:50:44,300
YOU'RE AWARE AND HAVEN'T TALKED 

5256
03:50:44,300 --> 03:50:48,070
ABOUT THE MORE COMMON EPILEPSY 

5257
03:50:48,070 --> 03:50:51,273
AND IT WILL REQUIRE THE CAREFUL 

5258
03:50:51,273 --> 03:50:52,908
PHENOTYPING OF MANY PATIENTS AND

5259
03:50:52,908 --> 03:50:55,711
I'VE BEEN IN THAT WORLD A BIT 

5260
03:50:55,711 --> 03:50:58,414
AND HAVE MY OWN EXPERIENCE.

5261
03:50:58,414 --> 03:50:59,715
I CAN'T IMAGINE HOW HARD TO THE 

5262
03:50:59,715 --> 03:51:00,449
WORK HAS BEEN FOR YOU.

5263
03:51:00,449 --> 03:51:02,251
WE TALKED ABOUT THE CHALLENGES.

5264
03:51:02,251 --> 03:51:04,653
CAN YOU EXPAND ON TWO AREAS.

5265
03:51:04,653 --> 03:51:06,288
ONE, WHAT IS YOUR EXPECTED 

5266
03:51:06,288 --> 03:51:08,290
ENROLLMENT BY THIS POINT AND DID

5267
03:51:08,290 --> 03:51:12,495
YOU COME ACROSS DIFFICULTIES AND

5268
03:51:12,495 --> 03:51:13,629
HOW DO YOU THINK OF THE ABILITY 

5269
03:51:13,629 --> 03:51:16,932
TO USE THE METHODS FOR FOLLOWING

5270
03:51:16,932 --> 03:51:20,269
PATIENTS OVER TIME?

5271
03:51:20,269 --> 03:51:24,039
 IN OTHER WORDS ONCE THEY GET 

5272
03:51:24,039 --> 03:51:26,408
ENGAGED WE SEE A FALL OFF IN THE

5273
03:51:26,408 --> 03:51:26,675
PROTOCOL.

5274
03:51:26,675 --> 03:51:28,277
WHAT DO YOU THINK WILL BE THE 

5275
03:51:28,277 --> 03:51:29,945
FUTURE IN THAT REGARD?

5276
03:51:29,945 --> 03:51:31,313
>> SO TWO QUESTIONS.

5277
03:51:31,313 --> 03:51:39,622
WHAT WAS THE EXPECTED ENROLLMENT

5278
03:51:39,622 --> 03:51:42,224
WE HAD TO READJUST OUR 

5279
03:51:42,224 --> 03:51:48,364
ENROLLMENT GOAL AND IN THE 

5280
03:51:48,364 --> 03:51:52,868
ORIGINAL IT WAS LIKE 1,000 

5281
03:51:52,868 --> 03:51:53,936
SUBJECTS AND WHEN COVID HAPPENED

5282
03:51:53,936 --> 03:51:57,339
THEY READJUSTED THE GOAL.

5283
03:51:57,339 --> 03:52:02,878
THE NEW GOAL IS LIKE LIKE 670 

5284
03:52:02,878 --> 03:52:03,646
INDIVIDUALS.

5285
03:52:03,646 --> 03:52:05,114
I'M NOT SURE THEY CAME UP WITH 

5286
03:52:05,114 --> 03:52:08,617
THE NUMBER BUT WE WERE HAPPY.

5287
03:52:08,617 --> 03:52:12,121
WE GOT CLOSE TO OUR GOAL AND 

5288
03:52:12,121 --> 03:52:20,262
HAVE THE TRIPLE ENROLLMENT NOW.

5289
03:52:20,262 --> 03:52:24,200
WE WEENDED OUR FUNDING PSYCH AN 

5290
03:52:24,200 --> 03:52:28,270
THE GOAL OF RESUBMISSION IS NOT 

5291
03:52:28,270 --> 03:52:32,908
TO DO FOLLOW-UP BUT TO EXPAND TO

5292
03:52:32,908 --> 03:52:34,944
OTHER PATIENT OR CLINICAL 

5293
03:52:34,944 --> 03:52:35,277
GROUPS.

5294
03:52:35,277 --> 03:52:37,646
FIRST PROJECT WAS IT A GROUP OF 

5295
03:52:37,646 --> 03:52:38,480
IBBRCs.

5296
03:52:38,480 --> 03:52:41,050
IN THE COURSE OF THIS STUDY WE 

5297
03:52:41,050 --> 03:52:44,286
HAVE HAD GROUP OUTREACH TO US 

5298
03:52:44,286 --> 03:52:47,756
CAN WE SEND YOU ALL OF OUR 

5299
03:52:47,756 --> 03:52:50,292
SUBJECTS AND PATIENTS?

5300
03:52:50,292 --> 03:52:51,227
SOME OF THE RARE DISEASE GROUPS 

5301
03:52:51,227 --> 03:52:52,494
HAVE ASKED IF WE CAN SUPPORT 

5302
03:52:52,494 --> 03:52:55,030
THEM BY ENROLLING THEM IN THE 

5303
03:52:55,030 --> 03:52:56,098
REGISTRY TO BECOME A DATA HUB 

5304
03:52:56,098 --> 03:53:00,269
AND DO THE PHENOTYPING AND 

5305
03:53:00,269 --> 03:53:03,472
COLLECT THEIR RECORDS.

5306
03:53:03,472 --> 03:53:04,840
THAT'S THE SPIRIT OF THE RENEWAL

5307
03:53:04,840 --> 03:53:09,078
IS EXPANSION NOT JUST TO THE 

5308
03:53:09,078 --> 03:53:10,713
IBBRCs NOT NECESSARILY 

5309
03:53:10,713 --> 03:53:11,046
LONGITUDINAL.

5310
03:53:11,046 --> 03:53:15,050
THE REGISTRY PURPOSE IS TO HELP 

5311
03:53:15,050 --> 03:53:16,452
INVESTIGATORS HAVE A PLACE TO 

5312
03:53:16,452 --> 03:53:18,020
LOOK FOR SUBJECTS AND PATIENTS 

5313
03:53:18,020 --> 03:53:22,024
AND DO ADDITIONAL STUDIES AND 

5314
03:53:22,024 --> 03:53:22,391
RECOMPACT THEM.

5315
03:53:22,391 --> 03:53:27,630
I DON'T HAVE A GOOD ANSWER TO 

5316
03:53:27,630 --> 03:53:29,565
HOW INVESTED THEY'LL REMAIN.

5317
03:53:29,565 --> 03:53:35,904
THEY'RE ALSO ENROLLED IN CLIN 

5318
03:53:35,904 --> 03:53:36,405
GEN.

5319
03:53:36,405 --> 03:53:37,840
THEY DO PERIODIC UPDATES AS 

5320
03:53:37,840 --> 03:53:38,040
WELL.

5321
03:53:38,040 --> 03:53:40,476
I DON'T HAVE A GOOD ANSWER FOR 

5322
03:53:40,476 --> 03:53:43,212
THAT QUESTION.

5323
03:53:43,212 --> 03:53:44,847
>> DO ANY SEQUENCING
COMPANIES 

5324
03:53:44,847 --> 03:53:49,918
COME TO YOU LOOK FOR ADVICE HOW 

5325
03:53:49,918 --> 03:53:54,556
TO IMPROVE THEIR DATA?

5326
03:53:54,556 --> 03:53:55,157
>> 

5327
03:53:55,157 --> 03:53:56,492
>> I DON'T THINK SO, NO.

5328
03:53:56,492 --> 03:53:57,259
I HAVE NOT PERSONALLY TALKED TO 

5329
03:53:57,259 --> 03:54:07,369
THEM.

5330
03:54:11,006 --> 03:54:16,545
>> OUR NEXT SPEAKER IS
LANIE IS 

5331
03:54:16,545 --> 03:54:17,946
ROSS FROM UNIVERSITY OF 

5332
03:54:17,946 --> 03:54:18,547
ROCHESTER ADDRESSING ETHICAL 

5333
03:54:18,547 --> 03:54:22,551
ISSUES.

5334
03:54:22,551 --> 03:54:24,320
>> THANK YOU.

5335
03:54:24,320 --> 03:54:28,257
I WANT TO THANK YOU VICKI AND 

5336
03:54:28,257 --> 03:54:28,957
THE ORGANIZERS.

5337
03:54:28,957 --> 03:54:32,094
I'M A GENERAL PEDIATRICIAN.

5338
03:54:32,094 --> 03:54:38,500
I HAVE A Ph.D. IN PHILOSOPHY AND

5339
03:54:38,500 --> 03:54:40,102
HERE AS AN ETHICISTS.

5340
03:54:40,102 --> 03:54:46,809
MY OWN WORK HAS BEEN IN 

5341
03:54:46,809 --> 03:54:47,109
MONOGENICS.

5342
03:54:47,109 --> 03:54:55,451
I'VE LOOKED AT MONOGENIC 

5343
03:54:55,451 --> 03:55:03,559
DIABETES AS WELL AS PARKINSON'S.

5344
03:55:03,559 --> 03:55:06,295
I'LL ACKNOWLEDGE MY IGNORANCE 

5345
03:55:06,295 --> 03:55:12,267
AND THERE'S A LOT I DON'T KNOW 

5346
03:55:12,267 --> 03:55:14,403
AND A LOT A LOT US DON'T KNOW 

5347
03:55:14,403 --> 03:55:18,006
AND USE THAT TO FRAME.

5348
03:55:18,006 --> 03:55:20,609
I'LL BEGIN WITH A QUOTE, THOSE 

5349
03:55:20,609 --> 03:55:22,244
WHO CANNOT REMEMBER THE PAST ARE

5350
03:55:22,244 --> 03:55:25,848
CONDEMNED TO REPEAT IT AND SOME 

5351
03:55:25,848 --> 03:55:27,950
OF THIS IS ON ISSUES THAT WERE 

5352
03:55:27,950 --> 03:55:31,653
RAISED AND THERE WERE A LOT OF 

5353
03:55:31,653 --> 03:55:32,588
ETHICAL ISSUES RAISED AND MANY 

5354
03:55:32,588 --> 03:55:34,890
COMMENTS WERE MADE BY OTHER 

5355
03:55:34,890 --> 03:55:36,158
SPEAKERS BUT SOME I WANT TO 

5356
03:55:36,158 --> 03:55:36,425
EMPHASIZE.

5357
03:55:36,425 --> 03:55:39,395
I WANT TO BEGIN WITH THIS QUOTE 

5358
03:55:39,395 --> 03:55:41,497
ABOUT REMEMBERING OUR HISTORY.

5359
03:55:41,497 --> 03:55:44,032
AS WE TALKED ABOUT GENETIC 

5360
03:55:44,032 --> 03:55:45,100
STRATEGIES.

5361
03:55:45,100 --> 03:55:46,835
WE HAVE TO REMEMBER THE GENE 

5362
03:55:46,835 --> 03:55:52,274
TRANSFER TRIAL HAS RISK AND WE 

5363
03:55:52,274 --> 03:55:56,011
MENTIONED AN 18-YEAR-OLD WHO HAD

5364
03:55:56,011 --> 03:56:01,316
AN OTC DEFICIENCY WHICH CAN BE 

5365
03:56:01,316 --> 03:56:11,827
TREAT ED AND THERE WAS AN AD 

5366
03:56:12,361 --> 03:56:21,603
VIRUS AND HE SUFFERED AN IMMUNE 

5367
03:56:21,603 --> 03:56:22,938
RESPONSE LEADING TO ORGAN 

5368
03:56:22,938 --> 03:56:24,406
FAILURE AND BRAIN DEATH.

5369
03:56:24,406 --> 03:56:25,374
WHAT WAS IMPORTANT WAS THE 

5370
03:56:25,374 --> 03:56:30,879
PROBLEMS WITH THE ETHICS.

5371
03:56:30,879 --> 03:56:32,281
THERE WERE A LOT OF ONLY CAL 

5372
03:56:32,281 --> 03:56:35,684
LAPSES AT THE FEDERAL AND WILL 

5373
03:56:35,684 --> 03:56:36,418
ADVISORY COMMITTEE.

5374
03:56:36,418 --> 03:56:44,626
FIRST THE APPROVED PROTOCOL SAID

5375
03:56:44,626 --> 03:56:46,295
IT WAS IN THE BLOODSTREAM BUT IT

5376
03:56:46,295 --> 03:56:47,129
WENT TO THE LIVER AND EXCLUSION 

5377
03:56:47,129 --> 03:56:50,065
CRITERIA WERE IGNORED.

5378
03:56:50,065 --> 03:56:52,734
HE HAD A HAMBURGER THE DAY 

5379
03:56:52,734 --> 03:56:56,238
BEFORE HE WAS SUPPOSED TO GET 

5380
03:56:56,238 --> 03:56:58,106
THE INFUSION AND HIS LACKS WERE 

5381
03:56:58,106 --> 03:57:00,008
OFF THE CHART AND DIDN'T MEET 

5382
03:57:00,008 --> 03:57:01,310
THE CRITERIA BUT DECIDED TO GO 

5383
03:57:01,310 --> 03:57:03,946
AHEAD ANYWAY.

5384
03:57:03,946 --> 03:57:10,252
SO ADVERSE EVENTS AND THIS WAS A

5385
03:57:10,252 --> 03:57:16,825
PHASE I SO THE FIRST HAD ADVERT 

5386
03:57:16,825 --> 03:57:18,627
EVENTS AND IT WAS NOT DONE AND 

5387
03:57:18,627 --> 03:57:23,065
HE WAS NOT GIVEN THE UPDATE AND 

5388
03:57:23,065 --> 03:57:24,867
THE CONSENT FORM HAD OTHER 

5389
03:57:24,867 --> 03:57:33,208
OMISSIONS AND IT THERE WERE 

5390
03:57:33,208 --> 03:57:38,213
CONFLICTS OF INTERESTS NOT 

5391
03:57:38,213 --> 03:57:45,687
DISCLOSED AND THEY WOULD HAVE 

5392
03:57:45,687 --> 03:57:49,024
EARNED QUITE A BIT OF MONEY IT 

5393
03:57:49,024 --> 03:57:49,525
WAS SUCCESSFUL.

5394
03:57:49,525 --> 03:57:50,359
THIS IS 1999.

5395
03:57:50,359 --> 03:57:56,265
YOU HAVE TO GO OVER A DECADE TO 

5396
03:57:56,265 --> 03:58:02,971
LOOK AT THE RATION TO RESEARCH 

5397
03:58:02,971 --> 03:58:05,974
DEVELOP AND COMMERCIALIZE OTHER 

5398
03:58:05,974 --> 03:58:09,378
CAR T CELLS AND THEN OVER 2600 

5399
03:58:09,378 --> 03:58:10,612
GENE THERAPY CLINICAL TRIALS 

5400
03:58:10,612 --> 03:58:12,814
WERE ONGOING, COMPLETED 

5401
03:58:12,814 --> 03:58:16,818
WORLDWIDE AND LISTED IN 

5402
03:58:16,818 --> 03:58:17,886
CLINICALTRIALS.gov AND SOME 

5403
03:58:17,886 --> 03:58:26,194
TREATMENTS ALREADY APPROVED.

5404
03:58:26,194 --> 03:58:28,463
DESPITE THEY'LL BE APPROVED SOME

5405
03:58:28,463 --> 03:58:36,939
RISKS KEPT COMING OUT AND THERE 

5406
03:58:36,939 --> 03:58:40,275
WAS A TREATMENT IN CANCERS AND 

5407
03:58:40,275 --> 03:58:44,279
CEREBRAL EDEMA IT. WASN'T 

5408
03:58:44,279 --> 03:58:47,082
RECORDED EARLY ON THOUGH THEY 

5409
03:58:47,082 --> 03:58:51,787
SAW NEUROLOGICAL TOXICITY WITH 

5410
03:58:51,787 --> 03:58:57,292
DELIRIUM AND CONFUSION AND IN 

5411
03:58:57,292 --> 03:59:01,663
PIGLETS ADMINISTERED THEY SAW 

5412
03:59:01,663 --> 03:59:02,297
TOXICITY AS IT GOT TO THE HIGHER

5413
03:59:02,297 --> 03:59:08,170
DOSES.

5414
03:59:08,170 --> 03:59:11,440
AND THERE WAS APPROVAL OF THE 

5415
03:59:11,440 --> 03:59:16,678
TREATMENT FOR WILL.

5416
03:59:16,678 --> 03:59:19,915
SMA AND WHILE WE CELEBRATE SOME 

5417
03:59:19,915 --> 03:59:24,519
OF THE CRITICAL ADVANCES WE ALSO

5418
03:59:24,519 --> 03:59:28,090
REMEMBER DELAYS RISK AND NEED TO

5419
03:59:28,090 --> 03:59:30,425
ACKNOWLEDGE AS WE TALK ABOUT 

5420
03:59:30,425 --> 03:59:37,666
TRANE TRANSFER STUDIES IN THE 

5421
03:59:37,666 --> 03:59:39,968
PEDIATRIC COMMUNITY.

5422
03:59:39,968 --> 03:59:44,206
AND THERE WAS CHRIS PER 

5423
03:59:44,206 --> 03:59:54,750
TECHNOLOGY LOOKING AT IT IT T

5424
04:00:07,362 --> 04:00:07,896
THALAS

5425
04:00:07,896 --> 04:00:08,497
THALASSEMIA AND AT THIS TIME 

5426
04:00:08,497 --> 04:00:09,164
IT'S BEEN REPORTED THERE'S BEEN 

5427
04:00:09,164 --> 04:00:10,999
NO SIGNS OF AFFECTING OTHER 

5428
04:00:10,999 --> 04:00:19,708
GENES TO END THE CRISPR BUT 3 

5429
04:00:19,708 --> 04:00:21,576
BILLION BASE PAIRS MAY HAVE 

5430
04:00:21,576 --> 04:00:23,712
IMPACT BECAUSE OF THEIR 

5431
04:00:23,712 --> 04:00:24,746
INFLUENCE IN REGULATORY GENES 

5432
04:00:24,746 --> 04:00:26,314
WE'LL HAVE TO FOLLOW FOR YEARS 

5433
04:00:26,314 --> 04:00:28,250
IF NOT ED AS TO COME.

5434
04:00:28,250 --> 04:00:34,122
SO WHAT CAN GO WRONG WITH CHRIS 

5435
04:00:34,122 --> 04:00:35,991
PER?

5436
04:00:35,991 --> 04:00:37,759
IT MAY THEY CAN THE PATIENT 

5437
04:00:37,759 --> 04:00:44,132
WORSE OFF AND MAY CAUSE OTHER 

5438
04:00:44,132 --> 04:00:54,142
PROBLEMS OFF TARGET BEEN GREAT 

5439
04:00:54,142 --> 04:00:57,679
CRISPR TO ALLOW FOR TRANSPLANTS 

5440
04:00:57,679 --> 04:01:00,248
AND SO FAR IT'S LOOKING GOOD 

5441
04:01:00,248 --> 04:01:08,590
THOUGH THERE WERE UNANTICIPATED 

5442
04:01:08,590 --> 04:01:12,260
DIFFICULTIES IT'S HARD TO KNOW 

5443
04:01:12,260 --> 04:01:14,362
AND IT'S HARD TO DIRECTLY ASSESS

5444
04:01:14,362 --> 04:01:18,166
THESE GIVEN THEY CAN OCCUR YEARS

5445
04:01:18,166 --> 04:01:22,437
TO DECADES AFTER TREATED THE 

5446
04:01:22,437 --> 04:01:32,881
CRISPR TREATED THERAPIES.

5447
04:01:43,058 --> 04:01:46,128
SO I DO CLINICAL ETHICS AT MY 

5448
04:01:46,128 --> 04:01:46,695
RESEARCH INSTITUTION.

5449
04:01:46,695 --> 04:01:48,730
THE TRADITIONAL RESEARCH ETHICS 

5450
04:01:48,730 --> 04:01:52,300
WE ALL NEED TO DO ANY TYPE OF 

5451
04:01:52,300 --> 04:01:55,070
RESEARCH IS BASED ON THE BELMONT

5452
04:01:55,070 --> 04:01:58,039
REPORT FROM 1978 WHICH HAD A 

5453
04:01:58,039 --> 04:01:59,174
STRICT SEPARATION FROM 

5454
04:01:59,174 --> 04:02:00,942
RESEARCHER AND CLINICIAN AND 

5455
04:02:00,942 --> 04:02:04,279
HUMAN SUBJECTS AND RESEARCH 

5456
04:02:04,279 --> 04:02:14,523
PARTICIPANTS.

5457
04:02:20,962 --> 04:02:21,396
OKAY.

5458
04:02:21,396 --> 04:02:25,367
I'M GOING TO STAND OVER HERE.

5459
04:02:25,367 --> 04:02:26,501
SORRY.

5460
04:02:26,501 --> 04:02:28,103
SO RESEARCH ETHICS OR RARE 

5461
04:02:28,103 --> 04:02:30,872
DISEASES HAVE TO LOOK AT HUMAN 

5462
04:02:30,872 --> 04:02:32,374
SUBJECT PROTECTION AND THE 

5463
04:02:32,374 --> 04:02:33,542
CLINICIAN IS OFTEN THE SAME 

5464
04:02:33,542 --> 04:02:35,877
PERSON AS THE RESEARCHER AND THE

5465
04:02:35,877 --> 04:02:39,881
IS OFTEN THE SAME PERSON AS THE 

5466
04:02:39,881 --> 04:02:41,116
RESEARCH PARTICIPANT OR EVEN THE

5467
04:02:41,116 --> 04:02:43,552
PATIENT IS A PARTNER IN THE 

5468
04:02:43,552 --> 04:02:44,786
RESEARCH AS WE'VE HEARD WITH THE

5469
04:02:44,786 --> 04:02:46,621
PATIENT ADVOCACY GROUPS.

5470
04:02:46,621 --> 04:02:50,792
IT WAS 1978 RULES WERE MEANT FOR

5471
04:02:50,792 --> 04:02:52,928
STRICT CLINICAL TRIALS AND SOME 

5472
04:02:52,928 --> 04:02:53,662
CLINICAL RESEARCH CENTER MAY NOT

5473
04:02:53,662 --> 04:02:54,296
BE THE BEST.

5474
04:02:54,296 --> 04:02:56,698
ONE THING I'VE BEEN WORKING ON 

5475
04:02:56,698 --> 04:02:58,600
IN ONE OF THE GRANTS IS THE 

5476
04:02:58,600 --> 04:03:00,335
SUPPLEMENT LOOKING AT WHAT WE 

5477
04:03:00,335 --> 04:03:02,504
CALL TRANSLATIONAL BIOETHICS 

5478
04:03:02,504 --> 04:03:06,141
WHICH EMBRACES DUALITY AND THE 

5479
04:03:06,141 --> 04:03:07,475
PATIENT IS RESEARCHER AND THE 

5480
04:03:07,475 --> 04:03:10,212
PATIENT IS ALSO A RESEARCH 

5481
04:03:10,212 --> 04:03:11,546
PARTICIPANT EVEN POSSIBLY AN 

5482
04:03:11,546 --> 04:03:13,181
ADVOCATE FOR THE FAMILY IS THE 

5483
04:03:13,181 --> 04:03:13,548
ADVOCATE.

5484
04:03:13,548 --> 04:03:16,251
SO RATHER THAN SEPARATING THESE 

5485
04:03:16,251 --> 04:03:20,121
WE NEED TO LOOK AT MORE OF A 

5486
04:03:20,121 --> 04:03:22,457
LEARNING HEALTH SYSTEM WHERE THE

5487
04:03:22,457 --> 04:03:23,859
ELECTRONIC HEALTH RECORD CAN 

5488
04:03:23,859 --> 04:03:25,961
INCLUDE DATA, PATIENT CARE DATA 

5489
04:03:25,961 --> 04:03:26,795
AS WELL AS CLINICAL RESEARCH.

5490
04:03:26,795 --> 04:03:29,397
THAT IS SOMETHING THAT TO GIVE 

5491
04:03:29,397 --> 04:03:32,267
WITH THE COMMUNITY I'VE BEEN 

5492
04:03:32,267 --> 04:03:39,107
HEARING SO FAR TODAY.

5493
04:03:39,107 --> 04:03:40,175
THE ISSUES IN EPILEPSY GIVEN 

5494
04:03:40,175 --> 04:03:45,914
WHAT I'VE LEARNED IS HOW TO 

5495
04:03:45,914 --> 04:03:47,115
IDENTIFY CHURCH AND WHO SHOULD 

5496
04:03:47,115 --> 04:03:52,254
BE THE FIRST HUMAN PARTICIPANT 

5497
04:03:52,254 --> 04:03:55,223
AND WHAT RESEARCH METHODS AND 

5498
04:03:55,223 --> 04:03:56,258
DATA COLLECTED AND JUSTICE 

5499
04:03:56,258 --> 04:04:06,401
ISSUES.

5500
04:04:10,171 --> 04:04:15,410
FIRST, HOW TO IDENTIFY THOSE 

5501
04:04:15,410 --> 04:04:25,921
WITH A MONO AUAUTO.

5502
04:04:41,236 --> 04:04:42,404
AND AT TIMES THE PERSON HAS A 

5503
04:04:42,404 --> 04:04:43,672
RARE DISEASE AND YOU DON'T WANT 

5504
04:04:43,672 --> 04:04:44,806
YOUR CLINICIAN EVERY TIME YOU GO

5505
04:04:44,806 --> 04:04:47,275
IN WITH A HEADACHE YOU DON'T 

5506
04:04:47,275 --> 04:04:50,378
WANT THE DOCTOR TO ORDER A FULL 

5507
04:04:50,378 --> 04:04:53,014
SCALE WILL OF BLOOD TESTS AS 

5508
04:04:53,014 --> 04:04:56,351
WELL AS AN MRI BECAUSE OTHERWISE

5509
04:04:56,351 --> 04:05:02,958
AND THEN WE'LL FIND INCIDENTAL 

5510
04:05:02,958 --> 04:05:06,861
FINDINGS AND GO DOWN A RABBIT 

5511
04:05:06,861 --> 04:05:13,034
HOLE AND SO WE HAVE TO FIGURE 

5512
04:05:13,034 --> 04:05:14,803
OUT HOW TO REALIZE SOMETIMES 

5513
04:05:14,803 --> 04:05:20,742
IT'S A ZEBRA AND THAT WILL BE A 

5514
04:05:20,742 --> 04:05:24,112
REAL PROBLEM BECAUSE.

5515
04:05:24,112 --> 04:05:27,482
AND WE'RE LOOKING FOR RARE 

5516
04:05:27,482 --> 04:05:29,851
EPILEPSIES 93% OF THE TIME THEY 

5517
04:05:29,851 --> 04:05:31,486
CAN PROBABLY GO ON A STANDARD 

5518
04:05:31,486 --> 04:05:33,321
TREATMENT BUT HERE IN THESE 

5519
04:05:33,321 --> 04:05:36,024
CASES THEY CAN'T AND HOW DO WE 

5520
04:05:36,024 --> 04:05:37,158
TRAIN PEOPLE TO BE AWARE AND 

5521
04:05:37,158 --> 04:05:38,526
READY TO CHANGE THE WHOLE 

5522
04:05:38,526 --> 04:05:45,467
APPROACH WHEN IN A SENSE IT'S 

5523
04:05:45,467 --> 04:05:46,034
WHAT THEY'VE BEEN TAUGHT IN 

5524
04:05:46,034 --> 04:05:54,142
MEDICAL SCHOOL.

5525
04:05:54,142 --> 04:05:59,647
IT WILL REQUIRE A GENE CHIP AND 

5526
04:05:59,647 --> 04:06:02,584
A TENDENCY AND I'LL JUST POINT 

5527
04:06:02,584 --> 04:06:02,951
AT YOU.

5528
04:06:02,951 --> 04:06:05,787
AND MANY WILL WANT TO DO GENOMIC

5529
04:06:05,787 --> 04:06:07,322
SEQUENCE AND IT WON'T BE COVERED

5530
04:06:07,322 --> 04:06:10,358
BY MANY INSURANCE AND WILL NEED 

5531
04:06:10,358 --> 04:06:12,527
TO EDUCATE THE PEDIATRICIANS AND

5532
04:06:12,527 --> 04:06:18,033
PRIMARY CARE NEUROLOGIST WHAT TO

5533
04:06:18,033 --> 04:06:25,173
LOOK FOR AND WHY IT MAY BE A 

5534
04:06:25,173 --> 04:06:27,942
RARE DISEASE AND RIGHT NOW MOST 

5535
04:06:27,942 --> 04:06:28,843
TREATMENTS ARE EXPERIMENTAL AND 

5536
04:06:28,843 --> 04:06:31,346
IT'S NOT CLEAR WHO WILL PAY FOR 

5537
04:06:31,346 --> 04:06:32,747
IT AND THE CLINICIAN HAS LESS 

5538
04:06:32,747 --> 04:06:35,383
MOLE MOTIVATION TO DO THE 

5539
04:06:35,383 --> 04:06:35,617
TESTING.

5540
04:06:35,617 --> 04:06:39,154
YOU CAN SEE HOW IT SNOWBALLS IN 

5541
04:06:39,154 --> 04:06:40,922
TRYING TO GET PEOPLE TO DO THE 

5542
04:06:40,922 --> 04:06:42,624
RIGHT THING.

5543
04:06:42,624 --> 04:06:46,861
THE RESULT IS ONLY CHILDREN OF 

5544
04:06:46,861 --> 04:06:48,830
HIGHLY EDUCATED HIGHLY RESOURCED

5545
04:06:48,830 --> 04:06:51,599
PARENTS WILL GET THE DIAGNOSIS.

5546
04:06:51,599 --> 04:06:53,134
ONLY AFTER WILL DIAGNOSTIC 

5547
04:06:53,134 --> 04:06:58,907
ODYSSEY AND WE HEARD MANY 

5548
04:06:58,907 --> 04:07:01,109
STORIES ALREADY.

5549
04:07:01,109 --> 04:07:06,815
THERE'S TO IT WAS A TO TRY TO 

5550
04:07:06,815 --> 04:07:09,451
AVOID THE DIAGNOSTIC ODYSSEY.

5551
04:07:09,451 --> 04:07:14,022
THE FIRST ONE IS IT THINK OF 

5552
04:07:14,022 --> 04:07:18,760
ADDING IT WITH AND WE HAVE 4 

5553
04:07:18,760 --> 04:07:21,296
MILLION DONE ANNUALLY AND EVERY 

5554
04:07:21,296 --> 04:07:23,731
TITLE WOULD BE TEST FOR ALL 

5555
04:07:23,731 --> 04:07:28,136
KINDS OF MONOGENIC EPILEPSY THE 

5556
04:07:28,136 --> 04:07:33,208
PROBLEM IS IT DOESN'T MEET THE 

5557
04:07:33,208 --> 04:07:33,842
WORLD HEALTH ORGANIZATION 

5558
04:07:33,842 --> 04:07:40,315
CRITERIA FOR NEWBORN SCREENING.

5559
04:07:40,315 --> 04:07:43,751
IT WOULD SOLVE THE EQUITY ISSUE.

5560
04:07:43,751 --> 04:07:46,721
IT WOULD BE FAIR.

5561
04:07:46,721 --> 04:07:48,890
THE PROBLEM IS GENOTYPE DOESN'T 

5562
04:07:48,890 --> 04:07:49,390
EQUAL GENOTYPE.

5563
04:07:49,390 --> 04:07:51,392
WE'LL HAVE PEOPLE COMING IN FOR 

5564
04:07:51,392 --> 04:07:56,664
SPECIALIST CARE AND IT'S 

5565
04:07:56,664 --> 04:08:01,503
DIFFICULT TO OBTAIN PARTICULARLY

5566
04:08:01,503 --> 04:08:03,905
IF YOU LIVE IN A RURAL AREA AND 

5567
04:08:03,905 --> 04:08:06,641
MANY GENETIC VARIANTS WE KNOW 

5568
04:08:06,641 --> 04:08:08,276
OFTEN COME FROM EUROPEAN 

5569
04:08:08,276 --> 04:08:15,183
ANCESTRY AND THEY PARTICIPATE IN

5570
04:08:15,183 --> 04:08:19,187
RESEARCH AND IT WILL LEAD TO 

5571
04:08:19,187 --> 04:08:20,788
FURTHER DISPARITIES EARLY ON.

5572
04:08:20,788 --> 04:08:28,263
THE OTHER PROBLEMS ARE THAT 

5573
04:08:28,263 --> 04:08:31,599
UNTIL WE KNOW THE PHENOTYPE IT 

5574
04:08:31,599 --> 04:08:33,535
DOESN'T MEET THE CRITERIA FOR 

5575
04:08:33,535 --> 04:08:35,503
NEWBORN SCREEN WHICH CAN'T BE 

5576
04:08:35,503 --> 04:08:37,138
DONE WITHOUT PARENTAL CONSENT 

5577
04:08:37,138 --> 04:08:39,774
AND IF WE STARTED TO OFFER 

5578
04:08:39,774 --> 04:08:42,043
CONDITIONS FOR WHICH WE COULDN'T

5579
04:08:42,043 --> 04:08:46,214
OFFER TREATMENT WE WOULD THEN 

5580
04:08:46,214 --> 04:08:47,182
REQUIRE PARENTAL CONSENT AND 

5581
04:08:47,182 --> 04:08:53,855
WOULD BE UNACCEPTABLE BECAUSE WE

5582
04:08:53,855 --> 04:08:55,957
DON'T WANT TO MISS THE DISEASES 

5583
04:08:55,957 --> 04:09:01,696
ALREADY ON THE PANEL TO PREVENT 

5584
04:09:01,696 --> 04:09:02,964
MORBIDITY AND MORTALITY.

5585
04:09:02,964 --> 04:09:04,265
SHOULD WE THINK OF ALL 

5586
04:09:04,265 --> 04:09:06,901
SEQUENCING OF ALL PEOPLE WHO 

5587
04:09:06,901 --> 04:09:08,970
PRESENT WITH THE FIRST SEIZURE?

5588
04:09:08,970 --> 04:09:10,238
THIS WOULD SOLVE THE EQUITY 

5589
04:09:10,238 --> 04:09:10,638
ISSUE.

5590
04:09:10,638 --> 04:09:12,840
THE PROBLEM IS SCREENING IS NOT 

5591
04:09:12,840 --> 04:09:17,679
NECESSARILY COVERED BY INSURANCE

5592
04:09:17,679 --> 04:09:20,582
AND THE SCREENING WOULD BE HARD 

5593
04:09:20,582 --> 04:09:26,154
TO JUSTIFY WITHOUT A TREATMENT 

5594
04:09:26,154 --> 04:09:30,124
AND WE NEED TO MAKE SURE ALL 

5595
04:09:30,124 --> 04:09:30,959
INDIVIDUALS WHO COULD BENEFIT 

5596
04:09:30,959 --> 04:09:41,369
WILL HAVE ACCESS TO IT.

5597
04:09:41,636 --> 04:09:45,873
SO WHO SHOULD BE THE FIRST HUMAN

5598
04:09:45,873 --> 04:09:46,307
PARTICIPANT?

5599
04:09:46,307 --> 04:09:49,077
WE HEARD ABOUT THIS IN THE PAST 

5600
04:09:49,077 --> 04:09:52,280
FEW DAYS.

5601
04:09:52,280 --> 04:09:54,882
WE HAVE CONVERSATION POINTS.

5602
04:09:54,882 --> 04:09:56,384
FIRST WE'VE SEEN THE VARIABILITY

5603
04:09:56,384 --> 04:09:57,819
IN THE NATURAL HISTORY MAKES IT 

5604
04:09:57,819 --> 04:10:03,491
HARD TO KNOW WHEN WOULD BE THE 

5605
04:10:03,491 --> 04:10:08,763
IDEAL TIME WILL AND WE TALKED 

5606
04:10:08,763 --> 04:10:12,734
ABOUT THE FRONTAL TEMPORAL 

5607
04:10:12,734 --> 04:10:14,736
DEMENTIA UNLESS YOU UNDERSTAND 

5608
04:10:14,736 --> 04:10:17,171
THE NATURAL HISTORY OF THERAPY 

5609
04:10:17,171 --> 04:10:20,642
AND TO WHAT EXTENT WE WANT TO 

5610
04:10:20,642 --> 04:10:23,177
DEAL WITH THOSE ALREADY 

5611
04:10:23,177 --> 04:10:25,780
SYMPTOMATIC OR PRESYMPTOMATIC 

5612
04:10:25,780 --> 04:10:34,055
INVOLVING THOSE PRESYMPTOMATIC 

5613
04:10:34,055 --> 04:10:36,924
CAN BE PROBLEMATIC AND HAVE TO 

5614
04:10:36,924 --> 04:10:41,562
DECIDE THE END POINTS TO CHOOSE 

5615
04:10:41,562 --> 04:10:42,897
AND TO BE IN NEGOTIATION WITH 

5616
04:10:42,897 --> 04:10:45,600
THE PATIENTS AND FAMILIES 

5617
04:10:45,600 --> 04:10:46,167
THEMSELVES ABOUT ABOUT WHAT 

5618
04:10:46,167 --> 04:10:50,672
MATTERED FOR THEM AND HOW WILL 

5619
04:10:50,672 --> 04:10:52,273
THIS IMPACT EQUITY I THINK WE'LL

5620
04:10:52,273 --> 04:11:00,415
NEED TO CONSIDER.

5621
04:11:00,415 --> 04:11:05,820
IT WILL BE A SCIENTIFIC AND 

5622
04:11:05,820 --> 04:11:06,387
ETHICAL STAKEHOLDERS AND 

5623
04:11:06,387 --> 04:11:07,522
ADVOCACY GROUPS AND FAMILIES AS 

5624
04:11:07,522 --> 04:11:08,356
WELL AS THE CLINICIANS AS WELL 

5625
04:11:08,356 --> 04:11:15,830
AS THE FUNDERS.

5626
04:11:15,830 --> 04:11:18,399
AND THEN WE HAVE ETHICAL OR 

5627
04:11:18,399 --> 04:11:22,270
SCIENTIFIC ISSUES AND THEY'RE 

5628
04:11:22,270 --> 04:11:22,770
ONLY CAL ISSUES.

5629
04:11:22,770 --> 04:11:26,441
DO WE HAVE TO LOOK AT THE 

5630
04:11:26,441 --> 04:11:27,108
INCLUSION CRITERIA AND THE MORE 

5631
04:11:27,108 --> 04:11:30,211
DIFFICULT YOU MAKE IT THE MORE 

5632
04:11:30,211 --> 04:11:34,649
DEGREE OF SIGNIFICANCE UNLESS WE

5633
04:11:34,649 --> 04:11:36,284
HAVE A GOOD CURVE TO SAY WHEN 

5634
04:11:36,284 --> 04:11:37,585
WE'LL GET NATURAL HISTORY AND IT

5635
04:11:37,585 --> 04:11:41,956
WILL BE IMPORTANT TO DETERMINE 

5636
04:11:41,956 --> 04:11:44,125
THE END POINTS AND IT MAY NOT BE

5637
04:11:44,125 --> 04:11:46,661
JUST REDUCING THE NUMBER OF 

5638
04:11:46,661 --> 04:11:47,295
SEIZURES BUT COMMUNICATION IS 

5639
04:11:47,295 --> 04:11:50,965
MORE IMPORTANT FOR THE FAMILY 

5640
04:11:50,965 --> 04:11:54,202
AND THE ACCESSIBILITY OF RISK 

5641
04:11:54,202 --> 04:11:55,236
FROM THE FAMILIES.

5642
04:11:55,236 --> 04:11:57,405
FOR SOME THE RISK OF PUTTING 

5643
04:11:57,405 --> 04:11:59,607
THEIR CHILD TO BET EVERY NIGHT 

5644
04:11:59,607 --> 04:12:02,910
IS SO GREAT THEY'RE WILLING TO 

5645
04:12:02,910 --> 04:12:06,948
ENROLL IN ANY TRIAL FOR OTHERS 

5646
04:12:06,948 --> 04:12:12,820
THE RISK MAY NOT BE ACCESSIBLE.

5647
04:12:12,820 --> 04:12:13,654
AND FREQUENCY OF DATA COLLECTION

5648
04:12:13,654 --> 04:12:15,423
AND HOW DATA ARE COLLECTED AND 

5649
04:12:15,423 --> 04:12:18,326
THE EXTENT TO WHICH WE CAN USE 

5650
04:12:18,326 --> 04:12:19,627
PATIENT REPORTED OUTCOMES AND 

5651
04:12:19,627 --> 04:12:21,529
WHAT DO WE THINK OUTSIDE OF THE 

5652
04:12:21,529 --> 04:12:28,269
CLINIC AND THINGS OF THAT SORT.

5653
04:12:28,269 --> 04:12:35,610
SO AND WHEN WE THINK OF AN AAV A

5654
04:12:35,610 --> 04:12:36,711
VIRAL SECTOR SOMETIMES YOU ONLY 

5655
04:12:36,711 --> 04:12:42,750
HAVE ONE CHANCE AND USUALLY 

5656
04:12:42,750 --> 04:12:46,854
THERE HAS TO BE A TYPE OF STUDY.

5657
04:12:46,854 --> 04:12:49,490
AND A PARENT TRIES TO DECIDE 

5658
04:12:49,490 --> 04:12:53,094
WHEN TO ENROLL THEIR CHILD GETS 

5659
04:12:53,094 --> 04:12:56,264
INTO THIS PROBLEM OF WHAT IN 

5660
04:12:56,264 --> 04:13:00,101
PHILOSOPHY WE CALL THE BETTER 

5661
04:13:00,101 --> 04:13:07,909
BOTTLE OF WINE INTRODUCED BY JOP

5662
04:13:07,909 --> 04:13:10,578
POLYP IT MEANS EVERY DAY IT GETS

5663
04:13:10,578 --> 04:13:12,980
BETTER.

5664
04:13:12,980 --> 04:13:18,619
SO DO YOU HAVE TO TAKE TAKE THE 

5665
04:13:18,619 --> 04:13:20,288
PREVENTION AND WHEN SOMEBODY 

5666
04:13:20,288 --> 04:13:23,024
WILL LIVE PREFER WILL DRINK THE 

5667
04:13:23,024 --> 04:13:26,394
WINE AND BETTER TOMORROW BUT IF 

5668
04:13:26,394 --> 04:13:30,665
YOU KEEP WAITING IN A SENSE 

5669
04:13:30,665 --> 04:13:33,835
THEY'LL NEVER DRINK THE BOTTOM 

5670
04:13:33,835 --> 04:13:39,440
OF WINE BUT YEAR NOT IMMORTAL 

5671
04:13:39,440 --> 04:13:40,541
AND THEY'RE NEUROLOGICALLY 

5672
04:13:40,541 --> 04:13:41,509
PROGRESS AND THE PARENTS HAVE TO

5673
04:13:41,509 --> 04:13:43,211
DECIDE WHEN TO ENROLL.

5674
04:13:43,211 --> 04:13:48,115
IN THE FIRST TRIAL?

5675
04:13:48,115 --> 04:13:55,590
AND WE SAW THIS IN WAITING FOR A

5676
04:13:55,590 --> 04:13:57,091
BETTER THERAPY AND YOU MAY HAVE 

5677
04:13:57,091 --> 04:13:58,226
A ONE AND DONE AND NOT BE ABLE 

5678
04:13:58,226 --> 04:14:00,261
TO GET A SECOND CHANCE.

5679
04:14:00,261 --> 04:14:06,100
A SEPARATE ISSUE I WANT TO RAISE

5680
04:14:06,100 --> 04:14:15,643
ALSO THIS RAISES ISSUES AND THE 

5681
04:14:15,643 --> 04:14:20,948
PARTICIPANT CAN ALWAYS HAVE THE 

5682
04:14:20,948 --> 04:14:27,822
RIGHT TO IF WILL ENROLL IN THE 

5683
04:14:27,822 --> 04:14:31,926
RESEARCH AND IT'S NOT LIKE A 

5684
04:14:31,926 --> 04:14:34,729
CLINICAL TRIAL LIKE YOU CAN STOP

5685
04:14:34,729 --> 04:14:39,000
A DRUG BUT ONCE YOU'RE THERE 

5686
04:14:39,000 --> 04:14:40,635
YOU'RE THERE FOR THE DURATION 

5687
04:14:40,635 --> 04:14:43,971
AND HERE THE PATIENT CAN 

5688
04:14:43,971 --> 04:14:46,140
WITHDRAW AND SO THEN WE'RE NOT 

5689
04:14:46,140 --> 04:14:48,509
GETTING THE DATA.

5690
04:14:48,509 --> 04:14:49,911
UNSUCCESSFUL THERAPY YOU STILL 

5691
04:14:49,911 --> 04:14:54,415
WANT TO KNOW WHAT HAPPENS TO THE

5692
04:14:54,415 --> 04:14:54,982
INDIVIDUALS.

5693
04:14:54,982 --> 04:14:56,717
SO IS BAD OUTCOME FROM THE 

5694
04:14:56,717 --> 04:14:57,952
RESEARCH AND THIS GETS BACK TO 

5695
04:14:57,952 --> 04:15:03,324
THE NEED FOR TRUST AND 

5696
04:15:03,324 --> 04:15:04,592
PARTNERSHIP THAT HAS BEEN TALKED

5697
04:15:04,592 --> 04:15:06,994
ABOUT OFTEN AND WAS BEAUTIFUL TO

5698
04:15:06,994 --> 04:15:08,262
GO TO THE EVENT LAST NIGHT AND 

5699
04:15:08,262 --> 04:15:12,333
SEE ALL THE PARTNERSHIPS WORKING

5700
04:15:12,333 --> 04:15:13,200
TO HOPEFULLY AVOID EVENTS LIKE 

5701
04:15:13,200 --> 04:15:20,074
THAT.

5702
04:15:20,074 --> 04:15:25,613
AND WE'LL NEED TO TALK ABOUT 

5703
04:15:25,613 --> 04:15:29,116
THIS IT WE WANT SUPPORT AND WE 

5704
04:15:29,116 --> 04:15:30,551
NEED TO COLLECT THE NATURE 

5705
04:15:30,551 --> 04:15:30,785
HISTORY.

5706
04:15:30,785 --> 04:15:35,289
WE WANT TO HAVE AN EMPHASIS ON 

5707
04:15:35,289 --> 04:15:36,090
STANDARDIZING PATIENT REPORTED 

5708
04:15:36,090 --> 04:15:41,829
OUTCOME AND THE NEED TO DEVELOP 

5709
04:15:41,829 --> 04:15:49,070
SPECIFIC TO EPILEPSY AND WE ALSO

5710
04:15:49,070 --> 04:15:51,405
WILL LOOK AT THE CROSS S AND 

5711
04:15:51,405 --> 04:15:54,875
WILL NEED TO RECORD AND MAKE 

5712
04:15:54,875 --> 04:15:57,144
AVAILABLE SUCCESS AND FAILURE 

5713
04:15:57,144 --> 04:15:58,813
AND WE'RE ALWAYS TOLD JOURNALS 

5714
04:15:58,813 --> 04:16:00,348
ONLY WANT TO PUBLIC SUCCESSES 

5715
04:16:00,348 --> 04:16:02,683
BUT IN ORDER TO NOT REINVENT THE

5716
04:16:02,683 --> 04:16:04,685
WHEEL AND MAKE THE SAME MISTAKE 

5717
04:16:04,685 --> 04:16:08,356
THERE NEEDS TO BE COMMUNICATION.

5718
04:16:08,356 --> 04:16:09,757
THE COVID EPIDEMIC TAUGHT US ONE

5719
04:16:09,757 --> 04:16:10,825
THING IF YOU GET ENOUGH MONEY 

5720
04:16:10,825 --> 04:16:12,259
AND GET ALL THE SCIENTISTS IN 

5721
04:16:12,259 --> 04:16:14,195
THE COUNTRY TO WORK TOGETHER YOU

5722
04:16:14,195 --> 04:16:18,432
CAN CREATE A VACCINE IN LESS 

5723
04:16:18,432 --> 04:16:20,267
THAN A YEAR.

5724
04:16:20,267 --> 04:16:23,204
THAT WAS AN INCREDIBLE FEET AND 

5725
04:16:23,204 --> 04:16:27,141
THE FASTEST BEFORE THAT WAS FOUR

5726
04:16:27,141 --> 04:16:30,144
YEARS AND THIS WAS AN INCREDIBLE

5727
04:16:30,144 --> 04:16:32,947
FEAT BUT IT WILL REQUIRE A LOT 

5728
04:16:32,947 --> 04:16:35,116
OF TEAM WORK.

5729
04:16:35,116 --> 04:16:37,351
I'M EXCITED BY THE PARTNERSHIPS 

5730
04:16:37,351 --> 04:16:40,254
I SAW TODAY AND WANT TO 

5731
04:16:40,254 --> 04:16:44,258
ENCOURAGE THAT TO CONTINUE AND 

5732
04:16:44,258 --> 04:16:48,529
MAKE IT TO THE AND A HALF 

5733
04:16:48,529 --> 04:16:49,664
REGISTRIES AND INDIVIDUALS WOULD

5734
04:16:49,664 --> 04:16:53,634
AGREE IF IT CAN BE DONE AT HOME,

5735
04:16:53,634 --> 04:16:56,270
PATIENT REPORTED OUTCOME I THINK

5736
04:16:56,270 --> 04:16:59,407
WOULD BE REALLY USEFUL.

5737
04:16:59,407 --> 04:17:05,613
WE CAN HAVE MANY LIFE TIME OF 

5738
04:17:05,613 --> 04:17:05,880
FOLLOW-UP.

5739
04:17:05,880 --> 04:17:11,652
AND MOST IMPORTANTLY OUR EQUITY 

5740
04:17:11,652 --> 04:17:13,320
AND JUSTICE ISSUES ONE QUESTION 

5741
04:17:13,320 --> 04:17:15,723
WE'LL HAVE TO ASK IS HOW TO 

5742
04:17:15,723 --> 04:17:20,227
ENGAGE DIVERSE COMMUNITY AND 

5743
04:17:20,227 --> 04:17:21,095
ENSURE CHILDREN FROM 

5744
04:17:21,095 --> 04:17:22,730
UNREPRESENTED COMMUNITIES GET 

5745
04:17:22,730 --> 04:17:23,998
DIAGNOSED AND MAKE SURE ACCESS 

5746
04:17:23,998 --> 04:17:26,934
IS FAIR IN THE END OF ONE 

5747
04:17:26,934 --> 04:17:30,738
THERAPIES WHICH OFTEN REQUIRE 

5748
04:17:30,738 --> 04:17:32,840
PARENTS WHO ARE INCREDIBLY IT 

5749
04:17:32,840 --> 04:17:34,408
WILL HIGHLY LITERAL AND MOTIVATE

5750
04:17:34,408 --> 04:17:36,310
AND HIGHLY RESOURCED?

5751
04:17:36,310 --> 04:17:37,511
GIVEN THE COST OF THE STRATEGIES

5752
04:17:37,511 --> 04:17:42,917
WE'LL HAVE TO THINK ABOUT HOW 

5753
04:17:42,917 --> 04:17:46,754
WE'RE GOING TO DEVISE AN 

5754
04:17:46,754 --> 04:17:49,924
EQUITABLE STRATEGY AND ALL 

5755
04:17:49,924 --> 04:17:51,859
STUDIES NEED TO BE IF NOT 

5756
04:17:51,859 --> 04:17:53,527
PUBLISHED IN JOURNALS PUT INTO A

5757
04:17:53,527 --> 04:17:59,233
REPOSITORY AND NOT MAKE THE SAKE

5758
04:17:59,233 --> 04:18:00,868
MISTAKES DONE BEFORE AND MOVE 

5759
04:18:00,868 --> 04:18:01,602
THE SCIENCE FORWARD AS FAST 

5760
04:18:01,602 --> 04:18:07,575
POSSIBLE IN A SAFE WAY.

5761
04:18:07,575 --> 04:18:09,877
WE HAVE TO THINK WHETHER THERE 

5762
04:18:09,877 --> 04:18:14,949
WILL BE POST STUDY OBLIGATION 

5763
04:18:14,949 --> 04:18:18,285
AND WHOSE RESPONSIBILITY WILL IT

5764
04:18:18,285 --> 04:18:20,688
TAKE TO TL FOR A REGISTRY AND 

5765
04:18:20,688 --> 04:18:22,156
THEY TAKE TIME AND COST MONEY 

5766
04:18:22,156 --> 04:18:23,991
AND AFTER APPROVAL WE NEED TO 

5767
04:18:23,991 --> 04:18:26,127
HAVE THE REGISTRY BECAUSE WE 

5768
04:18:26,127 --> 04:18:30,765
NEED TO UNDERSTAND ADVERSE 

5769
04:18:30,765 --> 04:18:32,533
EVENTS AND OPPORTUNITIES TO 

5770
04:18:32,533 --> 04:18:36,537
ENROLL FOR THE PATIENT 

5771
04:18:36,537 --> 04:18:38,639
POPULATION WHO MAY BRING UP NEW 

5772
04:18:38,639 --> 04:18:43,811
SIDE EFFECTS WE MAY NOT HAVE 

5773
04:18:43,811 --> 04:18:51,385
SEEN FOR THE INCLUSION CRITERIA 

5774
04:18:51,385 --> 04:18:56,290
FOR CLINICAL TRIALS AND WILL 

5775
04:18:56,290 --> 04:18:59,193
NEED TO LOOK AT SUCCESSES OR 

5776
04:18:59,193 --> 04:19:06,567
FAIL AND THE OBLIGATION TO 

5777
04:19:06,567 --> 04:19:08,569
RE-EVALUATE GENOMIC DATA AND 

5778
04:19:08,569 --> 04:19:09,537
HAVE NOT MET CRITERIA FROM 

5779
04:19:09,537 --> 04:19:12,506
EARLIER STUDIES MAY NOW BENEFIT 

5780
04:19:12,506 --> 04:19:14,542
FROM WILL THERAPIES WE'VE BEEN 

5781
04:19:14,542 --> 04:19:14,842
DEVELOPING.

5782
04:19:14,842 --> 04:19:17,111
LET ME CONCLUDE HUMAN SUBJECT 

5783
04:19:17,111 --> 04:19:17,912
PROTECTS MUST HAVE 

5784
04:19:17,912 --> 04:19:20,781
CONSIDERATIONS OF SAFETY.

5785
04:19:20,781 --> 04:19:23,017
WE DO NEED EPISTEMIC HUMANITY ON

5786
04:19:23,017 --> 04:19:26,921
WHAT WE KNOW AND DON'T KNOW AND 

5787
04:19:26,921 --> 04:19:30,357
THERE'S A LOT WE DON'T KNOW IN 

5788
04:19:30,357 --> 04:19:32,393
MANY THE THEMED THERAPIES AND 

5789
04:19:32,393 --> 04:19:34,628
WE'LL DEVELOP THERAPIES AND I 

5790
04:19:34,628 --> 04:19:36,397
LOOKED AT POMPEII DISEASE NO ONE

5791
04:19:36,397 --> 04:19:41,435
WOULD HAVE DESCRIBED AS HAVING 

5792
04:19:41,435 --> 04:19:43,370
HEARING LOSS AND WE'RE SEEING 

5793
04:19:43,370 --> 04:19:44,004
NEW COMPLICATIONS THAT WEREN'T 

5794
04:19:44,004 --> 04:19:46,407
EXPECTED.

5795
04:19:46,407 --> 04:19:49,944
NOT READY TO ADD ANY OF THESE TO

5796
04:19:49,944 --> 04:19:52,279
NEWBORN SCREENING BUT MAY BE 

5797
04:19:52,279 --> 04:19:54,081
READY FOR SCREENING TO PROMOTE 

5798
04:19:54,081 --> 04:19:54,815
GREATER EQUITY.

5799
04:19:54,815 --> 04:19:59,720
AGAIN, THERE'S GOING TO BE 

5800
04:19:59,720 --> 04:20:02,790
PUSHBACK UNTIL THERAPIES AND 

5801
04:20:02,790 --> 04:20:04,291
WILL FINALLY FOCUSSING ON A 

5802
04:20:04,291 --> 04:20:07,161
REDUCTION OF FEATURES MAY NOT BE

5803
04:20:07,161 --> 04:20:08,929
THE PRIMARY END POINTS PARENTS 

5804
04:20:08,929 --> 04:20:13,367
WILL FOCUS ON AND THE LAST LINE 

5805
04:20:13,367 --> 04:20:17,738
WILL BE WE NEED REGISTRIES AND 

5806
04:20:17,738 --> 04:20:19,039
SHARING DATA AND THANK YOU FOR 

5807
04:20:19,039 --> 04:20:19,540
INVITING ME.

5808
04:20:19,540 --> 04:20:25,846
I HOPE THIS HAS BEEN HELPFUL AND

5809
04:20:25,846 --> 04:20:28,282
BEST OF LUCK AS WE GO AND THE 

5810
04:20:28,282 --> 04:20:28,682
JOURNEY TOGETHER.

5811
04:20:28,682 --> 04:20:38,859
THANK YOU.

5812
04:20:40,327 --> 04:20:43,097
>> WE HAVE ONE QUESTION
FROM 

5813
04:20:43,097 --> 04:20:45,065
BRENDA PORTER ASKING HOW DO WE 

5814
04:20:45,065 --> 04:20:47,268
DEAL WITH ALL THE ELIGIBLE 

5815
04:20:47,268 --> 04:20:48,769
FAMILIES FOR GENETIC STUDY IN 

5816
04:20:48,769 --> 04:20:50,304
KNOWING EACH OTHER?

5817
04:20:50,304 --> 04:20:53,507
>> HOW DO WE DEAL WITH --
IS AN 

5818
04:20:53,507 --> 04:20:53,974
AGAIN?

5819
04:20:53,974 --> 04:20:56,877
>> ALL THE ELIGIBLE
FAMILIES FOR

5820
04:20:56,877 --> 04:21:02,349
GENETIC STUDY KNOWING EACH 

5821
04:21:02,349 --> 04:21:04,151
OTHER?

5822
04:21:04,151 --> 04:21:05,686
>> WHAT'S THE PROBLEM WITH
THEM 

5823
04:21:05,686 --> 04:21:12,559
KNOWING EACH OTHER?

5824
04:21:12,559 --> 04:21:15,796
I'M ASSUMING THE PROBLEM COMES 

5825
04:21:15,796 --> 04:21:17,331
WITH A PLACEBO ARM VERSUS DRUG 

5826
04:21:17,331 --> 04:21:19,533
ARM AND MAYBE TALK AND TALK ON A

5827
04:21:19,533 --> 04:21:21,435
PLACEBO ARM AND WILL WANT TO 

5828
04:21:21,435 --> 04:21:21,969
DROP OUT.

5829
04:21:21,969 --> 04:21:23,904
IS THAT WHAT THE ISSUE IS?

5830
04:21:23,904 --> 04:21:25,572
THAT'S WHAT I'LL ASSUME.

5831
04:21:25,572 --> 04:21:28,909
THAT IS A BIG PROBLEM AND EVEN 

5832
04:21:28,909 --> 04:21:33,113
IF THEY DON'T KNOW EITHER SOCIAL

5833
04:21:33,113 --> 04:21:34,248
MEDIA MADE IT SO EVERYBODY KNOWS

5834
04:21:34,248 --> 04:21:35,916
REACH OTHER AND WHERE DATA CAN 

5835
04:21:35,916 --> 04:21:36,283
BE PUT.

5836
04:21:36,283 --> 04:21:39,286
WE'LL NEED FAMILIES TO BE PART 

5837
04:21:39,286 --> 04:21:40,287
OF THE STAKEHOLDER GROUP AND 

5838
04:21:40,287 --> 04:21:41,188
DECISION MAKING PROCESS HOW TO 

5839
04:21:41,188 --> 04:21:42,790
DESIGN THE STUDIES.

5840
04:21:42,790 --> 04:21:44,992
IF EVERYONE WERE TO GET THE 

5841
04:21:44,992 --> 04:21:48,228
TREATMENT IT MAY NOT BE THE BEST

5842
04:21:48,228 --> 04:21:50,064
SCIENTIFICALLY SO IT'S GOING TO 

5843
04:21:50,064 --> 04:21:52,066
TAKE COMPROMISE AND WE'LL TO 

5844
04:21:52,066 --> 04:21:53,100
WORK WITH THE STAKEHOLDER GROUP 

5845
04:21:53,100 --> 04:21:56,070
TO DO IT IN A WAY THAT IS 

5846
04:21:56,070 --> 04:21:57,171
ACCESSIBLE TO THE FAMILIES AND 

5847
04:21:57,171 --> 04:22:07,614
THAT'S GOING TO BE TOUGH.

5848
04:22:10,451 --> 04:22:11,218
>> DOING THE PLACEBO?

5849
04:22:11,218 --> 04:22:12,820
THE ANSWER IS PROBABLY YES.

5850
04:22:12,820 --> 04:22:15,389
SO THAT'S GOING TO MAKE IT HARD.

5851
04:22:15,389 --> 04:22:18,926
THE FACT IS NO ONE WILL SUGGEST 

5852
04:22:18,926 --> 04:22:21,095
A ONE TO ONE WHETHER A TWO OR 

5853
04:22:21,095 --> 04:22:22,863
THREE TO ONE BUT INDIVIDUALS 

5854
04:22:22,863 --> 04:22:23,564
DON'T GET IT.

5855
04:22:23,564 --> 04:22:31,972
IN A ONE AND DONE STUDY OF AN 

5856
04:22:31,972 --> 04:22:34,041
AAV VECTOR ISSUE PEOPLE CAN'T 

5857
04:22:34,041 --> 04:22:35,609
DROP OUT BUT THE REAL PROBLEM 

5858
04:22:35,609 --> 04:22:42,082
COMES WHEN YOU TALK ABOUT AN AS 

5859
04:22:42,082 --> 04:22:44,318
O YOU PLAY WANT TO DO EVERY FEW 

5860
04:22:44,318 --> 04:22:45,452
MONTHS AND KEEP PEOPLE IN THE 

5861
04:22:45,452 --> 04:22:45,652
TRIAL.

5862
04:22:45,652 --> 04:22:50,858
THAT'S WHY I WAS SO EXCITED TO 

5863
04:22:50,858 --> 04:23:00,300
BE HERE BECAUSE THERE'S AN 

5864
04:23:00,300 --> 04:23:01,702
ADVOCACY GROUPS AND WILL 

5865
04:23:01,702 --> 04:23:03,837
INPERSONALLY AND EXTERNALLY 

5866
04:23:03,837 --> 04:23:05,039
FUNDED AND TRY TO WORK TOGETHER 

5867
04:23:05,039 --> 04:23:08,542
AND WE'LL HAVE TO FIGURE OUT A 

5868
04:23:08,542 --> 04:23:09,843
WAY TO MAKE IT POSSIBLE MAYBE 

5869
04:23:09,843 --> 04:23:12,946
ONE WAY OF THINKING BIT FOR THE 

5870
04:23:12,946 --> 04:23:14,348
PEOPLE PUT ON THE PLACEBO IS 

5871
04:23:14,348 --> 04:23:16,383
WHETHER TO HAVE A CROSSOVER 

5872
04:23:16,383 --> 04:23:20,287
STUDY SIX OR NINE MONTHS LATER 

5873
04:23:20,287 --> 04:23:25,793
AND THOUGH UNDERSTANDING THE 

5874
04:23:25,793 --> 04:23:36,170
TRIAL HAS PROGRESSED.

5875
04:23:37,805 --> 04:23:39,506
>> THE QUESTION ABOUT THE 

5876
04:23:39,506 --> 04:23:41,775
FAMILIES KNOWING EACH OTHER MAY 

5877
04:23:41,775 --> 04:23:46,013
HAVE TO DO WITH TWO THINGS 

5878
04:23:46,013 --> 04:23:46,914
RECRUITING AND THE FAMILIES 

5879
04:23:46,914 --> 04:23:48,282
KNOWING EACH OTHER AND THEY TALK

5880
04:23:48,282 --> 04:23:53,754
TO EACH OTHER AND TRY TO FIGURE 

5881
04:23:53,754 --> 04:23:59,293
OUT WHY ONE PERSON IT HAS 

5882
04:23:59,293 --> 04:24:09,336
ANOTHER AND THEY AND CAN THEY 

5883
04:24:09,336 --> 04:24:16,276
TALK ABOUT THIS AND COMMUNICATE 

5884
04:24:16,276 --> 04:24:21,381
ED ON THE PRIMARY OUTCOME 

5885
04:24:21,381 --> 04:24:23,283
MEASURE AND THERE'S PEOPLE 

5886
04:24:23,283 --> 04:24:24,084
AFFECTED BECAUSE OF THAT.

5887
04:24:24,084 --> 04:24:25,552
THIS IS A GIANT ISSUE IN TERMS 

5888
04:24:25,552 --> 04:24:27,187
OF FAMILIES TALKING TO EACH 

5889
04:24:27,187 --> 04:24:31,258
OTHER AND THINKING THEY'RE 

5890
04:24:31,258 --> 04:24:34,361
HELPING EACH OTHER BUT ACTUALLY 

5891
04:24:34,361 --> 04:24:35,295
RUINING THE INTEGRITY OF THE 

5892
04:24:35,295 --> 04:24:44,771
TRIAL.

5893
04:24:44,771 --> 04:24:47,774
>> IF THE FIRST PATIENT
DOES 

5894
04:24:47,774 --> 04:24:49,910
POORLY, I THINK THERE WILL BE NO

5895
04:24:49,910 --> 04:24:51,745
FUTURE TRIAL BECAUSE EVEN IF 

5896
04:24:51,745 --> 04:24:56,450
THERE IS HOPE FOR THE THERAPY 

5897
04:24:56,450 --> 04:24:59,286
WHO GOES FIRST-WHY ISN'T SO AND 

5898
04:24:59,286 --> 04:24:59,920
SO GOING FIRST?

5899
04:24:59,920 --> 04:25:04,291
THERE'S ALL KIND OF COVERINGS 

5900
04:25:04,291 --> 04:25:06,426
GOING ON IN THE BACKGROUND.

5901
04:25:06,426 --> 04:25:07,761
>> THAT'S WHY I ASKED THE 

5902
04:25:07,761 --> 04:25:11,365
QUESTION ALSO ABOUT THE PATIENT 

5903
04:25:11,365 --> 04:25:13,000
REPORTED OUTCOMES BECAUSE ONE 

5904
04:25:13,000 --> 04:25:14,434
WAY TO TANK THE STUDY IS FOR 

5905
04:25:14,434 --> 04:25:15,869
EVERYONE TO KNOW AND THE FIRST 

5906
04:25:15,869 --> 04:25:17,804
PERSON DOESN'T DO WELL NOBODY 

5907
04:25:17,804 --> 04:25:20,507
ELSE WANTS TO PARTICIPATE.

5908
04:25:20,507 --> 04:25:21,708
AND SOME INDIVIDUALS GETTING 

5909
04:25:21,708 --> 04:25:22,943
BACK PATIENT REPORTED OUTCOME 

5910
04:25:22,943 --> 04:25:28,682
MAY IMPACT HOW THEY R7D -- 

5911
04:25:28,682 --> 04:25:29,583
RESPOND IN THE FUTURE AND MAY 

5912
04:25:29,583 --> 04:25:30,751
CHANGE THE DATA.

5913
04:25:30,751 --> 04:25:35,989
IT WILL MAKE IT MUCH HARDER TO 

5914
04:25:35,989 --> 04:25:37,824
HAVE THE PURITY OF THE DATA 

5915
04:25:37,824 --> 04:25:38,058
NEEDED.

5916
04:25:38,058 --> 04:25:39,660
SO IT'S PART OF A LEARNING FOR 

5917
04:25:39,660 --> 04:25:42,629
ALL OF US AND ALSO FOR THE 

5918
04:25:42,629 --> 04:25:43,730
PARTICIPANTS.

5919
04:25:43,730 --> 04:25:45,766
AND I REALLY UNDERSTAND WHEN 

5920
04:25:45,766 --> 04:25:52,272
HAVE YOU A SICK CHILD YOU FEEL 

5921
04:25:52,272 --> 04:25:57,144
LIKE I DON'T HAVE TIME TO WAIT 

5922
04:25:57,144 --> 04:25:59,379
AND IN' SENSE WHAT THEY'RE DOING

5923
04:25:59,379 --> 04:26:00,914
IS HARMING THEIR OWN CHILDREN 

5924
04:26:00,914 --> 04:26:01,949
AND FUTURE CHILDREN.

5925
04:26:01,949 --> 04:26:08,288
SO WE'LL HAVE TO FIGURE OUT A 

5926
04:26:08,288 --> 04:26:10,357
WAY IN EUROPE AN ETHICAL 

5927
04:26:10,357 --> 04:26:13,727
PRINCIPLE IS COMMUNITY AND MAYBE

5928
04:26:13,727 --> 04:26:18,332
WE ADD THAT TO OUR ETHICAL 

5929
04:26:18,332 --> 04:26:19,233
FRAMEWORK AND HAPPY TO BRAIN 

5930
04:26:19,233 --> 04:26:19,933
STORM WITH YOU.

5931
04:26:19,933 --> 04:26:23,303
I DON'T HAVE SOLUTIONS TODAY.

5932
04:26:23,303 --> 04:26:28,609
THANK YOU VERY MUCH.

5933
04:26:28,609 --> 04:26:32,279
>> UNFORTUNATELY, GIVEN
THE TIME

5934
04:26:32,279 --> 04:26:35,282
WE'LL ROLL ON TO THE WRAP-UP 

5935
04:26:35,282 --> 04:26:35,916
DISCUSSION AND TURN IT OVER TO 

5936
04:26:35,916 --> 04:26:40,921
DAN.

5937
04:26:40,921 --> 04:26:41,321
>> 

5938
04:26:41,321 --> 04:26:45,058
>> IN AN IMPOSSIBLE TASK
WITH 10

5939
04:26:45,058 --> 04:26:46,927
MINUTES OR LEFT BECAUSE WE HAVE 

5940
04:26:46,927 --> 04:26:49,162
TO STOP PROMPTLY AT 3:00 BECAUSE

5941
04:26:49,162 --> 04:26:50,831
PEOPLE HAVE TRAVEL PLANS.

5942
04:26:50,831 --> 04:26:54,334
HOW SHOULD WE DO THIS?

5943
04:26:54,334 --> 04:27:00,073
TWO POSSIBILITIES IS OPEN FORUM 

5944
04:27:00,073 --> 04:27:02,442
WITH AN ACTION ORIENTED 

5945
04:27:02,442 --> 04:27:05,612
CONVERSATION NOT WHAT WAS MOST 

5946
04:27:05,612 --> 04:27:10,584
EXCITING BUT THOUGHTS ABOUT NEXT

5947
04:27:10,584 --> 04:27:13,487
STEPS BECAUSE THAT'S A GOAL TO 

5948
04:27:13,487 --> 04:27:15,455
TAKE STOP OF EXTRAORDINARY 

5949
04:27:15,455 --> 04:27:16,290
ADVANCES BUT ALSO THINK ABOUT 

5950
04:27:16,290 --> 04:27:25,932
NEXT STEPS.

5951
04:27:25,932 --> 04:27:31,171
THE OTHER IS QUICK CAUCUSING AND

5952
04:27:31,171 --> 04:27:37,311
COME UP WITH ONE IDEA FOR NEXT 

5953
04:27:37,311 --> 04:27:38,979
STEP AND I'M THROWING THAT OUT 

5954
04:27:38,979 --> 04:27:39,980
THERE BECAUSE PEOPLE WHO DON'T 

5955
04:27:39,980 --> 04:27:41,281
WANT TO SPEAK IN A BIGGER GROUP 

5956
04:27:41,281 --> 04:27:42,649
MAY HAVE A CHANCE TO SPEAK.

5957
04:27:42,649 --> 04:27:53,126
ANYBODY HAVE A THIRD OPTION?

5958
04:27:57,764 --> 04:27:58,932
OPTION A, OPTION B, SMALLER 

5959
04:27:58,932 --> 04:27:59,299
GROUP.

5960
04:27:59,299 --> 04:28:06,239
THAT DIDN'T WORK.

5961
04:28:06,239 --> 04:28:16,650
THOUGHTS ON NEXT STEPS?

5962
04:28:41,908 --> 04:28:43,443
>> THE THOUGHT IS TO COME
UP 

5963
04:28:43,443 --> 04:28:45,412
WITH A SET OF COMMON CORE 

5964
04:28:45,412 --> 04:28:45,712
PRINCIPLES.

5965
04:28:45,712 --> 04:28:47,948
BUT THIS IS WHAT WE NEED BEFORE 

5966
04:28:47,948 --> 04:28:49,416
WE THINK ABOUT A TRIAL.

5967
04:28:49,416 --> 04:28:50,650
THESE ARE THE OUTCOMES WE WANT 

5968
04:28:50,650 --> 04:28:52,052
TO LOOK AT.

5969
04:28:52,052 --> 04:28:54,221
WE WANT TO LOOK AT DEVELOPMENT 

5970
04:28:54,221 --> 04:28:56,957
AND MAYBE THERE'S SOME 

5971
04:28:56,957 --> 04:28:59,226
CUSTOMIZATION GENE BY GENE BUT 

5972
04:28:59,226 --> 04:29:01,061
DON'T NECESSARILY NEED A 10 YEAR

5973
04:29:01,061 --> 04:29:05,165
STUDY FOR EVERY SINGLE GENETIC 

5974
04:29:05,165 --> 04:29:06,733
CONDITION BEFORE WE CAN HAVE 

5975
04:29:06,733 --> 04:29:08,034
GENE SPECIFIC OUTCOME.

5976
04:29:08,034 --> 04:29:09,536
HOW CAN WE EFFICIENT SO THE 

5977
04:29:09,536 --> 04:29:10,871
PROGRESS MADE SO FAR IS TANGIBLE

5978
04:29:10,871 --> 04:29:14,775
AND MOVE FORWARD MORE QUICKLY.

5979
04:29:14,775 --> 04:29:20,747
>> EFFICIENCY.

5980
04:29:20,747 --> 04:29:22,516
>> LONG THE SAME LINES WE
HEARD 

5981
04:29:22,516 --> 04:29:26,820
A LOT ABOUT THE POTENTIAL FOR 

5982
04:29:26,820 --> 04:29:28,155
COLLABORATION WHICH IS WILL 

5983
04:29:28,155 --> 04:29:28,555
WONDERFUL.

5984
04:29:28,555 --> 04:29:29,923
CURIOUS TO WHAT HOW PEOPLE THINK

5985
04:29:29,923 --> 04:29:35,962
ABOUT THAT, WHAT CAN WE ACTIVELY

5986
04:29:35,962 --> 04:29:36,997
DO TO BRING GROUPS TOGETHER.

5987
04:29:36,997 --> 04:29:39,866
WE MAY NOT KNOW IN THE NEXT 

5988
04:29:39,866 --> 04:29:40,801
MINUTES BUT PERHAPS CAN PUT 

5989
04:29:40,801 --> 04:29:45,906
FORWARD A FORUM TO ENGAGE THAT 

5990
04:29:45,906 --> 04:29:50,977
AND SECOND QUESTION WHAT CAN 

5991
04:29:50,977 --> 04:29:53,213
NON-PROFIT LENDERS DO TO SUPPORT

5992
04:29:53,213 --> 04:29:54,648
MENT IN THIS AREA KNOWING WE 

5993
04:29:54,648 --> 04:29:56,983
HAVE NON-PROFIT FUNDERS FROM THE

5994
04:29:56,983 --> 04:30:00,120
BIGGEST, FROM NINDS TO CURE TO 

5995
04:30:00,120 --> 04:30:00,454
OTHERS.

5996
04:30:00,454 --> 04:30:08,595
HOW DO WE ENGAGE?

5997
04:30:08,595 --> 04:30:09,062
>> GREAT.

5998
04:30:09,062 --> 04:30:10,030
LET'S KEEP THIS GOING.

5999
04:30:10,030 --> 04:30:11,398
WE'RE RECORDING THESE QUESTIONS 

6000
04:30:11,398 --> 04:30:12,966
SO THERE ARE QUESTIONS THAT ARE 

6001
04:30:12,966 --> 04:30:13,366
ACTION ORIENTED.

6002
04:30:13,366 --> 04:30:23,777
WE NEED TO THINK ABOUT.

6003
04:30:33,954 --> 04:30:35,322
OTHER THOUGHTS.

6004
04:30:35,322 --> 04:30:35,722
ANYBODY 

6005
04:30:35,722 --> 04:30:38,592
>> I THINK WE NEED A 

6006
04:30:38,592 --> 04:30:39,593
STANDARDIZED OUTCOME MEASURE.

6007
04:30:39,593 --> 04:30:41,261
I SAID THIS BEFORE AT MANY 

6008
04:30:41,261 --> 04:30:44,164
MEETINGS BUT I DON'T THINK IT'S 

6009
04:30:44,164 --> 04:30:44,764
QUITE HAPPENED YET.

6010
04:30:44,764 --> 04:30:45,765
I KNOW THERE'S AN AN EFFORT 

6011
04:30:45,765 --> 04:30:49,836
GOING ON IN THE END OF ONE 

6012
04:30:49,836 --> 04:30:51,872
CONSORTIUM AND COMBINED BRAIN 

6013
04:30:51,872 --> 04:30:55,175
AND AN EFFORT IN LORUM BUT THERE

6014
04:30:55,175 --> 04:30:57,544
SHOULD NOT BE THREE BUT ONE 

6015
04:30:57,544 --> 04:31:00,280
EFFORT WHERE EVERYONE GETS 

6016
04:31:00,280 --> 04:31:04,284
TOGETHER AND MAYBE COORDINATED 

6017
04:31:04,284 --> 04:31:08,755
BY STNIH, I DON'T KNOW, BUT 

6018
04:31:08,755 --> 04:31:10,390
COMPARE ALL THE TRIALS OF ALL 

6019
04:31:10,390 --> 04:31:12,592
THE DISORDERS VERY SIMILAR 

6020
04:31:12,592 --> 04:31:13,760
THOUGH THEY HAVE DIFFERENT 

6021
04:31:13,760 --> 04:31:14,027
GENETICS.

6022
04:31:14,027 --> 04:31:15,762
I THINK THAT'S A REALLY 

6023
04:31:15,762 --> 04:31:17,330
IMPORTANT PROJECT AND WE VA TO 

6024
04:31:17,330 --> 04:31:18,465
BRING IN ALL THOSE GROUPS WHO 

6025
04:31:18,465 --> 04:31:21,268
THINK THEY'RE DOING THIS ON 

6026
04:31:21,268 --> 04:31:23,203
THEIR OWN AND MAKE THEM ALL WORK

6027
04:31:23,203 --> 04:31:26,072
TOGETHER.

6028
04:31:26,072 --> 04:31:31,845
>> IT BUILDING ON WHAT WAS
SAID.

6029
04:31:31,845 --> 04:31:32,846
>> IF WE WANT TO DEVELOP 

6030
04:31:32,846 --> 04:31:35,949
EFFECTIVE THERAPIES WE NEED TO 

6031
04:31:35,949 --> 04:31:38,685
HAVE A PLACE A COMMON PLACE TO 

6032
04:31:38,685 --> 04:31:41,821
HAVE RESOURCES TO FIND ALL THE 

6033
04:31:41,821 --> 04:31:43,890
RESOURCES BEGINNING FROM WILL 

6034
04:31:43,890 --> 04:31:52,265
BASIC SCIENCE LEVEL TO CLINICAL 

6035
04:31:52,265 --> 04:32:02,809
TRIAL AND USING MANY WHICH ONE 

6036
04:32:05,312 --> 04:32:11,318
WE'LL USE AND WORK ON THE 

6037
04:32:11,318 --> 04:32:21,461
EFFORTS 

6038
04:32:23,096 --> 04:32:28,868
>> HI, EVERYONE.

6039
04:32:28,868 --> 04:32:31,871
I'VE BEEN LISTENING TO THE 

6040
04:32:31,871 --> 04:32:40,146
PRESENTATIONS THE PAST FEW DAYS 

6041
04:32:40,146 --> 04:32:41,514
THERE WASN'T ENOUGH TIME FOR THE

6042
04:32:41,514 --> 04:32:47,187
PANEL BUT WANTED TO GIVE THE 

6043
04:32:47,187 --> 04:32:53,326
MESSAGE WE'RE EXCITED FOR THE 

6044
04:32:53,326 --> 04:32:59,966
FIELD AND THE SPIRIT OF 

6045
04:32:59,966 --> 04:33:01,735
COLLABORATION AND READY TO 

6046
04:33:01,735 --> 04:33:02,035
COLLABORATE.

6047
04:33:02,035 --> 04:33:06,940
THERE'S DIFFERENT AVENUES FOR 

6048
04:33:06,940 --> 04:33:12,479
HAVING FEEDBACK FROM THE REVIEW 

6049
04:33:12,479 --> 04:33:18,351
TEAM FOR THE DEVELOPMENT EVEN 

6050
04:33:18,351 --> 04:33:27,494
BEFORE IT START ED FORMAL AND 

6051
04:33:27,494 --> 04:33:28,995
INFORMAL WAY TO PARTICIPATE AND 

6052
04:33:28,995 --> 04:33:34,834
COLLABORATE IN THE DEVELOPMENT.

6053
04:33:34,834 --> 04:33:41,641
AND SO MUCH NEEDED THERAPIES 

6054
04:33:41,641 --> 04:33:42,275
FOR.

6055
04:33:42,275 --> 04:33:43,877
JUST WANTED TO MENTION THAT.

6056
04:33:43,877 --> 04:33:44,544
>> THANK YOU.

6057
04:33:44,544 --> 04:33:46,279
VICKY AND I WERE TALKING ABOUT 

6058
04:33:46,279 --> 04:33:47,313
THIS YESTERDAY.

6059
04:33:47,313 --> 04:33:50,517
WE NEED TO MAKE SURE OUR YOUNG 

6060
04:33:50,517 --> 04:33:52,318
PEOPLE KNOW NIH IS A VERY 

6061
04:33:52,318 --> 04:33:53,520
WILLING PARTNER IN THE WORK 

6062
04:33:53,520 --> 04:33:55,121
WE'RE ALL DOING.

6063
04:33:55,121 --> 04:33:57,090
I THINK YOUNG FOLKS SOMETIME 

6064
04:33:57,090 --> 04:34:00,060
THINK IT'S OFTEN A DISTANCE AND 

6065
04:34:00,060 --> 04:34:01,294
I BETTER NOT BOTHER MY PROGRAM 

6066
04:34:01,294 --> 04:34:01,628
OFFICER.

6067
04:34:01,628 --> 04:34:02,328
IT'S THE OPPOSITE.

6068
04:34:02,328 --> 04:34:06,599
THEY WANT TO BE A MEMBER OF THE 

6069
04:34:06,599 --> 04:34:09,069
TEAM AND WE SHOULD ENCOURAGE OUR

6070
04:34:09,069 --> 04:34:10,670
YOUNG INVESTIGATORS TO RECOGNIZE

6071
04:34:10,670 --> 04:34:18,945
THAT AS A RESOURCE SO THANK YOU.

6072
04:34:18,945 --> 04:34:21,815
>> AND WILL HOW DO WE DO
NATURAL

6073
04:34:21,815 --> 04:34:23,149
HISTORY STUDIES ACROSS THESE 

6074
04:34:23,149 --> 04:34:24,818
DISORDERS AND WHEN DO WE NEED TO

6075
04:34:24,818 --> 04:34:30,223
DO THEM IN A GENE SPECIFIC WAY?

6076
04:34:30,223 --> 04:34:33,126
SO WE NEED TO THINK ABOUT THAT 

6077
04:34:33,126 --> 04:34:34,394
AND EVERYTHING HAS BEEN DONE ON 

6078
04:34:34,394 --> 04:34:38,998
A GENE BY GENE BASIS WHICH IS 

6079
04:34:38,998 --> 04:34:44,771
HOW IT CAN HAPPEN AND NEED TO 

6080
04:34:44,771 --> 04:34:50,477
SCALE THIS AND CLASSES OF GENES 

6081
04:34:50,477 --> 04:34:52,846
AND WHICH THERAPEUTIC STRATEGIES

6082
04:34:52,846 --> 04:34:58,017
WORK FOR AND DO IS IN A MORE 

6083
04:34:58,017 --> 04:34:59,385
MODERATE GROUP WAY AND HAVE TWO 

6084
04:34:59,385 --> 04:35:00,286
OR THREE POTENTIAL THERAPIES 

6085
04:35:00,286 --> 04:35:07,393
NEARLY READY TO GO AND DO SOME 

6086
04:35:07,393 --> 04:35:09,829
PRE CLINICAL WORK AND WHAT 

6087
04:35:09,829 --> 04:35:12,832
CLINICAL TRIALS MAKE SENSE AND 

6088
04:35:12,832 --> 04:35:15,568
DO IT RECESSIVE ORDERS AND GAIN 

6089
04:35:15,568 --> 04:35:17,303
OF FUNCTION MUTATIONS THAT ALL 

6090
04:35:17,303 --> 04:35:20,607
THE OF US CAN POINT OUT AND WE 

6091
04:35:20,607 --> 04:35:22,175
CAN DEVELOP THERAPIES NOW NOT 

6092
04:35:22,175 --> 04:35:23,710
JUST WHEN THE PATIENT WALKS IN 

6093
04:35:23,710 --> 04:35:25,044
THE DOOR.

6094
04:35:25,044 --> 04:35:29,249
IT'S BEEN VERY REACTIVE AND END 

6095
04:35:29,249 --> 04:35:31,384
OF ONE THERAPY AND WE HAVE A 

6096
04:35:31,384 --> 04:35:36,890
PATIENT WHO SHOWED UP WHO HAS 

6097
04:35:36,890 --> 04:35:43,797
MEANS OR WHATEVER AND WE NEED TO

6098
04:35:43,797 --> 04:35:46,966
GET AHEAD OF THAT SO WE DON'T 

6099
04:35:46,966 --> 04:35:49,536
SPEND TWO YEARS DEVELOPING 

6100
04:35:49,536 --> 04:35:50,870
THERAPIES BUT HAVE SOMETHING OFF

6101
04:35:50,870 --> 04:35:52,739
THE SHELF AND THAT'S SOMETHING 

6102
04:35:52,739 --> 04:35:54,307
FOR NIH AND CURE CAN THINK ABOUT

6103
04:35:54,307 --> 04:35:55,909
HOW TO FUND COLLABORATIVE 

6104
04:35:55,909 --> 04:36:05,652
EFFORTS TO DO THIS EFFICIENTLY.

6105
04:36:05,652 --> 04:36:05,985
>> GREAT.

6106
04:36:05,985 --> 04:36:06,486
LAST POINT.

6107
04:36:06,486 --> 04:36:09,122
>> I THINK THE KEY IS 

6108
04:36:09,122 --> 04:36:10,256
COLLABORATION AND GUIDANCE AND 

6109
04:36:10,256 --> 04:36:12,258
USING ALL THE EXPERTISE IN THE 

6110
04:36:12,258 --> 04:36:17,297
ROOM AND  OTHERS WHO COULDN'T 

6111
04:36:17,297 --> 04:36:19,933
MAKE IT FOR HELPING GUIDE 

6112
04:36:19,933 --> 04:36:20,400
CLINICAL DEVELOPMENT.

6113
04:36:20,400 --> 04:36:23,303
WE ALL KNOW CLINICAL TRIALS WHO 

6114
04:36:23,303 --> 04:36:26,506
HAVE FAILED BECAUSE OF DESIGN 

6115
04:36:26,506 --> 04:36:29,809
ISSUES AND I THINK PEOPLE IN THE

6116
04:36:29,809 --> 04:36:32,011
ROOM WOULD ALSO BE VERY WELL 

6117
04:36:32,011 --> 04:36:36,649
POSITIONED TO DEVELOP ADDITIONAL

6118
04:36:36,649 --> 04:36:38,418
GUIDANCE HOW WE DEVELOP CLINICAL

6119
04:36:38,418 --> 04:36:43,556
TRIALS FOR PATIENTS WITH RARE 

6120
04:36:43,556 --> 04:36:44,390
GENETIC EPILEPSIES AND FEATURES 

6121
04:36:44,390 --> 04:36:47,327
THAT WILL IMPACT HOW THE TRIALS 

6122
04:36:47,327 --> 04:36:51,831
ARE DESIGN AND IF THEY CAN BE 

6123
04:36:51,831 --> 04:36:53,399
IMPROVED AT ALL.

6124
04:36:53,399 --> 04:36:55,368
MORE GUIDANCE AROUND THAT.

6125
04:36:55,368 --> 04:37:01,975
>> AND VICKI YOU'LL GET
THE LAST

6126
04:37:01,975 --> 04:37:02,308
WORD.

6127
04:37:02,308 --> 04:37:02,609
>> 

6128
04:37:02,609 --> 04:37:04,677
>> ONCE AGAIN, THANKS,
EVERYONE.

6129
04:37:04,677 --> 04:37:06,880
IT'S BEEN A FANTASTIC WORKSHOP.

6130
04:37:06,880 --> 04:37:10,650
I LEARNED A TREMENDOUS AMOUNT.

6131
04:37:10,650 --> 04:37:12,986
WE'LL DO FOLLOW-UP AND THINK OF 

6132
04:37:12,986 --> 04:37:13,987
WAYS TO CONTINUE THE 

6133
04:37:13,987 --> 04:37:16,422
CONVERSATION AND WAYS TO ADDRESS

6134
04:37:16,422 --> 04:37:19,559
SOME OF THESE LAST POINTS AND 

6135
04:37:19,559 --> 04:37:24,497
MOVING FORWARD AS FAST WE CAN 

6136
04:37:24,497 --> 04:37:26,766
AND SAFE TRAVELS AND BE IN TOUCH

6137
04:37:26,766 --> 04:37:28,268
AND ANY THOUGHTS OR IDEAS SEND 

6138
04:37:28,268 --> 04:37:28,601
THEM OUR WAY.

6139
04:37:28,601 --> 04:37:38,945
THANK YOU VERY MUCH.