1
00:00:08,274 --> 00:00:11,411
--WITH BASIC SCIENCE AND

2
00:00:11,478 --> 00:00:12,879
CERTAINLY THIS PARTICULAR

3
00:00:12,946 --> 00:00:14,381
INSTALLMENT WILL DO JUST THAT.

4
00:00:14,447 --> 00:00:17,784
THE SERIES GOES ON TUESDAY

5
00:00:17,851 --> 00:00:19,486
AFTERNOONS FROM 4-6:00 P.M.

6
00:00:19,552 --> 00:00:20,920
EASTERN TIME FROM JANUARY

7
00:00:20,987 --> 00:00:21,254
THROUGH MAY.

8
00:00:21,321 --> 00:00:24,290
AND YOU CAN WATCH IT ON THE LINK

9
00:00:24,357 --> 00:00:26,393
SHOWN HERE ON THE SLIDE.

10
00:00:26,459 --> 00:00:27,761
CME CREDIT IS AVAILABLE, YOU

11
00:00:27,827 --> 00:00:33,032
HAVE TO USE THE CME CODE WHICH

12
00:00:33,099 --> 00:00:33,466
TODAY IS 52092.

13
00:00:33,533 --> 00:00:36,002
IF YOU HAVE QUESTIONS, DURING

14
00:00:36,069 --> 00:00:37,203
THE COURSE OF THE 2

15
00:00:37,270 --> 00:00:39,672
PRESENTATIONS, YOU CAN SUBMIT

16
00:00:39,739 --> 00:00:43,443
THEM VIA THE SEND LIVE FEEDBACK

17
00:00:43,510 --> 00:00:45,078
BUTTON ON THE VIDEOCAST DISPLAY.

18
00:00:45,145 --> 00:00:47,480
ALL OF THE PREVIOUS SESSIONS ARE

19
00:00:47,547 --> 00:00:50,016
ARCHIVED AT THE LINK SHOWN HERE

20
00:00:50,083 --> 00:00:51,251
ON THE SCREEN.

21
00:00:51,317 --> 00:00:52,185
AND FOR ADDITIONAL INFORMATION,

22
00:00:52,252 --> 00:00:55,989
YOU CAN GO TO THE WALS OFFICE

23
00:00:56,055 --> 00:01:00,460
E-MAIL ADDRESS SHOWN THERE.

24
00:01:00,527 --> 00:01:02,195
IN ANY CASE, IF WE COULD HAVE

25
00:01:02,262 --> 00:01:05,398
THE NEXT SLIDE, IT SIMPLY GIVES

26
00:01:05,465 --> 00:01:07,934
US THE CME INFORMATION AGAIN,

27
00:01:08,001 --> 00:01:10,470
AGAIN THE CME CODE IS 52092.

28
00:01:10,537 --> 00:01:21,047
YOU HAVE TO TEXT THAT CODE TO

29
00:01:21,581 --> 00:01:21,748
18449801555.

30
00:01:21,815 --> 00:01:23,750
YOU WILL SEE THAT NEITHER OF THE

31
00:01:23,817 --> 00:01:27,320
SPEAKERS TODAY HAS ANY FINANCIAL

32
00:01:27,387 --> 00:01:28,354
CONFLICKS TO DISCLOSE.

33
00:01:28,421 --> 00:01:30,223
IF WE GO GO ON THOUGH TO THE

34
00:01:30,290 --> 00:01:31,724
NEXT SLIDE, I WILL TELL YOU A

35
00:01:31,791 --> 00:01:34,694
LITTLE BIT ABOUT TODAY'S

36
00:01:34,761 --> 00:01:34,994
PRESENTERS.

37
00:01:35,061 --> 00:01:36,896
SO THE TITLE OF TODAY'S

38
00:01:36,963 --> 00:01:38,765
PRESENTATION IN CASE YOU HADN'T

39
00:01:38,832 --> 00:01:41,367
GUESSED IS SICKLE CELL ANEMIA, A

40
00:01:41,434 --> 00:01:42,402
GLOBAL PERSPECTIVE.

41
00:01:42,469 --> 00:01:44,437
AND AS OUR FIRST SPEAKER, WE

42
00:01:44,504 --> 00:01:47,507
HAVE THE GOOD DR. COURTNEY

43
00:01:47,574 --> 00:01:49,409
FITZHUGH WHO IS A LASKER

44
00:01:49,476 --> 00:01:50,443
CLINICAL RESEARCH SCHOLAR AND

45
00:01:50,510 --> 00:01:52,512
SHE CHIEF OF THE EARLY SICKLE

46
00:01:52,579 --> 00:01:54,247
MORTALITY SECTION OF THE

47
00:01:54,314 --> 00:01:56,115
CELLULAR AND MOLECULAR

48
00:01:56,182 --> 00:01:59,719
THERAPEUTIC BRANCH OF THE

49
00:01:59,786 --> 00:02:01,120
NATIONAL HEART, LUNG, AND BLOOD

50
00:02:01,187 --> 00:02:01,754
INSTITUTE.

51
00:02:01,821 --> 00:02:08,061
SHE GOT HER BACHELOR'S DEGREE IN

52
00:02:08,127 --> 00:02:10,897
BIOLOGY MAGNUM CUM LAUDE AT UCLA

53
00:02:10,964 --> 00:02:12,765
AND COMPLETED HER MEDICAL

54
00:02:12,832 --> 00:02:14,801
TRAINING AT UCSF, AND COMBINED

55
00:02:14,868 --> 00:02:17,504
RESIDENCY IN INTERNAL MEDICINE

56
00:02:17,570 --> 00:02:22,609
AND PEDIATRICS AT DUKE AND

57
00:02:22,675 --> 00:02:26,379
COMBINED FELLOWSHIP IN ADULT

58
00:02:26,446 --> 00:02:27,881
HEMEATOLOGY, AND SHE IS THE

59
00:02:27,947 --> 00:02:30,350
MEMBER OF THE AMERICAN SOCIETY

60
00:02:30,416 --> 00:02:32,552
OF HEMEATOLOGY AND AMERICAN

61
00:02:32,619 --> 00:02:33,253
TRANSPLANSATION AND CELLULAR

62
00:02:33,319 --> 00:02:38,124
THERAPY EMPLOY HER RESEARCH

63
00:02:38,191 --> 00:02:40,093
INCLUSIONS ARE NONMILE ABLATIVE

64
00:02:40,159 --> 00:02:42,095
TRANSPLANTATION AND SICKLE CELL

65
00:02:42,161 --> 00:02:43,229
ANEMIA, HALF MATCHED

66
00:02:43,296 --> 00:02:45,331
TRANSPLANTATION IN SICKLE CELL

67
00:02:45,398 --> 00:02:46,933
ANEMIA, AND LONG-TERM ORGAN

68
00:02:47,000 --> 00:02:48,601
FUNCTION IN PATIENTS UNDERGOING

69
00:02:48,668 --> 00:02:50,436
CURIAATIVE THERAPIES FOR SICKLE

70
00:02:50,503 --> 00:02:53,907
CELL DEC, AND GENETIC RISK

71
00:02:53,973 --> 00:02:56,676
FACTORS FOR MYELOID MALIGNANCY

72
00:02:56,743 --> 00:02:57,944
DEVELOPMENT AFTER CURATIVE

73
00:02:58,011 --> 00:02:58,745
THERAPIES FOR SICKLE CELL

74
00:02:58,811 --> 00:02:59,045
DISEASE.

75
00:02:59,112 --> 00:03:00,079
IF YOU COULD HAVE THE NEXT

76
00:03:00,146 --> 00:03:02,181
SLIDE, I WILL TELL YOU ABOUT THE

77
00:03:02,248 --> 00:03:04,617
SECOND PEEKER WHO IS

78
00:03:04,684 --> 00:03:08,354
THE--SPEAKER WHO IS THE GOOD

79
00:03:08,421 --> 00:03:09,789
AMBROISE WONKAM, HE IS WITH THE

80
00:03:09,856 --> 00:03:11,090
DEPARTMENT OF GENETIC MEDICINE

81
00:03:11,157 --> 00:03:12,258
AND PROFESSOR OF GENETIC

82
00:03:12,325 --> 00:03:13,993
MEDICINE AT JOHNS HOPKINS

83
00:03:14,060 --> 00:03:14,294
UNIVERSITY.

84
00:03:14,360 --> 00:03:19,065
HE GOT HIS MEDICAL DEGREE IN

85
00:03:19,132 --> 00:03:24,203
CAMMA ROON AT THE UNIVERSITY OF

86
00:03:24,270 --> 00:03:28,141
YAOUNDE, AND HE GOT HIS DEGREE

87
00:03:28,207 --> 00:03:30,243
AT UNIVERSITY OF GENEVA AND GOT

88
00:03:30,310 --> 00:03:32,345
A Ph.D. AT HUMAN GENETICS AT

89
00:03:32,412 --> 00:03:34,080
THE UNIVERSITY OF CAPE TOWN.

90
00:03:34,147 --> 00:03:37,150
HE HAS HAD HUMAN GENETICS

91
00:03:37,216 --> 00:03:39,052
FACULTY APPOINTMENTS AT THE

92
00:03:39,118 --> 00:03:39,986
UNIVERSITY OF YAOUNDE AND THE

93
00:03:40,053 --> 00:03:41,354
UNIVERSITY OF CAPE TOWN AND HE

94
00:03:41,421 --> 00:03:44,090
ROSE TO THE RANK OF DEPUTY DEAN

95
00:03:44,157 --> 00:03:46,526
FOR RESEARCH AT THE UNIVERSITY

96
00:03:46,593 --> 00:03:47,360
OF CAPE TOWN.

97
00:03:47,427 --> 00:03:49,796
HE IS THE RECIPIENT OF A NUMBER

98
00:03:49,862 --> 00:03:54,133
OF PRESTIGIOUS AWARDS AND PRIZES

99
00:03:54,200 --> 00:03:55,201
INCLUDING THE DENBER-PIN ARD

100
00:03:55,268 --> 00:03:57,270
PRIZE AT THE UNIVERSITY OF

101
00:03:57,337 --> 00:03:59,706
GENEVA FOR HIS DOCTORAL

102
00:03:59,772 --> 00:04:02,909
DISSERTATION AND THE ALAN PIFER

103
00:04:02,976 --> 00:04:03,810
AWARD FROM THE UNIVERSITY OF

104
00:04:03,876 --> 00:04:04,677
CAPE TOWN.

105
00:04:04,744 --> 00:04:07,747
HE IS CURRENTLY THE PF THE

106
00:04:07,814 --> 00:04:09,082
AFRICAN SOCIETY OF HUMAN

107
00:04:09,148 --> 00:04:11,451
GENETICS AND CHAIR, STEERING

108
00:04:11,517 --> 00:04:14,754
COMMITTEE OF THE H3 AFRICA

109
00:04:14,821 --> 00:04:15,088
CONSORTIUM.

110
00:04:15,154 --> 00:04:16,956
AND HIS RESEARCH INCLUDES

111
00:04:17,023 --> 00:04:21,728
PSYCHOSOCIAL BURDEN AND GENOMICS

112
00:04:21,794 --> 00:04:24,030
MODIFIERS OF SICKLE CELL

113
00:04:24,097 --> 00:04:25,632
DISEASE, GENETICS OF HEARING

114
00:04:25,698 --> 00:04:27,634
LOSS AND ETHICAL AND EDUCATIONAL

115
00:04:27,700 --> 00:04:29,869
ISSUES IN HUMAN GENETICS IN

116
00:04:29,936 --> 00:04:30,203
AFRICA.

117
00:04:30,269 --> 00:04:32,372
HOWEVER, WITHOUT FURTHER ADO, I

118
00:04:32,438 --> 00:04:35,475
GIVE YOU THE GOOD DR. FITZHUGH

119
00:04:35,541 --> 00:04:45,518
AND THAT RHYMES, TOO.

120
00:04:45,585 --> 00:04:46,853
>> GOOD AFTERNOON AND THANK YOU

121
00:04:46,919 --> 00:04:47,887
FOR THE WONDERFUL INTRODUCTION,

122
00:04:47,954 --> 00:04:51,457
I DON'T KNOW HOW I CAN FOLLOW

123
00:04:51,524 --> 00:04:52,125
THAT.

124
00:04:52,191 --> 00:04:55,161
MY TALK IS ENTITLED AN UPDATE ON

125
00:04:55,228 --> 00:04:56,229
HEMEAT O PETRESSABLEETIC

126
00:04:56,295 --> 00:04:58,498
TRANSPLANTATION FOR SICKLE CELL

127
00:04:58,564 --> 00:04:58,831
DISEASE.

128
00:04:58,898 --> 00:05:00,366
SO I'M GOING TO START BY

129
00:05:00,433 --> 00:05:01,434
INTRODUCING YOU TO 1 OF MY

130
00:05:01,501 --> 00:05:03,803
PATIENTS THAT I WILL REFER TO AS

131
00:05:03,870 --> 00:05:05,738
MISSIAC SON, 26 YEAR-OLD AFRICAN

132
00:05:05,805 --> 00:05:07,240
AMERICAN WOMAN WITH HOMOZYGOUS

133
00:05:07,306 --> 00:05:12,211
SICKLE CELL DEE, SHE HAD A

134
00:05:12,278 --> 00:05:14,414
REGURNLGENT VELOCITY AS SHOWN BY

135
00:05:14,480 --> 00:05:18,317
ECHO CARDIOGRAM, HE HAD RIGHT

136
00:05:18,384 --> 00:05:19,752
HATTER CATHETERIZATION,

137
00:05:19,819 --> 00:05:20,987
PULMONARY TENSION, CHRONIC RENAL

138
00:05:21,054 --> 00:05:21,554
INSUFFICIENCY.

139
00:05:21,621 --> 00:05:23,890
SHE WAS EASILY FATIGUED, SHE HAD

140
00:05:23,956 --> 00:05:24,924
SHORTNESS OF BREATH AFTER

141
00:05:24,991 --> 00:05:29,862
WALKING ABOUT 2 BLOCKS SHE HAD

142
00:05:29,929 --> 00:05:31,230
INTERMITTENT PALPITATIONS WEEKLY

143
00:05:31,297 --> 00:05:34,167
LASTING A FEW MINUTES OF WITH NO

144
00:05:34,233 --> 00:05:34,734
KNOWN HISTORY.

145
00:05:34,801 --> 00:05:45,244
NO HISTORY OF PASSING OUT.

146
00:06:08,367 --> 00:06:18,644
SHE HAD 3 PILLAR ORTHOPNEA, AND

147
00:06:18,711 --> 00:06:24,584
NO PARO SIMIAL NOCTERERNAL.

148
00:06:24,650 --> 00:06:26,219
SHE HAD TRANSFUSION ASSOCIATED

149
00:06:26,285 --> 00:06:29,088
IRON OVERLOAD, SHE HAD BEEN

150
00:06:29,155 --> 00:06:30,356
TRANSFUSED MORE THAN 50 UNITS OF

151
00:06:30,423 --> 00:06:31,791
RED BLOOD CELLS IN HER LIFETIME.

152
00:06:31,858 --> 00:06:35,795
SHE HAD A LIVER BIOPSY WITH

153
00:06:35,862 --> 00:06:36,729
INFLAMMATION, SHE HAD FIBROSIS

154
00:06:36,796 --> 00:06:39,599
AND LIVER SCARVING AND

155
00:06:39,665 --> 00:06:41,367
CONCENTRATION AT 5.4-MILLIGRAMS

156
00:06:41,434 --> 00:06:42,135
PER GRAM.

157
00:06:42,201 --> 00:06:44,737
SHE HAD REATURENT PAINFUL

158
00:06:44,804 --> 00:06:47,006
CRISIS, 16 HOSPITALIZED IN THE

159
00:06:47,073 --> 00:06:48,241
PREVIOUS YEAR AND 20 IN THE

160
00:06:48,307 --> 00:06:49,809
PREVIOUS 3 YEARS.

161
00:06:49,876 --> 00:06:53,579
SHE HAD CHRONIC BACK PAIN, ACUTE

162
00:06:53,646 --> 00:06:54,781
CHEST SYNDROME, JEIMER TENSION

163
00:06:54,847 --> 00:06:56,983
AND AS I MENTIONED SHE HAD

164
00:06:57,049 --> 00:06:59,952
PULMONARY HYPERTENSION WITH THE

165
00:07:00,019 --> 00:07:03,156
MAIN PRESSURE OF 30-METERS OF

166
00:07:03,222 --> 00:07:04,223
MERCURY AND A [INDISCERNIBLE]

167
00:07:04,290 --> 00:07:14,066
AND BECAUSE THAT SHE HAD BEEN

168
00:07:14,133 --> 00:07:24,610
STARTED IN AMBRISENTAN SINCE

169
00:07:24,944 --> 00:07:25,144
2012.

170
00:07:25,211 --> 00:07:31,150
I'M TRYING TO FIND THE--AND IT

171
00:07:31,217 --> 00:07:33,286
LEADS TO, THE ORGANS NOT GETTING

172
00:07:33,352 --> 00:07:34,987
ENOUGH OXYGEN, SO SICKLE CELL

173
00:07:35,054 --> 00:07:39,192
DISEASE AND ALSO ASSOCIATE WIDE

174
00:07:39,258 --> 00:07:40,026
HYPOXIA POLYMERIZATION,

175
00:07:40,092 --> 00:07:41,761
SHORTENED RED SURVIVAL LEADING

176
00:07:41,828 --> 00:07:45,431
TO STRESS, DAMAGE TO THE BONE

177
00:07:45,498 --> 00:07:47,433
MARROW MICROENVIRONMENT,

178
00:07:47,500 --> 00:07:48,067
INFLAMMATION ANDOXIDATIVE

179
00:07:48,134 --> 00:07:48,434
STRESS.

180
00:07:48,501 --> 00:07:50,169
SO THE GLOBAL BURDEN OF SICKLE

181
00:07:50,236 --> 00:07:51,737
CELL DISEASE AND ENORMOUS, THE

182
00:07:51,804 --> 00:07:53,706
ESTIMATED NUMBER OF NEWBORNS

183
00:07:53,773 --> 00:07:55,308
WITH SICKLE CELL DISEASE

184
00:07:55,374 --> 00:07:57,143
GLOBALLY WILL INCREASE FROM

185
00:07:57,210 --> 00:08:01,280
305,000 IN 2010 TO OVER 404,000

186
00:08:01,347 --> 00:08:03,749
IN 2050 AND IN 2010 AN ESTIMATED

187
00:08:03,816 --> 00:08:06,219
79 NEWBORNS OF SICKLE CELL

188
00:08:06,285 --> 00:08:07,820
DISEASE WERE IN SUB-SAHARAN

189
00:08:07,887 --> 00:08:10,089
AFRICA AND 3 COUNTRIES, NIGERIA,

190
00:08:10,156 --> 00:08:11,891
INDIA AND THE DEMOCRATIC

191
00:08:11,958 --> 00:08:13,492
REPUBLIC OF CONGO REPRESENT 57%

192
00:08:13,559 --> 00:08:16,128
OF THE ANNUAL NUMBER OF NEWBORNS

193
00:08:16,195 --> 00:08:17,196
WITH SICKLE CELL DISEASE

194
00:08:17,263 --> 00:08:24,170
GLOBALLY, SO YOU CAN SEE FROM

195
00:08:24,237 --> 00:08:32,378
THIS FIGURE HERE--LOOKING FOR

196
00:08:32,445 --> 00:08:33,112
THE POINTER.

197
00:08:33,179 --> 00:08:34,714
THAT THIS BURDEN OF SICKLE CELL

198
00:08:34,780 --> 00:08:36,816
DISEASE IN THE U.S. IS VERY

199
00:08:36,883 --> 00:08:40,586
SMALL COMPARED TO SUB-SAHARAN

200
00:08:40,653 --> 00:08:41,120
AFRICA AND INDIA.

201
00:08:41,187 --> 00:08:43,689
SO PATIENTS WITH SICKLE CELL

202
00:08:43,756 --> 00:08:44,724
DISEASE EXPERIENCING EXTENSIVE

203
00:08:44,790 --> 00:08:46,559
MORBIDITY, THE MOST COMMON

204
00:08:46,626 --> 00:08:48,427
COMPLICATION IS SEVERE

205
00:08:48,494 --> 00:08:50,830
DEBILITATING PAINFUL RICE

206
00:08:50,897 --> 00:08:52,565
CRISIS, PATIENT CAN HAVE

207
00:08:52,632 --> 00:08:53,766
STROKES, LIVER DISEASE, YOUNG

208
00:08:53,833 --> 00:08:55,935
PATIENTS REQUIRING HIP

209
00:08:56,002 --> 00:08:56,836
REPLACEMENT, INFECTIONS AND

210
00:08:56,903 --> 00:08:58,004
INFARCTIONS IN THE BONE, RETINAL

211
00:08:58,070 --> 00:08:58,938
LOCATION NUMBER OF PATIENTSATHY

212
00:08:59,005 --> 00:09:01,007
AND THE PATIENTS CAN BECOME

213
00:09:01,073 --> 00:09:03,709
BLIND, THEY CAN HAVE CARDIO

214
00:09:03,776 --> 00:09:05,878
PULMONARY COMPLICATIONS AND IN

215
00:09:05,945 --> 00:09:07,580
THE SEVERE NONHEALING LEG ULCERS

216
00:09:07,647 --> 00:09:09,515
AND MULTIPLE STUDIES INCLUDE

217
00:09:09,582 --> 00:09:10,783
STUDIES THAT HAVE SHOWN THAT

218
00:09:10,850 --> 00:09:11,751
PATIENTS WITH SICKLE CELL

219
00:09:11,817 --> 00:09:13,252
DISEASE HAVE LIVER DAMAGE, HEART

220
00:09:13,319 --> 00:09:14,320
AND LUNG DAMAGE, KIDNEY DAMAGE

221
00:09:14,387 --> 00:09:20,559
ARE AT RISK OF DYING EARLY.

222
00:09:20,626 --> 00:09:23,229
SO THIS FIGURE SHOWS THE

223
00:09:23,296 --> 00:09:24,764
CUMULATIVE SURVIVAL AND THE

224
00:09:24,830 --> 00:09:26,732
X-AXIS SHOWS AGE AT FOLLOW UP AT

225
00:09:26,799 --> 00:09:28,734
DEATH OR IN YEARS AND THEY

226
00:09:28,801 --> 00:09:29,669
FOLLOWED 225 PATIENTS MOST OF

227
00:09:29,735 --> 00:09:31,771
THEM HAVING THE MOST SEVERE TYPE

228
00:09:31,837 --> 00:09:33,172
OF SICKLE CELL DISEASE AND THEY

229
00:09:33,239 --> 00:09:34,974
FOLLOWED THEM FOR A MEDIAN OF 6

230
00:09:35,041 --> 00:09:35,975
AND HALF YEARS.

231
00:09:36,042 --> 00:09:39,211
IMPORTANTLY 60% OF THE PATIENTS

232
00:09:39,278 --> 00:09:40,479
WERE HYDROXY URIA WHICH IS THE

233
00:09:40,546 --> 00:09:42,815
BEST DRUG FOR IT AT THE TIME BUT

234
00:09:42,882 --> 00:09:44,583
THE MEDIAN SURVIVAL AGE AND ONLY

235
00:09:44,650 --> 00:09:46,385
48 YEARS WHICH HAS NOT REALLY

236
00:09:46,452 --> 00:09:48,254
CHANGE INDEED THE LAST 20 YEARS

237
00:09:48,321 --> 00:09:49,322
SO ADULTS WITH SICKLE CELL

238
00:09:49,388 --> 00:09:51,057
DISEASE HAVE A SHORTENED LIFE

239
00:09:51,123 --> 00:09:51,324
SPAN.

240
00:09:51,390 --> 00:09:54,060
THEY ALSO WANTED TO KNOW, THIS

241
00:09:54,126 --> 00:09:55,328
IS OUR INVESTIGATORS AT

242
00:09:55,394 --> 00:09:56,128
VANDERBILT, THEY WANT TO KNOW

243
00:09:56,195 --> 00:09:57,663
WHAT HAPPENS IF YOU HAVE MORE

244
00:09:57,730 --> 00:09:59,398
THAN 1 ORGAN INROFULLED SO THEY

245
00:09:59,465 --> 00:10:01,467
DEFINE HEART DAMAGE AS A TRI

246
00:10:01,534 --> 00:10:04,503
CUSPID OF AT LEAST 2.5-METERS

247
00:10:04,570 --> 00:10:06,472
PER SECOND, BLOWING DAMAGE OF

248
00:10:06,539 --> 00:10:08,708
THE 1% PREDICTED ON PULMONARY

249
00:10:08,774 --> 00:10:10,443
FUNCTION TESTING OF 70% AND

250
00:10:10,509 --> 00:10:13,312
THERE'S MULTIPLE DEFINITIONS FOR

251
00:10:13,379 --> 00:10:15,581
KIDNEY IMPAIRMENT INCLUDING AN

252
00:10:15,648 --> 00:10:16,449
ESTIMATED FILTRATION RATE OF

253
00:10:16,515 --> 00:10:17,516
LESS THAN 60 AND YOU CAN SEE

254
00:10:17,583 --> 00:10:19,418
THAT PATIENT WHO IS HAD NO

255
00:10:19,485 --> 00:10:20,686
ORGANS, OR 1 ORGAN IMPAIRED HAD

256
00:10:20,753 --> 00:10:22,555
A MEAN TIME TO DEATH OF 14

257
00:10:22,621 --> 00:10:24,757
YEARS, AND THIS WAS

258
00:10:24,824 --> 00:10:25,691
SIGNIFICANTLY SHORTER IN

259
00:10:25,758 --> 00:10:29,495
PATIENTS WHO HAD MORE THAN 1

260
00:10:29,562 --> 00:10:31,130
ORGAN IMPAIRED AT 7.8 YEARS SO

261
00:10:31,197 --> 00:10:32,631
BECAUSE MISSIAC SON HAD BOTH

262
00:10:32,698 --> 00:10:33,566
HEART AND KIDNEY IMPAIRMENT SHE

263
00:10:33,632 --> 00:10:38,537
WAS AT RISK FOR DYING EVEN

264
00:10:38,604 --> 00:10:39,372
EARLIER.

265
00:10:39,438 --> 00:10:40,439
SO MILE ABLATED TRANSPLANT

266
00:10:40,506 --> 00:10:41,841
OFFERS A POTENTIAL CURE FOR

267
00:10:41,907 --> 00:10:43,909
PATIENTS WITH SICKLE CELL

268
00:10:43,976 --> 00:10:45,544
DISEASE, MILE ABLATIVE MEANS YOU

269
00:10:45,611 --> 00:10:46,979
GIVE THE PATIENTS CHEMO THERAPY

270
00:10:47,046 --> 00:10:48,280
TO COMPLETE PLEA WIPE OUT BONE

271
00:10:48,347 --> 00:10:51,684
MARROW OR WIPE OUT THAT WITH THE

272
00:10:51,751 --> 00:10:53,886
DONEAR, HLA MATCH SIBLING MEANS

273
00:10:53,953 --> 00:10:56,188
THAT THE TISSUE IS A DIRECT

274
00:10:56,255 --> 00:10:59,191
MATCH, SO IT WAS REPORTED THAT

275
00:10:59,258 --> 00:11:01,560
MATCHING SIBLING BONE MARROW

276
00:11:01,627 --> 00:11:02,528
TRANSPLANT BETWEEN 1986 AND

277
00:11:02,595 --> 00:11:04,830
2013, THEY FOWBD THAT THE 5 YEAR

278
00:11:04,897 --> 00:11:06,966
OVERALL SURVIVAL IS 93%, AT 5

279
00:11:07,033 --> 00:11:08,934
YEARS 93% OF THE PATIENTS WERE

280
00:11:09,001 --> 00:11:15,274
ALIVE AND EVENT FREE SURVIVAL

281
00:11:15,341 --> 00:11:17,109
WAS 91% AND THEY FOUND THAT THE

282
00:11:17,176 --> 00:11:19,211
5 YEAR OVERALL SURVIVAL WAS

283
00:11:19,278 --> 00:11:20,446
SLIGHTLY HIGHER IN CHILDREN,

284
00:11:20,513 --> 00:11:23,516
LESS THAN 16 YEARS OF AGE AT

285
00:11:23,582 --> 00:11:24,950
95%, AND PRESURVIVAL IS 93%,

286
00:11:25,017 --> 00:11:26,052
THIS IS NOT SURPRISING SINCE

287
00:11:26,118 --> 00:11:28,587
MANY OF THE PATIENTS RECEIVE THE

288
00:11:28,654 --> 00:11:30,923
HIGH DOSE CHEMOTHERAPY I WAS

289
00:11:30,990 --> 00:11:31,457
TALKING ABOUT.

290
00:11:31,524 --> 00:11:32,925
THEN THEY FOUND THAT THE

291
00:11:32,992 --> 00:11:35,428
INCIDENCE OF ACUTE GRAFT VERSUS

292
00:11:35,494 --> 00:11:38,297
HOST DISEASE WAS END CHRONIC

293
00:11:38,364 --> 00:11:40,032
GRAFT VERSUS HOST DISEASE, AND

294
00:11:40,099 --> 00:11:43,135
THIS MEANS THAT THE DONOR IMMUNE

295
00:11:43,202 --> 00:11:45,604
IS ATTACKING THE PATIENT AND IT

296
00:11:45,671 --> 00:11:46,605
CAN CAUSE HARDENING AND SCARRING

297
00:11:46,672 --> 00:11:48,107
OF THE LUNGS AND COULD BE DEADLY

298
00:11:48,174 --> 00:11:50,042
SO I DON'T WANT TO INTRODUCE

299
00:11:50,109 --> 00:11:52,912
SOMETHING WORSE THAN SICKLE CELL

300
00:11:52,978 --> 00:11:53,345
DISEASE.

301
00:11:53,412 --> 00:11:55,514
SO THE FIRST MAJORB STACKLE FOR

302
00:11:55,581 --> 00:11:57,149
CARING FOR MISS JACKSON IS THAT

303
00:11:57,216 --> 00:11:59,385
MANY ADULT WHO IS RECEIVE THE

304
00:11:59,452 --> 00:12:01,587
STANDARD THERAPY WILL DIE

305
00:12:01,654 --> 00:12:05,558
BECAUSE OF PREEXISTING ORGAN

306
00:12:05,624 --> 00:12:06,025
DAMAGE.

307
00:12:06,092 --> 00:12:07,560
SO THERE WERE DATA AT TIME TO

308
00:12:07,626 --> 00:12:10,996
SUGGEST YOU DON'T NEED TO

309
00:12:11,063 --> 00:12:12,298
COMPLETELY REVERT THE PATIENT'S

310
00:12:12,364 --> 00:12:13,732
BONE MARROW IN ORDER TO REVERSE

311
00:12:13,799 --> 00:12:15,000
SICKLE CELL DISEASE, WE WANTED

312
00:12:15,067 --> 00:12:16,969
TO KNOW WHAT PERCENTAGE WAS

313
00:12:17,036 --> 00:12:20,306
SUFFICIENT TO REVERSE SICKLE

314
00:12:20,372 --> 00:12:22,041
CELL DEC AND WE WERE MOST

315
00:12:22,108 --> 00:12:25,244
IMPORTANT BECAUSE IN THE BONE

316
00:12:25,311 --> 00:12:27,046
MARROW THE MYELOID COMPART

317
00:12:27,113 --> 00:12:28,581
TRACKS WITH THE ERYTH ROADWAY

318
00:12:28,647 --> 00:12:30,382
DEPARTMENT, AND OF COURSE WE

319
00:12:30,449 --> 00:12:30,749
WERE INTERESTED.

320
00:12:30,816 --> 00:12:33,652
SO ON THE Y-AXIS YOU SEE THE

321
00:12:33,719 --> 00:12:34,920
CHIMERISM WHICH IS THE BLACK

322
00:12:34,987 --> 00:12:36,355
LINE AND THE SINGLE HEMOGLOBIN

323
00:12:36,422 --> 00:12:38,524
WHICH IS THE RED LINE, THERE

324
00:12:38,591 --> 00:12:42,928
WERE 67 PATIENTS WHO UNDERWEPT

325
00:12:42,995 --> 00:12:45,531
TRANSPLANTSA THE NIH, AND

326
00:12:45,598 --> 00:12:46,465
NONOBLADIVE MEANS YOU'RE GIVEN

327
00:12:46,532 --> 00:12:48,000
DRUGS TO SUPPRESS THE IMMUNE

328
00:12:48,067 --> 00:12:48,367
SYSTEM.

329
00:12:48,434 --> 00:12:51,103
AND 3 OF THESE PATIENTS HAD HIGH

330
00:12:51,170 --> 00:12:53,172
DONOR LEVEL ANDS THIS SLOWLY

331
00:12:53,239 --> 00:12:53,739
FELL OVER TIME.

332
00:12:53,806 --> 00:12:56,408
ALL 3 OF THE DONORS HAD SICKLE

333
00:12:56,475 --> 00:12:59,245
CELL TRAITS, YOU EXPECT THOSE TO

334
00:12:59,311 --> 00:12:59,645
BE 40%.

335
00:12:59,712 --> 00:13:05,117
AS LONG AS THE DONOR MYELOID WAS

336
00:13:05,184 --> 00:13:07,620
ABOVE 20%, THE SINGLE CELL

337
00:13:07,686 --> 00:13:09,155
SICKLE SEAL DISEASE WAS FREE

338
00:13:09,221 --> 00:13:11,657
BBUT AS THE CHIMERISM DECREASED

339
00:13:11,724 --> 00:13:12,992
BELOW TWEBT%, THE SICKLE CELL

340
00:13:13,058 --> 00:13:13,926
LEVEL INCREASE INDEED ALL THROW

341
00:13:13,993 --> 00:13:15,961
PATIENT ANDS THEY HAD A RETURN

342
00:13:16,028 --> 00:13:18,764
TO SICKLE CELL DISEASE, SO

343
00:13:18,831 --> 00:13:20,833
SEEING THE LEVELS LESS THAN 20%

344
00:13:20,900 --> 00:13:22,268
WAS ASSOCIATED WITH THE RETURN

345
00:13:22,334 --> 00:13:23,869
OF SICKLE CELL DISEASE, AND WE

346
00:13:23,936 --> 00:13:27,673
HAVE WORKED TO DEVELOP A

347
00:13:27,740 --> 00:13:28,674
MATHEMATICAL MODEL, WHICH SHOWS

348
00:13:28,741 --> 00:13:30,075
THAT THE VAST DIFFERENCES IN THE

349
00:13:30,142 --> 00:13:31,977
RED CELL HALF LIFE OF THE DONOR

350
00:13:32,044 --> 00:13:34,313
RED CELLS WHICH IS ABOUT 3

351
00:13:34,380 --> 00:13:35,147
MONTHS VERSUS THE RECIPIENT RED

352
00:13:35,214 --> 00:13:39,818
CELLS WHICH IS OHM ABOUT 5-20

353
00:13:39,885 --> 00:13:40,052
DAYS.

354
00:13:40,119 --> 00:13:47,293
SO THIS IS A REGIMEN THAT

355
00:13:47,359 --> 00:13:52,064
NONMILE ABLATIVE REGIMEN, DONORS

356
00:13:52,131 --> 00:13:56,001
AND THE PATIENTS RECEIVE

357
00:13:56,068 --> 00:13:57,603
ALEMTUZUMAB, AND IT STAYS AROUND

358
00:13:57,670 --> 00:14:03,375
FOR ABOUT A MONTH, WE ALSO GIVE

359
00:14:03,442 --> 00:14:05,778
300 CENTIGRADE TOTAL BODY

360
00:14:05,844 --> 00:14:07,213
IRERATIONIATION AND THIS ALLOWS

361
00:14:07,279 --> 00:14:08,047
MORE SUPPRESSIVENESS AND CREATES

362
00:14:08,113 --> 00:14:10,115
SPACE IN THE BONE MARROW, AND SO

363
00:14:10,182 --> 00:14:12,218
THIS IS A DRUG THAT REEDUCATES

364
00:14:12,284 --> 00:14:13,652
THE IMMUNE SYSTEM SO THAT

365
00:14:13,719 --> 00:14:15,487
HOPEFULLY THE DONOR AND

366
00:14:15,554 --> 00:14:18,123
RECIPIENT CELLS WILL NO LONGER

367
00:14:18,190 --> 00:14:19,725
RECOGNIZE EACH OTHER AS BEING

368
00:14:19,792 --> 00:14:20,192
FOREIGN.

369
00:14:20,259 --> 00:14:22,728
SO THIS REGIMEN WAS USED BY

370
00:14:22,795 --> 00:14:25,564
PATIENTS AT THE NIH, AND ALSO,

371
00:14:25,631 --> 00:14:28,200
THE UNIVERSITY OF ILLINOIS,

372
00:14:28,267 --> 00:14:33,138
CHICAGO, AND OUTSIDE OF SAUDI

373
00:14:33,205 --> 00:14:35,474
ARABIA, AND AT 5 YEARS POST

374
00:14:35,541 --> 00:14:36,942
TRANSPLANT THE OVERALL SURVIVAL

375
00:14:37,009 --> 00:14:40,079
WAS 93% WITH AN EVENT FREE

376
00:14:40,145 --> 00:14:40,746
SURVERIFY AFRONS 85%.

377
00:14:40,813 --> 00:14:43,148
IMPORTANTLY NONE OF THE PATIENTS

378
00:14:43,215 --> 00:14:45,684
HAD ACUTESOEVER OR GRAPHIC HOST

379
00:14:45,751 --> 00:14:48,420
VERSUS HOST DEC, SO OVER HERE,

380
00:14:48,487 --> 00:14:51,390
YOU CAN SEE THAT THE MYELOIDISM

381
00:14:51,457 --> 00:14:52,658
WAS 80-A HUNDRED% LONG-TERM AND

382
00:14:52,725 --> 00:14:57,997
THIS IS THE DONOR LYMPHOID

383
00:14:58,063 --> 00:14:58,964
SYSTEM, AND THIS ALLOWS

384
00:14:59,031 --> 00:15:00,232
SUPPRESSION IF THE LEVEL IS AT

385
00:15:00,299 --> 00:15:00,399
50%.

386
00:15:00,466 --> 00:15:05,371
SO CAN YOU SEE THAT AT 5 YEARS

387
00:15:05,437 --> 00:15:11,577
POST TRANSPLANT, 83% OF THE

388
00:15:11,644 --> 00:15:16,382
TRANSPLANTS ARE OFF OF

389
00:15:16,448 --> 00:15:16,682
SERILUMABS.

390
00:15:16,749 --> 00:15:18,350
SO WE WANT TO KNOW HOW MANY

391
00:15:18,417 --> 00:15:21,854
PATIENTS WERE ABLE TO HAVE

392
00:15:21,920 --> 00:15:24,723
CHILDREN BECAUSE SOME OF THE

393
00:15:24,790 --> 00:15:26,558
PRESCRIPTIONS CAUSE

394
00:15:26,625 --> 00:15:27,426
STERILEAISEITION, THERE WERE 21

395
00:15:27,493 --> 00:15:30,329
PREGNANCIES FROM 7 WOMEN AND 7

396
00:15:30,396 --> 00:15:33,365
MEN, 1 MALE PATIENT RECEIVED

397
00:15:33,432 --> 00:15:35,000
ASSISTED REPRODUCTIVE

398
00:15:35,067 --> 00:15:35,567
MEDICATIONS FOR AZOOSPERMIA

399
00:15:35,634 --> 00:15:38,237
WHICH LED TO A HEALTHY GIRL AND

400
00:15:38,304 --> 00:15:40,539
THE OTHER PREGNANCIES WERE

401
00:15:40,606 --> 00:15:42,041
UNCOMPLICATED AND RESULT INDEED

402
00:15:42,107 --> 00:15:45,044
HEALTHY LIVE BIRTHS EXCEPT FOR 3

403
00:15:45,110 --> 00:15:46,645
ELECTIVE OBORGZS.

404
00:15:46,712 --> 00:15:48,180
SINCE I'VE HAD PEDIATRICS

405
00:15:48,247 --> 00:15:49,248
TRAINING, I'M PROUD THIS HAS

406
00:15:49,315 --> 00:15:50,649
BEEN USED AS WELL IN CHILDREN,

407
00:15:50,716 --> 00:15:52,184
THIS IS A SLIDE FROM A COUPLE

408
00:15:52,251 --> 00:15:54,153
YEARS AGO AND THAT THAT POINT

409
00:15:54,219 --> 00:15:55,321
THEY TRANSPLANTED 24 PATIENTS

410
00:15:55,387 --> 00:15:57,056
SINCE TWEBT 18, THE MEDIAN AGE

411
00:15:57,122 --> 00:15:59,558
WAS 14 YEARS WITH A RANGE OF

412
00:15:59,625 --> 00:16:01,593
3-22 YEARS, ALL OF THE PATIENTS

413
00:16:01,660 --> 00:16:03,295
WERE ALIVE, 19 WERE FREE OF

414
00:16:03,362 --> 00:16:05,497
SICKLE CELL DISEASE, SO 79%

415
00:16:05,564 --> 00:16:07,232
EVENT FREE SURVIVAL OR THE PATES

416
00:16:07,299 --> 00:16:08,667
REYECT THEIR GRAPH AND HAVE A

417
00:16:08,734 --> 00:16:09,802
RETURN OF SICKLE CELL DISEASE

418
00:16:09,868 --> 00:16:11,870
AND 1 PATIENT REQUIRED A STEM

419
00:16:11,937 --> 00:16:13,839
CELL BOOST BUT AGAIN NONE OF THE

420
00:16:13,906 --> 00:16:15,240
PATIENTS DEVELOPED GRAFT VERSUS

421
00:16:15,307 --> 00:16:18,077
HOAFORT DEC AND THIS HADN'T BEEN

422
00:16:18,143 --> 00:16:20,479
PREPORTED PREVIOUSLY AND 13 OF

423
00:16:20,546 --> 00:16:24,750
19 INGRAFTED PATIENTS ARE OFF OF

424
00:16:24,817 --> 00:16:25,150
SIROLIMUS.

425
00:16:25,217 --> 00:16:27,653
SO THERE'S ALSO A SECOND MAJOR

426
00:16:27,720 --> 00:16:29,054
OBSTACLE FOR MISSIAC SON AND

427
00:16:29,121 --> 00:16:31,290
THAT'S WELL LESS THAN 15% OF

428
00:16:31,357 --> 00:16:33,525
PATIENTS HAVE A FULLY HLA MATCH

429
00:16:33,592 --> 00:16:34,760
RELATED DONOR.

430
00:16:34,827 --> 00:16:36,929
OT OTHER HAND HAPPEN LO

431
00:16:36,995 --> 00:16:39,431
IDENTICAL OR HALF MATCHED

432
00:16:39,498 --> 00:16:40,499
EXPANDS THE DONOR POOL BECAUSE

433
00:16:40,566 --> 00:16:42,634
MOST PATIENTS WILL HAVE A

434
00:16:42,701 --> 00:16:43,836
PARENT, CHILD OR HALF MET

435
00:16:43,902 --> 00:16:45,838
SIBLING THAT CAN 7 AS A DONOR SO

436
00:16:45,904 --> 00:16:46,905
THIS INCREASES THE CHANCE THEY

437
00:16:46,972 --> 00:16:49,641
WILL HAVE A DONOR FROM 15% TO

438
00:16:49,708 --> 00:16:53,912
90% AND LESS TOXIC OR NONMILE

439
00:16:53,979 --> 00:16:55,381
ABLATIVE CONDITIONING ALLOWS

440
00:16:55,447 --> 00:16:57,216
THEM TO ENROLL WITH ORGAN

441
00:16:57,282 --> 00:16:59,752
DAMAGE, SO THIS GREATLY EXPANDS

442
00:16:59,818 --> 00:17:01,620
THE DONOR POOL TO ADULTS WITH

443
00:17:01,687 --> 00:17:02,755
ORGAN DAMAGE.

444
00:17:02,821 --> 00:17:06,892
AND IN 2000 MINE, THE EFFICACY

445
00:17:06,959 --> 00:17:08,727
WERE NOT KNOWN AND THAT WERE

446
00:17:08,794 --> 00:17:11,163
ONLY 2 SITES DOING THIS WITH

447
00:17:11,230 --> 00:17:12,531
ADULT SICKLE CELL DISEASE AND

448
00:17:12,598 --> 00:17:14,099
THAT WAS HOPKINS AND THE NIH.

449
00:17:14,166 --> 00:17:17,002
SO FIRST I WILL TELL YOU ABOUT

450
00:17:17,069 --> 00:17:18,904
THE HOPKINS REGIMEN BECAUSE THEY

451
00:17:18,971 --> 00:17:20,506
PUBLISHED THEIR RESULTS FIRST,

452
00:17:20,572 --> 00:17:22,608
17 PATIENTS RECEIVED A

453
00:17:22,674 --> 00:17:24,676
TRANSPLANT, 14 PATIENTS THAT ARE

454
00:17:24,743 --> 00:17:29,281
LAP LO IDENTICAL DONORS WAS 14,

455
00:17:29,348 --> 00:17:31,450
THE RANGE WAS 15-46 YEARS AND I

456
00:17:31,517 --> 00:17:34,453
WILL GO THROUGH THIS REGIMEN

457
00:17:34,520 --> 00:17:35,854
BECAUSE I WILL COME BACK TO IT.

458
00:17:35,921 --> 00:17:38,323
SO CAN YOU SEE THAT THE PATIENTS

459
00:17:38,390 --> 00:17:40,225
RECEIVED ATG, THEY RECEIVED 2

460
00:17:40,292 --> 00:17:41,927
SMALL BOWS DOSES OF CYCLOFOSTER

461
00:17:41,994 --> 00:17:44,096
NURSED MID BEFORE THE

462
00:17:44,163 --> 00:17:46,098
TRANSPLANT, 200 CENTIGRADE OF

463
00:17:46,165 --> 00:17:48,267
TOTAL BODY RADIATION, THEY USE

464
00:17:48,333 --> 00:17:49,902
BONE MARROW AS THE STEM CELL

465
00:17:49,968 --> 00:17:51,970
SOURCE, THEY GET 2 DOSES OF

466
00:17:52,037 --> 00:17:53,005
CYCLOFOSTER NURSED MADE POST

467
00:17:53,071 --> 00:17:55,541
TRANSPLANT AND THEY GET

468
00:17:55,607 --> 00:17:57,276
MICROFENNALLATE AND INITIALLY

469
00:17:57,342 --> 00:18:07,886
THEY REF CEIVED TBI, BUT CHANGED

470
00:18:08,220 --> 00:18:10,055
TO SIROLIMUS, EMPLOY THEY DON'T

471
00:18:10,122 --> 00:18:11,089
FRACTIONATE THE MYELOID

472
00:18:11,156 --> 00:18:13,492
COMPARTMENT SO THEY REPORT WHOLE

473
00:18:13,559 --> 00:18:15,461
BLOOD CHIMERISM, AND YOU CAN SEE

474
00:18:15,527 --> 00:18:17,663
WHEN THE CHIMERISM LEVELS ARE

475
00:18:17,729 --> 00:18:20,032
HIGH, THE PATIENT SICKLE

476
00:18:20,098 --> 00:18:21,333
HEMOGLOBIN AT 6 MONTHS POST

477
00:18:21,400 --> 00:18:22,734
TRANSPLANT IS THE SAME AS THE

478
00:18:22,801 --> 00:18:26,705
DONOR SO IF THE DONOR HAS SICKLE

479
00:18:26,772 --> 00:18:29,007
CELL TRAIT, AND THE DONOR AS

480
00:18:29,074 --> 00:18:31,343
SICKLE CELL TRAIT, AND THEN THE

481
00:18:31,410 --> 00:18:32,778
TOTAL HEMODPLOABIN LEVELS ARE

482
00:18:32,845 --> 00:18:33,545
CLOSE TO NORMAL.

483
00:18:33,612 --> 00:18:36,615
WE HAD 6 PATIENTS COMPLETELY

484
00:18:36,682 --> 00:18:38,350
REJECTED THIS SICKLE CELL

485
00:18:38,417 --> 00:18:39,751
DISEASE, THIS IS 1 GREEN PATIENT

486
00:18:39,818 --> 00:18:44,356
WHO HAD 5%, AND EVEN THOUGH THE

487
00:18:44,423 --> 00:18:47,426
DONORS HEMOGLOBIN LEVEL IS ABOUT

488
00:18:47,493 --> 00:18:49,595
40%, THE PATIENTS WAS 61% WITH

489
00:18:49,661 --> 00:18:51,063
THE VERY LOW HEMOGLOBIN OF 6

490
00:18:51,129 --> 00:18:51,730
PASSPORT 2.

491
00:18:51,797 --> 00:18:55,067
WE WOULD HAVE CALLED THAT A

492
00:18:55,133 --> 00:18:58,570
GRAPH FAILURE.

493
00:18:58,637 --> 00:18:59,938
SO, IMPORTANTLY THIS IS THE

494
00:19:00,005 --> 00:19:01,840
FIRST STUDY IN ADULTS IN ALL THE

495
00:19:01,907 --> 00:19:03,909
PATIENTS THAT SURVIVED, AND A

496
00:19:03,976 --> 00:19:05,978
50% FREE SURVIVAL BUT ALSO, NONE

497
00:19:06,044 --> 00:19:08,814
OF THE PATIENTS HAD DEVELOPED

498
00:19:08,881 --> 00:19:10,549
ACUTE OR CHRONIC GRAFT VERSUS

499
00:19:10,616 --> 00:19:13,085
HOST DEC AS 75% OF THE GRAFTED

500
00:19:13,151 --> 00:19:15,320
PATIENTS WERE OFF OF THE

501
00:19:15,387 --> 00:19:15,888
IMMUNOSUPPRESSIVE THERAPY.

502
00:19:15,954 --> 00:19:18,090
SO THIS IS THE STUDY THAT WE

503
00:19:18,156 --> 00:19:18,423
WROTE.

504
00:19:18,490 --> 00:19:20,893
HERE AT THE NIH AND THIS WAS

505
00:19:20,959 --> 00:19:22,961
BASED ON MIEWRINE DATA, WE WROTE

506
00:19:23,028 --> 00:19:32,638
IT AS A DOSE ESCALATION, ALL

507
00:19:32,704 --> 00:19:33,472
PATIENTS RECEIVED ALEMTUZUMAB,

508
00:19:33,539 --> 00:19:37,376
AND ALL PATIENTS RECEIVED

509
00:19:37,442 --> 00:19:38,810
SIRIOLOMUS, THIS IS THE FIRST

510
00:19:38,877 --> 00:19:40,646
DID NOT RECEIVE ANY CYCLOFOSTER

511
00:19:40,712 --> 00:19:42,614
NURSED MID AND THEY WERE

512
00:19:42,681 --> 00:19:44,550
STOPPING RULES BUILT INTO THE

513
00:19:44,616 --> 00:19:48,720
STUDY SO IF TOO MANY PATIENTS

514
00:19:48,787 --> 00:19:54,426
REJECT THE GRAFT, AND THEN IF

515
00:19:54,493 --> 00:19:56,395
THE STOP RULES WERE MET THEY

516
00:19:56,461 --> 00:19:58,096
WERE MOVED TO THE COHORT WHERE

517
00:19:58,163 --> 00:20:00,365
THEY RECEIVE 2 DOSES OF

518
00:20:00,432 --> 00:20:03,335
CYCLOFOSTER NURSED FOCUSED ON

519
00:20:03,402 --> 00:20:04,002
MID.

520
00:20:04,069 --> 00:20:05,604
SO 20 PATIENTS WERE TRANSPLANTED

521
00:20:05,671 --> 00:20:07,606
AND THE TIME THE MEDIAN FOLLOW

522
00:20:07,673 --> 00:20:09,608
UP WAS 6 YEARS, MOST PATIENTS AT

523
00:20:09,675 --> 00:20:12,444
SICKLE CELL DISEASE, 2 OF THEM

524
00:20:12,511 --> 00:20:13,178
HAD BETA THAT WILLASEMIA AND

525
00:20:13,245 --> 00:20:14,379
BECAUSE OF THE TIME WE DIDN'T

526
00:20:14,446 --> 00:20:16,248
KNOW WHAT THE TOXICITY WOULD BE,

527
00:20:16,315 --> 00:20:16,982
WE TRANSPLANTED VERY SICK

528
00:20:17,049 --> 00:20:18,016
PATIENTS THAT WE THOUGHT WERE

529
00:20:18,083 --> 00:20:19,418
GOING TO DIE OTHERWISE,

530
00:20:19,484 --> 00:20:20,819
SOPHISTICATEDY THEY HAD SEVERE

531
00:20:20,886 --> 00:20:21,987
ORGAN DAMAGE INCLUDING HEART

532
00:20:22,054 --> 00:20:25,057
FAILURE, END STAGE RENAL DISEASE

533
00:20:25,123 --> 00:20:28,760
INCLUDING DIALYSIS, CIRRHOSIS

534
00:20:28,827 --> 00:20:29,461
AND PULMONARY HYPERTENSION.

535
00:20:29,528 --> 00:20:30,829
SO THESE ARE THE RESULTS OF THE

536
00:20:30,896 --> 00:20:32,998
TODAY, THE FIRST COHORT, THE

537
00:20:33,065 --> 00:20:34,700
PATIENTS DIDN'T RECEIVE ANY

538
00:20:34,766 --> 00:20:35,968
CYCLOFOSTER NURSED FOCUSED ON

539
00:20:36,034 --> 00:20:38,403
MID, 1 OF THEM INITIALLY

540
00:20:38,470 --> 00:20:40,672
INGRAFTED BUT SHE LOST HER GRAFT

541
00:20:40,739 --> 00:20:42,107
AT 7 MONTHS POST TRANSPLANT.

542
00:20:42,174 --> 00:20:45,510
SO WE MOVED TO THE SECOND COHORT

543
00:20:45,577 --> 00:20:47,312
WHERE THEY RECEIVED

544
00:20:47,379 --> 00:20:47,879
50-MILLIGRAMS OF CYCLOFOSTER

545
00:20:47,946 --> 00:20:49,448
NURSED FOCUSED ON MADE.

546
00:20:49,514 --> 00:20:53,285
EIGHT PATIENTS WERE

547
00:20:53,352 --> 00:20:54,886
TRANSPLANTED, SO WITH STOPPING

548
00:20:54,953 --> 00:20:57,556
RULES, WE MOVER TO THE THIRD AND

549
00:20:57,623 --> 00:20:59,124
FIEPAL COHORT WHERE THE PATIENTS

550
00:20:59,191 --> 00:21:02,294
RECEIVED A HUNDRED MEGS OF

551
00:21:02,361 --> 00:21:04,363
CYCLOPHOSPHOR MID, AND 10

552
00:21:04,429 --> 00:21:05,430
INGRAFTED BUT ONLY 6 REMAIN FREE

553
00:21:05,497 --> 00:21:06,264
OF SICKLE CELL DISEASE.

554
00:21:06,331 --> 00:21:11,336
CAN YOU SEE THAT REALLY NONOR

555
00:21:11,403 --> 00:21:13,105
VERY MINIMAL GRAFT VERSUS HOST

556
00:21:13,171 --> 00:21:13,271
DEC.

557
00:21:13,338 --> 00:21:14,740
SO DESPITE THESE PATIENTS BEING

558
00:21:14,806 --> 00:21:17,409
VERY SICK, NONE OF THEM DIED

559
00:21:17,476 --> 00:21:22,948
BEFORE TRANSPRANT AND 5 PATIENTS

560
00:21:23,015 --> 00:21:25,183
REJECTED THEIR GRAPHS BETWEEN

561
00:21:25,250 --> 00:21:27,352
3-AND 8 YEARS, MOSTLY FROM

562
00:21:27,419 --> 00:21:28,954
SICKLE CELL DISEASE RELATED

563
00:21:29,021 --> 00:21:29,388
COMPLICATIONS.

564
00:21:29,454 --> 00:21:31,923
SO BEFORE MOVING ON TO THE MORE

565
00:21:31,990 --> 00:21:32,958
RECENT TRANSPLANT STUDY, I WANT

566
00:21:33,025 --> 00:21:35,127
TO TALK ABOUT WHAT HAPPENS TO

567
00:21:35,193 --> 00:21:36,294
PAIN AFTER TRANSPLANT, THIS

568
00:21:36,361 --> 00:21:39,598
STUDY WAS LED BY ALEXIS LEONARD

569
00:21:39,665 --> 00:21:42,401
WHO IS NOW AT ST. JUDE, SHE

570
00:21:42,467 --> 00:21:43,335
EVALUATED 163 PATIENTS WITH SICK

571
00:21:43,402 --> 00:21:44,469
ELITE EXECUTIVE IS DISEASE, MOST

572
00:21:44,536 --> 00:21:52,811
OF THEM MALE AND MOST OF THEM

573
00:21:52,878 --> 00:21:55,013
HAD HOMOZYGOUS DISEASE, MOST

574
00:21:55,080 --> 00:21:55,981
PATIENTS RECEIVED NONMILE

575
00:21:56,048 --> 00:21:58,784
ABLATIVE CONDITIONING AND MOST

576
00:21:58,850 --> 00:22:01,453
OF THEM UNDERWENT HLAA SIBLING

577
00:22:01,520 --> 00:22:02,220
MATCH TRANSPLANT.

578
00:22:02,287 --> 00:22:04,923
SO WHEN YOU LOOK AT THE Y-AXIS,

579
00:22:04,990 --> 00:22:06,324
YOU SEE PAINFUL EVENTS BEFORE

580
00:22:06,391 --> 00:22:08,794
CAN AFTER TRANSPLANT AND THIS

581
00:22:08,860 --> 00:22:10,996
BLUE RECK TANGLE SHOWS THE

582
00:22:11,063 --> 00:22:12,664
AMOUNT OF PAINFUL EVENTS WE HAD

583
00:22:12,731 --> 00:22:13,565
2 YEARS BEFORE TRANSPLABT AND

584
00:22:13,632 --> 00:22:15,967
THEN THE YELL O SHOWS EVENTS

585
00:22:16,034 --> 00:22:18,503
BETWEEN 0 AND 12 MONTHS AND IN

586
00:22:18,570 --> 00:22:20,639
THIS 1 SHOWS BETWEEN 12 AND 24

587
00:22:20,706 --> 00:22:22,774
MONTHS, SO CAN YOU SEE, THAT

588
00:22:22,841 --> 00:22:25,944
PAIN PRETTY MUCH RESOLVES

589
00:22:26,011 --> 00:22:27,546
BETWEEN 1 AND 2 YEARS POST

590
00:22:27,612 --> 00:22:29,881
TRANSPLANT IN PATIENTS THAT HAVE

591
00:22:29,948 --> 00:22:30,916
SUCCESSFUL TRANSPLANTS WITHOUT

592
00:22:30,982 --> 00:22:31,783
GRAFT VERSUS HOST DISEASE, AND

593
00:22:31,850 --> 00:22:33,585
WHEN YOU LOOK AT THE PATIENT WHO

594
00:22:33,652 --> 00:22:35,220
IS DID DEVELOP GRAFT VERSUS HOST

595
00:22:35,287 --> 00:22:39,658
DEC, CAN YOU SEE THAT PAIN

596
00:22:39,725 --> 00:22:41,159
RESOLVES AFTER TRANSPLANT BUT

597
00:22:41,226 --> 00:22:42,227
INTERESTINGLY EVEN THOUGH

598
00:22:42,294 --> 00:22:43,929
PATIENTS REYECTED THEIR GRAFTS

599
00:22:43,995 --> 00:22:45,797
THEY HAD A SIGNIFICANT DECREASE

600
00:22:45,864 --> 00:22:46,932
IN SEVERE PAINFUL EVENTS IN THE

601
00:22:46,998 --> 00:22:53,605
YEAR OR 2 FOLLOWING TRANSPLANT.

602
00:22:53,672 --> 00:22:56,308
SO WHY WAS THE GRAFT REJECTION

603
00:22:56,374 --> 00:22:58,810
RATE IN THESE 2 STUDIES SO HIGH?

604
00:22:58,877 --> 00:23:01,346
WE HAD THOUGHT IT WAS

605
00:23:01,413 --> 00:23:02,147
IMMUNOSUPPRESSION THAT WAS GIVEN

606
00:23:02,214 --> 00:23:04,349
SO I WILL TALK ABOUT MORE RECENT

607
00:23:04,416 --> 00:23:07,219
STUDIES WHICH INCLUDED

608
00:23:07,285 --> 00:23:08,787
ADDITIONAL UPFRONT CONDITIONING

609
00:23:08,854 --> 00:23:10,088
WITH PSYCHE ON FOSTER NURSED

610
00:23:10,155 --> 00:23:12,758
FACAS MIDS AND THERE ARE IMPROVE

611
00:23:12,824 --> 00:23:14,960
OUTCOMES FOR HAPPEN LO RANS

612
00:23:15,026 --> 00:23:15,160
PLANT.

613
00:23:15,227 --> 00:23:17,829
SO THIS FIRST REPORT IS

614
00:23:17,896 --> 00:23:18,563
INVESTIGATED BY THE

615
00:23:18,630 --> 00:23:20,031
INVESTIGATORS AT UNIVERSITY OF

616
00:23:20,098 --> 00:23:21,600
CHICAGO, THEY TRANSPLANTED

617
00:23:21,666 --> 00:23:24,469
PATIENTS WITH THE AGE RANGING

618
00:23:24,536 --> 00:23:26,171
FROM 8-30 YEARS AND THIS WAS

619
00:23:26,238 --> 00:23:28,306
WHAT I WENT OVER EARLIER AND YOU

620
00:23:28,373 --> 00:23:30,408
CAN SEE THEY MADE 2 CHANGES OVER

621
00:23:30,475 --> 00:23:33,512
THE REGIMEN, THE FIRST IS THEY

622
00:23:33,578 --> 00:23:35,547
INCREASED RADIATION FROM 200 TO

623
00:23:35,614 --> 00:23:36,748
300 CENTIGRADE AND ALSO INSTEAD

624
00:23:36,815 --> 00:23:38,717
OF USING BONE MARROW AS A STEM

625
00:23:38,784 --> 00:23:40,786
CELL SOURCE, THEY USE PERIPHERAL

626
00:23:40,852 --> 00:23:42,187
BLOOD CELLS, SO JUST WITH THOSE

627
00:23:42,254 --> 00:23:45,524
2 CHANGES AND MEDIAN FOLLOW UP

628
00:23:45,590 --> 00:23:47,492
OF 17 MONTHS, 7 OF THE 8

629
00:23:47,559 --> 00:23:49,528
PATIENTS WERE ALIVE SO OVERALL

630
00:23:49,594 --> 00:23:51,296
SURVIVAL WAS 88%, WITH THE EVENT

631
00:23:51,363 --> 00:23:56,701
FREE SURVIVAL OF 75%, 2 OF THE

632
00:23:56,768 --> 00:23:58,403
PATIENTS DEVELOPED MODERATE TO

633
00:23:58,470 --> 00:24:01,673
SEVERE GRAFT VERSUS HOST DEC AND

634
00:24:01,740 --> 00:24:07,179
1 CHRONIC GRAFT VERSUS HOST DEC

635
00:24:07,245 --> 00:24:09,581
THE SECOND STUDY WAS THE HOPKINS

636
00:24:09,648 --> 00:24:10,982
GROUP AND THE ONLY CHANGE THEY

637
00:24:11,049 --> 00:24:14,419
MADE, THEY GIVE A SINGLE DOSE OF

638
00:24:14,486 --> 00:24:16,521
4 CENTIGRADE TOTAL BODY

639
00:24:16,588 --> 00:24:17,556
RADIATION, THEY TRANSPLANTED 17

640
00:24:17,622 --> 00:24:20,525
PATIENTS, 12 OF THEM HAVE SICKLE

641
00:24:20,592 --> 00:24:27,232
CELL DEC, AGE RANGING FROM 6-31

642
00:24:27,299 --> 00:24:27,899
YEARS.

643
00:24:27,966 --> 00:24:30,702
AND ALL PATIENTS WERE ALIVE SO

644
00:24:30,769 --> 00:24:36,474
OVERALL SURVIVAL 100%, WITH 83%

645
00:24:36,541 --> 00:24:39,110
PAIN FREE SURVIVAL, 6% THE MORE

646
00:24:39,177 --> 00:24:41,413
MODERATE TO SEVERE, 18% HAD

647
00:24:41,479 --> 00:24:44,049
CHRONIC GBHD BUT ONLY 1 WAS

648
00:24:44,115 --> 00:24:44,616
MODERATE.

649
00:24:44,683 --> 00:24:47,052
AND ALL GBHD WAS RESOLVED AS OF

650
00:24:47,118 --> 00:24:50,856
LAST FOLLOW UP WITH NO SYSTEMIC

651
00:24:50,922 --> 00:24:51,923
GBHD THERAPY AND 91% OF THE

652
00:24:51,990 --> 00:24:55,260
PATIENTS WERE OFF THE

653
00:24:55,327 --> 00:24:56,595
IMMUNOSUPPRESSIVE THERAPY SO

654
00:24:56,661 --> 00:24:57,329
VERY IMPRESSIVE RESULTS.

655
00:24:57,395 --> 00:25:00,265
AND IN THIS STUDY, IT WAS

656
00:25:00,332 --> 00:25:01,566
REPORTED BY INVESTIGATORS THAT

657
00:25:01,633 --> 00:25:04,302
THE UK AND VANDERBILT AND

658
00:25:04,369 --> 00:25:05,370
THEY--THE ONLY CHANGE THEY MADE

659
00:25:05,437 --> 00:25:12,244
WAS TO INCREASE OR TO GIVE A

660
00:25:12,310 --> 00:25:13,745
SINGLE DOZE OF [INDISCERNIBLE]

661
00:25:13,812 --> 00:25:19,117
SO THIS DRUG AS A BIT OF MILE O

662
00:25:19,184 --> 00:25:19,718
SUPPRESSION AND

663
00:25:19,784 --> 00:25:23,321
IMMUNOSUPPRESSION, THEY TREATED

664
00:25:23,388 --> 00:25:24,956
15 PATIENTS AGE 12-26.

665
00:25:25,023 --> 00:25:27,025
THEY DEVELOPED A LARGER GLOBAL

666
00:25:27,092 --> 00:25:28,493
GROUP INTERNAL AUDIT CLUEDS 3

667
00:25:28,560 --> 00:25:29,794
CONTINENTS SO 1 OF THEM WAS

668
00:25:29,861 --> 00:25:32,097
EUROPE, UK AND THE NETHERLANDS

669
00:25:32,163 --> 00:25:34,633
AND OF COURSE, THE US BUT PAISH

670
00:25:34,699 --> 00:25:37,135
ALSO IMPORTANT THAT PATIENTS

671
00:25:37,202 --> 00:25:38,737
WERE TRANSPLANTED IN BRAZIL SO

672
00:25:38,803 --> 00:25:40,272
THIS BECAME MORE OF A GLOBAL

673
00:25:40,338 --> 00:25:40,639
EFFORT.

674
00:25:40,705 --> 00:25:43,208
AND THEY REPORTED THEIR RESULTS

675
00:25:43,275 --> 00:25:45,543
IN 2002, SO FIRST I WILL FOCUS

676
00:25:45,610 --> 00:25:47,579
ON THE 39 ADULTS THAT WERE

677
00:25:47,646 --> 00:25:48,713
TRANSPLANTED SO THEY'RE AT LEAST

678
00:25:48,780 --> 00:25:51,082
18 YEARS OF ANAL, MEDIAN AGE OF

679
00:25:51,149 --> 00:25:52,250
TRANSPLANT WAS ABOUT 25 YEARS,

680
00:25:52,317 --> 00:25:54,452
MOST OF THEM HAD HYM O ZYGOUS

681
00:25:54,519 --> 00:25:56,488
SICKLE CELL DISEASE AND A MEDIAN

682
00:25:56,554 --> 00:25:57,856
FOLLOW UP OF JUST 2 YEARS AT THE

683
00:25:57,923 --> 00:26:00,692
TIME AND YOU CAN SEE THAT NONE

684
00:26:00,759 --> 00:26:03,628
OF THE PATIENTS EXPERIENCED

685
00:26:03,695 --> 00:26:05,297
GRAFT FAILURE, 2 PATIENTS DIED

686
00:26:05,363 --> 00:26:06,498
FROM INFECT YOWZ RELATED EVENTS

687
00:26:06,564 --> 00:26:10,268
AND 3 OF THE PATIENTS DEVELOPED

688
00:26:10,335 --> 00:26:12,704
GRADE 3-4 ACUTE GBHD AND ONLY 1

689
00:26:12,771 --> 00:26:14,239
MODERATE TO SEVERE GRAFT VERSUS

690
00:26:14,306 --> 00:26:14,673
HOST DISEASE.

691
00:26:14,739 --> 00:26:18,576
YOU LOOK AT THE 41 CHILDREN, THE

692
00:26:18,643 --> 00:26:19,644
MEDIAN AGE TRANSPLANT WAS 12 AND

693
00:26:19,711 --> 00:26:22,213
HALF YEARS, ALL OF THEM HAD

694
00:26:22,280 --> 00:26:24,349
HOMOZYGOUS SICKLE CELL DISEASE,

695
00:26:24,416 --> 00:26:26,117
AND THE MEDIAN WAS JUST OVER A

696
00:26:26,184 --> 00:26:30,455
YEAR.

697
00:26:30,522 --> 00:26:33,091
SO THEY HAD MORE PROBLEMS WITH

698
00:26:33,158 --> 00:26:34,159
GRAFT FAILURE, GRAFT FAILURE

699
00:26:34,225 --> 00:26:35,894
MEAN ITS NEVER TOOK, SECONDARY

700
00:26:35,961 --> 00:26:38,229
FAILURE MEANS IT TOOK BUT THEY

701
00:26:38,296 --> 00:26:39,698
REJECTED THE GRAFT, SO 10 OF THE

702
00:26:39,764 --> 00:26:42,200
41 PATIENTS REYECTED THE GRAFT.

703
00:26:42,267 --> 00:26:44,936
TWO PATIENTS DIED AND 10-15% OF

704
00:26:45,003 --> 00:26:46,338
THE PATIENTS TWEPPED GRAFT

705
00:26:46,404 --> 00:26:48,073
VERSUS HOST DISEASE, SO THE

706
00:26:48,139 --> 00:26:50,375
STUDY RESULTS WERE MUCH MORE

707
00:26:50,442 --> 00:26:52,310
IMPRESSIVE IN THE ADULT SETTING

708
00:26:52,377 --> 00:26:54,846
AND THEY'RE DOING MORE TO TRY TO

709
00:26:54,913 --> 00:26:59,117
IMPROVE RESULTS IN THE PEDIATRIC

710
00:26:59,184 --> 00:26:59,317
STUDY.

711
00:26:59,384 --> 00:27:02,020
THE BMCTN 1507 IS A MULTICENTER

712
00:27:02,087 --> 00:27:03,855
HAPPEN LO IDENTICAL PULMONARY

713
00:27:03,922 --> 00:27:04,789
TRANSPLANT TRIAL, FOR ADULTS

714
00:27:04,856 --> 00:27:07,359
WITH SICKLE CELL DISEASE, USING

715
00:27:07,425 --> 00:27:08,760
THAT REGIMEN, THEY HAVE 2

716
00:27:08,827 --> 00:27:10,996
STRATA, 1 FOR CHILDREN AND 1 FOR

717
00:27:11,062 --> 00:27:13,598
ADULTS AND THERE'S 40

718
00:27:13,665 --> 00:27:14,532
PARTICIPANTS PER STRATA.

719
00:27:14,599 --> 00:27:16,067
THEY'RE GETTING READY TO REPORT

720
00:27:16,134 --> 00:27:19,170
THEIR RESULTS THIS YEAR BUT THE

721
00:27:19,237 --> 00:27:20,005
PRELIMINARY REPORTS WERE VERY

722
00:27:20,071 --> 00:27:23,475
SIMILAR TO WHAT I SHOWED AT THE

723
00:27:23,541 --> 00:27:25,443
VINEDDER BUILT GLOBAL CONSORTIUM

724
00:27:25,510 --> 00:27:25,677
GROUP.

725
00:27:25,744 --> 00:27:27,078
I WILL TALK ABOUT 1 MORE BEFORE

726
00:27:27,145 --> 00:27:29,347
I TELL BUT OUR MORE RECENT

727
00:27:29,414 --> 00:27:29,948
STUDY.

728
00:27:30,015 --> 00:27:31,383
THIS IS A PEDIATRIC STUDY, THIS

729
00:27:31,449 --> 00:27:32,550
IS WHERE THEY INCLUDED 5

730
00:27:32,617 --> 00:27:35,320
PATIENTS AND ALL OF THE PATIENTS

731
00:27:35,387 --> 00:27:36,955
HAD DONOR SPECIFIC HLA ANTIBODY

732
00:27:37,022 --> 00:27:40,091
SO THEY RECEIVE THIS INTENSIVE

733
00:27:40,158 --> 00:27:41,926
PRECONDITIONING WITH RETUX MAB,

734
00:27:41,993 --> 00:27:44,262
JUST ALL KINDS OF THINGS AND

735
00:27:44,329 --> 00:27:54,806
THEN THEY RECEIVED AS FAR AS

736
00:27:55,273 --> 00:27:58,243
CONDITIONING ATG, THESE WERE

737
00:27:58,309 --> 00:27:59,744
PATIENTS BETWEEN 8-19 YEARS AGE

738
00:27:59,811 --> 00:28:01,413
AND THEY HAD IMPRESS OF RESULTS

739
00:28:01,479 --> 00:28:03,048
WITH THE MEDIAN FOLLOW UP OF ALL

740
00:28:03,114 --> 00:28:04,149
25 MONTHS ALL PATIENTS WERE

741
00:28:04,215 --> 00:28:06,084
ALIVE AND FREE OF SICKLE CELL

742
00:28:06,151 --> 00:28:09,421
DISEASE, NONE OF THE PATIENTS

743
00:28:09,487 --> 00:28:13,825
DEVELOPED OOH CUTE OR HOST

744
00:28:13,892 --> 00:28:16,027
VERSUS GRAFT DISEASE, SO 2

745
00:28:16,094 --> 00:28:16,961
PATIENTS EXPERIENCED CMV

746
00:28:17,028 --> 00:28:21,166
REACTION BUT NO CMV DISEASE.

747
00:28:21,232 --> 00:28:22,233
THERE'S BEEN ABOUT 153 PATIENTS

748
00:28:22,300 --> 00:28:23,568
THAT HAVE BEEN REPORTED.

749
00:28:23,635 --> 00:28:25,603
YOU CANEE THAT MOST OF THE

750
00:28:25,670 --> 00:28:26,905
PATIENTS ARE PRETTY YOUNG BUT

751
00:28:26,971 --> 00:28:28,606
86% OF THE PATIENTS ARE ALIVE

752
00:28:28,673 --> 00:28:32,077
AND FREE OF SICKLE CELL DISEASE.

753
00:28:32,143 --> 00:28:34,245
SEVENTEEN% OF THEM DEVELOPED

754
00:28:34,312 --> 00:28:35,780
ACUTE GBHD AND IT'S MORE ON THE

755
00:28:35,847 --> 00:28:38,249
GREAT 2 SIDES, AND IT'S MORE THE

756
00:28:38,316 --> 00:28:41,252
MILDER SIDE AND 70% DEVELOPED

757
00:28:41,319 --> 00:28:42,687
CHRONIC GBHD BUT MOSTLY THE

758
00:28:42,754 --> 00:28:45,457
MODERATE SIDE AND 5% HAD DIED SO

759
00:28:45,523 --> 00:28:49,694
THE RECENT HAPPEN LO IDENTICAL,

760
00:28:49,761 --> 00:28:55,600
HAVE A HIGH EVENT PREVURIVAL

761
00:28:55,667 --> 00:28:57,535
WITH HIGH GBHD AND MORTALITY.

762
00:28:57,602 --> 00:28:59,537
SO WHAT ABOUT OUR STUDY, I

763
00:28:59,604 --> 00:29:00,972
SHOWED YOU EARLIER OUR STUDY HAD

764
00:29:01,039 --> 00:29:02,941
GRAFT REYEKS AND WHAT WE DECIDED

765
00:29:03,007 --> 00:29:07,545
TO DO WAS BASED ON MURINE DATA

766
00:29:07,612 --> 00:29:08,880
ADD PRECONDITIONING AND ORAL

767
00:29:08,947 --> 00:29:10,782
BECAUSE THE 2 TOGETHER WORK

768
00:29:10,849 --> 00:29:12,617
SINNER GESTICLY TO DEPLETE THE

769
00:29:12,684 --> 00:29:14,486
IMMUNE SYSTEM, SO THEY GET 2

770
00:29:14,552 --> 00:29:16,888
WEEKS OF PENTINE REGIMEN STATIN

771
00:29:16,955 --> 00:29:17,555
AND ORAL CYCLOFOSTER NURSED

772
00:29:17,622 --> 00:29:19,290
FOCUSED ON MADE BEFORE ALOE

773
00:29:19,357 --> 00:29:21,392
TIEWZ MAB AND THEN THEY GET THE

774
00:29:21,459 --> 00:29:23,261
400 CENTIGRADE OF TBI AND WE

775
00:29:23,328 --> 00:29:25,597
DECIDE TO GIVE ONLY 1 DOSE OF

776
00:29:25,663 --> 00:29:26,464
THE CYCLOFOSTER NURSED MID

777
00:29:26,531 --> 00:29:29,000
BECAUSE WE PHOTTED WHEN WE GAVE

778
00:29:29,067 --> 00:29:31,636
2, THERE WAS MORE VIRAL

779
00:29:31,703 --> 00:29:34,005
REACTIVATION AND WE KNEW THAT

780
00:29:34,072 --> 00:29:34,572
ADDING PRECONDITIONING WOULD

781
00:29:34,639 --> 00:29:35,974
INCREASE RISK FOR VIRAL

782
00:29:36,040 --> 00:29:40,979
REACTIVATION AND THEN ALL

783
00:29:41,045 --> 00:29:42,614
PATIENTS RECEIVE SIROLIMUS, SO 2

784
00:29:42,680 --> 00:29:43,882
PATIENTS HAVE BEEN TRANSPLANT

785
00:29:43,948 --> 00:29:46,551
WIDE A MEDIAN AGE OF 29 AND HALF

786
00:29:46,618 --> 00:29:48,853
YEARS, A RANGE OF 19-55 YEARS,

787
00:29:48,920 --> 00:29:51,689
MOST OF THEM MALE, JUST ABOUT

788
00:29:51,756 --> 00:29:53,424
ALL ARE AFRICAN AMERICAN, AND

789
00:29:53,491 --> 00:29:59,597
MOST OF THEM HAVE HOMOZYGOUS

790
00:29:59,664 --> 00:30:01,499
SICKLE DISEASE AND MOST OF THEM

791
00:30:01,566 --> 00:30:03,835
HAVE THE SICKLE CELL STRAIGHT.

792
00:30:03,902 --> 00:30:05,837
SO MOST PATIENTS TRANSPLANTEDAR

793
00:30:05,904 --> 00:30:07,772
TRANSPLANTED FOR RECURRENT

794
00:30:07,839 --> 00:30:09,174
PAINFUL CRISES OR ACUTE CHEST

795
00:30:09,240 --> 00:30:10,909
SYNDROME, CAN YOU SEE PATIENTS

796
00:30:10,975 --> 00:30:12,777
WE CHOOSE PATIENTS WHO HAVE MORE

797
00:30:12,844 --> 00:30:14,979
ORGAN DAMAGE, SO ABOUT A QUARTER

798
00:30:15,046 --> 00:30:19,184
OF THE PATIENTS HAD SOME TYPE OF

799
00:30:19,250 --> 00:30:20,685
STROKE OR CEREBRAL VASCULOPATHY

800
00:30:20,752 --> 00:30:22,921
AND ABOUT 30% OF THEM HAVE

801
00:30:22,987 --> 00:30:24,989
ELEVATED TRV OR HYPERTENSION

802
00:30:25,056 --> 00:30:27,425
THAT WE HAVE 16% WITH LIVER

803
00:30:27,492 --> 00:30:27,926
DISEASE.

804
00:30:27,992 --> 00:30:32,096
WE ALSO HAD 22 PATIENTS, 59% OF

805
00:30:32,163 --> 00:30:33,731
THEM HAD 2 INDICATIONS FOR

806
00:30:33,798 --> 00:30:36,167
TRANSPLANT AND 14% HAD 3

807
00:30:36,234 --> 00:30:37,669
INDICATIONS FOR TRANSPLANT SO WE

808
00:30:37,735 --> 00:30:39,070
TRANSPLANT A PRETTY SICK

809
00:30:39,137 --> 00:30:41,372
POPULATION OF ADULTS WITH SICKLE

810
00:30:41,439 --> 00:30:43,875
CELL DISEASE EMPLOY SO THE GOOD

811
00:30:43,942 --> 00:30:46,010
NEWS IS WITH OUR FIRST PROTOCOL

812
00:30:46,077 --> 00:30:47,579
I SHOWED YOU THAT OUR GRAFT

813
00:30:47,645 --> 00:30:48,947
REJECTION RATE WAS HIGH, SO WE

814
00:30:49,013 --> 00:30:50,848
ONLY HAD 1 PATIENT, ACUTELY

815
00:30:50,915 --> 00:30:55,086
REYECT THE GRAFT, SO WE DID HAVE

816
00:30:55,153 --> 00:30:56,154
A SIGNIFICANTLY DECREASED GRAFT

817
00:30:56,221 --> 00:30:57,555
REYEKS RATE WITH THE SECOND

818
00:30:57,622 --> 00:30:59,090
PROTOCOL COMPARED TO THE FIRST

819
00:30:59,157 --> 00:30:59,457
1.

820
00:30:59,524 --> 00:31:05,430
SO ADDING THE PRECONDITIONING

821
00:31:05,496 --> 00:31:06,030
WITH PENTASTATIN AND

822
00:31:06,097 --> 00:31:08,333
CYCLOPHOSPHOR MADE DID HELP THAT

823
00:31:08,399 --> 00:31:10,902
BUT UNFORTUNATELY WE HAD MULTILE

824
00:31:10,969 --> 00:31:11,502
COMPLICATIONS, SHOWEDDER EARLY

825
00:31:11,569 --> 00:31:13,838
IN OF THE PATES HAVE THE

826
00:31:13,905 --> 00:31:15,139
FOLLOWING CHIMERISM, WE HAD 4

827
00:31:15,206 --> 00:31:16,841
PATIENTS EXPERIENCE THAT WITH 2

828
00:31:16,908 --> 00:31:18,042
OF THEM EXPERIENCING LATE GRAFT

829
00:31:18,109 --> 00:31:19,811
FAILURE WITH THE RETURN OF

830
00:31:19,877 --> 00:31:21,512
SICKLE CELL DEC 2 AND HALF YEARS

831
00:31:21,579 --> 00:31:22,580
POST TRANSPLANT.

832
00:31:22,647 --> 00:31:25,183
WE ALSO HAD 2 PATIENTS DEVELOP A

833
00:31:25,250 --> 00:31:26,584
SEVERE REFRACTORY EVIDENCE

834
00:31:26,651 --> 00:31:30,722
SYNDROME IT'S AN - AUTOIMMUNE

835
00:31:30,788 --> 00:31:31,889
PHENOMENON, IMPACTING RED BROOD

836
00:31:31,956 --> 00:31:34,125
CELLS AND PLATELETS BETWEEN 7-9

837
00:31:34,192 --> 00:31:35,727
MONTHS TRAB PLANT.

838
00:31:35,793 --> 00:31:36,794
BOTH PATIENTS DEVELOPED SEVERE

839
00:31:36,861 --> 00:31:39,030
HYPER INFLAMMA ARE TOY RESPONSE

840
00:31:39,097 --> 00:31:41,099
AND MULTIORGAN FAILURE AND

841
00:31:41,165 --> 00:31:42,400
PASSED AWAY.

842
00:31:42,467 --> 00:31:48,740
WE ALSO HAD 5 PATIENTS DEVELOP

843
00:31:48,806 --> 00:31:50,408
THE EPSTEIN BARRE DEC, IT WAS

844
00:31:50,475 --> 00:31:54,012
UNCONTROL INDEED 2 OF THE

845
00:31:54,078 --> 00:31:57,115
PATIENTS INCLUDING CHEMO THERAPY

846
00:31:57,181 --> 00:31:59,350
AND VIRAL SPECIFIC T-CELLS, 1 OF

847
00:31:59,417 --> 00:32:00,585
THE PATIENTS DIED.

848
00:32:00,652 --> 00:32:05,290
SO WITH THE MEDIAN FOLLOW UP OF

849
00:32:05,356 --> 00:32:06,924
0-46 YEARS, THE OVERALL SURVIVAL

850
00:32:06,991 --> 00:32:08,960
IS 82% WITH THE EVENT FREE

851
00:32:09,027 --> 00:32:09,427
SURVIVAL OF 68%.

852
00:32:09,494 --> 00:32:11,596
SO ON THIS STUDY, THE LONG-TERM

853
00:32:11,663 --> 00:32:20,505
SICKLE CELL DEC FREE SURVIVAL IS

854
00:32:20,571 --> 00:32:21,939
NOT OPTIMAL.

855
00:32:22,006 --> 00:32:23,474
SO MANY PATIENTS WITH OSM

856
00:32:23,541 --> 00:32:24,676
COMPROIZ ARE EXCLUDED FROM THE

857
00:32:24,742 --> 00:32:26,177
TYPE OF TRANSPLANT I'M TALKING

858
00:32:26,244 --> 00:32:28,012
ABOUT AND WE HYPOTHESIZED THAT

859
00:32:28,079 --> 00:32:30,915
OUR FIRST TRANSPLANT DID NOT

860
00:32:30,982 --> 00:32:31,816
HAVE ENOUGH IMMUNOSUPPRESSION

861
00:32:31,883 --> 00:32:34,352
AND OUR SECOND 1 HAD TOO MUCH

862
00:32:34,419 --> 00:32:36,888
IMMUNOSUPPRESSION SO WE RECENTLY

863
00:32:36,954 --> 00:32:39,924
OPENED A NEW PROTOCOL WITH A

864
00:32:39,991 --> 00:32:41,759
IMMUNOSUPPRESSION AND WHICH WILL

865
00:32:41,826 --> 00:32:42,927
INCLUDE PATIENTS WITH ORGAN

866
00:32:42,994 --> 00:32:44,095
FUNCTION IN OUR FIRST PATIENT'S

867
00:32:44,162 --> 00:32:45,930
GOING TO BE TRANSPLANT INDEED 2

868
00:32:45,997 --> 00:32:52,804
DAYS SO WE'RE VERY EXCITED ABOUT

869
00:32:52,870 --> 00:32:53,371
THAT.

870
00:32:53,438 --> 00:32:55,173
SO I COMPARED THIS A COUPLE

871
00:32:55,239 --> 00:32:56,507
YEARS AGO, THE RESULTS OF THE

872
00:32:56,574 --> 00:32:59,644
STUDY WERE EXCITING AT THE TIME.

873
00:32:59,711 --> 00:33:01,379
WE HAD 1 WITH MILE IMRAOF THE

874
00:33:01,446 --> 00:33:02,347
VERSUS HOST DISEASE AND THIS

875
00:33:02,413 --> 00:33:04,082
TIME WHEN IT PASSED AWAY, AND

876
00:33:04,148 --> 00:33:05,717
YOU CAN SEE THAT MANY OF THE

877
00:33:05,783 --> 00:33:07,051
FOLLOW UP WAS JUST OVER 2 YEARS

878
00:33:07,118 --> 00:33:08,619
WHICH WAS LONGER THAN THE OTHER

879
00:33:08,686 --> 00:33:10,121
STUDIES WE JUST PUBLISHED SO

880
00:33:10,188 --> 00:33:11,322
WHILE THESE RESULTS ARE VERY

881
00:33:11,389 --> 00:33:14,392
EXCITING ISSUES THE FOLLOW UP IS

882
00:33:14,459 --> 00:33:15,893
VERY SHORT AND AS CAN YOU SEE

883
00:33:15,960 --> 00:33:17,762
FROM WHAT I'VE SHOWN YOU, IT'S

884
00:33:17,829 --> 00:33:20,031
IMPORTANT TO FOLLOW THEM FROM

885
00:33:20,098 --> 00:33:21,566
WHAT HAPPENS, I'M NOT TRYING TO

886
00:33:21,632 --> 00:33:22,633
REVERSE SICKLE CELL DISEASE, I

887
00:33:22,700 --> 00:33:24,268
WANT THEM TO STAY ALIVE AND

888
00:33:24,335 --> 00:33:26,137
HEALTHY FOR A REALLY LONG TIME.

889
00:33:26,204 --> 00:33:32,977
SO I'M WORKING WITH

890
00:33:33,044 --> 00:33:34,812
INVESTIGATORS, AND INVESTIGATORS

891
00:33:34,879 --> 00:33:35,780
AT EMORY AND [INDISCERNIBLE], WE

892
00:33:35,847 --> 00:33:39,183
WANT TO LOOK AT THE LONG-TERM

893
00:33:39,250 --> 00:33:41,085
HEALTH EFFECTS OF CURATIVE

894
00:33:41,152 --> 00:33:42,453
THERAPY WITH PATIENTS WITHIC

895
00:33:42,520 --> 00:33:43,855
ISLE CELL DISEASE AND WAS

896
00:33:43,921 --> 00:33:45,490
BECAUSE WE KNOW THAT HEART LUNG

897
00:33:45,556 --> 00:33:47,024
AND KIDNEY DISEASE INCREASE THE

898
00:33:47,091 --> 00:33:48,760
RISK OF MORTALITY, WE ARE

899
00:33:48,826 --> 00:33:49,927
FOCUSING ON THESE ORGANS SO THE

900
00:33:49,994 --> 00:33:52,130
FITTER AIM IS TO EVALUATE THE

901
00:33:52,196 --> 00:33:53,965
INCIDENCE OF LUNG AND KIDNEY

902
00:33:54,031 --> 00:33:54,866
DISFUNCTION, FIRST IN CHILDREN

903
00:33:54,932 --> 00:33:56,567
WITH SICKLE CELL DISEASE,

904
00:33:56,634 --> 00:33:58,903
RECEIVE A MILE ABLATIVE

905
00:33:58,970 --> 00:34:00,605
THERAPIES AND ADULTS WEB

906
00:34:00,671 --> 00:34:02,006
CONNECTED CEIVING NONMILE

907
00:34:02,073 --> 00:34:03,741
ABLATIVE TRANSPLANT COMPARED TO

908
00:34:03,808 --> 00:34:05,243
PREEXISTING COHORT OF CHILDREN

909
00:34:05,309 --> 00:34:07,445
IN ADULTS DISEASE WHO DON'T GET

910
00:34:07,512 --> 00:34:09,313
TRANSPLANTED SO WE CAN COMPARE

911
00:34:09,380 --> 00:34:10,581
HUNDREDS OF PATIENT WITH SICKLE

912
00:34:10,648 --> 00:34:12,216
CELL DISEASE THAT GET TRANSPLANT

913
00:34:12,283 --> 00:34:16,421
THAD DON'T GET TRANSPLANTED WE

914
00:34:16,487 --> 00:34:19,724
CAN COMPARE MILD APLATIVE TO

915
00:34:19,791 --> 00:34:20,625
NONABLATIVE CONDIGGING AND WE'RE

916
00:34:20,691 --> 00:34:21,058
EXCITED ABOUT THAT.

917
00:34:21,125 --> 00:34:31,669
AND WE WANT TO DETERMINE WHETHER

918
00:34:39,043 --> 00:34:42,013
THERE WAS SIN CLALLY SIGNIFICANT

919
00:34:42,079 --> 00:34:45,149
IMPROVEMENT IN TRV IN ACULLS

920
00:34:45,216 --> 00:34:46,984
WITH SCD, SO 40 PATIENTS WHO

921
00:34:47,051 --> 00:34:48,619
UNDERWENT TRAN PLANT FOR THE NIH

922
00:34:48,686 --> 00:34:49,921
WERE FOLLOWED FOR AT LEAST 1

923
00:34:49,987 --> 00:34:51,122
YEAR POST TRAN PLANT AND IF YOU

924
00:34:51,189 --> 00:34:53,090
LOOK AT THE WHOLE POPULATION,

925
00:34:53,157 --> 00:34:54,058
THE TRV DID FOCUS ON THE CHANGE

926
00:34:54,125 --> 00:34:55,493
OVER TIME BUT IF YOU FOCUS ON

927
00:34:55,560 --> 00:34:58,362
THE 24 PATIENT WHO IS HAD A TRV

928
00:34:58,429 --> 00:35:00,097
OF AT LEAST 2.5-METERS PER

929
00:35:00,164 --> 00:35:03,234
SECOND, WE DID SEE A DECREASE IN

930
00:35:03,301 --> 00:35:06,771
TRV, SO TRV AT BASE LINE WAS ON

931
00:35:06,838 --> 00:35:08,005
AVERAGE 2.7-METERS PER SECOND,

932
00:35:08,072 --> 00:35:09,841
SO THAT'S ASSOCIATE WIDE EARLY

933
00:35:09,907 --> 00:35:13,010
MORTALITY AND BY 1 YEAR POST

934
00:35:13,077 --> 00:35:14,645
TRANSPLANT, AND DECREASED AT

935
00:35:14,712 --> 00:35:16,814
2.3, SO DECREASE TO THE NORMAL

936
00:35:16,881 --> 00:35:20,885
RANGE, A YEAR AFTER TRANSPLANT.

937
00:35:20,952 --> 00:35:22,353
SO WHAT ABOUT THE LUNGS, THIS IS

938
00:35:22,420 --> 00:35:24,622
A TODAY WE'RE WORKING ON WITH

939
00:35:24,689 --> 00:35:26,357
PARKER RULE WHO'S A PULL

940
00:35:26,424 --> 00:35:27,058
MONITORROLOGYIST WHO, WOS WITH

941
00:35:27,125 --> 00:35:31,395
US AND WE LOOKEDDA THE 97

942
00:35:31,462 --> 00:35:33,631
PATIENT WHO IS WORK AT THE NIH,

943
00:35:33,698 --> 00:35:36,367
53 OF THEM WERE FOLLOWED UP TO 3

944
00:35:36,434 --> 00:35:38,135
YEARS AND AT BASE LINE AGE OF

945
00:35:38,202 --> 00:35:40,304
THE 32 YEARS, MOST PATIENTS WERE

946
00:35:40,371 --> 00:35:43,774
MALE AND ESPECIALLY THE

947
00:35:43,841 --> 00:35:45,009
HEMOGLOBIN IMPROVES AFTER

948
00:35:45,076 --> 00:35:48,079
TRANSPLANT FROM 8.8 TO 12.5, 3

949
00:35:48,145 --> 00:35:48,546
YEARS POST TRANSPLANT.

950
00:35:48,613 --> 00:35:51,182
MOST OF THE PATIENTS HAD

951
00:35:51,249 --> 00:35:52,016
HOMOZYGOUS SICKLE CELL DISEASE,

952
00:35:52,083 --> 00:35:55,086
AND IF YOU LOOK AT THE PERCENT

953
00:35:55,152 --> 00:35:56,721
PREDICTED WHICH IS A MARKER OF

954
00:35:56,787 --> 00:35:59,056
LUNG FUNCTION, YOU CAN SEE IT

955
00:35:59,123 --> 00:35:59,891
REMAINS STABLE AFTER TRANSPLANT

956
00:35:59,957 --> 00:36:01,526
AND YOU EXPECT IF YOU DON'T GET

957
00:36:01,592 --> 00:36:05,663
TRANSPLANT THAD THE FEV 1 CAN

958
00:36:05,730 --> 00:36:07,698
DECREASE OVER TIME.

959
00:36:07,765 --> 00:36:10,468
AND THEN DLCO WAS ANOTHER MARKER

960
00:36:10,535 --> 00:36:11,536
OF PULMONARY FUNCTION, AND YOU

961
00:36:11,602 --> 00:36:13,871
CAN SEE THE UNADJUSTED DLCO

962
00:36:13,938 --> 00:36:15,273
LOOKS TO UMPIRES PROVE SOME

963
00:36:15,339 --> 00:36:16,707
AFTER TRANSPLANT AND IF YOU LOOK

964
00:36:16,774 --> 00:36:18,209
AT THE DISTANCE THAT THE PATIENT

965
00:36:18,276 --> 00:36:23,114
CANS WALK AFTER TRANSPLANT, IT

966
00:36:23,180 --> 00:36:24,515
INCREASES FROM 490-METERS AT

967
00:36:24,582 --> 00:36:28,920
BASE LINE TO 520-METERS AFTER

968
00:36:28,986 --> 00:36:29,487
TRANSPLANT.

969
00:36:29,554 --> 00:36:30,922
AND THEP LASTLY WE WANT TO LOOK

970
00:36:30,988 --> 00:36:33,591
AT KIDNEY FUNCTION AND HOW MILD

971
00:36:33,658 --> 00:36:35,326
APLATIVE TRANSPLANT WORKS WITH

972
00:36:35,393 --> 00:36:37,895
THE KIDNEYS SO WE WORKED ON THIS

973
00:36:37,962 --> 00:36:39,630
WITH EMILY LIMERICK, WE LOOKEDDA

974
00:36:39,697 --> 00:36:41,599
THE 100 PATIENTS WHO UNDERWENT

975
00:36:41,666 --> 00:36:43,100
THIS FOR AT WERE FOLLOWED FOR AT

976
00:36:43,167 --> 00:36:45,002
LEAST A YEAR AND 63 OF THEM WERE

977
00:36:45,069 --> 00:36:46,070
FOLLOWED FOR AT LEAST 3 YEAR

978
00:36:46,137 --> 00:36:46,771
ANDS WE FOWBD THAT THE

979
00:36:46,837 --> 00:36:48,272
PREVENTIVE LICENSE OF THE

980
00:36:48,339 --> 00:36:50,374
CHRONIC KID NO DISEASE INCREASED

981
00:36:50,441 --> 00:36:52,276
AT 1 YEAR POST TRANSPLANT BUT

982
00:36:52,343 --> 00:36:53,811
NOT DEFINITE FROM BASE LINE 3

983
00:36:53,878 --> 00:36:54,845
YEARS COMPARED TO 1 YEAR AND WE

984
00:36:54,912 --> 00:36:59,984
FOUND THAT THE MEDIAN ESTIMATED

985
00:37:00,051 --> 00:37:00,952
FILTRATION RATE DECLINED

986
00:37:01,018 --> 00:37:05,756
ANNUALLY AND THE BASE LINE ON

987
00:37:05,823 --> 00:37:08,859
EGFR WAS 140 AND DECLINED AND

988
00:37:08,926 --> 00:37:12,530
20.9 AT 3 YEARS, BUT THE MEDIAN

989
00:37:12,597 --> 00:37:13,831
EGFR REMAIN NORMAL WITHIN THE

990
00:37:13,898 --> 00:37:14,865
NORMAL RANGE AND IT'S

991
00:37:14,932 --> 00:37:17,401
INTERESTING BECAUSE THE EGFR WAS

992
00:37:17,468 --> 00:37:18,769
ACTUALLY ABNORMALITIES NORMALLY

993
00:37:18,836 --> 00:37:20,871
HIGH BEFORE THE TRANSPLANT.

994
00:37:20,938 --> 00:37:22,039
SO IT DECREASED TO THE NORMAL

995
00:37:22,106 --> 00:37:23,574
RANGE BUT WE HAVE TO HAVE LONGER

996
00:37:23,641 --> 00:37:26,477
FOLLOW UP TO SEE WHAT HAPPENS

997
00:37:26,544 --> 00:37:28,312
AFTER 3 YEARS.

998
00:37:28,379 --> 00:37:31,015
SO IN CONCLUSION, HLA MAX

999
00:37:31,082 --> 00:37:33,017
SIBLING TRANSPLANT WITH MILD

1000
00:37:33,084 --> 00:37:35,753
ABLATIVE CONDITIONING HAS HIGH

1001
00:37:35,820 --> 00:37:37,088
EFFICACY, WITH NONMILE ABLATIVE

1002
00:37:37,154 --> 00:37:38,489
CONDITIONING AND THERE'S A LOWER

1003
00:37:38,556 --> 00:37:39,991
RATE OF GRAFT VERSUS HOST

1004
00:37:40,057 --> 00:37:50,601
DISEASE DESPITE THE USE OF STEM

1005
00:37:52,870 --> 00:37:53,804
CELLS.

1006
00:37:53,871 --> 00:37:55,039
NONMILE OABLAISIVE CONDITIONING

1007
00:37:55,106 --> 00:37:57,908
AIMED AT TOLERANCE INDUCTION HAS

1008
00:37:57,975 --> 00:38:01,445
LOWER RATE OF GVHD AND DESPITE

1009
00:38:01,512 --> 00:38:07,485
THE USE OF PBS Cs AND REEBT

1010
00:38:07,551 --> 00:38:09,320
STUDIES WITH PT-CY AND 2 YEARS

1011
00:38:09,387 --> 00:38:11,422
POST TRAN PLANT OR CHIMERISM IS

1012
00:38:11,489 --> 00:38:15,493
88% AND HER LYMPHOID CHIMERISM

1013
00:38:15,559 --> 00:38:19,163
AND WAS 32%, HER HEMOGLOBIN WAS

1014
00:38:19,230 --> 00:38:21,899
LOW BUT WE WERE DOING

1015
00:38:21,966 --> 00:38:23,534
THERAPEUTIC FLEBOT ME TO GET RID

1016
00:38:23,601 --> 00:38:24,335
OF THE IRON.

1017
00:38:24,402 --> 00:38:25,970
HER DONOR HAD SICKLE CELL

1018
00:38:26,037 --> 00:38:26,904
STRAIGHTS AND SO DID SHE.

1019
00:38:26,971 --> 00:38:29,073
SHE WAS OFF OF NARCOTIC THERAPY

1020
00:38:29,140 --> 00:38:34,979
AND SHE WAS OFF OF OTHER MEDS

1021
00:38:35,046 --> 00:38:36,080
WITH HER PULMONARY HYPERTENSION,

1022
00:38:36,147 --> 00:38:39,050
SO CAN YOU SEE THE TRV WAS

1023
00:38:39,116 --> 00:38:41,419
REALLY ELEVATED AT 3.9-METERS

1024
00:38:41,485 --> 00:38:42,219
PER SECOND.

1025
00:38:42,286 --> 00:38:45,089
HER EJECTION FRACTION WAS NORMAL

1026
00:38:45,156 --> 00:38:47,224
AT 60, 6 MINUTE WALK DISTANCE

1027
00:38:47,291 --> 00:38:49,026
WAS 324-METER WHICH IS IS LOW,

1028
00:38:49,093 --> 00:38:50,661
DECREASED OXYGEN LEVEL WHEN HE

1029
00:38:50,728 --> 00:38:55,766
WALKS, THIS IS ALSO ABNORMAL AND

1030
00:38:55,833 --> 00:38:57,034
MAIN PULMONARY ARTERIOLE

1031
00:38:57,101 --> 00:39:00,271
PRESSURE AND ABNORMAL WAS 25 AND

1032
00:39:00,337 --> 00:39:01,205
HIGHER, HER CARDIAC OUTPUT WAS

1033
00:39:01,272 --> 00:39:05,309
HIGH SO SHE STARTED ON ABERR SIN

1034
00:39:05,376 --> 00:39:06,677
TAN IN AUGUST 2012.

1035
00:39:06,744 --> 00:39:10,848
AND AFTER A YEAR LATER HER TRV

1036
00:39:10,915 --> 00:39:14,452
HAD DECREASED TO 3.1, HER WALK

1037
00:39:14,518 --> 00:39:16,721
DISTANCE DID INCREASE FROM 324

1038
00:39:16,787 --> 00:39:17,755
TO 359.

1039
00:39:17,822 --> 00:39:19,623
SHE STILL HAD AN ABNORMAL

1040
00:39:19,690 --> 00:39:21,025
DECREASE IN HER OXYGEN

1041
00:39:21,092 --> 00:39:22,960
SATURATION WHEN SHE WALKED, AND

1042
00:39:23,027 --> 00:39:24,595
BECAUSE SHE HAD A PAIN CRISIS AT

1043
00:39:24,662 --> 00:39:27,231
THE TIME WE WERE NOT ABLE TO DO

1044
00:39:27,298 --> 00:39:30,134
A RIGHT HATTER CATH RIGHT BEFORE

1045
00:39:30,201 --> 00:39:31,268
THE TRANSPLANT.

1046
00:39:31,335 --> 00:39:33,738
SHOW SHE UNDERWENT TRANSPLANT IN

1047
00:39:33,804 --> 00:39:36,307
AUGUST 2013 AND HER AMBER SAN

1048
00:39:36,373 --> 00:39:38,642
TAN WAS DISCONTINUED IN APRIL OF

1049
00:39:38,709 --> 00:39:38,843
2014.

1050
00:39:38,909 --> 00:39:42,179
AND YOU CAN SEE IN AUGUST, A FEW

1051
00:39:42,246 --> 00:39:44,882
MONTHS LATER HER TRV HAD

1052
00:39:44,949 --> 00:39:46,417
DECREASE AT 2.8-METERS PER

1053
00:39:46,484 --> 00:39:47,418
SECOND, HER 6 MINUTE WALK

1054
00:39:47,485 --> 00:39:51,455
DISTANCE HAD GONE UP TO 456, HER

1055
00:39:51,522 --> 00:39:53,157
OX GENERATEDDATION NORMALIZED

1056
00:39:53,224 --> 00:39:57,461
AND HER CARDIAC OUTPUT IS NOW

1057
00:39:57,528 --> 00:39:59,063
NORMAL BUT IMPORTANTLY, HER

1058
00:39:59,130 --> 00:40:01,532
ARTERIOLE PRESSURE IS NOW NORMAL

1059
00:40:01,599 --> 00:40:03,734
SO HER PULMONARY HYPERTENSION

1060
00:40:03,801 --> 00:40:05,703
WENT AWAY AND 2 YEARS AFTER

1061
00:40:05,770 --> 00:40:07,738
TRANSPLANT NOW HER TRV IS DOWN

1062
00:40:07,805 --> 00:40:10,274
TO THE NORMAL RANGE STILL WITH

1063
00:40:10,341 --> 00:40:11,575
NORMALIDES OF HER OXYGEN GIGZ,

1064
00:40:11,642 --> 00:40:14,912
SO IF YOU LOOK AT A SURVIVAL

1065
00:40:14,979 --> 00:40:17,314
CURVE, BECAUSE HER TRV WAS 3.1

1066
00:40:17,381 --> 00:40:19,083
BEFORE THE TRAN PLANT, BUT AFTER

1067
00:40:19,150 --> 00:40:22,153
THE TRANSPLABT WITH THE TRV OF

1068
00:40:22,219 --> 00:40:24,054
2.4, SHE'S ON THIS SURVIVAL

1069
00:40:24,121 --> 00:40:26,423
CURVE SO SHE'S OPENING THAT THIS

1070
00:40:26,490 --> 00:40:28,392
WILL IMPROVE SURVOOFAL.

1071
00:40:28,459 --> 00:40:30,961
THIS IS HER, I PRESENTED HER AT

1072
00:40:31,028 --> 00:40:33,697
GRAND ROUNDS AND SHE SURPRISED

1073
00:40:33,764 --> 00:40:34,865
OUGHTIENCE, WELL, MY SON KNOWS

1074
00:40:34,932 --> 00:40:35,933
I'M HIS MOTHER NOW BECAUSE I'M

1075
00:40:36,000 --> 00:40:38,068
NOT IN THE HOSPITAL, I CAN PLAY

1076
00:40:38,135 --> 00:40:40,638
WITH HIM, GO TO THE PLAYGROUND,

1077
00:40:40,704 --> 00:40:42,807
DO NORMAL THINGS, I CAN KEEP MY

1078
00:40:42,873 --> 00:40:44,575
PROMISE, WHEN I SAY I WILL BE

1079
00:40:44,642 --> 00:40:45,643
SOMEWHERE, I CAN ACTUALLY BE

1080
00:40:45,709 --> 00:40:46,110
THERE.

1081
00:40:46,177 --> 00:40:47,344
IT'S INKRE TINSIBLE WORKING WITH

1082
00:40:47,411 --> 00:40:48,279
THIS POPULATION, SHE WAS LIVING

1083
00:40:48,345 --> 00:40:50,014
IN THE HOSPITAL BEFORE THE TRAN

1084
00:40:50,080 --> 00:40:53,184
PLANT, SHE WAS TALKING ABOUT HOW

1085
00:40:53,250 --> 00:40:56,921
WE WERE IN LIPSETT AUDITORIUM,

1086
00:40:56,987 --> 00:40:58,189
AND SHE SAID BEFORE THE TRAN

1087
00:40:58,255 --> 00:41:00,224
PLANT SHE HAD TO STOP MULTIPLE

1088
00:41:00,291 --> 00:41:01,826
TYPES, SO THINGS THAT WE TAKE

1089
00:41:01,892 --> 00:41:04,028
FOR GRANTED SHE WAS ABLE TO DO

1090
00:41:04,094 --> 00:41:05,429
SO I REALLY, REALLY THANKFUL I

1091
00:41:05,496 --> 00:41:08,165
GET TO WORK WITH THIS

1092
00:41:08,232 --> 00:41:08,699
POPULATION.

1093
00:41:08,766 --> 00:41:09,466
SO THANK YOU.

1094
00:41:09,533 --> 00:41:09,834
THAT'S IT.

1095
00:41:09,900 --> 00:41:12,169
I WANT TO THANK THE PATIENTS AND

1096
00:41:12,236 --> 00:41:13,137
FAMILIES ESPECIALLY, ALL THE

1097
00:41:13,204 --> 00:41:17,474
MEMBERS OF MY LAB AND THE

1098
00:41:17,541 --> 00:41:20,444
TISDALE LAB, WHO PROVIDE PROT

1099
00:41:20,511 --> 00:41:22,279
COLSUPPORT, THE STATISTICAL

1100
00:41:22,346 --> 00:41:24,548
ANALYSIS, ALL OF THE KACCTA

1101
00:41:24,615 --> 00:41:25,816
LESSED INVESTIGATORS IN WE WORK

1102
00:41:25,883 --> 00:41:27,484
WITH AND THE PEOPLE WHO

1103
00:41:27,551 --> 00:41:29,653
COLLABORATED ON THE HEART AND

1104
00:41:29,720 --> 00:41:31,755
LUNG STUDIES HERE, AND ALL THE

1105
00:41:31,822 --> 00:41:32,823
CLINICAL STAFF, SO THANK YOU SO

1106
00:41:32,890 --> 00:41:43,300
MUCH FOR YOUR ATTENTION.

1107
00:41:43,500 --> 00:41:49,006
>> ALL RIGHT, WELL, THANK YOU

1108
00:41:49,073 --> 00:41:52,343
DR. FITZHUGH FOR THAT FANTASTIC

1109
00:41:52,409 --> 00:41:54,845
PRESENTATION, AND HOPEFULLY AS I

1110
00:41:54,912 --> 00:42:00,451
STEP BACK, WE WILL HAVE LESS

1111
00:42:00,517 --> 00:42:04,221
FEEDBACK AND OUR SECOND PEEKER

1112
00:42:04,288 --> 00:42:06,824
PROFESSOR WONKAM WILL YOIN US AT

1113
00:42:06,891 --> 00:42:09,727
THE PODIUM.

1114
00:42:09,793 --> 00:42:20,104
PROFESSOR WONKAM?

1115
00:42:58,742 --> 00:43:01,078
>> THANK YOU.

1116
00:43:01,145 --> 00:43:01,512
THANK YOU.

1117
00:43:01,578 --> 00:43:09,186
THANK YOU FOR THE INVITATION, I

1118
00:43:09,253 --> 00:43:12,156
AM GRATEFUL FOR IT YOU SPOKE TO

1119
00:43:12,222 --> 00:43:14,491
THE WAR ON SICKLE CELL DISEASE,

1120
00:43:14,558 --> 00:43:16,660
THE WAY I WILL BE SPEAKING TO

1121
00:43:16,727 --> 00:43:18,395
THE WORLD OF SICKLE CELL

1122
00:43:18,462 --> 00:43:20,064
DISEASE, THE WAY IT COULD BE,

1123
00:43:20,130 --> 00:43:24,368
MOSTLY FROM A GENETIC RESEARCH

1124
00:43:24,435 --> 00:43:24,668
PERSPECTIVE.

1125
00:43:24,735 --> 00:43:26,870
AND FOCUSING ON AN AFRICAN

1126
00:43:26,937 --> 00:43:29,940
POPULATION AND WHAT COULD BE THE

1127
00:43:30,007 --> 00:43:33,677
MYSTERY BEHIND THE GENOME THAT

1128
00:43:33,744 --> 00:43:38,983
WE CAN EXPLODE, PERHAPS IN

1129
00:43:39,049 --> 00:43:40,484
FUTURE TREATMENT IMPROVEMENT OF

1130
00:43:40,551 --> 00:43:41,518
SICKLE CELL DISEASE.

1131
00:43:41,585 --> 00:43:43,387
AS AWE ALL KNOW THE CONDITION

1132
00:43:43,454 --> 00:43:46,991
WAS DESCRIBED IN THIS COUNTRY

1133
00:43:47,057 --> 00:43:49,193
113 YEARS AGO AND AS WAS ALLUDED

1134
00:43:49,259 --> 00:43:55,032
TO BEFORE,  MAYBE BEFORE THAT,

1135
00:43:55,099 --> 00:43:56,567
AND THE MENTORSHIP OF GREAT

1136
00:43:56,633 --> 00:44:00,437
LEADERS ON SICKLE CELL RESEARCH

1137
00:44:00,504 --> 00:44:05,242
FROM MIGRATE PENTINE REGIMENNOR

1138
00:44:05,309 --> 00:44:06,076
[INDISCERNIBLE] SEBD ME THE

1139
00:44:06,143 --> 00:44:13,117
E-MAIL BEFORE HE PASSED.

1140
00:44:13,183 --> 00:44:15,619
I ALWAYS KEEP THIS 1, I FIRST

1141
00:44:15,686 --> 00:44:17,388
SPOKE TO BONE MARROW

1142
00:44:17,454 --> 00:44:18,822
TRANSPLANTATION, BUT IT IS

1143
00:44:18,889 --> 00:44:19,990
IMPORTANT TO REALIZE IT IS A

1144
00:44:20,057 --> 00:44:22,993
PRIVILEGE TO DO IT HERE IN

1145
00:44:23,060 --> 00:44:23,560
AMERICA.

1146
00:44:23,627 --> 00:44:24,962
IN AFRICA WHERE MOST PEOPLE ARE

1147
00:44:25,029 --> 00:44:26,230
FOR EXAMPLE ISSUES ON THE RIGHT

1148
00:44:26,296 --> 00:44:29,099
HAND SIDE THERE IS ONLY 3

1149
00:44:29,166 --> 00:44:31,535
CENTERS WHO ARE ABLE TO DO BONE

1150
00:44:31,602 --> 00:44:36,540
MARROW TRANSPLANT TISSUE, IN

1151
00:44:36,607 --> 00:44:37,741
NIGERIA, TANZANIA, AND AFRICA,

1152
00:44:37,808 --> 00:44:44,415
WE HAVE A LOT OF WORK TO DO.

1153
00:44:44,481 --> 00:44:45,716
THE EXPANDED CONDITION WAS

1154
00:44:45,783 --> 00:44:47,785
DRIEBED 113 YEARS AGO, WE KNOW

1155
00:44:47,851 --> 00:44:49,753
TREATMENT HAVE NOT IMPROVED

1156
00:44:49,820 --> 00:44:51,488
REALLY SO DRASTICALLY, ONLY 1

1157
00:44:51,555 --> 00:44:54,458
MEDICATION ACTUALLY HAD BEG YOUR

1158
00:44:54,525 --> 00:44:57,061
PARDON WIDELY USED, THE

1159
00:44:57,127 --> 00:44:58,128
MORTALITY DON'T HAVE NO CHANGE

1160
00:44:58,195 --> 00:45:00,397
IN THE UNITED STATES OVER THE

1161
00:45:00,464 --> 00:45:03,033
PAST 50 YEARS AS THE DIAGRAM

1162
00:45:03,100 --> 00:45:05,436
WILL INDICATION, BUT I WILL NOT

1163
00:45:05,502 --> 00:45:07,538
SEE IT IN 50% OF THE

1164
00:45:07,604 --> 00:45:07,905
[INDISCERNIBLE].

1165
00:45:07,971 --> 00:45:13,310
THAT MEANS WE HAVE TO DRAIN

1166
00:45:13,377 --> 00:45:14,344
[INDISCERNIBLE] GLOBAL FOR

1167
00:45:14,411 --> 00:45:17,181
EXAMPLE IN AMERICA TO FIND A

1168
00:45:17,247 --> 00:45:20,584
SOLUTION FOR THE SICKLE CELL

1169
00:45:20,651 --> 00:45:21,218
DISEASE PATIENT, MORTALITY IN

1170
00:45:21,285 --> 00:45:24,755
THE U.S. IS USUALLY DUE TO

1171
00:45:24,822 --> 00:45:26,690
CARDIOVASCULAR COMPLICATION SOME

1172
00:45:26,757 --> 00:45:28,292
OF WHICH HIGHLIGHTED HERE AND I

1173
00:45:28,358 --> 00:45:30,594
THINK MOST OF THOSE

1174
00:45:30,661 --> 00:45:31,829
CARDIOVASCULAR ARE SUBJECTED TO

1175
00:45:31,895 --> 00:45:33,197
GENETIC VARIATION AND I WILL TRY

1176
00:45:33,263 --> 00:45:37,801
TO EXPLORE FROM OUR DATA HOW WE

1177
00:45:37,868 --> 00:45:40,571
CAN HARNESS THAT.

1178
00:45:40,637 --> 00:45:44,241
WHY SHOULD YOU INVEST IN AFRICA

1179
00:45:44,308 --> 00:45:45,142
VARIATIONS FOR SICKLE CELL

1180
00:45:45,209 --> 00:45:46,143
DISEASE, THE FIRST REASON IS

1181
00:45:46,210 --> 00:45:50,447
THAT THE DISEASE, MUTATION

1182
00:45:50,514 --> 00:45:52,282
EVOLVED IN AFRICA,

1183
00:45:52,349 --> 00:45:54,251
[INDISCERNIBLE] 20,000S YEARS

1184
00:45:54,318 --> 00:45:56,353
AGO, WE WILL PROVE IT.

1185
00:45:56,420 --> 00:45:58,856
THE [INDISCERNIBLE] OF AFRICA

1186
00:45:58,922 --> 00:46:00,757
HAVE SHAPED THE COLLECTION OF

1187
00:46:00,824 --> 00:46:03,393
THE SPECIFIC VARIANT ASK THEY BE

1188
00:46:03,460 --> 00:46:05,462
IMPORTANT FOR THE COMPLICATION

1189
00:46:05,529 --> 00:46:07,764
AND THE CAUSE OF SICKLE CELL

1190
00:46:07,831 --> 00:46:08,699
DISEASE, WE JUST HAVEN'T ADDRESS

1191
00:46:08,765 --> 00:46:10,501
THE QUESTION OF THE

1192
00:46:10,567 --> 00:46:10,868
[INDISCERNIBLE].

1193
00:46:10,934 --> 00:46:12,369
THE OTHER REASON BESIDES SICK

1194
00:46:12,436 --> 00:46:14,771
CELL CELL DISEASE THAT WE ARE

1195
00:46:14,838 --> 00:46:17,241
ALL AFRICAN BECAUSE HUMANS LIVE

1196
00:46:17,307 --> 00:46:19,643
IN AFRICA AT LEAST A HUNDRED

1197
00:46:19,710 --> 00:46:20,944
THOUSAND YEARS BEFORE COMING OUT

1198
00:46:21,011 --> 00:46:23,147
OF AFRICA, THERE ARE STILL

1199
00:46:23,213 --> 00:46:25,315
VARIATION THAT MOVE OUT OF

1200
00:46:25,382 --> 00:46:26,283
AFRICA AND ARE CRITICAL TO

1201
00:46:26,350 --> 00:46:27,484
UNDERSTAND THE PATHING  ON OF

1202
00:46:27,551 --> 00:46:28,552
SICKLE CELL DISEASE, I WILL SHOW

1203
00:46:28,619 --> 00:46:30,154
YOU A FEW EXAMPLE OF THAT.

1204
00:46:30,220 --> 00:46:32,356
ON THE LEFT-HAND SIDE, FOR

1205
00:46:32,422 --> 00:46:35,759
EXAMPLE, ON TOP SIDE, HIS NAME

1206
00:46:35,826 --> 00:46:39,530
IS LEE BURGER HE'S ANAN LOPOLOGY

1207
00:46:39,596 --> 00:46:41,165
GENETICIST, THE LOWER GUY BEFORE

1208
00:46:41,231 --> 00:46:42,566
AND [INDISCERNIBLE] HE IS THE

1209
00:46:42,633 --> 00:46:44,101
CURRENT PRESIDENT OF SOUTH

1210
00:46:44,168 --> 00:46:45,836
AFRICA, AND THEY'RE ENGAGE

1211
00:46:45,903 --> 00:46:50,340
INDEED A KISS COMPETITION

1212
00:46:50,407 --> 00:46:52,442
[INDISCERNIBLE] AND THAT IS

1213
00:46:52,509 --> 00:46:57,047
[INDISCERNIBLE] AFRICA THIS IS

1214
00:46:57,114 --> 00:47:01,618
THIS NEANDERTHAL OUT OF AFRICA,

1215
00:47:01,685 --> 00:47:06,356
WE KNOW THIS LIVES IN THEM.

1216
00:47:06,423 --> 00:47:07,758
THE MODEL ON THE OTHER SIDE

1217
00:47:07,824 --> 00:47:09,393
SHOWS THE TRUE WAVE OF

1218
00:47:09,459 --> 00:47:10,861
INTEGRATION OF THOSE GENOME AND

1219
00:47:10,928 --> 00:47:13,096
IF WE DO NOT STUDY AFRICA

1220
00:47:13,163 --> 00:47:15,165
POPULATION AND BE ABOUT TO

1221
00:47:15,232 --> 00:47:15,766
HARNESS THAT KNOWLEDGE, AND

1222
00:47:15,832 --> 00:47:18,936
THESE ARE THE LATE OF THE

1223
00:47:19,002 --> 00:47:20,204
POPULATION OF YESTERDAY, AND

1224
00:47:20,270 --> 00:47:23,407
THIS DATA HAVE BEEN IN REACH BY

1225
00:47:23,473 --> 00:47:26,276
50,000 GENOME OF PEOPLE OF

1226
00:47:26,343 --> 00:47:26,643
AFRICA.

1227
00:47:26,710 --> 00:47:28,912
BUT WE COMPARE JUST THE GENOME

1228
00:47:28,979 --> 00:47:30,847
ACROSS ANCESTRY WITHIN THE

1229
00:47:30,914 --> 00:47:33,483
UNITED STATES, WE CAN PICK FOR

1230
00:47:33,550 --> 00:47:36,353
EXAMPLE, THAT VARIANT THAT IS

1231
00:47:36,420 --> 00:47:38,055
ASSOCIATED WITH LOWER WHITE

1232
00:47:38,121 --> 00:47:40,857
BLOOD CELLS, PEOPLE OF AFRICAN

1233
00:47:40,924 --> 00:47:41,558
ANCESTRY, AGAIN THAT SHOWS THAT

1234
00:47:41,625 --> 00:47:44,528
SOME OF THE VARIATION THAT WE

1235
00:47:44,595 --> 00:47:47,497
HAVE IN AFRICAN POPULATION AND

1236
00:47:47,564 --> 00:47:48,632
NOT THE [INDISCERNIBLE] UNLESS

1237
00:47:48,699 --> 00:47:50,767
WE STUDY IS PROPERLY AND YOU

1238
00:47:50,834 --> 00:47:55,005
WILL SEE WHY IT'S IMPORTANT FOR

1239
00:47:55,072 --> 00:47:56,907
SICKLE CELL DISEASE.

1240
00:47:56,974 --> 00:48:00,043
WE APPROACH SICKLE CELL 3 WAYS

1241
00:48:00,110 --> 00:48:02,212
USING THE GENOMICS.

1242
00:48:02,279 --> 00:48:04,881
FIRST IS EXTENDING GENETIC

1243
00:48:04,948 --> 00:48:06,650
DIAGNOSTICS BEFORE BIRTH.

1244
00:48:06,717 --> 00:48:08,285
THIS WAS THE FIRST BABY BORN

1245
00:48:08,352 --> 00:48:10,721
AFTER GENETIC TESTING IN CAMMA

1246
00:48:10,787 --> 00:48:17,361
ROON, I AM VERY PROUD TO SAY I

1247
00:48:17,427 --> 00:48:19,029
DID THAT MYSELF, YOU CAN DO IT

1248
00:48:19,096 --> 00:48:20,831
ANYWHERE, BUT WE ALSO KNOW THAT

1249
00:48:20,897 --> 00:48:23,600
BEFORE BIRTH, YOU OPEN DOORS TO

1250
00:48:23,667 --> 00:48:24,635
VERY DIFFICULT QUESTIONS SOME OF

1251
00:48:24,701 --> 00:48:25,936
WHICH THAT ARE MEDICAL ABORG AND

1252
00:48:26,003 --> 00:48:29,172
WE KNOW IN THE CONTEXT OF--ON

1253
00:48:29,239 --> 00:48:30,374
THAT COUNTRY SPECIFICALLY MANY

1254
00:48:30,440 --> 00:48:31,875
STUDIES THAT WE PERFORM OVER

1255
00:48:31,942 --> 00:48:37,147
MANY YEARS, HAVE SHOWN THAT MANY

1256
00:48:37,214 --> 00:48:38,548
PARENT ARE OPEN TO

1257
00:48:38,615 --> 00:48:39,349
[INDISCERNIBLE] OF SICK ELITE

1258
00:48:39,416 --> 00:48:40,517
EXECUTIVE DISEASE, PLUS A VERY

1259
00:48:40,584 --> 00:48:43,954
HIGH BURDEN AND THAT IS

1260
00:48:44,021 --> 00:48:44,788
JEOPARDIZING THEIR LIVES, SOME

1261
00:48:44,855 --> 00:48:47,658
OF THEM ARE HOSPITAL, SOME OF

1262
00:48:47,724 --> 00:48:48,825
THEM ARE RELATED TO FINANCE,

1263
00:48:48,892 --> 00:48:50,160
SOME OF THEM ARE DISEASE BURDEN,

1264
00:48:50,227 --> 00:48:52,062
SOME OF THEM ARE THE DYNAMIC OF

1265
00:48:52,129 --> 00:48:56,300
THE CONDITION OF THE FAMILY AND

1266
00:48:56,366 --> 00:48:57,100
ALSO TO [INDISCERNIBLE] THE

1267
00:48:57,167 --> 00:49:00,737
CHILD THAT WILL PASS AWAY.

1268
00:49:00,804 --> 00:49:02,272
SO HOW SOCIETY IS NOT HAVING THE

1269
00:49:02,339 --> 00:49:05,609
SAME ATTITUDE FOR THAT APPROACH,

1270
00:49:05,676 --> 00:49:08,745
FOR EXAMPLE, IN THE 3 GROUP OF

1271
00:49:08,812 --> 00:49:09,613
STAKEHOLDERS, DOCTORS, PARENTS,

1272
00:49:09,680 --> 00:49:11,982
AT LEAST 1 AFFECTED CHILD AND

1273
00:49:12,049 --> 00:49:13,950
ALSO PATIENT, ADULT PATIENT WITH

1274
00:49:14,017 --> 00:49:15,786
SICKLE CELL DISEASE, WOULD

1275
00:49:15,852 --> 00:49:16,920
REALIZE THAT THEY

1276
00:49:16,987 --> 00:49:17,954
[INDISCERNIBLE] MEDICAL ABORTION

1277
00:49:18,021 --> 00:49:18,922
WAS VERY DIFFERENT.

1278
00:49:18,989 --> 00:49:20,190
FOR EXAMPLE, DOCTOR WAS LESS

1279
00:49:20,257 --> 00:49:22,826
OPEN TO THAT, WHILE A PARENT OR

1280
00:49:22,893 --> 00:49:23,760
ADULT PATIENT SURPRISINGLY WERE

1281
00:49:23,827 --> 00:49:25,295
OPEN TO IT, BUT JUST BECAUSE OF

1282
00:49:25,362 --> 00:49:28,932
THE BURREDIN OF THE CONDITION.

1283
00:49:28,999 --> 00:49:32,235
WHEN THAT MEANS THAT THIS WOULD

1284
00:49:32,302 --> 00:49:33,870
POSE CERTAINLY AN EDUCATIONAL

1285
00:49:33,937 --> 00:49:35,072
ISSUE, THE REASON WHY WE SHOULD

1286
00:49:35,138 --> 00:49:36,506
NOT BE DOING THIS, WE PROBABLY

1287
00:49:36,573 --> 00:49:38,342
NEED TO LOOK FOR THE KEY NUMBER

1288
00:49:38,408 --> 00:49:41,778
2, THAT'S HOW DO WE USE GENETIC

1289
00:49:41,845 --> 00:49:45,382
FOR PREVENTION, SOME OF YOU MAY

1290
00:49:45,449 --> 00:49:47,517
HAVE SEEN THIS SLIDE BECAUSE I

1291
00:49:47,584 --> 00:49:50,053
BORROWED IT WITH APPROVAL FROM

1292
00:49:50,120 --> 00:49:52,456
DR. GREEN, THAT SHOWS A LITTLE

1293
00:49:52,522 --> 00:49:55,625
BIT HOW GENETIC CONDITION,

1294
00:49:55,692 --> 00:49:56,827
CLASSIFIED, WE HAVE THOSE THAT

1295
00:49:56,893 --> 00:50:00,263
ARE AS SIMPLE AND MONOGENIC LIKE

1296
00:50:00,330 --> 00:50:06,703
SICKLE CELL, SOME THAT ARE

1297
00:50:06,770 --> 00:50:08,905
CONFLICTS MULTIGENIC, THIS IS

1298
00:50:08,972 --> 00:50:10,941
SINGLE DISORDER BUT IT'S ALSO

1299
00:50:11,007 --> 00:50:12,442
COMPLEX BECAUSE ENVIRONMENT AND

1300
00:50:12,509 --> 00:50:14,778
ALL THAT GENETIC MODIFIER ACTION

1301
00:50:14,845 --> 00:50:17,180
CHANGES THE DYNAMIC OF THE

1302
00:50:17,247 --> 00:50:18,148
CLINICAL EXPLANATION, 1 EXAMPLE

1303
00:50:18,215 --> 00:50:19,983
IS KIDNEY DISEASE IN SICKLE CELL

1304
00:50:20,050 --> 00:50:20,350
DISEASE.

1305
00:50:20,417 --> 00:50:23,420
OUR DATA FROM AFRICA AND THE

1306
00:50:23,487 --> 00:50:24,154
[INDISCERNIBLE] PEOPLE, HAVE

1307
00:50:24,221 --> 00:50:28,125
SHOWN THAT AT LEAST 3 VARIANT,

1308
00:50:28,191 --> 00:50:29,626
KIDNEY DISEASE IN SICKLE CELL,

1309
00:50:29,693 --> 00:50:33,630
THE 1 IS [INDISCERNIBLE], THE

1310
00:50:33,697 --> 00:50:34,965
SECOND IS APOL1, AND CURRENTLY

1311
00:50:35,031 --> 00:50:37,434
SOMEONE IN NIGH GROUP IS DOING

1312
00:50:37,501 --> 00:50:39,302
SOME GWAS ON THE POPULATION OF

1313
00:50:39,369 --> 00:50:43,740
SICKLE CELL AND WE ARE CONFIDENT

1314
00:50:43,807 --> 00:50:44,908
WE SHOW ADJUVANT SOME OTHER

1315
00:50:44,975 --> 00:50:48,879
VARIANT THAT IS SPECIFIC TO

1316
00:50:48,945 --> 00:50:50,347
SICKLE CELL DISEASE.

1317
00:50:50,414 --> 00:50:52,983
HAVING SICKLE CELL ACTUALLY

1318
00:50:53,049 --> 00:50:54,451
CHANGES, POSITIVELY THE OUTCOME

1319
00:50:54,518 --> 00:50:55,852
ADDING 1 EXPERIMENT THAT WE DID

1320
00:50:55,919 --> 00:50:56,953
MORE THAN 10 YEARS AGO WAS TO

1321
00:50:57,020 --> 00:51:00,924
LOOK AT THE EFFECT OF THE

1322
00:51:00,991 --> 00:51:04,461
[INDISCERNIBLE] TO THE CLINICAL

1323
00:51:04,528 --> 00:51:05,195
MANIFESTATION, AND WE FOUND THAT

1324
00:51:05,262 --> 00:51:06,897
IN THE CONTEXT OF THE KREEN, IF

1325
00:51:06,963 --> 00:51:10,066
YOU HAVE 1 DELETION, YOU HAD

1326
00:51:10,133 --> 00:51:12,602
THAT MORE LATER, AND HAVE YOU 2

1327
00:51:12,669 --> 00:51:14,438
DELETION, HAVE YOU DIAGNOSED AT

1328
00:51:14,504 --> 00:51:16,440
6 YEARS OLD AND WHEN WE COMPARE

1329
00:51:16,506 --> 00:51:19,543
THE PROPORTION OF PEOPLE OF

1330
00:51:19,609 --> 00:51:21,077
SICKLE CELL DISEASE, OF THIS IN

1331
00:51:21,144 --> 00:51:22,579
THE SAME COUNTRY, THOSE WHO DO

1332
00:51:22,646 --> 00:51:25,549
NOT HAVE IT, DELETION OF THIS,

1333
00:51:25,615 --> 00:51:27,984
ARE MORE THE POPULATION OF THE

1334
00:51:28,051 --> 00:51:29,920
SICKLE CELL DISEASE, BUT

1335
00:51:29,986 --> 00:51:34,357
[INDISCERNIBLE]  COMPARED TO 20,

1336
00:51:34,424 --> 00:51:37,427
THAT IS A SELECTION OF THAT

1337
00:51:37,494 --> 00:51:40,997
VARIANT IN THE SICKLE CELL

1338
00:51:41,064 --> 00:51:42,499
DISEASE, FORTUNATELY FOR SOMEONE

1339
00:51:42,566 --> 00:51:44,000
IN KENYA, FOUND THE EXACT SAME

1340
00:51:44,067 --> 00:51:52,275
AND THEY FOUND FIRST OF ALL THAT

1341
00:51:52,342 --> 00:51:56,913
OF COURSE, THEY FOUND THAT THE

1342
00:51:56,980 --> 00:51:57,848
PATIENTS WITH SICKLE CELL

1343
00:51:57,914 --> 00:51:59,716
DISEASE WAS MUCH INDUCED IF THEY

1344
00:51:59,783 --> 00:52:02,819
HAVE A DOUBLE DELETION IN THE

1345
00:52:02,886 --> 00:52:03,186
[INDISCERNIBLE].

1346
00:52:03,253 --> 00:52:04,154
AGAIN, THOSE KNOWLEDGE MAY ALLOW

1347
00:52:04,221 --> 00:52:06,089
US FOR EXAMPLE, A NEW BORN

1348
00:52:06,156 --> 00:52:08,625
SCREENING TO KNOW WHAT WHICH

1349
00:52:08,692 --> 00:52:09,593
PATIENT, BABY, WOULD BE MORE

1350
00:52:09,659 --> 00:52:12,462
EXPECTED TO BE SICKER THAN OTHER

1351
00:52:12,529 --> 00:52:12,629
1S.

1352
00:52:12,696 --> 00:52:15,665
SOME OF THE STUDIES SAID THIS

1353
00:52:15,732 --> 00:52:17,868
WAS A DIFFICULT 1 WAS TO LOOK AT

1354
00:52:17,934 --> 00:52:21,404
SOME VARIANT ASSOCIATED WITH AN

1355
00:52:21,471 --> 00:52:22,839
EPISODE OF PAIN IN SICKLE CELL

1356
00:52:22,906 --> 00:52:26,042
DISEASE, WE CAN ALSO DESIGN AND

1357
00:52:26,109 --> 00:52:27,911
MODEL TO THIS OCCURRENCE IN THE

1358
00:52:27,978 --> 00:52:30,113
SICKLE CELL DISEASE, AND ALSO

1359
00:52:30,180 --> 00:52:31,448
USING TRANSCRIPT ORDER OF

1360
00:52:31,515 --> 00:52:32,816
MICRONSIC IN THE PERIPHERAL

1361
00:52:32,883 --> 00:52:35,619
BLOOD, SO WE CAN DECIDE WHICH

1362
00:52:35,685 --> 00:52:36,086
PATIENT OR NOT.

1363
00:52:36,152 --> 00:52:39,322
AND ALL OF THESE HAVE NOT HAD

1364
00:52:39,389 --> 00:52:40,257
CLINICAL APPLICATION AND/OR

1365
00:52:40,323 --> 00:52:41,992
IMPLEMENTATION AND WE NEED

1366
00:52:42,058 --> 00:52:46,162
INVEST MORE IN THOSE AREA AND WE

1367
00:52:46,229 --> 00:52:47,464
KNOW THAT [INDISCERNIBLE] SICKLE

1368
00:52:47,531 --> 00:52:50,367
CELL DISEASE MAY BE CONDITIONED

1369
00:52:50,433 --> 00:52:52,435
BY BLOOD PRESSURE, BUT THE ONLY

1370
00:52:52,502 --> 00:52:53,904
DIFFERENCE IN SICKLE CELL IS THE

1371
00:52:53,970 --> 00:52:56,072
DEFINITION OF BLOOD PRESSURE OR

1372
00:52:56,139 --> 00:52:58,608
THAT WE CALL RELATIVE BLOOD

1373
00:52:58,675 --> 00:52:59,242
PRESSURE, SIS SEMESTERRIC BLOOD

1374
00:52:59,309 --> 00:53:01,611
PRESSURE THAT IS LOWER THAN THE

1375
00:53:01,678 --> 00:53:03,013
GENERAL POPULATION, THESE ARE

1376
00:53:03,079 --> 00:53:05,515
VERY RECENTLY BACK FROM THE

1377
00:53:05,582 --> 00:53:07,918
GROUP WHERE WE PERFORM THESE IME

1378
00:53:07,984 --> 00:53:11,621
NOAM WIDE ASSOCIATION STUDIES

1379
00:53:11,688 --> 00:53:13,156
FROM THE [INDISCERNIBLE] AND

1380
00:53:13,223 --> 00:53:15,492
THAT WE ADDED G5 THAT

1381
00:53:15,559 --> 00:53:17,060
REASSOCIATED WITH THE SICKLE

1382
00:53:17,127 --> 00:53:18,962
CELL DISEASE, AND THIS IS THE

1383
00:53:19,029 --> 00:53:23,366
MICE MODEL, THIS IS SUGGESTED

1384
00:53:23,433 --> 00:53:24,901
ASSOCIATION WITH

1385
00:53:24,968 --> 00:53:25,268
[INDISCERNIBLE].

1386
00:53:25,335 --> 00:53:28,738
AND WE HAVE ANALYZED THE DATA,

1387
00:53:28,805 --> 00:53:30,774
FROM AFRICAN AMERICAN, AND YOU

1388
00:53:30,840 --> 00:53:34,144
CAN SEE THAT, THEY'RE--WE HAVE

1389
00:53:34,210 --> 00:53:36,012
REPLICATED AT LEAST 1 OF THE

1390
00:53:36,079 --> 00:53:41,785
LOCI, AT A NORMAL INTERVAL IN A

1391
00:53:41,851 --> 00:53:44,087
SMALL COHORT, THE

1392
00:53:44,154 --> 00:53:44,654
[INDISCERNIBLE] COHORT AMONG

1393
00:53:44,721 --> 00:53:45,789
AFRICAN AMERICAN.

1394
00:53:45,855 --> 00:53:48,858
THIS IS A STUDY WE FOLLOW IN BMI

1395
00:53:48,925 --> 00:53:51,127
WITH SICKLE CELL DISEASE AND 3

1396
00:53:51,194 --> 00:53:52,062
LOCI VERY PROMISING.

1397
00:53:52,128 --> 00:53:53,930
WE ARE CURRENTLY WORKING IN 1 OF

1398
00:53:53,997 --> 00:53:55,465
THE LOCI, AT THE CELL LEVEL AND

1399
00:53:55,532 --> 00:53:57,200
1 OF THEM ACTUALLY IN THE MOUSE

1400
00:53:57,267 --> 00:54:01,871
MODEL, THEY SEEM TO CONFIRM OUR

1401
00:54:01,938 --> 00:54:03,273
ASSOCIATION FOUND IN PATIENT

1402
00:54:03,340 --> 00:54:09,512
WITH SICKLE CELL DISEASE.

1403
00:54:09,579 --> 00:54:12,182
SO, SOME WOULD SAY WHY GWAS, IN

1404
00:54:12,248 --> 00:54:14,517
SICKLE CELL DEC FROM AFRICA?

1405
00:54:14,584 --> 00:54:16,252
IT'S IMPORTANT THAT WE PERFORM

1406
00:54:16,319 --> 00:54:18,622
GWAS FOR ANYTHING ELSE IN

1407
00:54:18,688 --> 00:54:19,289
AFRICAN POPULATION, AGAIN, 1 OF

1408
00:54:19,356 --> 00:54:22,158
THE REASONS IS THAT THERE ARE

1409
00:54:22,225 --> 00:54:23,927
SOME VARIANT THAT A ARE OUT OF

1410
00:54:23,994 --> 00:54:27,897
AFRICA AND HAD IS THE TYPICAL

1411
00:54:27,964 --> 00:54:28,632
EXAMPLE, [INDISCERNIBLE] FOR

1412
00:54:28,698 --> 00:54:30,900
STUDY SHOWS NOW FOR HIGH BLOOD

1413
00:54:30,967 --> 00:54:31,901
PRESSURE, THE VARIANT FOR

1414
00:54:31,968 --> 00:54:34,838
EXAMPLE, DO IN THE EXIST IN THE

1415
00:54:34,904 --> 00:54:36,306
EUROPEAN AND ASIAN, THAT MEANS

1416
00:54:36,373 --> 00:54:37,841
YOU WILL NOT FIND THOSE VARIANT

1417
00:54:37,907 --> 00:54:41,378
IF YOU PERFORM THE STUDY ONLY ON

1418
00:54:41,444 --> 00:54:43,913
ASIANS, IT IS NOT IN THAT

1419
00:54:43,980 --> 00:54:44,214
POPULATION.

1420
00:54:44,280 --> 00:54:48,051
FOR THE RESULT OF BMI, THIS IS

1421
00:54:48,118 --> 00:54:50,987
MORE DRASTIC, ALL THE LEAD

1422
00:54:51,054 --> 00:54:52,589
VARIANT WE FOUND AND

1423
00:54:52,656 --> 00:54:53,390
[INDISCERNIBLE].

1424
00:54:53,456 --> 00:54:56,459
THAT MEANS THIS VARIANT IS

1425
00:54:56,526 --> 00:54:57,193
AFRICA SPECIFIC.

1426
00:54:57,260 --> 00:54:59,162
SO IT ALSO SUGGESTS THAT IF THIS

1427
00:54:59,229 --> 00:55:04,534
VARIANT WAS ALSO TO BE USED FOR

1428
00:55:04,601 --> 00:55:09,839
ANY MANIPULATION, THERE IS NO

1429
00:55:09,906 --> 00:55:11,441
WAY [INDISCERNIBLE] AND YOU WILL

1430
00:55:11,508 --> 00:55:12,409
HEAR THIS STORY AGAIN AND AGAIN

1431
00:55:12,475 --> 00:55:13,677
DURING THIS ECTOMYOSIN WELLURE.

1432
00:55:13,743 --> 00:55:21,551
SO THE KEY NUMBER 2 IS FINDING

1433
00:55:21,618 --> 00:55:26,823
MARKERS THAT MAY ALLOW US TO BE

1434
00:55:26,890 --> 00:55:30,460
TARGETED [INDISCERNIBLE].

1435
00:55:30,527 --> 00:55:35,198
THE [INDISCERNIBLE] WHICH IS THE

1436
00:55:35,265 --> 00:55:37,067
MODIFICATION OF [INDISCERNIBLE]

1437
00:55:37,133 --> 00:55:37,934
THERAPEUTICS.

1438
00:55:38,001 --> 00:55:40,503
A VERY LONG TIME AGO, IN THE

1439
00:55:40,570 --> 00:55:42,906
STUDY AS SHOWNOT PANEL ON THE

1440
00:55:42,972 --> 00:55:44,207
LEFT-HAND SIDE, IT SHOWED IF YOU

1441
00:55:44,274 --> 00:55:46,710
HAVE HIGH LEVEL OF

1442
00:55:46,776 --> 00:55:47,911
[INDISCERNIBLE], YOU WILL LIVE

1443
00:55:47,977 --> 00:55:51,548
MUCH LONGER, THIS QUANTITATIVE

1444
00:55:51,614 --> 00:55:55,085
SUBJEK, AND THERE IS MEASURABLE,

1445
00:55:55,151 --> 00:55:57,721
ASSOCIATED, WITH THE INHIBIT

1446
00:55:57,787 --> 00:56:01,891
ANTS OF THE HEMODPLOABIN WITH

1447
00:56:01,958 --> 00:56:02,959
THE POPULATION, AMERICAN OR SOME

1448
00:56:03,026 --> 00:56:07,130
CELLS WITH THIS PATIENT IN

1449
00:56:07,197 --> 00:56:07,363
AFRICA.

1450
00:56:07,430 --> 00:56:11,701
NOW THE POPULATION OF 1 OF THE

1451
00:56:11,768 --> 00:56:15,371
GENES CALLED BCL11 A FOR THE

1452
00:56:15,438 --> 00:56:16,272
TREATMENT OF SICKLE CELL

1453
00:56:16,339 --> 00:56:17,841
DISEASE, AND THIS WAS APPROVED

1454
00:56:17,907 --> 00:56:19,576
BY THE FTA ON DECEMBER 8th OF

1455
00:56:19,642 --> 00:56:21,444
LAST YEAR, THIS WAS THE FIRST

1456
00:56:21,511 --> 00:56:22,846
PATIENT VICTORIA GRAY WHO WAS

1457
00:56:22,912 --> 00:56:24,180
TREATED A FEW YEARS BEFORE USING

1458
00:56:24,247 --> 00:56:28,918
THAT,A PROACH FOR SICKLE CELL

1459
00:56:28,985 --> 00:56:29,753
DISEASE.

1460
00:56:29,819 --> 00:56:30,353
DEFINITIVE TREATMENT BY

1461
00:56:30,420 --> 00:56:32,188
MODIFYING THAT GENE THAT

1462
00:56:32,255 --> 00:56:34,491
CONTROLLED FOR THE HEMEAT O

1463
00:56:34,557 --> 00:56:34,758
DPLOABIN.

1464
00:56:34,824 --> 00:56:37,060
I WILL REPEAT THAT THE STORY

1465
00:56:37,127 --> 00:56:38,261
SHOULD NOT STOP THERE AND IT

1466
00:56:38,328 --> 00:56:44,033
NEEDS TO BE EXPANDED FOR EXAMPLE

1467
00:56:44,100 --> 00:56:48,571
BY INVESTIGATING THE AFRICAN

1468
00:56:48,638 --> 00:56:48,872
POPULATION.

1469
00:56:48,938 --> 00:56:52,842
BCL11 THAT'S WELL KNOWN, LOI MYB

1470
00:56:52,909 --> 00:56:56,946
THAT'S LESS KNOWN AND THE 1

1471
00:56:57,013 --> 00:56:59,749
AROUND [INDISCERNIBLE], THE

1472
00:56:59,816 --> 00:57:01,684
COMBINATION OF THE 3 EXPLAIN

1473
00:57:01,751 --> 00:57:04,788
[INDISCERNIBLE] IN THE

1474
00:57:04,854 --> 00:57:05,288
POPULATION IN ANCESTRY.

1475
00:57:05,355 --> 00:57:07,223
BUT IF YOU DO THE SAME ANALYSIS

1476
00:57:07,290 --> 00:57:14,264
FOR AVAILABLE DATA INCLUDING OUR

1477
00:57:14,330 --> 00:57:16,366
OWN DATA IN POPULATION, MAXIMUM

1478
00:57:16,432 --> 00:57:20,236
50% ISSUES THERE WAS INDEED FROM

1479
00:57:20,303 --> 00:57:22,205
NIGERIA PUBLISHED YESTERDAY OR

1480
00:57:22,272 --> 00:57:26,843
TODAY IN THAT POPULATION EXPLAIN

1481
00:57:26,910 --> 00:57:27,577
EXACTLY 14% [INDISCERNIBLE].

1482
00:57:27,644 --> 00:57:31,714
THAT MEANS WE STILL HAVE 80%

1483
00:57:31,781 --> 00:57:32,448
MISSING [INDISCERNIBLE] JUST FOR

1484
00:57:32,515 --> 00:57:35,084
THE LEVEL IN POPULATION OF

1485
00:57:35,151 --> 00:57:37,387
AFRICA ANCESTRY AND ALL OF THEM

1486
00:57:37,453 --> 00:57:40,657
A POTENTIAL TARGET FOR

1487
00:57:40,723 --> 00:57:41,024
THERAPEUTICS.

1488
00:57:41,090 --> 00:57:43,092
SOMEONE WILL ARGUE THAT THE GWAS

1489
00:57:43,159 --> 00:57:45,195
WERE PUBLISHED 10 YEARS AGO FROM

1490
00:57:45,261 --> 00:57:50,366
A POPULATION IN TANZANIA, AND

1491
00:57:50,433 --> 00:57:51,935
THIS IS FROM CHROME ON STUDIES

1492
00:57:52,001 --> 00:57:53,336
OF MULTIPLE ENDOCRINE 2 AND

1493
00:57:53,403 --> 00:57:55,572
YAWBD FROM CHROMOSOME 6,

1494
00:57:55,638 --> 00:57:57,540
ALLOWING THERE WAS 1 PROBLEM

1495
00:57:57,607 --> 00:58:02,745
WITH GWAS, THE 1 PROBLEM WAS THE

1496
00:58:02,812 --> 00:58:03,847
USE OF AFFYMETRIC 6, THAT WAS

1497
00:58:03,913 --> 00:58:06,216
DEVELOPED ON THE BACK GROUPED OF

1498
00:58:06,282 --> 00:58:07,083
EUROPEAN HAPLOTYPE.

1499
00:58:07,150 --> 00:58:08,651
NOW REMEMBER THOSE HAPLOTYPE ARE

1500
00:58:08,718 --> 00:58:12,121
LONGER, THAT MEANS YOU MAY NOT

1501
00:58:12,188 --> 00:58:14,424
HAVE ALL THE TIME THAT MAY

1502
00:58:14,490 --> 00:58:18,294
IDENTIFY FOR PATIENT ASSOCIATION

1503
00:58:18,361 --> 00:58:18,895
OF GENES.

1504
00:58:18,962 --> 00:58:22,198
THOSE HAPPEN LO DOZE USING GY,

1505
00:58:22,265 --> 00:58:24,701
BIEWSED ON THE EUROPEAN

1506
00:58:24,767 --> 00:58:25,435
HAPLOTYPE HAVE ALREADY BEEN

1507
00:58:25,501 --> 00:58:30,473
SHOWN THAT THEY DO NOT

1508
00:58:30,540 --> 00:58:31,207
[INDISCERNIBLE] FOR QUANTITATIVE

1509
00:58:31,274 --> 00:58:34,544
THREAD, AND SHOWN ON PURPLE IN

1510
00:58:34,611 --> 00:58:36,446
THIS SLIDE.

1511
00:58:36,512 --> 00:58:40,984
LET'S GO BACK, PRESENTING ON THE

1512
00:58:41,050 --> 00:58:42,085
POSTER GAME, [INDISCERNIBLE],

1513
00:58:42,151 --> 00:58:44,921
MANY THINGS HAPPEN OVER THE PAST

1514
00:58:44,988 --> 00:58:47,891
300,000 YEARS IN AFRICA,

1515
00:58:47,957 --> 00:58:48,791
MIGRATION WITHIN AFRICA,

1516
00:58:48,858 --> 00:58:50,994
MIGRATION OUT OF AFRICA,

1517
00:58:51,060 --> 00:58:53,196
MIGRATION BACK TO APRICKA.

1518
00:58:53,263 --> 00:58:57,600
IF YOU HAVE A CONTINENT THAT'S

1519
00:58:57,667 --> 00:58:59,669
ON THE SOUTH AXIS, DIVERSE LAYER

1520
00:58:59,736 --> 00:59:01,838
OF DIRECT CLIMATE, THE FOOD AND

1521
00:59:01,905 --> 00:59:03,473
INFECTION, HAVE YOU DIFFERENT

1522
00:59:03,539 --> 00:59:05,174
TYPE OF NATURAL SELECTION, YOU

1523
00:59:05,241 --> 00:59:08,111
KNOW GENOME THAT CHANGES

1524
00:59:08,177 --> 00:59:11,114
DRASTICALLY, WITH THAT SPECIFIC

1525
00:59:11,180 --> 00:59:11,648
GENOME COMPOSITION.

1526
00:59:11,714 --> 00:59:12,849
THESE HAVE BEEN SHOWN AGAIN AND

1527
00:59:12,916 --> 00:59:18,021
AGAIN BY A STUDY FROM AFRICA

1528
00:59:18,087 --> 00:59:20,156
FROM A COUPLE YEARS BACK AND BY

1529
00:59:20,223 --> 00:59:22,292
SHOWING THIS BIG DIVERSITY IN

1530
00:59:22,358 --> 00:59:24,894
THAT STUDY, WE TOOK THE

1531
00:59:24,961 --> 00:59:27,063
OPPORTUNITY TO DECIDE A GWAS

1532
00:59:27,130 --> 00:59:31,434
STUDY THAT [INDISCERNIBLE] VALUE

1533
00:59:31,501 --> 00:59:33,603
SHEET USING ABOUT 500 CHROMOSOME

1534
00:59:33,670 --> 00:59:35,138
AND HOPEFULLY TRY TO TAKE

1535
00:59:35,204 --> 00:59:36,773
ADVANTAGE OF THE SHORTER

1536
00:59:36,839 --> 00:59:39,108
HAPLOTYPE THAT WE ALREADY KNEW

1537
00:59:39,175 --> 00:59:40,610
BEFORE THAT WOULD IMPROVE THE

1538
00:59:40,677 --> 00:59:46,749
FINE MAPPING IN GWAS.

1539
00:59:46,816 --> 00:59:50,553
SO THESE ARE WHERE THE GNA WERE

1540
00:59:50,620 --> 00:59:53,056
TAKEN, WERE TAKEN TO DEVELOP

1541
00:59:53,122 --> 00:59:56,492
ALLEY, WE SAW THAT 2.5%.

1542
00:59:56,559 --> 01:00:00,964
WE USE THE VERY SAME

1543
01:00:01,030 --> 01:00:02,665
[INDISCERNIBLE] TO PERFORM

1544
01:00:02,732 --> 01:00:04,267
AGAINST IN POPULATION TO

1545
01:00:04,334 --> 01:00:06,469
DETERMINE SICKLE CELL DISEASE

1546
01:00:06,536 --> 01:00:07,136
FROM CAMMA ROON.

1547
01:00:07,203 --> 01:00:13,910
FOR THOSE THAT DO NOT KNOW WHERE

1548
01:00:13,977 --> 01:00:16,112
CAMEROON WAS AT, IT IS IN AFFRIC

1549
01:00:16,179 --> 01:00:17,747
AIT'S A HIGHLY DIVERSE

1550
01:00:17,814 --> 01:00:19,782
POPULATION LIVING IN CAMEROON,

1551
01:00:19,849 --> 01:00:21,651
THIS IS PROBABLY THE PERFECT

1552
01:00:21,718 --> 01:00:22,819
PLACE TO PERFORM SUCH STUDY.

1553
01:00:22,885 --> 01:00:26,222
SO THESE ARE THE 2 CLINIC THAT

1554
01:00:26,289 --> 01:00:28,758
DID THE HARD WORK ON THE GROUND

1555
01:00:28,825 --> 01:00:32,295
BUT WITH THE EQUIPMENT AND

1556
01:00:32,362 --> 01:00:36,799
[INDISCERNIBLE], DID ALL THE

1557
01:00:36,866 --> 01:00:37,066
ANALYSIS.

1558
01:00:37,133 --> 01:00:38,901
AND BEFORE WE DID AANALYSIS, WE

1559
01:00:38,968 --> 01:00:41,104
WANTED TO KNOW WHICH WOULD BE

1560
01:00:41,170 --> 01:00:43,072
THE BEST AMPUTATION PANEL OF OUR

1561
01:00:43,139 --> 01:00:45,274
GWAS, SO WE DID A COMPARATIVE

1562
01:00:45,341 --> 01:00:47,410
ANALYSIS OF ALL THIS, OF

1563
01:00:47,477 --> 01:00:49,145
6-AMPUTATION PANEL THAT WE KNOW,

1564
01:00:49,212 --> 01:00:50,580
OF AT THE MOMENT, THE FITTER

1565
01:00:50,646 --> 01:00:52,882
PANEL IS THE TOP MET 1, JUST

1566
01:00:52,949 --> 01:00:56,319
DAYS ON THE NUMBER OF VARIANT,

1567
01:00:56,386 --> 01:00:57,620
THE PANEL SEEMS TO BE THE BEST

1568
01:00:57,687 --> 01:01:00,490
TREATED FOR OUR STUDY.

1569
01:01:00,556 --> 01:01:04,327
WE ALSO MEASUREOT AMPUTATION,

1570
01:01:04,394 --> 01:01:05,862
AGAIN, THE TOP MET PANEL SEEMS

1571
01:01:05,928 --> 01:01:09,732
TO BE THE MOST ACCURATE BUT YOU

1572
01:01:09,799 --> 01:01:10,199
CANNOT [INDISCERNIBLE]

1573
01:01:10,266 --> 01:01:11,634
CHROMOSOME 19 ALL PANELS SEEM TO

1574
01:01:11,701 --> 01:01:12,468
BE LESS [INDISCERNIBLE].

1575
01:01:12,535 --> 01:01:13,736
THAT I THINK THAT WILL BE A

1576
01:01:13,803 --> 01:01:14,804
STORY OF A DIFFERENT DAY.

1577
01:01:14,871 --> 01:01:18,908
WHEN WE ALSO LOOK AT THE

1578
01:01:18,975 --> 01:01:20,376
ACCURACY BASAL MINOR FREQUENCY,

1579
01:01:20,443 --> 01:01:21,978
AGAIN THE PANEL SEEMS TO BE THE

1580
01:01:22,045 --> 01:01:24,047
BEST PANEL FOR THE STUDY IN

1581
01:01:24,113 --> 01:01:25,148
AFRICAN POPULATION AND LASTLY,

1582
01:01:25,214 --> 01:01:28,785
WHEN WE LOOK AT THE NUMBER OF

1583
01:01:28,851 --> 01:01:31,721
VARIANT ACROSS PANEL, ACTUALLY

1584
01:01:31,788 --> 01:01:33,589
WE REALIZE THAT THOSE 6 PANELS

1585
01:01:33,656 --> 01:01:35,091
SHARE ONLY ONE-THIRD OF THE

1586
01:01:35,158 --> 01:01:37,060
VARIANT, AND EACH OF THEM HAVE

1587
01:01:37,126 --> 01:01:38,327
SPECIFIC VARIANT THAT OTHER

1588
01:01:38,394 --> 01:01:40,463
PANELS DO NOT HAVE, WHAT DOES

1589
01:01:40,530 --> 01:01:43,566
THAT--IT MEANS IF YOU ARE NOT

1590
01:01:43,633 --> 01:01:44,867
DOING A GWAS BASED ON GENOMES,

1591
01:01:44,934 --> 01:01:46,402
IF YOU ARE WORKING ON THE

1592
01:01:46,469 --> 01:01:49,138
POPULATION, THAT HAVE NOT BEEN

1593
01:01:49,205 --> 01:01:50,573
STUDIED, YOU BETTER USE AS MUCH

1594
01:01:50,640 --> 01:01:54,510
PANEL AS YOU CAN BECAUSE THE

1595
01:01:54,577 --> 01:01:55,812
TRUTH IS NOT IN 1.

1596
01:01:55,878 --> 01:01:59,348
IF YOU CAN CHOOSE 1, YOU SHOULD

1597
01:01:59,415 --> 01:01:59,715
[INDISCERNIBLE].

1598
01:01:59,782 --> 01:02:05,721
IF YOU CAN, ON MANY PANEL, TRY

1599
01:02:05,788 --> 01:02:06,756
TO DO IT.

1600
01:02:06,823 --> 01:02:08,958
SO THAT MESSAGE I JUST DID NOW,

1601
01:02:09,025 --> 01:02:11,194
WHAT WE DID IS WE START BY STAGE

1602
01:02:11,260 --> 01:02:14,397
1 ON OUR DISCOVERY CARD IN

1603
01:02:14,464 --> 01:02:17,366
CAMEROON, WE ANALYZE THE DATA

1604
01:02:17,433 --> 01:02:18,701
FROM TANZANIA USING THE IMPROVED

1605
01:02:18,768 --> 01:02:22,538
PANEL WE HAVE NOW.

1606
01:02:22,605 --> 01:02:24,574
WE PERFORMED ANALYSIS ON AFRICAN

1607
01:02:24,640 --> 01:02:27,810
BASED COHORT, WE PAY FOR

1608
01:02:27,877 --> 01:02:29,078
TBLOABAL ANALYSIS BY ADDING ALL

1609
01:02:29,145 --> 01:02:31,948
THE DATA WE HAVE FROM AMERICAN

1610
01:02:32,014 --> 01:02:33,149
FROM VARIOUS COHORT, ABOUT 7

1611
01:02:33,216 --> 01:02:35,451
COHORT IN AMERICA, AND I MUST

1612
01:02:35,518 --> 01:02:38,721
SAY ALL THE THIS WE HAD FOR THE

1613
01:02:38,788 --> 01:02:40,022
STUDY WAS VERY [INDISCERNIBLE]

1614
01:02:40,089 --> 01:02:41,090
TO SHARE THE DATA, IT WAS

1615
01:02:41,157 --> 01:02:42,859
DIFFICULT TO HAVE THE DATA FROM

1616
01:02:42,925 --> 01:02:44,627
THE COHORT THAT WE REQUESTED TO

1617
01:02:44,694 --> 01:02:45,194
HAVE ACCESS TO.

1618
01:02:45,261 --> 01:02:48,397
AND THESE ARE THE DATA.

1619
01:02:48,464 --> 01:02:50,633
THE FIRST LINE IS THE DORPHY

1620
01:02:50,700 --> 01:02:53,069
COHORT, SHOWING THE B-CELL

1621
01:02:53,136 --> 01:02:54,103
RELEVANT THAT'S REPLICATED ON

1622
01:02:54,170 --> 01:02:57,974
THE THAT AND CLEARLY IN LOCI,

1623
01:02:58,040 --> 01:03:01,043
[INDISCERNIBLE] 1.

1624
01:03:01,110 --> 01:03:05,281
THE SECOND PATTERN IS THE AFRICA

1625
01:03:05,348 --> 01:03:06,215
BASED COHORT META-ANALYSIS, CAN

1626
01:03:06,282 --> 01:03:08,184
YOU REALIZE THIS ARE 7 NEW LOCI

1627
01:03:08,251 --> 01:03:11,988
AND THE THIRD IS THE GLOBAL

1628
01:03:12,054 --> 01:03:19,061
META-ANALYSIS TO THE TRADITIONAL

1629
01:03:19,128 --> 01:03:21,964
LOCI, AND THE WAY WE HAVE THE

1630
01:03:22,031 --> 01:03:23,299
ABILITY, BEFORE THE STUDY WE HAD

1631
01:03:23,366 --> 01:03:27,803
THE ABILITY OF LESS THAN 20%,

1632
01:03:27,870 --> 01:03:30,606
AFTER THIS, USING H3 AFRICAN

1633
01:03:30,673 --> 01:03:31,340
SPECIFIC [INDISCERNIBLE], WE

1634
01:03:31,407 --> 01:03:34,477
HAVE THE ABILITY OF 90%.

1635
01:03:34,544 --> 01:03:35,678
AND THIS 90% OF THE ABILITY IS

1636
01:03:35,745 --> 01:03:38,648
THE EXACT SAME THAT WAS FOUND IN

1637
01:03:38,714 --> 01:03:41,284
THE FIRST STUDY PERFORMED IN THE

1638
01:03:41,350 --> 01:03:42,351
UK POPULATION USING

1639
01:03:42,418 --> 01:03:43,085
[INDISCERNIBLE] STUDY, SO THAT

1640
01:03:43,152 --> 01:03:50,626
WE HAVE CLOSE TO WHAT THE NATURE

1641
01:03:50,693 --> 01:03:53,963
AND [INDISCERNIBLE] AFRICAN

1642
01:03:54,030 --> 01:03:54,297
SPECIFICALLY.

1643
01:03:54,363 --> 01:04:01,470
SO THE PAPER, IN THIS

1644
01:04:01,537 --> 01:04:06,676
RATEABILITY WE USE IT--IT'S

1645
01:04:06,742 --> 01:04:17,286
STILL ABOUT 50% COMPARED TO WHAT

1646
01:04:23,226 --> 01:04:24,193
WE KNEW BEFORE.

1647
01:04:24,260 --> 01:04:27,296
--THIS CHAIN WAS OR SEEMED TO BE

1648
01:04:27,363 --> 01:04:29,065
ACROSS THE PANEL THAT WE USE, IT

1649
01:04:29,131 --> 01:04:39,542
SEEMS TO BE THE SECOND.

1650
01:04:40,309 --> 01:04:42,778
AGAIN, THE VALUE WE FOUND WAS

1651
01:04:42,845 --> 01:04:46,282
THE FIRST GROUP OF BAD CHART,

1652
01:04:46,349 --> 01:04:49,285
AND BE FOUND THAT TAN SWRANNIAN,

1653
01:04:49,352 --> 01:04:53,155
ARE MOSTLY AMERICAN, AND WE

1654
01:04:53,222 --> 01:04:54,323
FOUND A FEW CATEGORY POPULATIONS

1655
01:04:54,390 --> 01:04:58,561
THAT MOST OF THEM ARE EUROPEAN

1656
01:04:58,628 --> 01:04:59,362
AND AFRICAN POPULATION, AGAIN IF

1657
01:04:59,428 --> 01:05:00,896
YOU DON'T DO THAT IN THE

1658
01:05:00,963 --> 01:05:06,002
POPULATION, YOU DON'T SEE IT, AS

1659
01:05:06,068 --> 01:05:06,702
SIMPLE AS THAT.

1660
01:05:06,769 --> 01:05:12,074
AND SOMEONE WILL SAY WHY IS THAT

1661
01:05:12,141 --> 01:05:14,076
THE GWAS NOT FIND IT JUST

1662
01:05:14,143 --> 01:05:24,654
BECAUSE THE HAPLOTYPE AROUND A

1663
01:05:27,923 --> 01:05:31,060
IF YOU TAKE AN AFRICAN DIET FROM

1664
01:05:31,127 --> 01:05:32,228
CAMEROON, GENETICALLY IT WILL BE

1665
01:05:32,295 --> 01:05:34,964
SO DIFFERENT FROM A GUY IN

1666
01:05:35,031 --> 01:05:36,532
[INDISCERNIBLE], AS FOR EXAMPLE,

1667
01:05:36,599 --> 01:05:38,534
SOMEONE [INDISCERNIBLE].

1668
01:05:38,601 --> 01:05:39,869
BECAUSE OF THE [INDISCERNIBLE]

1669
01:05:39,935 --> 01:05:42,938
OF THE MODIFICATION THAT

1670
01:05:43,005 --> 01:05:44,206
HAPPENED 300,000 YEARS WITHIN

1671
01:05:44,273 --> 01:05:46,342
AFRICA BECAUSE OF LIVING WITHIN

1672
01:05:46,409 --> 01:05:47,843
AFRICA, IT SUGGESTS THAT

1673
01:05:47,910 --> 01:05:49,679
REPLICATION OF GWAS STUDY, EVEN

1674
01:05:49,745 --> 01:05:54,617
WITHIN AFRICAN MIGHT BE

1675
01:05:54,684 --> 01:06:01,457
DIFFICULT BECAUSE THE DIVERSITY

1676
01:06:01,524 --> 01:06:03,192
IS TOO HUGE, BECAUSE THE PABLE

1677
01:06:03,259 --> 01:06:03,826
WILL NOT NECESSARILY CAPTURE

1678
01:06:03,893 --> 01:06:11,967
WHAT YOU WANT TO SEE.

1679
01:06:12,034 --> 01:06:14,603
SO IF WE FINE MAP, THIS HERE, WE

1680
01:06:14,670 --> 01:06:17,273
REALIZE THAT MOST OF THE VARIANT

1681
01:06:17,340 --> 01:06:20,409
THAT THE GWAS SIGNIFICANT AND

1682
01:06:20,476 --> 01:06:24,113
NOT ACTUALLY ON THE CORRECT LINE

1683
01:06:24,180 --> 01:06:26,749
FOR THE TRANSCRIPT OHM, THAT

1684
01:06:26,816 --> 01:06:29,852
SIDE, BEFORE THAT, WE SEE A

1685
01:06:29,919 --> 01:06:31,887
GROUP OF ENHANCER, TO SPARE

1686
01:06:31,954 --> 01:06:33,723
ABOUT 50 KB BEFORE THE

1687
01:06:33,789 --> 01:06:34,757
TRANSCRIPTION SITE AND THIS IS

1688
01:06:34,824 --> 01:06:38,060
WHERE MOST OF OUR VARIANTS ARE

1689
01:06:38,127 --> 01:06:38,661
FOUND.

1690
01:06:38,728 --> 01:06:42,031
WE TRIED TO TRACK THE RELATION

1691
01:06:42,098 --> 01:06:43,899
WITH TD VARIANT AND POTENTIAL

1692
01:06:43,966 --> 01:06:47,069
BYPASSING SITE AND THE GENES ARE

1693
01:06:47,136 --> 01:06:47,603
LOCATED THERE.

1694
01:06:47,670 --> 01:06:55,644
AND WE LOOK AT THE ATAQSEQ LOAD

1695
01:06:55,711 --> 01:06:56,912
AND REALIZED THAT EEIVETTIVELY

1696
01:06:56,979 --> 01:06:59,181
WHERE WE HAVE MOST OF THE

1697
01:06:59,248 --> 01:07:01,751
VARIANT THAT GWAS HAVE

1698
01:07:01,817 --> 01:07:04,320
SIGNIFICANT ENHANCER ACTIVITY.

1699
01:07:04,387 --> 01:07:09,091
AND BELOW, ON THE CHART BELOW,

1700
01:07:09,158 --> 01:07:11,594
WE CAN SEE THAT, AND THE 1 IN

1701
01:07:11,660 --> 01:07:13,295
THE MISD IS MOST INTERESTING,

1702
01:07:13,362 --> 01:07:17,767
THE BAND THERE IS GIF01 AND THAT

1703
01:07:17,833 --> 01:07:20,703
VARIANT IS SOAB WIDE UP TO 40%

1704
01:07:20,770 --> 01:07:22,705
OF THE [INDISCERNIBLE] THE

1705
01:07:22,772 --> 01:07:26,041
CUT-OFF FOR A MANIPULATION IS

1706
01:07:26,108 --> 01:07:26,509
USUALLY AROUND 20%.

1707
01:07:26,575 --> 01:07:28,177
WHAT HAPPEN FIST YOU KNOCK OUT A

1708
01:07:28,244 --> 01:07:29,912
GENE, IF YOU KNOCK OUT THE YEEN,

1709
01:07:29,979 --> 01:07:32,348
THE MICE SURVIVE, WE DON'T DO

1710
01:07:32,415 --> 01:07:33,949
IT, AND THE MICE DOESN'T SURVIVE

1711
01:07:34,016 --> 01:07:35,584
BUZZ THE MICE DOESN'T MAKE BLOOD

1712
01:07:35,651 --> 01:07:39,422
VESSEL AND THE MICE DOESN'T MAKE

1713
01:07:39,488 --> 01:07:41,090
BLOOD AT ALL.

1714
01:07:41,157 --> 01:07:43,959
AND THAT YEEN, ANOTHER GENE WHEN

1715
01:07:44,026 --> 01:07:46,796
WE LOOK AT IT, THE KNOCK OUT

1716
01:07:46,862 --> 01:07:47,963
AGAIN DOESN'T ALLOW THE

1717
01:07:48,030 --> 01:07:48,798
[INDISCERNIBLE] OF THAT MICE.

1718
01:07:48,864 --> 01:07:51,534
SO THAT MEANS IF WE WANT TO

1719
01:07:51,600 --> 01:07:52,968
EXPLORE THIS GENE AT THE

1720
01:07:53,035 --> 01:07:54,370
MOLECULAR LEVEL, YOU NEED TO

1721
01:07:54,437 --> 01:07:57,973
HAVE A CONDITIONAL KNOCK OUT.

1722
01:07:58,040 --> 01:08:00,576
SO BECAUSE WE WANTED TO KNOW HOW

1723
01:08:00,643 --> 01:08:02,878
DID THIS GENE ACTUALLY WORK, WE

1724
01:08:02,945 --> 01:08:08,551
JUST DID THE SIMPLE THING THAT 1

1725
01:08:08,617 --> 01:08:10,719
OF MY FRIEND, [INDISCERNIBLE]

1726
01:08:10,786 --> 01:08:12,221
AND WE REALIZE THAT

1727
01:08:12,288 --> 01:08:14,990
[INDISCERNIBLE] BELONGED TO THE

1728
01:08:15,057 --> 01:08:17,193
PATHWAY OF HYPOXIA AND THAT

1729
01:08:17,259 --> 01:08:19,161
PATHWAY IS DIRECTLY CONNECTED TO

1730
01:08:19,228 --> 01:08:20,463
THE [INDISCERNIBLE] PRODUCK, WE

1731
01:08:20,529 --> 01:08:23,966
ARE STARTING TO GET IN CLOSER TO

1732
01:08:24,033 --> 01:08:24,633
THE MECHANISM.

1733
01:08:24,700 --> 01:08:27,036
AND WHAT WHY IS A PATHWAY OF

1734
01:08:27,102 --> 01:08:28,537
HYPOXIA IMPORTANT FOR

1735
01:08:28,604 --> 01:08:29,171
[INDISCERNIBLE] PRODUCTION, WE

1736
01:08:29,238 --> 01:08:32,341
DID NOT DO THE WORK, SOMEONE

1737
01:08:32,408 --> 01:08:35,444
ELSE ALREADY SHOWN THAT I POXIA

1738
01:08:35,511 --> 01:08:38,581
INDUCIBLE FACTOR A, THAT WAS

1739
01:08:38,647 --> 01:08:48,724
DISCOVERED BY DR. GREG ZEPHYR

1740
01:08:48,791 --> 01:08:49,225
.

1741
01:08:49,291 --> 01:08:51,827
SO OUR CURRENT DIAGNOSIS IS THAT

1742
01:08:51,894 --> 01:08:55,598
1 CAN INCREASE CAN ALLOW FOR

1743
01:08:55,664 --> 01:08:58,667
[INDISCERNIBLE] PRODUCTION

1744
01:08:58,734 --> 01:09:01,303
PRODUCTION OF F-CELLS, PAIR UP

1745
01:09:01,370 --> 01:09:04,306
OF [INDISCERNIBLE] AND

1746
01:09:04,373 --> 01:09:04,573
ENHANCERS.

1747
01:09:04,640 --> 01:09:07,042
SO WE HAVE A MODEL WE TRYING TO

1748
01:09:07,109 --> 01:09:08,911
EXPERIMENTAL VERY FINAL THIS

1749
01:09:08,978 --> 01:09:09,745
MODEL IS COMPLEX, BUT IT'S

1750
01:09:09,812 --> 01:09:11,280
IMPORTANT FOR US TO HAVE A

1751
01:09:11,347 --> 01:09:13,549
COMPLEX, BECAUSE EACH OF THE

1752
01:09:13,616 --> 01:09:17,319
LINE, EACH OF THE STICK WILL BE

1753
01:09:17,386 --> 01:09:18,721
VERIFIED EXPERIMENTAL.

1754
01:09:18,787 --> 01:09:20,723
SO, THE FIRST THING TO DO FOR US

1755
01:09:20,789 --> 01:09:23,559
WAS TO KNOCK OUT THAT GENE, AND

1756
01:09:23,626 --> 01:09:24,827
UDEPRIVATION CELL LINE, AND THAT

1757
01:09:24,894 --> 01:09:31,700
IS THE CLASSICAL CELL LINE THAT

1758
01:09:31,767 --> 01:09:37,239
I USED TO EXPLORE PRODUCTION FOR

1759
01:09:37,306 --> 01:09:40,442
BCL11A, AND THIS BCL11A, NEW

1760
01:09:40,509 --> 01:09:42,077
SALE LINE ASSOCIATE AS CAN YOU

1761
01:09:42,144 --> 01:09:44,346
SEE HIGH PRODUCTION OF

1762
01:09:44,413 --> 01:09:46,982
[INDISCERNIBLE] BUT THE DELETION

1763
01:09:47,049 --> 01:09:48,250
OF [INDISCERNIBLE] 1 IS NOT

1764
01:09:48,317 --> 01:09:50,619
ASSOCIATE TD WITH IT AT ALL.

1765
01:09:50,686 --> 01:09:53,155
IT IS NOT EXPRESSING THIS ALIKE.

1766
01:09:53,222 --> 01:09:58,994
THIS MEANS IT'S NOT THE

1767
01:09:59,061 --> 01:09:59,361
[INDISCERNIBLE].

1768
01:09:59,428 --> 01:10:00,296
SO WE LOOK AT THE LITERATE AND

1769
01:10:00,362 --> 01:10:05,634
YOU ARE LOOK AT THE EXPRESSION

1770
01:10:05,701 --> 01:10:07,736
OF F LT1 BELOW AT A TIME.

1771
01:10:07,803 --> 01:10:09,772
THE 1 BELOW IS THE RED BLOOD

1772
01:10:09,838 --> 01:10:11,640
CELL, AS CAN YOU OBSERVE BLUE

1773
01:10:11,707 --> 01:10:14,410
MEANS IT'S NOT EXPRESSING THE

1774
01:10:14,476 --> 01:10:15,678
DOUBLE RED BLOOD CELLS AS WEB

1775
01:10:15,744 --> 01:10:16,512
CONNECTED EXPECTED.

1776
01:10:16,579 --> 01:10:18,147
IF YOU MOVE UPWARDS YOU RAZE

1777
01:10:18,213 --> 01:10:21,050
THAT THIS IS A BETA CELLS IN

1778
01:10:21,116 --> 01:10:23,953
EACH, IN B-CELL LINEAGE, AND

1779
01:10:24,019 --> 01:10:25,154
PERHAPS IN THE HEMATOPOIETIC

1780
01:10:25,220 --> 01:10:26,455
STEM CELL, THAT MEANS SHOULD

1781
01:10:26,522 --> 01:10:29,458
SHOULD BE THE MODEL THAT WE

1782
01:10:29,525 --> 01:10:31,260
SHOULD USE.

1783
01:10:31,327 --> 01:10:32,828
GOING TO [INDISCERNIBLE].

1784
01:10:32,895 --> 01:10:37,266
WE NOW USE K562, WHICH IS

1785
01:10:37,333 --> 01:10:40,436
[INDISCERNIBLE] CELL LINE, AND

1786
01:10:40,502 --> 01:10:44,773
WE EXPOSE THEM TO HYPOXIA AND

1787
01:10:44,840 --> 01:10:46,108
FLT1, AND IT INCREASEOT RIGHT

1788
01:10:46,175 --> 01:10:52,081
HAND SIDE, THE BAR IN RED, WITH

1789
01:10:52,147 --> 01:10:55,851
EXPOSURE OF K56 TO THE HYPOXIA

1790
01:10:55,918 --> 01:10:58,454
AND THAT HYPOXIA ASSURES US

1791
01:10:58,520 --> 01:11:01,256
INCREASING OF HIERK F ALPHA,

1792
01:11:01,323 --> 01:11:02,758
WHICH AGAIN IS VERY REASSURING

1793
01:11:02,825 --> 01:11:04,526
TO US BECAUSE THAT MEANS THAT

1794
01:11:04,593 --> 01:11:15,137
THERE IS A RELATION BETWEEN FLT1

1795
01:11:15,537 --> 01:11:17,940
AND HIFA, AND WE ALWAYS REALIZE

1796
01:11:18,007 --> 01:11:20,976
THAT KNF 1 SPECIFICALLY AT THE

1797
01:11:21,043 --> 01:11:22,811
TIME OF THE [INDISCERNIBLE]

1798
01:11:22,878 --> 01:11:24,780
SEEMS TO BE INCREASED AT THE

1799
01:11:24,847 --> 01:11:26,548
SAME TIME, AGAIN, UP UNTIL THEN,

1800
01:11:26,615 --> 01:11:30,619
WE STILL DON'T HAVE THE

1801
01:11:30,686 --> 01:11:30,986
MECHANISM.

1802
01:11:31,053 --> 01:11:33,922
SO LET'S GO BACK TO THE MAP.

1803
01:11:33,989 --> 01:11:36,859
BY LOOKING AT THE AREA OF THE

1804
01:11:36,925 --> 01:11:42,364
FIRE MAP WHERE WE FOCUS ON 1

1805
01:11:42,431 --> 01:11:44,700
SPECIFIC GENE CALLED GIF1, AND

1806
01:11:44,767 --> 01:11:50,372
WE KNOW THE MODIFIER FOR THE

1807
01:11:50,439 --> 01:11:53,208
[INDISCERNIBLE].

1808
01:11:53,275 --> 01:11:54,376
THE ATAC-SEQ INFORMATION AGAIN,

1809
01:11:54,443 --> 01:11:55,678
I THINK THE EXPERIMENT WE DID

1810
01:11:55,744 --> 01:11:57,079
LAST WEEK, I THINK IT WAS THE

1811
01:11:57,146 --> 01:11:58,747
LAST TIME I PRESENT THIS

1812
01:11:58,814 --> 01:12:01,617
PUBLICLY, WE XOK OUT THAT

1813
01:12:01,684 --> 01:12:02,985
REGION, WE DID 2 EXHIBITING OUT,

1814
01:12:03,052 --> 01:12:05,020
THE FITTER KNOCK OUT WAS THE

1815
01:12:05,087 --> 01:12:05,654
WHOLE REGION, THE SECOND KNOCK

1816
01:12:05,721 --> 01:12:08,323
OUT WAS JUST THE AREA WHERE WE

1817
01:12:08,390 --> 01:12:10,993
THINK WE HAVE BINDING SIDE OF

1818
01:12:11,060 --> 01:12:15,531
GIF-1 AND WE HAVE A 3.74

1819
01:12:15,597 --> 01:12:19,668
INCREASE OF FLT1 AND 4.16

1820
01:12:19,735 --> 01:12:20,335
INCREASE.

1821
01:12:20,402 --> 01:12:21,970
SO I THINK WE ARE GETTING CLOSE

1822
01:12:22,037 --> 01:12:22,604
TO THE MECHANISMS.

1823
01:12:22,671 --> 01:12:24,373
WE BELIEVE THAT THE REGION WHERE

1824
01:12:24,440 --> 01:12:27,976
WE FOUND THE GY SALARY ARE SOME

1825
01:12:28,043 --> 01:12:30,379
PERTURBED THE BINDING SITE ON 1

1826
01:12:30,446 --> 01:12:32,347
OF THE [INDISCERNIBLE] OF FLT1,

1827
01:12:32,414 --> 01:12:34,083
SO OF COURSE WE HAVE TO HAVE 1

1828
01:12:34,149 --> 01:12:39,488
OR 2 OF THE EXPERIMENT TO SHOW

1829
01:12:39,555 --> 01:12:39,688
THAT.

1830
01:12:39,755 --> 01:12:43,726
WE MOVE TO THE CD34, WHICH IS A

1831
01:12:43,792 --> 01:12:44,927
NATURAL LINE AND CLOSER TO WHAT

1832
01:12:44,993 --> 01:12:49,031
WE SHOULD SEE IN ADULT BECAUSE

1833
01:12:49,098 --> 01:12:52,768
K562, IS THE CONTROL, SO IT

1834
01:12:52,835 --> 01:12:55,437
BEHAVES SOMETIME STRANGELY

1835
01:12:55,504 --> 01:12:59,575
INVITRO, BY TALKING OUT FLT1, IN

1836
01:12:59,641 --> 01:13:02,277
CD34, AND ALSO KNOCK OUT IT

1837
01:13:02,344 --> 01:13:03,879
BCL11 AS A CONTROL EXPERIMENT,

1838
01:13:03,946 --> 01:13:04,847
THE VARIABILITY UNDER THE

1839
01:13:04,913 --> 01:13:07,950
COVERRABILITY OF THE CELL ARE

1840
01:13:08,016 --> 01:13:09,685
VERY ACCEPTABLE.

1841
01:13:09,752 --> 01:13:11,453
AND WE NOW CULTURE AND

1842
01:13:11,520 --> 01:13:14,056
DIFFERENTIATE THOSE CELLS ON

1843
01:13:14,123 --> 01:13:16,492
THAT INHIBITION OF FLT1 AND YOU

1844
01:13:16,558 --> 01:13:19,795
CAN SEE THAT WHEN YOU INHIBIT

1845
01:13:19,862 --> 01:13:20,963
THE [INDISCERNIBLE] ON THE

1846
01:13:21,029 --> 01:13:25,400
VASCULAR AND GROWTH FACTOR

1847
01:13:25,467 --> 01:13:26,268
THERE'S NO GROWTH OF

1848
01:13:26,335 --> 01:13:27,736
[INDISCERNIBLE] AT ALL.

1849
01:13:27,803 --> 01:13:29,238
AND WE REPEAT THIS EXPERIMENT IN

1850
01:13:29,304 --> 01:13:31,707
A VERY DIFFERENT WAY, MEASURING

1851
01:13:31,774 --> 01:13:38,213
CELL, AGAIN, THERE IS NO

1852
01:13:38,280 --> 01:13:39,047
PRODUCTION, OF FLT-AMOUNT OF

1853
01:13:39,114 --> 01:13:41,717
EXPERIENCE O GLOBIN AND THAT IS

1854
01:13:41,784 --> 01:13:42,451
REDUCED UNDER HYPOXIA.

1855
01:13:42,518 --> 01:13:45,921
SO A LOT HAVE BEEN REFEIGNED WE

1856
01:13:45,988 --> 01:13:50,692
BELIEVE FLT 1 IS ASSOCIATE WIDE

1857
01:13:50,759 --> 01:13:51,260
INDUCED [INDISCERNIBLE]

1858
01:13:51,326 --> 01:13:53,562
POTENTIALLY, WE ALREADY HAVE 2

1859
01:13:53,629 --> 01:13:54,863
ON POTENTIAL GENES THAT WILL BE

1860
01:13:54,930 --> 01:13:57,065
INVOLVE THAD WILL GUIDE OUR NEXT

1861
01:13:57,132 --> 01:13:57,466
EXPERIMENT.

1862
01:13:57,533 --> 01:14:00,569
AND I WILL STOP THERE FOR THIS

1863
01:14:00,636 --> 01:14:00,769
PART.

1864
01:14:00,836 --> 01:14:02,871
SO THIS IS THE LIMPIFIED MODEL

1865
01:14:02,938 --> 01:14:05,207
THAT WE HAVE AND WE WILL TRY TO

1866
01:14:05,274 --> 01:14:07,976
FOLLOW ALL THE QUESTION MARKS OF

1867
01:14:08,043 --> 01:14:09,611
EXPERIMENT THAT WE NEED TO

1868
01:14:09,678 --> 01:14:12,214
DECIDE AND PERFORM TO TRY TO

1869
01:14:12,281 --> 01:14:13,982
UNDERSTAND WHY AND WHY FLT1 IS

1870
01:14:14,049 --> 01:14:16,618
THE NEXT TARGET FOR SICKLE CELL

1871
01:14:16,685 --> 01:14:20,389
DISEASE, FOR THERAPEUTICS AND WE

1872
01:14:20,455 --> 01:14:21,957
NEED TO PUSH LIKE MANY OTHERS

1873
01:14:22,024 --> 01:14:24,259
ARE PUSHING HERE TO FIND A NEW

1874
01:14:24,326 --> 01:14:25,327
TARGET BECAUSE UNLIKE VICTORIA

1875
01:14:25,394 --> 01:14:27,062
GRAY, THERE ARE MANY PATIENTS IN

1876
01:14:27,129 --> 01:14:30,132
AFRICA THAT WILL NOT HAVE ACCESS

1877
01:14:30,199 --> 01:14:33,268
IF YOU DON'T MAKE DOSE 30 AND TO

1878
01:14:33,335 --> 01:14:34,570
MAKE IT THERAPEUTABLE, THIS IS 1

1879
01:14:34,636 --> 01:14:38,740
OF OUR PASHTS FROM CAPE TOWN,

1880
01:14:38,807 --> 01:14:40,275
HE'S SICKLE CELL DISEASE, HE'S A

1881
01:14:40,342 --> 01:14:43,378
GRADUATE STUDENT AND BELIEVER OF

1882
01:14:43,445 --> 01:14:44,947
GENE EDITING OR THERAPY FOR SICK

1883
01:14:45,013 --> 01:14:47,382
ELITE EXECUTIVE DISEASE.

1884
01:14:47,449 --> 01:14:50,018
I WILL MOVE TO KEY 4 AND 5, THE

1885
01:14:50,085 --> 01:14:51,553
KEY 4 AND 5 LESS CLOSE AFTER

1886
01:14:51,620 --> 01:14:52,888
TRANSLATION, THEY ARE MORE

1887
01:14:52,955 --> 01:14:53,589
[INDISCERNIBLE].

1888
01:14:53,655 --> 01:14:54,957
I THINK 1 OF THE PERSPECTIVE OF

1889
01:14:55,023 --> 01:14:59,027
YEEN THERAPY OF SICK CELL CELL

1890
01:14:59,094 --> 01:15:05,934
DISEASE TO EXPLORE RNA, FOR

1891
01:15:06,001 --> 01:15:07,536
EXAMPLE HYDROXY URIA, IS

1892
01:15:07,603 --> 01:15:08,503
TRADITIONAL FOR SICKLE CELL

1893
01:15:08,570 --> 01:15:15,077
DISEASE, WE DON'T KNOW  IT MAY

1894
01:15:15,143 --> 01:15:17,346
ACT AS TRUE MIKE ARE RNA AND

1895
01:15:17,412 --> 01:15:18,513
THIS IF THATIA TRUE WE CAN

1896
01:15:18,580 --> 01:15:22,251
PACKAGE IT IN A SPECIFIC WAY TO

1897
01:15:22,317 --> 01:15:23,919
MODIFY FOR EXAMPLE,

1898
01:15:23,986 --> 01:15:24,753
[INDISCERNIBLE] PRODUCTION

1899
01:15:24,820 --> 01:15:26,088
WITHOUT CHANGING THE WHOLE

1900
01:15:26,154 --> 01:15:27,155
TRANSCRIPT ORDER OF MICRONSIC,

1901
01:15:27,222 --> 01:15:29,892
WE CAN ALSO PACKAGE MICRORNA

1902
01:15:29,958 --> 01:15:33,595
JUST FOR HEMODPLOABIN A, ITSELF,

1903
01:15:33,662 --> 01:15:36,698
WE KNOW THAT WORKING FOR

1904
01:15:36,765 --> 01:15:38,100
COVID-19 FOR EXAMPLE, VACCINE,

1905
01:15:38,166 --> 01:15:39,701
WHY SHOULD IT WORK FOR EXAMPLE,

1906
01:15:39,768 --> 01:15:46,341
IN SICKLE CELL DISEASE?

1907
01:15:46,408 --> 01:15:48,176
ANOTHER UNSOLVED QUESTION IS

1908
01:15:48,243 --> 01:15:51,246
RARE VARIANT OF SICKLE CELL

1909
01:15:51,313 --> 01:15:52,414
DISEASE, THAT WAS ENTIRELY POSED

1910
01:15:52,481 --> 01:15:55,050
BY A PATIENT AND FRIEND AND HE'S

1911
01:15:55,117 --> 01:15:57,486
ABOUT 63 TODAY, HE LIVES WITH

1912
01:15:57,552 --> 01:15:59,321
SICKLE CELL DISEASE, HE IS THE

1913
01:15:59,388 --> 01:16:00,822
LEADER OF THE SICKLE CELL

1914
01:16:00,889 --> 01:16:01,790
SUPPORT GROUP IN

1915
01:16:01,857 --> 01:16:02,157
[INDISCERNIBLE].

1916
01:16:02,224 --> 01:16:03,659
AND HE ASKED ME WHY DID I

1917
01:16:03,725 --> 01:16:03,892
SURVIVE.

1918
01:16:03,959 --> 01:16:05,327
AND I SAID I DON'T KNOW.

1919
01:16:05,394 --> 01:16:07,996
HE SAID I NEVER TOOK PROPER

1920
01:16:08,063 --> 01:16:09,498
TREATMENT BUT WHY I DEPARTMENT

1921
01:16:09,564 --> 01:16:10,565
DIE LIKE MANY OTHERS.

1922
01:16:10,632 --> 01:16:13,902
I SAID MAYBE YOU HAVE GOOD GENES

1923
01:16:13,969 --> 01:16:15,170
AND THEN MAYBE YOU HAVE GOOD

1924
01:16:15,237 --> 01:16:16,838
JEEPS AND THEN I WAS THINKING HE

1925
01:16:16,905 --> 01:16:18,674
MAY HAVE GOOD GENES AND THEN I

1926
01:16:18,740 --> 01:16:21,710
LOOK FOR PEOPLE LIKE HIM, 25 OF

1927
01:16:21,777 --> 01:16:24,146
THEM THAT SURVIVE IN AFRICA

1928
01:16:24,212 --> 01:16:24,646
WITHOUT TREATMENT.

1929
01:16:24,713 --> 01:16:26,248
IT WAS HARD TO FIND IT AND I

1930
01:16:26,315 --> 01:16:29,017
LOOK AT THE REVERSE, THE REVERSE

1931
01:16:29,084 --> 01:16:30,652
SHOULD BE PEOPLE WHO HAVE THAT

1932
01:16:30,719 --> 01:16:35,290
TREATMENT, I COULDN'T FIND THOSE

1933
01:16:35,357 --> 01:16:35,991
BECAUSE [INDISCERNIBLE].

1934
01:16:36,058 --> 01:16:39,061
SO SECOND BASE WAS THOSE WHO

1935
01:16:39,127 --> 01:16:40,595
HAVE STROKE BEFORE YOU'RE 10 AND

1936
01:16:40,662 --> 01:16:42,464
A WHOLE SEQUENCE, WHOLE EXOHM

1937
01:16:42,531 --> 01:16:46,835
SEQUENCE 2 OR 3 AND WE HAVE  A

1938
01:16:46,902 --> 01:16:48,236
MITSD GROUP LOWER THAN 50 YEARS

1939
01:16:48,303 --> 01:16:49,871
OLD AND WITHOUT STROKE AND BY

1940
01:16:49,938 --> 01:16:54,409
DOING SO REALIZE THAT ACTUALLY

1941
01:16:54,476 --> 01:16:56,511
THE LONG SURVIVOR, HAVE MUTATION

1942
01:16:56,578 --> 01:16:59,081
IN THE IMPORTANT YEEN, 1 THAT'S

1943
01:16:59,147 --> 01:17:00,449
CHLORIDE, CHANNEL, THE SECOND 1

1944
01:17:00,515 --> 01:17:03,218
THAT'S A YEEN THAT MODIFY

1945
01:17:03,285 --> 01:17:04,786
L-GLUTEA MIN, YOU KNOW IT WAS

1946
01:17:04,853 --> 01:17:07,422
APPROVED BY THE FDA LIKE IN 2017

1947
01:17:07,489 --> 01:17:09,224
FOR THE TREATMENT OF SICKLE CELL

1948
01:17:09,291 --> 01:17:09,925
DISEASE, SO SUGGESTING THAT

1949
01:17:09,992 --> 01:17:12,995
MAYBE SOME OF THESE PATIENTS

1950
01:17:13,061 --> 01:17:14,529
LONG SURVIVORS HAVE RECURRENT

1951
01:17:14,596 --> 01:17:17,699
VARIANT THAT ALLOWED THEM TO

1952
01:17:17,766 --> 01:17:19,534
HAVE PRODUCTION OF L-GLUTEA

1953
01:17:19,601 --> 01:17:19,735
MINE.

1954
01:17:19,801 --> 01:17:21,003
AND THEN AGAIN WE LOOK WHEN WE

1955
01:17:21,069 --> 01:17:22,504
DO THOSE THINGS YOU THINK YOU

1956
01:17:22,571 --> 01:17:23,772
MIGHT BE CRAZY RIGHT?

1957
01:17:23,839 --> 01:17:25,640
AND THEN WE WENT IN AND

1958
01:17:25,707 --> 01:17:27,642
LITERATURE AND LOOKAD THE

1959
01:17:27,709 --> 01:17:28,577
TRANSCRIPTOMIC DATA FROM

1960
01:17:28,643 --> 01:17:30,045
COMPLETELY DIFFERENT OTHER

1961
01:17:30,112 --> 01:17:32,614
PEOPLE AND THEY EXACTLY THE SAME

1962
01:17:32,681 --> 01:17:33,749
PATHWAY, NOT USING EXORDER OF

1963
01:17:33,815 --> 01:17:35,384
MICRONS DATA BUT THE BLOOD

1964
01:17:35,450 --> 01:17:36,184
TRANSCREPT ORDER OF MICRONSIC,

1965
01:17:36,251 --> 01:17:41,123
AND THESE ARE THE DATA IN THAT

1966
01:17:41,189 --> 01:17:41,356
PAPER.

1967
01:17:41,423 --> 01:17:43,792
YOU MAY NOT KNOW, THIS GUY, IS

1968
01:17:43,859 --> 01:17:48,096
MY

1969
01:17:48,163 --> 01:17:49,598
MY COUSIN OF A DIFFERENT TIME

1970
01:17:49,664 --> 01:17:52,367
BECAUSE OF MY NIEWBIAN ANCESTRY,

1971
01:17:52,434 --> 01:17:53,535
BUT [INDISCERNIBLE] MAY HAVE

1972
01:17:53,602 --> 01:18:02,377
DIED FROM SICKLE CELL DISEASE,

1973
01:18:02,444 --> 01:18:09,718
AND THE WAY WE KNOW IT IS THAT

1974
01:18:09,785 --> 01:18:13,455
THERE IS A WAY TO STUDY HIS

1975
01:18:13,522 --> 01:18:15,424
BONES AND KNOW HE HAS THE

1976
01:18:15,490 --> 01:18:17,059
DISEASE AND HE TIED 5000 YEARS

1977
01:18:17,125 --> 01:18:20,729
AGO AND IF HE HAD IT 5000 YEARS

1978
01:18:20,796 --> 01:18:22,164
AGO, IT SUGGEST IT SHOULD HAVE

1979
01:18:22,230 --> 01:18:23,799
BEEN FIXED IN THE POPULATION

1980
01:18:23,865 --> 01:18:25,067
LONG BEFORE THAT, IT ALSO

1981
01:18:25,133 --> 01:18:28,170
SUGJERTS THAT OVER THE LAST 5000

1982
01:18:28,236 --> 01:18:30,038
YEARS, THERE ARE MANY PEOPLE,

1983
01:18:30,105 --> 01:18:31,506
SICKLE CELL MAY HAVE PUT

1984
01:18:31,573 --> 01:18:33,375
PRESSURE ON OUR OWN GENOME AND

1985
01:18:33,442 --> 01:18:36,144
POTENTIALLY SELECT SOME OF THE

1986
01:18:36,211 --> 01:18:39,915
VARIANT IN A SIMILAR WAY MALARIA

1987
01:18:39,981 --> 01:18:41,183
SELECTED ENVIRONMENT IN THE

1988
01:18:41,249 --> 01:18:42,984
YEERN, WE SELECTED THE

1989
01:18:43,051 --> 01:18:44,052
HYPOTHESIS, USING THE DATA FROM

1990
01:18:44,119 --> 01:18:46,521
THE SICKLE CELL DISEASE, FROM

1991
01:18:46,588 --> 01:18:49,057
CAMEROON AND CONGO AND COMPARE

1992
01:18:49,124 --> 01:18:50,092
POTENTIAL SELECTION TO A

1993
01:18:50,158 --> 01:18:52,060
POPULATION THAT WERE

1994
01:18:52,127 --> 01:18:52,761
[INDISCERNIBLE].

1995
01:18:52,828 --> 01:18:55,230
IT WAS HOMOZYGOUS, IT IS, AND

1996
01:18:55,297 --> 01:18:58,633
THAT HOMOZYGOUS IS THE FESTER

1997
01:18:58,700 --> 01:19:00,268
MANHATTAN PLOT, ALL OTHER

1998
01:19:00,335 --> 01:19:01,970
MANHATTAN PLOT FROM SICKLE CELL

1999
01:19:02,037 --> 01:19:04,840
COHORT AND YOU CAN IDENTIFY

2000
01:19:04,906 --> 01:19:06,341
MUTATIONS IN CHROMOSOME 11 IN

2001
01:19:06,408 --> 01:19:08,176
BLUE BUT AT LEAST 2 AREA IN

2002
01:19:08,243 --> 01:19:13,048
VARIOUS COHORT THAT ARE SELECTED

2003
01:19:13,115 --> 01:19:14,216
OR NATURALLY SELECTED IN OUR

2004
01:19:14,282 --> 01:19:16,284
GENOME AND THE JEERNS ASSOCIATED

2005
01:19:16,351 --> 01:19:18,687
IN THOSE AREA OF SELECTION ARE

2006
01:19:18,753 --> 01:19:20,155
ON THE LOWER RIGHT.

2007
01:19:20,222 --> 01:19:24,159
I DON'T THINK THE DATA ARE

2008
01:19:24,226 --> 01:19:25,260
PUBLISHABLE, ACTUALLY THESE DATA

2009
01:19:25,327 --> 01:19:25,894
ARE PRELIMINARY BECAUSE IF YOU

2010
01:19:25,961 --> 01:19:27,562
WANT TO DO A PROPER SELECTION

2011
01:19:27,629 --> 01:19:30,031
AND ANALYSIS, YOU NEED TO DO THE

2012
01:19:30,098 --> 01:19:32,234
EXACT SAME ANALYSIS ON THE

2013
01:19:32,300 --> 01:19:33,368
GENERAL POPULATION, WE DID NOT

2014
01:19:33,435 --> 01:19:36,138
DO IT IN THIS SPECIFIC STUDY,

2015
01:19:36,204 --> 01:19:37,439
THIS WAS JUST PRELIMINARY BUT WE

2016
01:19:37,506 --> 01:19:40,008
HAVE NOW, THE POWER, THE NUMBER,

2017
01:19:40,075 --> 01:19:44,946
THE SEQUENCE TO PERFORM THIS

2018
01:19:45,013 --> 01:19:47,382
STUDIES BECAUSE WE HAVE ENOUGH

2019
01:19:47,449 --> 01:19:51,386
GENOMES AND ENOUGH SAMPLES FOR

2020
01:19:51,453 --> 01:19:52,354
THE STUDY.

2021
01:19:52,420 --> 01:19:53,288
ANOTHER QUESTION WE SHOULD

2022
01:19:53,355 --> 01:19:55,423
INVESTIGATE IS THE EVOLUTION OF

2023
01:19:55,490 --> 01:19:56,925
SICKLE CELL BARRIERS OR THAT

2024
01:19:56,992 --> 01:19:57,125
AREA.

2025
01:19:57,192 --> 01:19:59,594
FOR EXAMPLE, 1 OF MY STUDENTS

2026
01:19:59,661 --> 01:20:01,263
KEVIN HE DID THIS HEAT MAP

2027
01:20:01,329 --> 01:20:03,899
STUDY, SHOWING FOR EXAMPLE, THAT

2028
01:20:03,965 --> 01:20:07,102
SICKLE CELL DISEASE,

2029
01:20:07,169 --> 01:20:08,203
[INDISCERNIBLE] AND AFTER A MAP

2030
01:20:08,270 --> 01:20:09,838
OF THE AREA IN AFRICA, THAT

2031
01:20:09,905 --> 01:20:11,840
MEANS THAT THE GOOD AFRICAN

2032
01:20:11,907 --> 01:20:16,378
MYSELF I MAY HAVE THE 3 VARIANTS

2033
01:20:16,444 --> 01:20:18,146
IN MY BLOOD, WE KNOW WHAT IT

2034
01:20:18,213 --> 01:20:19,548
WOULD DO, IF SOME VARIANT WILL

2035
01:20:19,614 --> 01:20:21,983
LEAD YOU TO HAVE MORE KIDNEY

2036
01:20:22,050 --> 01:20:23,084
DISEASE THAN OTHERS.

2037
01:20:23,151 --> 01:20:24,753
AND IT ACTUALLY PROTECTIONS YOU

2038
01:20:24,819 --> 01:20:25,820
AGAINST KIDNEY DISEASE, WHAT IF

2039
01:20:25,887 --> 01:20:28,456
YOU HAVE THE COP BINNATION OF

2040
01:20:28,523 --> 01:20:29,357
ALL OF THEM?

2041
01:20:29,424 --> 01:20:31,293
SO YOUNG MIND AND CLEVER MIND

2042
01:20:31,359 --> 01:20:34,496
NEED TO WORK ON MODELS ON HOW

2043
01:20:34,563 --> 01:20:38,600
THESE ISHT ACT TOGETHER, THESE

2044
01:20:38,667 --> 01:20:41,937
ARE DATA FROM MARIA, A PROJECT

2045
01:20:42,003 --> 01:20:44,005
THAT SHOWED THAT THERE'S NOT

2046
01:20:44,072 --> 01:20:45,674
JUST [INDISCERNIBLE] SELECT FOR

2047
01:20:45,740 --> 01:20:46,875
MALARIA, THESE ARE RECENTLY

2048
01:20:46,942 --> 01:20:51,179
PUBLISHED FROM OUR LAB, WE FOUND

2049
01:20:51,246 --> 01:20:54,216
2 [INDISCERNIBLE], AND SPECIFIC,

2050
01:20:54,282 --> 01:20:56,518
AND THE LASTLY, THE RESULT

2051
01:20:56,585 --> 01:20:57,686
QUESTION IS WHERE THE SICKLE

2052
01:20:57,752 --> 01:21:03,858
CELL DEC COME FROM.

2053
01:21:03,925 --> 01:21:05,827
THE 50 POPULATION CLEANING FOR

2054
01:21:05,894 --> 01:21:08,930
SICKLE CELL DEC WAS NOT IN

2055
01:21:08,997 --> 01:21:11,600
AFFRIC AHE WAS IN GREECE AND

2056
01:21:11,666 --> 01:21:12,901
SICKLE SEALS IN GREECE HAVE BEEN

2057
01:21:12,968 --> 01:21:15,203
THERE FOR A LOCK TIME, AND

2058
01:21:15,270 --> 01:21:16,972
SICKLE CELL IN DEC IN PEOPLE IN

2059
01:21:17,038 --> 01:21:18,607
THE SOUTHERN PART OF ITALY AND

2060
01:21:18,673 --> 01:21:20,909
THEY HAVE BEEN THERE FOR A LONG

2061
01:21:20,976 --> 01:21:21,142
TIME.

2062
01:21:21,209 --> 01:21:22,978
SICKLE CELL DISEASE HAVE BEEN

2063
01:21:23,044 --> 01:21:24,946
[INDISCERNIBLE] FOR A VERY LONG

2064
01:21:25,013 --> 01:21:25,146
TIME.

2065
01:21:25,213 --> 01:21:26,915
IF WE ARE [INDISCERNIBLE] SICKLE

2066
01:21:26,982 --> 01:21:29,184
CELL EVOLVE IN AFRICA, LET'S SAY

2067
01:21:29,251 --> 01:21:31,052
20,000 YEARS AGO, HOW DOES THAT

2068
01:21:31,119 --> 01:21:35,390
MUTATION HAPPEN TO GO TO GREECE?

2069
01:21:35,457 --> 01:21:37,292
SO SOMEONE SHOULD HAVE RUN, SWAM

2070
01:21:37,359 --> 01:21:40,128
AND LANDED IN GREECE AND MIXED

2071
01:21:40,195 --> 01:21:41,229
AND LET SICKLE CELL DISEASE IN

2072
01:21:41,296 --> 01:21:43,999
THERE, AND THE SAME PERSON OR

2073
01:21:44,065 --> 01:21:45,267
SISTER OR COUSIN, PROBABLY MOVED

2074
01:21:45,333 --> 01:21:47,068
TO THE MITSD EAST OR INDIA AT

2075
01:21:47,135 --> 01:21:48,470
THE SAME TIME, ACTUALLY WE HAVE

2076
01:21:48,536 --> 01:21:51,706
NO IDEA, WE HAVE NO IDEA

2077
01:21:51,773 --> 01:21:53,074
EVOLUTIONARY POPULATION WIDE HOW

2078
01:21:53,141 --> 01:21:58,513
IT LANDED IN OUR PART OF THE

2079
01:21:58,580 --> 01:21:59,281
WORLD.

2080
01:21:59,347 --> 01:22:00,815
AND WE ARE UNAWARE OF WHERE IT

2081
01:22:00,882 --> 01:22:03,018
COMES FROM IN THE FIRST PLACE.

2082
01:22:03,084 --> 01:22:04,419
SO THOSE ARE SOME STUDIES WE

2083
01:22:04,486 --> 01:22:05,353
KNOW SHOULD BE DONE.

2084
01:22:05,420 --> 01:22:07,555
FOR EXAMPLE WE DID A SIMPLE

2085
01:22:07,622 --> 01:22:08,690
ANALYSIS LOOKING AT THE

2086
01:22:08,757 --> 01:22:09,291
HAPLOTYPE AND YOU SLEEP APNEA

2087
01:22:09,357 --> 01:22:12,394
AND OBESITYY A LOT OF DIVERSITY

2088
01:22:12,460 --> 01:22:14,896
WITHIN 4 OR 5 DIFFERENT GROUP IN

2089
01:22:14,963 --> 01:22:15,430
AFROM FRICCA.

2090
01:22:15,497 --> 01:22:16,865
THIS MEANS THERE HAVE BEEN A LOT

2091
01:22:16,931 --> 01:22:19,167
OF MIXTURE OR MOVEMENTOT

2092
01:22:19,234 --> 01:22:20,702
COMBINATION AROUND IN THAT AREA

2093
01:22:20,769 --> 01:22:22,470
ASK THATY WE HAVEN'T YET

2094
01:22:22,537 --> 01:22:24,306
PROPERLY CAPTURE AND WE KNOW

2095
01:22:24,372 --> 01:22:26,474
THAT ALL THOSE COMBINATION

2096
01:22:26,541 --> 01:22:27,976
LISTENED WITH SINGLE ORIGINAL

2097
01:22:28,043 --> 01:22:29,611
SHOWN BY [INDISCERNIBLE] AND HIS

2098
01:22:29,678 --> 01:22:34,049
PAPER, NOW, WE SHOULD BE ABLE TO

2099
01:22:34,115 --> 01:22:35,750
REFINE THE ORIGINAL SICKLE CELL

2100
01:22:35,817 --> 01:22:37,819
DEC BY USING [INDISCERNIBLE].

2101
01:22:37,886 --> 01:22:39,554
FOR EXAMPLE, THEY ARE CURRENTLY

2102
01:22:39,621 --> 01:22:41,690
[INDISCERNIBLE] FOR A GROUP OF

2103
01:22:41,756 --> 01:22:44,459
PEOPLE THAT LIVE IN SOME PLACE

2104
01:22:44,526 --> 01:22:46,294
TODAY, CALLED CAMEROON 8000

2105
01:22:46,361 --> 01:22:46,995
YEARS AGO.

2106
01:22:47,062 --> 01:22:49,497
IF WE STUDIED THOSE DNA PROPERLY

2107
01:22:49,564 --> 01:22:50,765
BETTER WE COULD KNOW BETTER WHEN

2108
01:22:50,832 --> 01:22:51,800
THE DISEASE IMETS SPONTANEOUS

2109
01:22:51,866 --> 01:22:52,901
ACTIVITY THE POPULATION IN A

2110
01:22:52,967 --> 01:22:54,536
CERTAIN WAY, IN A SIMILAR WAY,

2111
01:22:54,602 --> 01:23:00,208
WE WOULD BE ABLE TO NOX FAMILY

2112
01:23:00,275 --> 01:23:01,009
--NAVIGATE

2113
01:23:01,076 --> 01:23:02,310
THE PATH OF MIGRATION WITHIN THE

2114
01:23:02,377 --> 01:23:04,245
COUNTRY AND NOW THE CONTINENT.

2115
01:23:04,312 --> 01:23:06,247
SO I HOPE I CONVINCED YOU OF 3

2116
01:23:06,314 --> 01:23:08,516
THINGS ISSUES THE FIRST IS THAT

2117
01:23:08,583 --> 01:23:10,018
WE USE IME NATIONAL LIBRARY OF

2118
01:23:10,085 --> 01:23:11,519
MEDICINIC VARIATION IN AFRICA TO

2119
01:23:11,586 --> 01:23:15,023
DISCOVER A NEW VARIANT AT

2120
01:23:15,090 --> 01:23:16,091
MODIFYING THE CLINICAL

2121
01:23:16,157 --> 01:23:16,925
EXPRESSION OF SICKLE CELL

2122
01:23:16,991 --> 01:23:18,760
DISEASE ISSUE THE SECOND, THE

2123
01:23:18,827 --> 01:23:20,595
BEST MODIFIER OF SICKLE CELL

2124
01:23:20,662 --> 01:23:22,430
DISEASE AND [INDISCERNIBLE] BUT

2125
01:23:22,497 --> 01:23:24,499
THE MISSION IRRITABILITY OF THE

2126
01:23:24,566 --> 01:23:27,602
BETA GLOBIN CAN BE FOUND IN

2127
01:23:27,669 --> 01:23:30,305
AFRICAN GENOMES AND CAN OPEN UP

2128
01:23:30,372 --> 01:23:31,106
FOR MANIPULATION, THE THIRD IS

2129
01:23:31,172 --> 01:23:33,775
THAT THERE IS STILL AN AREA THAT

2130
01:23:33,842 --> 01:23:35,777
YOU CAN EXPLORE FOR THE AREA OF

2131
01:23:35,844 --> 01:23:37,846
SICKLE CELL DISEASE, BUT ALSO

2132
01:23:37,912 --> 01:23:39,614
THE EVOLUTIONARY OF SICKLE CELL

2133
01:23:39,681 --> 01:23:40,548
DISEASE, ESPECIALLY IN THE

2134
01:23:40,615 --> 01:23:42,417
GENOME, THAT CAN OPEN UP AGAIN A

2135
01:23:42,484 --> 01:23:44,452
NEW TARGET FOR THERAPEUTICS THAT

2136
01:23:44,519 --> 01:23:45,887
SHOULD GO AS THE WAY WE IMAGINE

2137
01:23:45,954 --> 01:23:47,055
IT AS SCIENTISTS AND WE HOPE

2138
01:23:47,122 --> 01:23:49,057
THAT IN A COUPLE YEARS IT WILL

2139
01:23:49,124 --> 01:23:50,825
BE THE WORLD THE WAY WE LEAVE IT

2140
01:23:50,892 --> 01:23:54,763
FOR THE PATIENTS OF SICKLE CELL

2141
01:23:54,829 --> 01:24:05,340
DISEASE, THANK YOU VERY MUCH.

2142
01:24:23,725 --> 01:24:24,025
>> GREAT.

2143
01:24:24,092 --> 01:24:24,926
THANKS A LOT.

2144
01:24:24,993 --> 01:24:27,028
WE HAVE A HAND HELD FLOATING

2145
01:24:27,095 --> 01:24:27,395
AROUND.

2146
01:24:27,462 --> 01:24:28,730
THOSE WERE REALLY FABULOUS

2147
01:24:28,797 --> 01:24:29,764
PRESENTATIONS FROM BOTH OF OUR

2148
01:24:29,831 --> 01:24:34,169
SPEAKERS TODAY AND WELL'S JUST A

2149
01:24:34,235 --> 01:24:38,506
WHOLE PANOPLY OF QUESTIONS THAT

2150
01:24:38,573 --> 01:24:40,141
HAVE BEEN SUBMITTED BOTH ONLINE

2151
01:24:40,208 --> 01:24:42,577
AND I KNOW THERE ARE PROBABLY

2152
01:24:42,644 --> 01:24:44,512
SOME INQUIRING MINDS HERE IN THE

2153
01:24:44,579 --> 01:24:50,385
ROOM JUST WAITING TO POSE THEIR

2154
01:24:50,452 --> 01:24:50,952
QUESTIONS AS WELL.

2155
01:24:51,019 --> 01:24:55,523
O I'LL TART WITH 1 THAT IS TIME

2156
01:24:55,590 --> 01:24:58,259
HONORED, NOT TO MAKE A PUN,

2157
01:24:58,326 --> 01:25:01,963
QUESTION, WITH REGARD TO THE

2158
01:25:02,030 --> 01:25:04,599
TREATMENT OF SICKLE CELL DISEASE

2159
01:25:04,666 --> 01:25:06,434
IN THE UNITED STATES AND PERHAPS

2160
01:25:06,501 --> 01:25:09,370
THIS WOULD GO TO DR. FITZHUGH

2161
01:25:09,437 --> 01:25:12,040
FIRST BUT I THINK DR. WONKAM MAY

2162
01:25:12,106 --> 01:25:14,309
HAVE THOUGHTS ABOUT IT, TOO.

2163
01:25:14,375 --> 01:25:17,812
AND THAT WOULD BE WHAT IS THE

2164
01:25:17,879 --> 01:25:20,248
OPTIMAL AGE FOR TRANSPLANTATION

2165
01:25:20,315 --> 01:25:21,316
FOR SICKLE CELL DISEASE, JUST

2166
01:25:21,382 --> 01:25:25,620
BASED ON THE FACT THAT

2167
01:25:25,687 --> 01:25:26,154
HEMATOPOIETIC STEM CELL

2168
01:25:26,221 --> 01:25:27,388
TRANSPLANT IS SOMETHING THAT'S

2169
01:25:27,455 --> 01:25:30,458
BEING DONE A LOT IN PATIENTS

2170
01:25:30,525 --> 01:25:31,726
WITH PRIMARY IMMUNO DEFICIENCY

2171
01:25:31,793 --> 01:25:34,963
DISEASES AND OFTEN TIMES THE

2172
01:25:35,029 --> 01:25:35,997
PREFERENCE IS TO TRANSPLANT

2173
01:25:36,064 --> 01:25:38,733
THOSE PATIENTS AS EARLY AS

2174
01:25:38,800 --> 01:25:40,301
POSSIBLE BECAUSE THE OUTCOMES

2175
01:25:40,368 --> 01:25:42,670
OFTEN TIMES ARE A LOT BETTER,

2176
01:25:42,737 --> 01:25:44,506
THE EARLIER 1 INTERVENES.

2177
01:25:44,572 --> 01:25:47,342
SO HAVE THERE BEEN ANY STUDIES

2178
01:25:47,408 --> 01:25:50,545
DONE IN YOUNG CHILDREN WITH

2179
01:25:50,612 --> 01:25:51,746
REGARD TO TRANSPLANT AND ARE

2180
01:25:51,813 --> 01:25:55,149
THERE ANY DATA WITH REGARD TO

2181
01:25:55,216 --> 01:25:56,117
OPTIMAL AGE.

2182
01:25:56,184 --> 01:25:57,185
NTHAT'S A GREAT QUESTION AND THE

2183
01:25:57,252 --> 01:25:59,988
WAY I ANSWER IT IS IT MIGHT NOT

2184
01:26:00,054 --> 01:26:01,055
BE HOW EVERYBODY WOULD ANSWER IT

2185
01:26:01,122 --> 01:26:03,458
BUT I CAN SAY THAT THE ISSUE

2186
01:26:03,525 --> 01:26:04,893
WITH THIS QUESTION IN SICKLE

2187
01:26:04,959 --> 01:26:05,960
CELL DISEASE IS SURVIVAL IN THE

2188
01:26:06,027 --> 01:26:07,862
UNITED STATES IS REALLY, REALLY

2189
01:26:07,929 --> 01:26:08,162
HIGH.

2190
01:26:08,229 --> 01:26:09,497
NINETY-EIGHT% OF CHILDREN WILL

2191
01:26:09,564 --> 01:26:10,698
SURVIVE TO ADULTHOOD WITH SICKLE

2192
01:26:10,765 --> 01:26:13,568
CELL DISEASE, SO IF YOU HAVE ANY

2193
01:26:13,635 --> 01:26:15,970
SIGNIFICANT MORTALITY ASSOCIATED

2194
01:26:16,037 --> 01:26:17,438
WITH THESE, INVESTIGATIONAL

2195
01:26:17,505 --> 01:26:18,673
CURATIVE THERAPIES, IT'S A BIG

2196
01:26:18,740 --> 01:26:21,109
DEAL IN CHILDREN, AND YOU ALSO

2197
01:26:21,175 --> 01:26:23,077
CAN'T PREDICT WHO WILL HAVE THE

2198
01:26:23,144 --> 01:26:25,213
MORE SEVERE DISEASE, SO, IT'S

2199
01:26:25,280 --> 01:26:27,682
NOT LIKE YOU CAN--YOU CAN LOOK

2200
01:26:27,749 --> 01:26:28,883
AT THIS HEALTHY CHILD AND SAY

2201
01:26:28,950 --> 01:26:30,818
YOU HAVE THIS GENETIC RISK

2202
01:26:30,885 --> 01:26:32,353
FACTOR, YOU WILL HAVE SEVERE

2203
01:26:32,420 --> 01:26:33,621
DISEASE, YOU JUSTIFY HAVING THIS

2204
01:26:33,688 --> 01:26:34,923
TRANSPLANT AT SUCH A YOUNG AGE.

2205
01:26:34,989 --> 01:26:36,791
THERE HAVE BEEN STUDIES TO SHOW

2206
01:26:36,858 --> 01:26:38,226
WITH DATA GOING BACK TO THE

2207
01:26:38,293 --> 01:26:40,428
1980S THAT THE YOUNGER PASHTS DO

2208
01:26:40,495 --> 01:26:44,799
HAVE BETTER OUTCOMES BUT NOW

2209
01:26:44,866 --> 01:26:47,035
THAT WE HAVE NONMILE O ABLAISIVE

2210
01:26:47,101 --> 01:26:47,969
CONDITIONING, AND ENOUGH THAT

2211
01:26:48,036 --> 01:26:49,837
I'VE SHOWN THE SURVIVAL IN

2212
01:26:49,904 --> 01:26:51,239
ADULTS NOW, IT'S A CONTROVERSIAL

2213
01:26:51,306 --> 01:26:53,575
QUESTION, THE NEW GENE THERAPY,

2214
01:26:53,641 --> 01:26:55,109
EDITING STUDIES HAVE BEEN

2215
01:26:55,176 --> 01:26:57,045
ENCLOUDING CHILDREN, AND THERE

2216
01:26:57,111 --> 01:27:00,782
ARE SOME RISKS ASSOCIATED WITH

2217
01:27:00,848 --> 01:27:01,916
TRANSPLANTING ADULTS AND ALSO

2218
01:27:01,983 --> 01:27:04,085
ONCE PATIENTS ARE ON DIALYSIS

2219
01:27:04,152 --> 01:27:05,954
AND HAVE SEVERE ORGAN

2220
01:27:06,020 --> 01:27:06,988
DYSFUNCTION, IT'S NOT

2221
01:27:07,055 --> 01:27:09,290
REVERSIBLE, SO MY FREE RADICALS

2222
01:27:09,357 --> 01:27:11,092
FERENCE, SINCE I'M GOING FIRST

2223
01:27:11,159 --> 01:27:12,760
IN HUMAN STUDY SYSTEM TO INCLUDE

2224
01:27:12,827 --> 01:27:14,696
ADULTS BUT WHEN WE GET MORE DATA

2225
01:27:14,762 --> 01:27:16,664
THE GOAL WOULD BE TO START

2226
01:27:16,731 --> 01:27:20,101
TRANSPLANTING CHILDREN, WITH THE

2227
01:27:20,168 --> 01:27:22,170
EFFICACY AND TOXICITY PROFILE

2228
01:27:22,236 --> 01:27:23,605
LOOKS REALLY GOOD NAND FROM WHAT

2229
01:27:23,671 --> 01:27:25,406
YOU SAID IT MAY BE A FOLLOW UP

2230
01:27:25,473 --> 01:27:26,741
QUESTION THAT 1 COULD MAYBE FIND

2231
01:27:26,808 --> 01:27:30,478
SOME SORT OF A COMPROMISE

2232
01:27:30,545 --> 01:27:32,313
POSITION, SOME AGE SOUNDS LIKE

2233
01:27:32,380 --> 01:27:34,048
FOR VERY YOUNG CHILDREN AS WOULD

2234
01:27:34,115 --> 01:27:36,784
BE DONE WITH PRIMARY IMMUNO

2235
01:27:36,851 --> 01:27:37,719
DEFICIENCY DISEASES BECAUSE THE

2236
01:27:37,785 --> 01:27:39,020
CHILDREN LIVE AT LEAST THROUGH

2237
01:27:39,087 --> 01:27:42,156
THAT AGE GROUP, IT'S PROBABLY

2238
01:27:42,223 --> 01:27:44,959
NOT OPTIMAL BUT PERHAPS LATER IN

2239
01:27:45,026 --> 01:27:46,327
CHILDHOOD OR ADOLESCENCE, AT

2240
01:27:46,394 --> 01:27:50,365
SOME POINT BEFORE MAJOR ORGAN

2241
01:27:50,431 --> 01:27:56,104
DAMAGE OCCURS BUT AFTER THE

2242
01:27:56,170 --> 01:27:57,972
NORMAL AGE CURVE, THAT MAY BE

2243
01:27:58,039 --> 01:28:00,608
SOMEWHERE IN THERE, 1 COULD FIND

2244
01:28:00,675 --> 01:28:01,175
AN OPTIMAL TIME.

2245
01:28:01,242 --> 01:28:03,344
>> I DO THINK IT'S ALSO

2246
01:28:03,411 --> 01:28:04,278
IMPORTANT TO INFORM, I CAN'T

2247
01:28:04,345 --> 01:28:06,047
HAVE THE DOCTOR SAY THIS IS WHAT

2248
01:28:06,114 --> 01:28:07,782
YOU SHOULD DO FOR YOUR CHILD, SO

2249
01:28:07,849 --> 01:28:09,417
I THINK IT'S IMPORTANT TO LET

2250
01:28:09,484 --> 01:28:12,186
FAMILIES BEEN THIS AND WITH

2251
01:28:12,253 --> 01:28:13,254
THEIR OWN NONTRANSPLANT

2252
01:28:13,321 --> 01:28:13,921
PHYSICIANS, FAMILY MEMBERS TO

2253
01:28:13,988 --> 01:28:15,023
RESPECT COME UP WITH THE

2254
01:28:15,089 --> 01:28:17,358
DECISION, I CAN SAY WE DO HAVE A

2255
01:28:17,425 --> 01:28:18,960
PATIENT THAT WAS TRANSPLANTED AS

2256
01:28:19,027 --> 01:28:22,363
A CHILD AND HAD NONMILE ABLATIVE

2257
01:28:22,430 --> 01:28:23,131
CONDITIONING AND THE TRANSPLANT

2258
01:28:23,197 --> 01:28:24,565
DIDN'T WORK AND WE'RE GETTING

2259
01:28:24,632 --> 01:28:26,668
READY TO RETRAN PLANT HIM BUT HE

2260
01:28:26,734 --> 01:28:28,403
LOST HIS FERTILITY AND HIS

2261
01:28:28,469 --> 01:28:29,570
PARENTS FEEL VERY GUILT NOW THAT

2262
01:28:29,637 --> 01:28:31,005
WE WENT THROUGH THAT AS A CHILD

2263
01:28:31,072 --> 01:28:32,407
AND IS NOT GOING TO BE ABLE TO

2264
01:28:32,473 --> 01:28:34,142
HAVE CHILDREN ON HIS OWN.

2265
01:28:34,208 --> 01:28:36,744
SO IT'S JUST A DECISION THAT

2266
01:28:36,811 --> 01:28:38,012
IT'S IMPORTANT NOW THAT WE HAVE

2267
01:28:38,079 --> 01:28:39,781
ALL DIFFERENT TYPES OF CURATIVE

2268
01:28:39,847 --> 01:28:41,649
THERAPIES AND YOU KNOW TRUGS

2269
01:28:41,716 --> 01:28:42,717
THAT ARE BEING STUDIED, I THINK

2270
01:28:42,784 --> 01:28:44,052
IT'S IMPORTANT TO KEEP FAMILIES

2271
01:28:44,118 --> 01:28:45,453
AWARE AND LET THEM BE THAT

2272
01:28:45,520 --> 01:28:48,856
TRANSPLANT IS AN OPTION.

2273
01:28:48,923 --> 01:28:49,657
NOKAY, WELL THANK YOU VERY MUCH.

2274
01:28:49,724 --> 01:28:51,959
SO I HAVE ANOTHER QUESTION FROM

2275
01:28:52,026 --> 01:28:56,064
1 OF OUR ONLINE VIEWERS, WHO

2276
01:28:56,130 --> 01:28:59,000
WANTS TO JUST EXPRESS THE VIEW

2277
01:28:59,067 --> 01:29:00,401
THAT THIS WAS A IMRAIT

2278
01:29:00,468 --> 01:29:01,502
PRESENTATION FROM BOTH OF THE

2279
01:29:01,569 --> 01:29:02,804
SPEAKERS AND WISHING TO ASK, IF

2280
01:29:02,870 --> 01:29:06,074
IT IS POSSIBLE TO USE CELL FREE

2281
01:29:06,140 --> 01:29:12,513
DNA FOR THE DIAGNOSIS OF SICKLE

2282
01:29:12,580 --> 01:29:12,980
CELL DISEASE?

2283
01:29:13,047 --> 01:29:17,051
>> YES, I THINK THAT SHOULD BE

2284
01:29:17,118 --> 01:29:23,558
THE WAY OF EARLY DETECTION, CELL

2285
01:29:23,624 --> 01:29:26,728
FREE, SO THE ANSWER IS YES.

2286
01:29:26,794 --> 01:29:27,895
>> OKAY, SO THAT COULD BE

2287
01:29:27,962 --> 01:29:29,931
SOMETHING THAT'S OFFERED IN THE

2288
01:29:29,997 --> 01:29:37,138
NURSERY, IN THE  NEW BORN NURSEY

2289
01:29:37,205 --> 01:29:39,774
NYES, CERTAINLY I HOPE THAT IT

2290
01:29:39,841 --> 01:29:42,744
WILL EXTEND TO PRENATAL

2291
01:29:42,810 --> 01:29:44,112
TREATMENT, IN UTERO TREATMENT,

2292
01:29:44,178 --> 01:29:45,179
SPECIFICALLY IF WE'RE ABLE TO

2293
01:29:45,246 --> 01:29:51,018
HAVE A MUCH MORE SAFER

2294
01:29:51,085 --> 01:29:51,986
[INDISCERNIBLE] APPROACH ANDS

2295
01:29:52,053 --> 01:29:54,722
SPECIFIC IN VIVO APPROACHES IN

2296
01:29:54,789 --> 01:29:57,024
WHICH CASE THE CELL-FREE DNA

2297
01:29:57,091 --> 01:29:58,292
WILL HAVE GREAT IMPORTANCE

2298
01:29:58,359 --> 01:30:00,695
BECAUSE YOU CAN IDENTIFY THE

2299
01:30:00,762 --> 01:30:04,365
CHILD AREA AS SOON AS POSSIBLE,

2300
01:30:04,432 --> 01:30:05,767
REMEMBER MY ROLE IS TO SPEAK TO

2301
01:30:05,833 --> 01:30:08,402
THE WORLD THE WAY IT SHOULD BE,

2302
01:30:08,469 --> 01:30:11,506
IT COULD BE, BUT THE WAY IT IS

2303
01:30:11,572 --> 01:30:11,672
NOT.

2304
01:30:11,739 --> 01:30:12,907
>> YES, INDEED.

2305
01:30:12,974 --> 01:30:13,141
INDEED.

2306
01:30:13,207 --> 01:30:16,944
OKAY, SO, HERE'S A QUESTION THAT

2307
01:30:17,011 --> 01:30:18,880
SORT OF BRINGS TOGETHER SOME OF

2308
01:30:18,946 --> 01:30:21,649
WHAT DR. FITZHUGH WAS TALKING

2309
01:30:21,716 --> 01:30:24,519
ABOUT THEN SOME OF THE MORE

2310
01:30:24,585 --> 01:30:26,721
GLOBAL CONCERNS THAT DR. WONKAM

2311
01:30:26,788 --> 01:30:29,824
MENTIONED, SO, WHAT ARE THE

2312
01:30:29,891 --> 01:30:34,662
COMPARATIVE COSTS OF HAPPEN LO

2313
01:30:34,729 --> 01:30:37,064
TRANSPLANTATION IN DIFFERENT

2314
01:30:37,131 --> 01:30:37,331
COUNTRIES?

2315
01:30:37,398 --> 01:30:39,500
>> YEAH, SO, I DON'T KNOW THAT

2316
01:30:39,567 --> 01:30:41,002
THE HAPPEN LO IDENTICAL

2317
01:30:41,068 --> 01:30:43,204
TRANSPLANTS BEING DONE IN TOO

2318
01:30:43,271 --> 01:30:46,174
MANY COUNTRIES ESPECIALLY NOT IN

2319
01:30:46,240 --> 01:30:47,308
SUB-SAHARAN AFRICA THAT I'VE

2320
01:30:47,375 --> 01:30:47,775
HEARD.

2321
01:30:47,842 --> 01:30:49,277
IT'S PROBABLY BETWEEN 2 AND

2322
01:30:49,343 --> 01:30:52,413
$400,000 IN THE U.S., BUT THAT

2323
01:30:52,480 --> 01:30:53,948
COMPARES TO GENE THERAPY AND

2324
01:30:54,015 --> 01:30:57,051
GENE EDITING THAT WERE JUST

2325
01:30:57,118 --> 01:30:59,654
APPROVED, THEIR ESTIMATED COST

2326
01:30:59,720 --> 01:31:01,189
IS 2-$3 MILLION, BUT EVEN THE

2327
01:31:01,255 --> 01:31:02,356
TYPE OF TRANSPLANT THAT WE'RE

2328
01:31:02,423 --> 01:31:04,792
DOING NOW WILL BE TOO EXPENSIVE

2329
01:31:04,859 --> 01:31:07,295
TO BE ABLE TO APPLY IT IN THESE

2330
01:31:07,361 --> 01:31:09,363
REGIONS IN AFRICA, SO THERE'S A

2331
01:31:09,430 --> 01:31:11,799
LOT THAT HAS TO BE DONE TO MAKE

2332
01:31:11,866 --> 01:31:13,434
IT MORE AFFORDABLE AND

2333
01:31:13,501 --> 01:31:15,970
APPLICABLE TO PLACES ALL OVER

2334
01:31:16,037 --> 01:31:16,304
THE WORLD.

2335
01:31:16,370 --> 01:31:18,906
>> SO JUST AS A FOLLOW UP

2336
01:31:18,973 --> 01:31:20,675
QUESTION, YOU MENTIONED THE

2337
01:31:20,741 --> 01:31:22,643
COMPARATIVE COST OF JEEP THERAPY

2338
01:31:22,710 --> 01:31:25,746
OR YEEN EDITING AS BEING ON THE

2339
01:31:25,813 --> 01:31:29,050
ORDER OF AT LEAST, I THINK YOU

2340
01:31:29,116 --> 01:31:33,354
SAID 10 FOLD, THE COST OF WHAT A

2341
01:31:33,421 --> 01:31:38,326
TRANSPLANT WOULD BE BUT YET 1

2342
01:31:38,392 --> 01:31:39,627
MIGHT THINK THAT THE EDITING

2343
01:31:39,694 --> 01:31:43,264
WOULD NOT HAVE THE SAME ISSUES

2344
01:31:43,331 --> 01:31:46,901
WITH REGARD TO

2345
01:31:46,968 --> 01:31:47,835
IMMUNOSUPPRESSION, LATER ON AND

2346
01:31:47,902 --> 01:31:49,136
WITH THE POSSIBILITY OF

2347
01:31:49,203 --> 01:31:51,205
INFECTION, AND ALL OF THE

2348
01:31:51,272 --> 01:31:52,273
COMPLI--MAYBE NOT ALL OF, BUT

2349
01:31:52,340 --> 01:31:57,144
MANY OF THE COMPLICATIONS, MOST

2350
01:31:57,211 --> 01:31:57,445
TRANSPLANT.

2351
01:31:57,511 --> 01:31:59,513
SO, WHY IS IT SO MUCH MORE

2352
01:31:59,580 --> 01:31:59,780
EXPENSIVE?

2353
01:31:59,847 --> 01:32:02,783
>> YEAH, THAT'S A GOOD QUESTION

2354
01:32:02,850 --> 01:32:03,317
FOR THESE COMPANIES.

2355
01:32:03,384 --> 01:32:06,087
I THINK A LOT OF THE WORK IS

2356
01:32:06,153 --> 01:32:07,188
DONE EXVERIFY O SO YOU'RE HAVING

2357
01:32:07,255 --> 01:32:09,624
TO DO ALL THESE COMPLICATED

2358
01:32:09,690 --> 01:32:11,926
THINGS TO EDIT THE YEENS AND DO

2359
01:32:11,993 --> 01:32:13,461
THE EDITING AND GENE THERAPY, I

2360
01:32:13,527 --> 01:32:15,429
CAN SAY I KNOW THAT PEOPLE ARE

2361
01:32:15,496 --> 01:32:16,864
WORKING ON AN IN VIVO OOH PROACH

2362
01:32:16,931 --> 01:32:18,699
SO THAT ALL YOU HAVE TO DO IS

2363
01:32:18,766 --> 01:32:20,201
JUST INJECT THE GENE AND YOU CAN

2364
01:32:20,268 --> 01:32:21,569
KILL THEM THAT WAY AND POTENTIA

2365
01:32:21,636 --> 01:32:23,304
WILY AND THAT WOULD BE A WHOLE

2366
01:32:23,371 --> 01:32:24,372
LOT CHEAPER THAN WHAT WE'RE

2367
01:32:24,438 --> 01:32:24,805
DOING NOW.

2368
01:32:24,872 --> 01:32:27,975
SO THIS IS JUST THE CURRENT COST

2369
01:32:28,042 --> 01:32:28,910
BUT FOR THE FEATURE, THE COST

2370
01:32:28,976 --> 01:32:30,912
WILL HAVE TO COME DOWN EVEN FOR

2371
01:32:30,978 --> 01:32:33,214
AMERICANS TO BE ABLE TO GET GENE

2372
01:32:33,281 --> 01:32:35,917
THERAPY OR GENE EDITING.

2373
01:32:35,983 --> 01:32:36,350
NYES, YES.

2374
01:32:36,417 --> 01:32:46,761
YEAH, OKAY, WELL, THANK YOU FOR

2375
01:32:46,827 --> 01:32:46,994
THAT.

2376
01:32:47,061 --> 01:32:47,728
HERE'S ANOTHER QUESTION THAT

2377
01:32:47,795 --> 01:32:52,166
CAME IN A WHILE AGO, C WONKAM

2378
01:32:52,233 --> 01:32:56,437
HAS TALKED ALET  ALET--LITTLE BT

2379
01:32:56,504 --> 01:32:58,506
ABOUT THE POSSIBILITY OF WHETHER

2380
01:32:58,572 --> 01:33:01,976
SICKLE CELL DISEASE WENT FROM

2381
01:33:02,043 --> 01:33:03,644
AFRICA TO INDIA OR GREECE OR ALL

2382
01:33:03,711 --> 01:33:06,914
OF THE OTHER COUNTRIES SO ARE

2383
01:33:06,981 --> 01:33:07,715
THERE CLINICAL DIFFERENCES

2384
01:33:07,782 --> 01:33:09,583
BETWEEN SICKLE CELL THAT IS SEEN

2385
01:33:09,650 --> 01:33:11,919
IN SOME OF THESE OTHER

2386
01:33:11,986 --> 01:33:14,522
COUNTRIES, GREASE OR INDIA OR

2387
01:33:14,588 --> 01:33:15,623
OTHER PLACES?

2388
01:33:15,690 --> 01:33:21,963
VERSUS WHAT HAS BEEN OBSERVED IN

2389
01:33:22,029 --> 01:33:24,799
THE AFRICAN POPULATION?

2390
01:33:24,865 --> 01:33:28,502
>> THE SWU IS YES, IN AFRICA

2391
01:33:28,569 --> 01:33:30,204
THERE ARE DIFFERENTIA PLACES,

2392
01:33:30,271 --> 01:33:32,807
BUT AT THIS TIME, THE WAY IT'S

2393
01:33:32,873 --> 01:33:34,342
CLASSIFIED IS ON 4 DIFFERENT

2394
01:33:34,408 --> 01:33:35,943
HAPLOTYPE BACKGROUND, THE OLDEST

2395
01:33:36,010 --> 01:33:39,380
1 WILL BE CAMEROON, AND THEN

2396
01:33:39,447 --> 01:33:40,448
[INDISCERNIBLE], AND THEN

2397
01:33:40,514 --> 01:33:42,817
[INDISCERNIBLE], AND THEN

2398
01:33:42,883 --> 01:33:46,220
[INDISCERNIBLE] AND THEN SENEGAL

2399
01:33:46,287 --> 01:33:51,459
TYPE, THE TYPE FOUND IN SENEGAL,

2400
01:33:51,525 --> 01:33:51,892
ASSOCIATED INCREASED

2401
01:33:51,959 --> 01:33:53,594
[INDISCERNIBLE], SO YOU WILL BE

2402
01:33:53,661 --> 01:33:55,062
MUCH LESS [INDISCERNIBLE], AND

2403
01:33:55,129 --> 01:33:56,597
THAT VERY SAME HAPLOTYPE IS

2404
01:33:56,664 --> 01:33:59,000
FOUND IN SICKLE SALE DISEASE

2405
01:33:59,066 --> 01:34:02,403
THIS PATIENT MOSTLY FROM INDIA,

2406
01:34:02,470 --> 01:34:03,371
SO THE FIRST [INDISCERNIBLE]

2407
01:34:03,437 --> 01:34:06,007
VARIES BECAUSE OF THE GENOMICS

2408
01:34:06,073 --> 01:34:07,975
BACKGROUND OF SICKLE CELL DEC,

2409
01:34:08,042 --> 01:34:09,477
SO IT WILL ALSO VARY BECAUSE OF

2410
01:34:09,543 --> 01:34:11,946
THE ENVIRONMENT THAT ARE THE

2411
01:34:12,013 --> 01:34:13,314
STRONGEST MODIFIERS AND THAT

2412
01:34:13,381 --> 01:34:14,849
ENVIRONMENT IN AFRICA IS MARKED

2413
01:34:14,915 --> 01:34:16,550
BY THE [INDISCERNIBLE], BY THE

2414
01:34:16,617 --> 01:34:20,955
[INDISCERNIBLE] BY THE RATE OF

2415
01:34:21,022 --> 01:34:25,393
BACTERIAEREMMIA, AND BY THE

2416
01:34:25,459 --> 01:34:27,762
[INDISCERNIBLE] OF THE

2417
01:34:27,828 --> 01:34:29,063
[INDISCERNIBLE] AND MUCH MORE

2418
01:34:29,130 --> 01:34:29,997
SIGNIFICANT THAN OTHERS THAT YOU

2419
01:34:30,064 --> 01:34:32,633
WILL NOT SEE IMMEDIATELY SO NOT

2420
01:34:32,700 --> 01:34:35,336
NECESSARILY IMMEDIATELY BUT AT

2421
01:34:35,403 --> 01:34:37,405
LEAST AND OF COURSE THE

2422
01:34:37,471 --> 01:34:40,941
STRONGEST MODIFIER IS THE ACCESS

2423
01:34:41,008 --> 01:34:43,344
TO CARE, [INDISCERNIBLE] NOT YET

2424
01:34:43,411 --> 01:34:45,513
IMPLEMENTED ACROSS MANY AFRICAN

2425
01:34:45,579 --> 01:34:50,418
COUNTRY FROM THE LAST COUNT,

2426
01:34:50,484 --> 01:34:51,218
PENICILLIN, PROPHYLAXIS ACCESS

2427
01:34:51,285 --> 01:34:55,723
WHICH IS NOT WIDELY IMPLEMENTED

2428
01:34:55,790 --> 01:35:04,498
AND ACCESS TO  HIDE ROXYUREIA IS

2429
01:35:04,565 --> 01:35:04,799
CONTINUING.

2430
01:35:04,865 --> 01:35:06,400
NSO ANY DATA WITH REGARD TO

2431
01:35:06,467 --> 01:35:11,038
THESE HAPLOTYPES THAT YOU

2432
01:35:11,105 --> 01:35:12,540
MENTIONED THAT YOU WOULD SUGGEST

2433
01:35:12,606 --> 01:35:16,444
IN CERTAIN PARTS OF AFRICA OR

2434
01:35:16,510 --> 01:35:18,712
WHATEVER, THAT THERE'S BEEN ANY

2435
01:35:18,779 --> 01:35:20,481
SELECTION FOR 1 OR ANOTHER

2436
01:35:20,548 --> 01:35:22,016
HAPLOTYPE IN TERMS EVER, I FIST

2437
01:35:22,083 --> 01:35:23,517
THERE HAVE BEEN JUST BY VIRTUE

2438
01:35:23,584 --> 01:35:26,287
OF THE PRESENCE OF MALARIA AND

2439
01:35:26,353 --> 01:35:27,822
THESE OTHER FACTORS THAT YOU'VE

2440
01:35:27,888 --> 01:35:30,491
TALKED ABOUT, BUT WITH THE FETAL

2441
01:35:30,558 --> 01:35:31,892
HEMODPLOABIN IT WOULD SEEM LIKE

2442
01:35:31,959 --> 01:35:38,165
MAYBE THAT'S SORT OF A COUNTER

2443
01:35:38,232 --> 01:35:39,800
VAILING PROCESS THAT WOULD BE

2444
01:35:39,867 --> 01:35:42,436
SELECTED FOR.

2445
01:35:42,503 --> 01:35:43,370
NOH, YEAH, THAT'S, MAYBE THEY

2446
01:35:43,437 --> 01:35:48,476
ARE TRULY TO YOUR QUESTION, THE

2447
01:35:48,542 --> 01:35:49,910
FIRST IS HAPLOTYPE, TO THE

2448
01:35:49,977 --> 01:35:54,849
GEOGRAPHY, I WOULD SAY YES,

2449
01:35:54,915 --> 01:35:56,984
ACTUALLY THE--1 OF THE 15--ABOUT

2450
01:35:57,051 --> 01:35:58,853
10 YEARS AGO WHO STUDIED THE

2451
01:35:58,919 --> 01:35:59,820
GLOBAL DISTRIBUTION OF

2452
01:35:59,887 --> 01:36:01,322
HAPLOTYPE, WHEN WE REALIZE THAT

2453
01:36:01,388 --> 01:36:04,558
IN A SINGLE COUNTRY AT LEAST 2

2454
01:36:04,625 --> 01:36:05,493
COUNTRY, CAMEROON, EI DIDN'T

2455
01:36:05,559 --> 01:36:06,794
WANT AND SUDAN THEY WERE ALL

2456
01:36:06,861 --> 01:36:07,962
THERE, IT WAS BASED ON THAT,

2457
01:36:08,028 --> 01:36:10,397
THAT WE PUT OUR DATA HYPOTHESIS

2458
01:36:10,464 --> 01:36:13,501
THAT THERE IS A SINGLE WHOLE

2459
01:36:13,567 --> 01:36:14,368
GENOME SINGLE SICKLE CELL

2460
01:36:14,435 --> 01:36:16,670
DISEASE, BUT IF WE LOOK

2461
01:36:16,737 --> 01:36:21,876
GROSSLYOT WESTERN PART OF AFFRIC

2462
01:36:21,942 --> 01:36:24,612
ATHE HAPLOTYPE IS THE MOST

2463
01:36:24,678 --> 01:36:25,913
COMMON, SENEGAL HAPLOTYPE IS

2464
01:36:25,980 --> 01:36:27,882
REALLY RESTRICTED TO THE EASTERN

2465
01:36:27,948 --> 01:36:31,986
PART OF AFFRIC ATHE CAMEROON IS

2466
01:36:32,052 --> 01:36:34,221
BETWEEN SUDAN AND CAMEROON AND

2467
01:36:34,288 --> 01:36:35,456
THAT SPECIFIC CORRIDOR.

2468
01:36:35,523 --> 01:36:36,857
THE SECONDLY OF YOUR QUESTION IS

2469
01:36:36,924 --> 01:36:41,328
THEN THE SELECTION THAT MAY HAVE

2470
01:36:41,395 --> 01:36:43,297
AND REACHED SOME VARIANT

2471
01:36:43,364 --> 01:36:44,231
[INDISCERNIBLE] FOR THE WORKS

2472
01:36:44,298 --> 01:36:46,233
FOR EXAMPLE, THE VARIANT FOUND

2473
01:36:46,300 --> 01:36:50,538
IN THE HAPLOTYPE, IS THERE ANY

2474
01:36:50,604 --> 01:36:52,072
INDICATION THAT IT HAS BEEN

2475
01:36:52,139 --> 01:36:53,707
SELECTED IN WEST AFRICA, BUT A

2476
01:36:53,774 --> 01:36:56,577
STUDY THAT SHOULD BE DONE.

2477
01:36:56,644 --> 01:36:57,978
>> ALL RIGHT, WELL THANK YOU

2478
01:36:58,045 --> 01:37:04,451
VERY MUCH FOR THAT.

2479
01:37:04,518 --> 01:37:08,956
OKAY, NOW HERE'S A QUESTION FROM

2480
01:37:09,023 --> 01:37:11,292
THE PAST, THE DISTANT PAST, I

2481
01:37:11,358 --> 01:37:12,293
THINK.

2482
01:37:12,359 --> 01:37:13,894
SO THIS IS A QUESTION WITH

2483
01:37:13,961 --> 01:37:16,897
HAVING TO DO WITH WHETHER THERE

2484
01:37:16,964 --> 01:37:18,832
ARE ANY PHARMAICOLOGGIC AGENT

2485
01:37:18,899 --> 01:37:21,802
COULD HAVE AN EFFECT ON THE

2486
01:37:21,869 --> 01:37:23,771
FLEXIBILITY OF SICKLED RED CELLS

2487
01:37:23,837 --> 01:37:25,272
THAT WOULD HAVE ANY CRUCIATE

2488
01:37:25,339 --> 01:37:27,308
LIGAMENTTILITY FOR THE TREATMENT

2489
01:37:27,374 --> 01:37:28,042
OF PATIENTS?

2490
01:37:28,108 --> 01:37:32,046
NYEAH, THERE ARE DRUGS THAT ARE

2491
01:37:32,112 --> 01:37:40,020
TRYING TO INCREASE  OXYGEN

2492
01:37:40,087 --> 01:37:42,289
AFFINITY AND IF YOU'RE ABLE TO

2493
01:37:42,356 --> 01:37:44,425
INCREASE OX GENERATED TO THE

2494
01:37:44,491 --> 01:37:45,559
HEMODPLOABIN, YOU DECREASE

2495
01:37:45,626 --> 01:37:47,094
SICKLE, SO THE FIRST DRUG

2496
01:37:47,161 --> 01:37:48,929
APPROVED FOR THIS IS VOCES CELL

2497
01:37:48,996 --> 01:37:49,897
TOR, BUT THERE'S ALSO

2498
01:37:49,964 --> 01:37:52,600
[INDISCERNIBLE] AND BOTH OF

2499
01:37:52,666 --> 01:37:56,770
THESE ARE STUDIED AND SHOWING TO

2500
01:37:56,837 --> 01:37:57,705
DECREASE MARKERS OF HEME OLDER

2501
01:37:57,771 --> 01:38:00,374
PEOPLE SIS, AND THEN THERE'S

2502
01:38:00,441 --> 01:38:01,976
ANTIP-SELECTIN WHICH HAS BEEN

2503
01:38:02,042 --> 01:38:04,278
SHOWN TO DECREASE PAINFUL

2504
01:38:04,345 --> 01:38:06,313
CRISIS, THAT'S AN EFFUSION

2505
01:38:06,380 --> 01:38:07,848
WHEREAS THE OTHERS ARE ORAL SO

2506
01:38:07,915 --> 01:38:10,918
THAT'S 1 OF THE LIMITATIONS OF

2507
01:38:10,985 --> 01:38:12,486
THOSE BUT THERE'S ALSO ALBEAUTA

2508
01:38:12,553 --> 01:38:15,222
MIN, BUT IT'S THOUGHT TO

2509
01:38:15,289 --> 01:38:16,156
DECREASEOXIDATIVE STRESS AND

2510
01:38:16,223 --> 01:38:19,860
SHOWN TO DECREASE PAINFUL

2511
01:38:19,927 --> 01:38:23,097
CRISIS, SO DRI DROKSYUARY WAS

2512
01:38:23,163 --> 01:38:24,698
APPROVE INDEED 2017, SO IT WAS A

2513
01:38:24,765 --> 01:38:26,233
LONG TIME IT WHERE IT OHM HAD 1

2514
01:38:26,300 --> 01:38:28,569
DRUG AND I THINK WE HAVE 4 OR

2515
01:38:28,636 --> 01:38:30,571
ALMOST 5, SO IT'S EXCITE THRG'S

2516
01:38:30,638 --> 01:38:37,311
A LOT OF DRUGS NOW FOR THE

2517
01:38:37,378 --> 01:38:38,245
SICKLE CELL DISEASE.

2518
01:38:38,312 --> 01:38:41,415
NSO HERE'S ANOTHER QUESTION FOR

2519
01:38:41,482 --> 01:38:43,417
DR. FITZHUGH, FOR THE RELATED

2520
01:38:43,484 --> 01:38:47,288
DONORS WHAT ARE THE

2521
01:38:47,354 --> 01:38:48,789
HEMOGLOBIN-ESQUE STATUS WITH

2522
01:38:48,856 --> 01:38:51,525
REGARD TO SICKLE CELL TRAIT AND

2523
01:38:51,592 --> 01:38:57,698
ALSO WHAT ARE THE RECIPIENTS

2524
01:38:57,765 --> 01:38:58,465
ANTIBODY PROFILES?

2525
01:38:58,532 --> 01:38:59,333
>> SO THOSE ARE 2 DIFFERENT

2526
01:38:59,400 --> 01:39:03,037
THINGS SO LIKE I SAID LESS THAN

2527
01:39:03,103 --> 01:39:06,240
15% PATIENTS HAVE AN HLA-MATCHED

2528
01:39:06,307 --> 01:39:09,443
SIBLING BUT YOU KNOW MOST OF OUR

2529
01:39:09,510 --> 01:39:10,844
PATIENTS HAVE SICKLE CELL TRAITS

2530
01:39:10,911 --> 01:39:13,113
SO AS I SAID, IN THE HAPPEN LO

2531
01:39:13,180 --> 01:39:14,214
STUDIES THERE ARE 3-QUARTERS OF

2532
01:39:14,281 --> 01:39:16,083
A PATIENTS HAD SICKLE CELL

2533
01:39:16,150 --> 01:39:17,885
TRAITS,IME NOT SURE EXACTLY WHAT

2534
01:39:17,951 --> 01:39:19,520
THE HLA MATCH SIBLING BUT I

2535
01:39:19,586 --> 01:39:22,690
WOULD SAY A GOOD PROPORTION OF

2536
01:39:22,756 --> 01:39:25,092
THEM ALSO HAD SICKLE CELL TRAIT

2537
01:39:25,159 --> 01:39:26,960
AND AS FAR AS ANTIBODY AT THAT

2538
01:39:27,027 --> 01:39:29,596
TIMEUS, WE HAVE PATIENT WHO IS

2539
01:39:29,663 --> 01:39:32,032
HAVE [INDISCERNIBLE] SO FROM THE

2540
01:39:32,099 --> 01:39:33,534
FREQUENT RED CELL TRANSFUSIONS

2541
01:39:33,600 --> 01:39:34,268
THEY CAN DEVELOP ANTIBODY WHICH

2542
01:39:34,335 --> 01:39:35,803
IS CAN MAKE IT MORE AND MORE

2543
01:39:35,869 --> 01:39:37,638
DIFFICULT TO TRANSFUSE THEM AND

2544
01:39:37,705 --> 01:39:39,740
INVOLVE THESE THE SEVERE

2545
01:39:39,807 --> 01:39:40,374
HEMOLYTIC TRANSFUSION REACTION

2546
01:39:40,441 --> 01:39:43,110
SO WE DO HAVE PATIENTS WHO ARE

2547
01:39:43,177 --> 01:39:44,845
IMMUNIZED WHO HAVE THESE SO WE

2548
01:39:44,912 --> 01:39:46,647
WORK CLOSELY WITH OUR

2549
01:39:46,714 --> 01:39:47,514
TRANSFUSION MEDICINE DEPARTMENT

2550
01:39:47,581 --> 01:39:49,350
AND IF THEY HAVE REALLY

2551
01:39:49,416 --> 01:39:50,284
CHALLENGING ANTIBODIES THEY CAN

2552
01:39:50,351 --> 01:39:52,686
GET BLOOD AND FREEZE IT SO THAT

2553
01:39:52,753 --> 01:39:56,790
THEY CAN PREPARE OUR PATIENTS TO

2554
01:39:56,857 --> 01:40:03,297
GET TRANSFUSED AFTER TRANSPLANT.

2555
01:40:03,364 --> 01:40:04,198
NALL RIGHT.

2556
01:40:04,264 --> 01:40:05,132
SO LET'S SEE.

2557
01:40:05,199 --> 01:40:09,036
HERE'S ANOTHER QUESTION WITH

2558
01:40:09,103 --> 01:40:12,039
REGARD TO DR. FITZHUGH SPOKE

2559
01:40:12,106 --> 01:40:12,506
ABOUT POST TRANSPLANT

2560
01:40:12,573 --> 01:40:13,107
CYCLOFOSTER NURSED FOCUSED ON

2561
01:40:13,173 --> 01:40:14,775
MID THAT SEEMS TO BE AN

2562
01:40:14,842 --> 01:40:18,545
IMPORTANT PART OF THE EVOLVING

2563
01:40:18,612 --> 01:40:25,753
REGIMEN FOR HAPPEN LO IDENTICAL

2564
01:40:25,819 --> 01:40:26,553
TRANSPLANT DISP SO THE QUESTION

2565
01:40:26,620 --> 01:40:29,156
IS ARE THERE ANY OTHER AGENTS

2566
01:40:29,223 --> 01:40:30,491
BEING TRIED INSTEAD OF

2567
01:40:30,557 --> 01:40:31,258
CYCLOFOSTER NURSED FOCUSED ON

2568
01:40:31,325 --> 01:40:33,127
MADE THAT MIGHT ALSO HAVE A

2569
01:40:33,193 --> 01:40:35,429
BENEFICIAL EFFECT IN TERMS OF

2570
01:40:35,496 --> 01:40:36,130
THESE REGIMENS.

2571
01:40:36,196 --> 01:40:40,667
>> YEAH, I MEAN WE'RE STUDYING

2572
01:40:40,734 --> 01:40:43,137
ABACITIB, IT'S A CTL4A, SO IT

2573
01:40:43,203 --> 01:40:45,205
ACTS WHERE IT ALLOWS, THERE'S 2

2574
01:40:45,272 --> 01:40:46,407
DIFFERENT SIGNALS THAT OCCUR IN

2575
01:40:46,473 --> 01:40:47,708
IMMUNE RESPONSE AND THE FIRST 1

2576
01:40:47,775 --> 01:40:50,077
IS THE ANTIGEN ENGAGING THE

2577
01:40:50,144 --> 01:40:52,813
T-CELL RECEPTOR BUT THEN THERE'S

2578
01:40:52,880 --> 01:40:54,581
A SECOND CO STIMLATTORY REACTION

2579
01:40:54,648 --> 01:40:56,483
THAT LEADS TO IMMUNE RESPONSE,

2580
01:40:56,550 --> 01:40:57,885
SO THE FIRST THAT OCCURS WITHOUT

2581
01:40:57,951 --> 01:41:01,522
THE SIGNAL, THAT CAN LEAD TO

2582
01:41:01,588 --> 01:41:03,257
TOLERANCE OR ENERGY, WHERE THE

2583
01:41:03,323 --> 01:41:04,992
CELL BECOMES ENERGIC OR

2584
01:41:05,058 --> 01:41:08,128
UNRESPONSIVE TO THE ANTIGEN, SO

2585
01:41:08,195 --> 01:41:10,664
CTLA 4 ACTUALLY PLOKS THE IG,

2586
01:41:10,731 --> 01:41:12,399
BLOCKS THAT, INTERACTION FOR

2587
01:41:12,466 --> 01:41:14,168
SIGNAL, TOO, SO THAT'S A DRUG

2588
01:41:14,234 --> 01:41:17,037
THAT'S BEEN SHOWN TO DECREASE

2589
01:41:17,104 --> 01:41:18,505
GRAFT VERSUS HOST DISEASE IN

2590
01:41:18,572 --> 01:41:22,509
PATIENT WHO IS HAVE HEMEAT O TO

2591
01:41:22,576 --> 01:41:23,510
LOGIC MALIGNANCIES AND USE

2592
01:41:23,577 --> 01:41:27,047
STARTING TO BE USED MORE WITH AN

2593
01:41:27,114 --> 01:41:28,115
UNRELATED DONOR STUDY WHERE THEY

2594
01:41:28,182 --> 01:41:31,852
HAD A HIGH RISK OF IT AND REALLY

2595
01:41:31,919 --> 01:41:33,353
DECREASE THE RISK FOR GRAFT

2596
01:41:33,420 --> 01:41:34,321
VERSUS HOST DISEASE AND SINCE

2597
01:41:34,388 --> 01:41:36,690
OUR PROBLEM HAS BEEN MORE GRAFT

2598
01:41:36,757 --> 01:41:41,094
REJECTION, OUR NEW STUDY, DOES

2599
01:41:41,161 --> 01:41:42,262
INCLUDE ABACITINIB TO TRY TO

2600
01:41:42,329 --> 01:41:44,131
DECREASE THE GRAFT REJECTION

2601
01:41:44,198 --> 01:41:45,632
RATE NOKAY, ALL RIGHT.

2602
01:41:45,699 --> 01:41:46,533
WELL, THANK YOU.

2603
01:41:46,600 --> 01:41:49,937
SO THIS IS A QUESTION THAT

2604
01:41:50,003 --> 01:41:53,474
PERHAPS BOTH OF YOU MIGHT WANT

2605
01:41:53,540 --> 01:41:55,776
TO ADDRESS, IT'S SORT OF RELATED

2606
01:41:55,843 --> 01:41:57,177
THAT SOMETHING THAT DR. WONKAM

2607
01:41:57,244 --> 01:41:58,912
TALKED ABOUT A LITTLE BIT BUT

2608
01:41:58,979 --> 01:42:01,114
ARE THERE ANY PROGRAMS FOR

2609
01:42:01,181 --> 01:42:02,616
POPULATIONS SCREENING OF SICKLE

2610
01:42:02,683 --> 01:42:13,093
CELL TRAIT FOR MARRIAGE

2611
01:42:15,095 --> 01:42:15,262
COUNSELING?

2612
01:42:15,329 --> 01:42:18,765
>>  YES, THERE ARE.

2613
01:42:18,832 --> 01:42:20,968
THERE ARE 3 LAYER OF SCREENING,

2614
01:42:21,034 --> 01:42:22,703
THE FIRST 1 IS NEW BORN

2615
01:42:22,769 --> 01:42:24,605
SCREENING, THE SECOND IS THE

2616
01:42:24,671 --> 01:42:26,540
SCREENING FOR PREGNANCY BECAUSE

2617
01:42:26,607 --> 01:42:29,543
IT'S WHERE YOU MAY ANTICIPATE

2618
01:42:29,610 --> 01:42:32,746
PERHAPS IF THERE'S NEW BORN

2619
01:42:32,813 --> 01:42:35,382
SCREENING, THERE MIGHT BE

2620
01:42:35,449 --> 01:42:36,783
SCREENING FOR AT-RISK PREGNANCY

2621
01:42:36,850 --> 01:42:39,353
AND THEN THERE'S POPULATION

2622
01:42:39,419 --> 01:42:40,454
SCREENING THAT INVOLVE AN

2623
01:42:40,521 --> 01:42:42,523
EFFICIENT WAY TO DO IT, 1 IS

2624
01:42:42,589 --> 01:42:45,492
THAT THE HIGH SCHOOL, IS THE

2625
01:42:45,559 --> 01:42:48,462
MOST RECOMMEND ASKED THERE IS

2626
01:42:48,529 --> 01:42:49,429
PREMARITAL SCREENING THAT

2627
01:42:49,496 --> 01:42:53,033
SOMETIME SYSTEM SUGGESTED BY THE

2628
01:42:53,100 --> 01:42:54,234
LAW OR ACTUALLY RECOMMENDED BY

2629
01:42:54,301 --> 01:42:56,403
THE LAW BUT VERY HARD TO

2630
01:42:56,470 --> 01:43:00,607
IMPLEMENT ALMOST IN PRACTICE.

2631
01:43:00,674 --> 01:43:07,548
IT'S HARD BECAUSE THE CONCEPT OF

2632
01:43:07,614 --> 01:43:09,449
MARRIAGE INVOLVE [INDISCERNIBLE]

2633
01:43:09,516 --> 01:43:10,651
PATHOLOGICAL, SOME PEOPLE CALL

2634
01:43:10,717 --> 01:43:12,586
IT LOVE, IT'S QUITE HARD TO MEET

2635
01:43:12,653 --> 01:43:14,888
SOMEONE AND JUST SAY, OKAY, I

2636
01:43:14,955 --> 01:43:17,224
LIKE YOUR EYES BUT WHAT IS YOUR

2637
01:43:17,291 --> 01:43:19,760
HEMOGLOBIN, SO YOU CAN DO THAT.

2638
01:43:19,826 --> 01:43:21,361
BUT BY EXPERIENCE, A LOT OF

2639
01:43:21,428 --> 01:43:25,632
PATIENT I SAW IN MY CLINIC IN

2640
01:43:25,699 --> 01:43:27,401
YAONDE FOR EXAMPLE, ENCLOUDING A

2641
01:43:27,467 --> 01:43:30,938
COUPLE DOCTORS, THEY KNEW THEY

2642
01:43:31,004 --> 01:43:33,807
WERE HETEROZYGOUS BUT THEY CHOSE

2643
01:43:33,874 --> 01:43:34,608
TO GET MARRIED.

2644
01:43:34,675 --> 01:43:37,611
SO WILL W. H. O. WILL COME IN TO

2645
01:43:37,678 --> 01:43:39,179
DO THE SCREENING AT THE

2646
01:43:39,246 --> 01:43:40,347
UNIVERSITY BECAUSE PEOPLE SHOULD

2647
01:43:40,414 --> 01:43:43,216
KNOW THEIR STATUS AND THENAR P

2648
01:43:43,283 --> 01:43:44,718
HARES THEY CONDITION THE WAY

2649
01:43:44,785 --> 01:43:46,853
THEY CHOOSE THEIR PARTNER BUT

2650
01:43:46,920 --> 01:43:48,221
INFORMATION IS HARD WHERE 1

2651
01:43:48,288 --> 01:43:54,928
PERSON OUT OF 4 SOMETIMES IS

2652
01:43:54,995 --> 01:43:55,329
CARRIER.

2653
01:43:55,395 --> 01:43:56,330
>> OKAY, ALL RIGHT.

2654
01:43:56,396 --> 01:43:59,967
SO THEN HERE'S ANOTHER QUESTION

2655
01:44:00,033 --> 01:44:01,501
THAT PERHAPS BOTH OF YOU WOULD

2656
01:44:01,568 --> 01:44:05,939
BE INTERESTED IN, AND THAT IS

2657
01:44:06,006 --> 01:44:07,808
DR. WONKAM TALKED ABOUT VARIOUS

2658
01:44:07,874 --> 01:44:09,443
MODIFIER LOCI THAT ARE INVOLVED

2659
01:44:09,509 --> 01:44:12,412
IN THE NATURAL HISTORY OF OR THE

2660
01:44:12,479 --> 01:44:14,581
PROGRESSION OF SICKLE CELL

2661
01:44:14,648 --> 01:44:17,651
DISEASE, ARE THOSE MODIFIER LOCI

2662
01:44:17,718 --> 01:44:21,655
BEING CONSIDERED IN THINKING

2663
01:44:21,722 --> 01:44:23,457
ABOUT CANDIDATES FOR

2664
01:44:23,523 --> 01:44:25,058
HEMATOPOIETIC STEM CELL

2665
01:44:25,125 --> 01:44:26,627
TRANSPLANTATION, YOU KNOW OR

2666
01:44:26,693 --> 01:44:36,236
EITHER FROM THE RECIPIENT OR THE

2667
01:44:36,303 --> 01:44:36,436
DONOR.

2668
01:44:36,503 --> 01:44:38,205
>>  SURE.

2669
01:44:38,271 --> 01:44:39,373
I REALLY--I DON'T KNOW I'M THE

2670
01:44:39,439 --> 01:44:41,141
RIGHT PERSON BECAUSE I DON'T SEE

2671
01:44:41,208 --> 01:44:42,409
PATIENTS FOR SICKLE CELL DEC,

2672
01:44:42,476 --> 01:44:44,711
YOU ONLY THING I CAN IMAGINE IF

2673
01:44:44,778 --> 01:44:45,779
THE MODIFIER IS STRONG ENOUGH TO

2674
01:44:45,846 --> 01:44:50,417
HAVE A HIGH LEVEL OF BETA

2675
01:44:50,484 --> 01:44:52,686
FLOABIN, YOU WON'T SEE THE

2676
01:44:52,753 --> 01:44:54,554
DOCTOR BECAUSE [INDISCERNIBLE]

2677
01:44:54,621 --> 01:44:57,591
IN THE STUDY 50 YEARS AGO, THE

2678
01:44:57,658 --> 01:45:01,862
BAR FOR HAVING OR LOWERING, OR

2679
01:45:01,928 --> 01:45:04,364
TO INCREASE SURVIVAL, IS USUALLY

2680
01:45:04,431 --> 01:45:05,899
IN GENE EDITING, AND YEEN

2681
01:45:05,966 --> 01:45:09,202
THERAPY IS THE TARGET IS 20% OF

2682
01:45:09,269 --> 01:45:10,604
THE HEMOFLOABIN, SO IT SUGGEST

2683
01:45:10,671 --> 01:45:13,407
FIST YOU ARE A MODIFIER LIKE

2684
01:45:13,473 --> 01:45:16,309
HAPLOTYPE, I DON'T KNOW, HAVE

2685
01:45:16,376 --> 01:45:19,446
THE TYPE OF SENEGAL HAPLOTYPE,

2686
01:45:19,513 --> 01:45:21,081
THAT ALLOW AN ANIMAL THAT IS

2687
01:45:21,148 --> 01:45:24,418
MORE THAN 20% CERTAIN, YOU MAY

2688
01:45:24,484 --> 01:45:28,321
NOT NEED TRANSPLANTS.

2689
01:45:28,388 --> 01:45:29,489
BUT [INDISCERNIBLE] STUDY FROM

2690
01:45:29,556 --> 01:45:32,025
SENEGAL, WE HAD A COHORT FROM

2691
01:45:32,092 --> 01:45:33,427
SENEGAL, THEY ALL HAVE HIGH

2692
01:45:33,493 --> 01:45:37,364
LEVEL OF BETA TBLOABIN, BETA

2693
01:45:37,431 --> 01:45:38,999
ALSO HAVE KIDNEY MALFUNCTION

2694
01:45:39,066 --> 01:45:40,267
TSUGGESTS THAT THE BETA TBLOABIN

2695
01:45:40,333 --> 01:45:41,768
DOESN'T DO IT ALL, IT IS

2696
01:45:41,835 --> 01:45:45,205
POSSIBLE THERE IS SOME CLINICAL

2697
01:45:45,272 --> 01:45:46,039
COMPLICATION, THAT WILL STILL

2698
01:45:46,106 --> 01:45:51,445
HAPPEN IF EVEN IF YOU HAVE THE

2699
01:45:51,511 --> 01:45:57,084
ANIMAL AND THEIR DATA FROM WHERE

2700
01:45:57,150 --> 01:45:58,919
PEOPLE HAVE [INDISCERNIBLE]

2701
01:45:58,985 --> 01:46:00,487
COMPLICATION.

2702
01:46:00,554 --> 01:46:01,988
I THINK THERE'S AN AREA OF

2703
01:46:02,055 --> 01:46:03,857
INVESTIGATION WHERE WE NEED MORE

2704
01:46:03,924 --> 01:46:07,494
PERSPECTIVE COHORT FOR THAT.

2705
01:46:07,561 --> 01:46:07,761
>> OKAY.

2706
01:46:07,828 --> 01:46:08,028
ALL RIGHT.

2707
01:46:08,095 --> 01:46:10,530
SO LET ME SEE IF THERE ARE ANY

2708
01:46:10,597 --> 01:46:11,231
OTHER QUESTIONS.

2709
01:46:11,298 --> 01:46:14,835
ARE THERE ANY QUESTIONS FROM THE

2710
01:46:14,901 --> 01:46:18,472
GROUP HERE WHO WOULD LIKE TO

2711
01:46:18,538 --> 01:46:18,839
POSE A QUESTION?

2712
01:46:18,905 --> 01:46:23,877
>> OH AND I THINK THAT DR. ARIAS

2713
01:46:23,944 --> 01:46:25,045
WOULD LIKE TO POSE A QUESTION SO

2714
01:46:25,112 --> 01:46:28,148
LET ME TURN IT OVER TO HIM FOR A

2715
01:46:28,215 --> 01:46:28,381
MOMENT.

2716
01:46:28,448 --> 01:46:32,185
>> WELL, THANK YOU BOTH FOR A

2717
01:46:32,252 --> 01:46:32,986
VERY EXCITING PRESENTATIONS.

2718
01:46:33,053 --> 01:46:37,190
IT'S A LOT TO THINK ABOUT.

2719
01:46:37,257 --> 01:46:40,594
SO MY QUESTION HAS TO DO WITH

2720
01:46:40,660 --> 01:46:43,697
URIA, WHICH YOU'RE FROM A

2721
01:46:43,764 --> 01:46:47,033
PHYSICAL CHEMICAL POINT OF VIEW,

2722
01:46:47,100 --> 01:46:50,203
SHOULD BE A VERY EFFECTIVE

2723
01:46:50,270 --> 01:46:56,977
COMPOUND TO USE TO MODIFY THE

2724
01:46:57,043 --> 01:46:57,310
HEMOFLOABIN.

2725
01:46:57,377 --> 01:47:01,148
BUT YET, A VERY LARGE PROPORTION

2726
01:47:01,214 --> 01:47:05,585
OF PATIENTS ARE LISTED AS

2727
01:47:05,652 --> 01:47:06,820
UNSUCCESSFUL WHEN TREATED OR I

2728
01:47:06,887 --> 01:47:08,588
DON'T KNOW WHETHER IT'S THEY

2729
01:47:08,655 --> 01:47:10,323
STOPPED RESPONDING OR WHETHER

2730
01:47:10,390 --> 01:47:11,725
THEY WEREN'T RESPONDING IN THE

2731
01:47:11,792 --> 01:47:14,227
FIRST PLACE, SO MY QUESTION IS:

2732
01:47:14,294 --> 01:47:16,329
ARE THERE ANY STUDIES

2733
01:47:16,396 --> 01:47:19,266
ASSOCIATING THE HAPLOTYPES WHEN

2734
01:47:19,332 --> 01:47:21,568
YOU DESCRIBED TO THE PHENOTYPE

2735
01:47:21,635 --> 01:47:28,241
OF THE RESPONSE OR LACK LIFE OF

2736
01:47:28,308 --> 01:47:30,944
URIA, AND THE SECOND FOR

2737
01:47:31,011 --> 01:47:34,014
DR. WONKAM IS, IS SICKLE DISEASE

2738
01:47:34,080 --> 01:47:37,150
FOUND AMONGST THE

2739
01:47:37,217 --> 01:47:40,921
[INDISCERNIBLE] IN AFRICA?

2740
01:47:40,987 --> 01:47:43,156
>> THE SECOND QUESTION, CAN YOU

2741
01:47:43,223 --> 01:47:45,125
REPEAT, PLEASE?

2742
01:47:45,192 --> 01:47:47,727
>> IS SICKLE DEC FOUND AMONGST

2743
01:47:47,794 --> 01:47:49,496
THE [INDISCERNIBLE] IN AFRICA.

2744
01:47:49,563 --> 01:47:55,769
>> YES, THAT'S A GOOD 1.

2745
01:47:55,836 --> 01:47:56,203
>> YEAH.

2746
01:47:56,269 --> 01:47:57,871
>> THE FIRST 1, IS THERE ANY

2747
01:47:57,938 --> 01:48:01,975
MODIFIER THAT IMPROVE THE

2748
01:48:02,042 --> 01:48:03,710
RESPONSE TO HYDROXIA, YES, MOST

2749
01:48:03,777 --> 01:48:06,746
OF THE VARIANT THAT ACTUALLY

2750
01:48:06,813 --> 01:48:10,951
CHANGES THE ROLE OF HEMEAT O

2751
01:48:11,017 --> 01:48:12,819
FLOABUE LYNN WITH HYDROXURIA,

2752
01:48:12,886 --> 01:48:16,790
BUT THE I THINK HYDROXURIA

2753
01:48:16,857 --> 01:48:18,291
DOESN'T ACT ONLY BY IPT GREATER

2754
01:48:18,358 --> 01:48:19,726
CREASING LEVEL OF GLUTEA MINE,

2755
01:48:19,793 --> 01:48:22,929
BUT ALSO BY REDUCING THE AMOUNT

2756
01:48:22,996 --> 01:48:25,131
OF WHITE BLOOD CELL REDUCING

2757
01:48:25,198 --> 01:48:28,535
INFLAMMATION, SO IN SOME

2758
01:48:28,602 --> 01:48:32,472
PATIENT, RESPONSE IS NOT

2759
01:48:32,539 --> 01:48:33,974
NECESSARILY MEASURED BY THE BETA

2760
01:48:34,040 --> 01:48:38,612
GLOBIN BUT BY THE COMPLICATION

2761
01:48:38,678 --> 01:48:39,813
LIKE PAIN COMPLICATION THAT ARE

2762
01:48:39,880 --> 01:48:46,920
SOMETIMES ASSOCIATED WITH THE

2763
01:48:46,987 --> 01:48:47,354
INFLAMMATION.

2764
01:48:47,420 --> 01:48:50,790
SO I DON'T THINK THE MECHANISM,

2765
01:48:50,857 --> 01:48:53,326
HYDROXIA, FOR THE BETA GLOBIN IS

2766
01:48:53,393 --> 01:48:56,396
STILL--WE BELIEVE IT'S TRUE POST

2767
01:48:56,463 --> 01:48:58,732
TRANSCRIPTIONAL CHANGES IN THE

2768
01:48:58,798 --> 01:49:00,033
MICROARE, NA, AND THE

2769
01:49:00,100 --> 01:49:01,434
EXPERIMENTAL DATA AND ALSO DAT

2770
01:49:01,501 --> 01:49:04,404
PRODUCED BY [INDISCERNIBLE] AND

2771
01:49:04,471 --> 01:49:04,838
HIS GROUP.

2772
01:49:04,905 --> 01:49:08,308
BUT WE STILL ARE THE SUBJECT OF

2773
01:49:08,375 --> 01:49:09,476
AN INVESTIGATION.

2774
01:49:09,542 --> 01:49:10,443
THE SECOND QUESTION DO

2775
01:49:10,510 --> 01:49:13,580
[INDISCERNIBLE] I GUESS YOU ARE

2776
01:49:13,647 --> 01:49:14,948
SPEAKING TO THE ETHIOPIAN,

2777
01:49:15,015 --> 01:49:20,887
SPECIFIC THAT GROUP OF ETHIOPIAN

2778
01:49:20,954 --> 01:49:24,157
WHO ARE JEWS, I CAN'T GIVE YOU A

2779
01:49:24,224 --> 01:49:24,524
DISEASE.

2780
01:49:24,591 --> 01:49:27,394
BUT THE ANSWER I CAN GIVE IS

2781
01:49:27,460 --> 01:49:29,496
THAT GENERALLY IN ETHIOPIA,

2782
01:49:29,562 --> 01:49:32,465
SOUTHERN PART OF ETHIOPIA, STILL

2783
01:49:32,532 --> 01:49:34,467
HAVE MALARIA AND EVERYWHERE YOU

2784
01:49:34,534 --> 01:49:36,069
HAVE MALARIA, ANYTIME YOU HAVE

2785
01:49:36,136 --> 01:49:41,641
SICKLE CELL, THE NORTHERN PART

2786
01:49:41,708 --> 01:49:43,243
OF ETHIOPIA, HAVE LESS, AND

2787
01:49:43,310 --> 01:49:45,445
PEOPLE THAT THAT PART OF

2788
01:49:45,512 --> 01:49:47,514
ETHIOPIA, WHO HAVE SICKLE CELL

2789
01:49:47,580 --> 01:49:52,185
TRAIT IS MUCH LOWER.

2790
01:49:52,252 --> 01:49:53,553
[INDISCERNIBLE], HISTORICALLY,

2791
01:49:53,620 --> 01:49:56,656
IS SUBJECT OF A LOVE STORY

2792
01:49:56,723 --> 01:50:01,494
BETWEEN KING SOLOMON AND THE

2793
01:50:01,561 --> 01:50:02,462
QUEEN OF SABBA.

2794
01:50:02,529 --> 01:50:05,098
IT ALL DEPENDS ON WHERE THE

2795
01:50:05,165 --> 01:50:06,433
DESCENDANT LIVES, IF THEIR

2796
01:50:06,499 --> 01:50:07,701
DESCEND ANTILIVE IN THE SOUTHERN

2797
01:50:07,767 --> 01:50:09,169
PART, I THINK SOME OF THEM WILL

2798
01:50:09,235 --> 01:50:13,373
HAVE SICKLE CELL DISEASE, 1 OF

2799
01:50:13,440 --> 01:50:16,242
THE WAYS TO QUICKLY KNOW THAT IS

2800
01:50:16,309 --> 01:50:18,945
PERHAPS TO WORK WITH ISRAEL AND

2801
01:50:19,012 --> 01:50:20,480
THE BIOREPOSITTORY THAT HAVE

2802
01:50:20,547 --> 01:50:22,482
BEEN COLLECTED NOW.

2803
01:50:22,549 --> 01:50:24,384
I KNOW THE JEWS IN ISRAEL NOW,

2804
01:50:24,451 --> 01:50:28,722
THEY WILL BE CALLED BETA-ISRAEL

2805
01:50:28,788 --> 01:50:32,392
POPULATION, JUST REALLY DOJ SOME

2806
01:50:32,459 --> 01:50:34,361
SCREENING IN THAT POPULATION,

2807
01:50:34,427 --> 01:50:38,098
BUT I WILL PERHAPS MOVE ON A

2808
01:50:38,164 --> 01:50:39,065
DIFFERENT POPULATION BUT IT'S

2809
01:50:39,132 --> 01:50:43,436
JUST A DIVERSE BUT A AN

2810
01:50:43,503 --> 01:50:44,637
IMPORTANT DIVERSION.

2811
01:50:44,704 --> 01:50:46,973
THE PEOPLE WHO ASSOCIATE SICKLE

2812
01:50:47,040 --> 01:50:50,043
CELL DISEASE, YOU KNOW IN THE

2813
01:50:50,110 --> 01:50:52,612
POPULATION WHO INITIALLY EVOLVED

2814
01:50:52,679 --> 01:50:55,982
IN CENTRAL AFRICA, IN A TRIANGLE

2815
01:50:56,049 --> 01:50:58,852
BETWEEN NIGERIA, CAMEROON AND

2816
01:50:58,918 --> 01:51:00,553
CONGO, AND MIGRATED, EXPANSION

2817
01:51:00,620 --> 01:51:01,321
ACROSS AFRICA.

2818
01:51:01,388 --> 01:51:03,523
AFTER YEARINGS LATER, THERE'S

2819
01:51:03,590 --> 01:51:05,825
SOME IN AFRICA WHO DON'T HAVE

2820
01:51:05,892 --> 01:51:06,526
SICKLE CELL, ALSO

2821
01:51:06,593 --> 01:51:08,228
[INDISCERNIBLE] DO NOT HAVE

2822
01:51:08,294 --> 01:51:11,164
SICKLE CELL DISOAZ SO ZULU, AND

2823
01:51:11,231 --> 01:51:12,198
[INDISCERNIBLE] PEOPLE DO NOT

2824
01:51:12,265 --> 01:51:17,337
HAVE SICKLE CELL DEC.

2825
01:51:17,404 --> 01:51:19,072
BECAUSE AFTER AT LEAST 1000

2826
01:51:19,139 --> 01:51:22,008
YEARS OR 1000 AND A HALF YEARS

2827
01:51:22,075 --> 01:51:22,842
LIVING IN MALARIA ENVIRONMENT,

2828
01:51:22,909 --> 01:51:25,278
THERE WAS NO NEED FOR OUR GENOME

2829
01:51:25,345 --> 01:51:28,248
TO MAINTAIN THE VARIANT.

2830
01:51:28,314 --> 01:51:31,184
SO I WOULD SUPPOSE THAT SUCH

2831
01:51:31,251 --> 01:51:33,720
DYNAMIC WOULD PROBABLY HAPPEN IN

2832
01:51:33,787 --> 01:51:36,156
PLACES LIKE ETHIOPIA, IF YOU ARE

2833
01:51:36,222 --> 01:51:39,426
LIVING IN A HIGH MOUNTAIN OF

2834
01:51:39,492 --> 01:51:40,493
ETHIOPIA, WHERE THEOXIEN IS

2835
01:51:40,560 --> 01:51:42,695
LOWER AND MALARIA WILL NOT

2836
01:51:42,762 --> 01:51:44,197
SURVIVE, OVER TIME, PERHAPS AT

2837
01:51:44,264 --> 01:51:44,831
LEAST 1000 YEARS YOU WILL

2838
01:51:44,898 --> 01:51:46,266
NONAPOPTOTIC THE NEED TO HAVE

2839
01:51:46,332 --> 01:51:48,001
THE SICKLE VARIANT AND THE

2840
01:51:48,068 --> 01:51:50,670
VARIANT WILL BE MUCH LOWER AND I

2841
01:51:50,737 --> 01:51:54,240
GUESS, IN POPULATION LIKE IN THE

2842
01:51:54,307 --> 01:51:56,109
POPULATION, THE SICKLE CELL DEC

2843
01:51:56,176 --> 01:51:58,645
IS RESISTANT AND IT COULD BE

2844
01:51:58,711 --> 01:52:01,514
RELATED TO THAT.

2845
01:52:01,581 --> 01:52:02,082
>> THANK YOU.

2846
01:52:02,148 --> 01:52:03,383
>> ALL RIGHT, ARE THERE ANY

2847
01:52:03,450 --> 01:52:06,719
OTHER QUESTIONS FOR OUR

2848
01:52:06,786 --> 01:52:07,020
SPEAKERS?

2849
01:52:07,087 --> 01:52:08,788
IF NOT, I THINK THAT WE'RE JUST

2850
01:52:08,855 --> 01:52:11,758
ABOUT AT THE END OF OUR TIME

2851
01:52:11,825 --> 01:52:13,660
ANYWAY, SO I WOULD LIKE TO THANK

2852
01:52:13,726 --> 01:52:15,161
YOU BOTH, AGAIN, VERY, VERY

2853
01:52:15,228 --> 01:52:18,898
MUCH, THIS HAS BEEN REALLY JUST

2854
01:52:18,965 --> 01:52:22,302
A VERY STIMULATING TERRIFIC

2855
01:52:22,368 --> 01:52:23,236
THOUGHT PROVOKING SET OF

2856
01:52:23,303 --> 01:52:24,337
PRESENTATIONS AND I WANT TO

2857
01:52:24,404 --> 01:52:26,506
THANK YOU AGAIN VERY, VERY MUCH

2858
01:52:26,573 --> 01:52:31,144
FOR JOINING US THIS AFTERNOON.

2859
01:52:31,211 --> 01:52:32,378
ALL RIGHT AND WITH THAT, I THINK

2860
01:52:32,445 --> 01:52:34,414
THAT WE WILL CALL IT TO A CLOSE

2861
01:52:34,481 --> 01:52:38,251
AND WE LOOK FORWARD TO SEEING

2862
01:52:38,318 --> 01:52:41,354
EVERYONE AGAIN NEXT WEEK FOR

2863
01:52:41,421 --> 01:52:42,522
ANOTHER INSTALLMENT, THE EIGHTH

2864
01:52:42,589 --> 01:52:43,756
IN THE SERIES.

2865
01:52:43,823 --> 01:52:54,400
SO, ANYWAY, THANK YOU VERY MUCH