1 00:00:06,558 --> 00:00:08,771 >> WELL, GREETINGS AND 2 00:00:08,771 --> 00:00:09,138 SALUITATIONS! 3 00:00:09,138 --> 00:00:11,907 I AM DAN KASTNER, I AM THE 4 00:00:11,907 --> 00:00:15,277 DIRECTOR OF THE NATIONAL HUMAN 5 00:00:15,277 --> 00:00:16,979 GENOME RESEARCH INSTITUTE AND 6 00:00:16,979 --> 00:00:19,448 STILL ACTIVE PHYSICIAN SCIENTIST 7 00:00:19,448 --> 00:00:21,183 IN THE ACTIVE PORTION OF THE NIH 8 00:00:21,183 --> 00:00:23,152 AND IT IS MY ENORMOUS PLEASURE 9 00:00:23,152 --> 00:00:25,221 THIS AFTERNOON TO WELCOME YOU TO 10 00:00:25,221 --> 00:00:27,923 THE 15th INSTALLMENT OF THE 11 00:00:27,923 --> 00:00:29,792 2025 DEMYSTIFYING MEDICINE A 12 00:00:29,792 --> 00:00:31,160 SERIES OF PRESENTATIONS THAT 13 00:00:31,160 --> 00:00:33,996 BRIDGE THE EXCITING DEVELOPMENTS 14 00:00:33,996 --> 00:00:35,798 IN BIOLOGY, ENGINEERING AND 15 00:00:35,798 --> 00:00:37,333 COMPUTER SCIENCE WITH MEDICINE. 16 00:00:37,333 --> 00:00:39,301 AND YOU SEE, UP IN THE UPPER 17 00:00:39,301 --> 00:00:42,071 RIGHT HAND CORNER, THE ICONIC 18 00:00:42,071 --> 00:00:44,206 PHOTO OF THE CONSTRUCTION OF THE 19 00:00:44,206 --> 00:00:46,041 BROOKLYN BRIDGE BACK IN THE LATE 20 00:00:46,041 --> 00:00:49,211 1800S AND IF YOU LOOK CAREFULLY, 21 00:00:49,211 --> 00:00:53,716 YOU CAN SEE ON THE CAT WALK UP 22 00:00:53,716 --> 00:00:56,385 THERE, A NEUROPHYSIOLOGIST FROM 23 00:00:56,385 --> 00:00:59,155 MANHATTAN AND A NEUROLOGIST FROM 24 00:00:59,155 --> 00:01:01,257 BROOKLYN WHO HAVE HAVING A VERY 25 00:01:01,257 --> 00:01:03,793 LIVELY DISCUSSION ABOUT THE 26 00:01:03,793 --> 00:01:05,628 FINDINGS OF SHARCO, ESTABLISHING 27 00:01:05,628 --> 00:01:07,129 THE DIAGNOSIS OF MULTIPLE 28 00:01:07,129 --> 00:01:09,331 SCLEROSIS AND IN FACT, WE WILL 29 00:01:09,331 --> 00:01:11,634 BE TALKING ABOUT MULTIPLE 30 00:01:11,634 --> 00:01:13,636 SCLEROSIS THIS AFTERNOON. 31 00:01:13,636 --> 00:01:15,237 BUT BEFORE WE LAUNCH INTO THAT, 32 00:01:15,237 --> 00:01:18,240 LET ME JUST REMIND YOU THAT THIS 33 00:01:18,240 --> 00:01:19,308 SERIES DEMYSTIFYING MEDICINE 34 00:01:19,308 --> 00:01:22,011 OCCURS ON TUESDAY AFTERNOONS 35 00:01:22,011 --> 00:01:25,347 FROM 3-5 EASTERN TIME FROM 36 00:01:25,347 --> 00:01:26,882 JANUARY-MAY OF 2025. 37 00:01:26,882 --> 00:01:30,486 YOU CAN WATCH IT AT THE VIDEO 38 00:01:30,486 --> 00:01:32,421 LINK SHOWN THERE, GET CME CREDIT 39 00:01:32,421 --> 00:01:37,893 WITH THE CME CODE OF 58794. 40 00:01:37,893 --> 00:01:38,227 THAT'S 58794. 41 00:01:38,227 --> 00:01:40,196 AND IF YOU HAVE QUESTIONS DURING 42 00:01:40,196 --> 00:01:41,897 THE PRESENTATIONS, THERE WILL BE 43 00:01:41,897 --> 00:01:44,233 A COUPLE OF PRESENTATIONS AS 44 00:01:44,233 --> 00:01:45,868 WELL AS A PATIENT PRESENTATION, 45 00:01:45,868 --> 00:01:48,204 CAN YOU USE THE SEND LIVE 46 00:01:48,204 --> 00:01:50,206 FEEDBACK BUTTON TO THE VIDEOCAST 47 00:01:50,206 --> 00:01:51,907 DISPLAY IN ORDER TO ENTER YOUR 48 00:01:51,907 --> 00:01:53,676 QUESTIONS AND THEY WILL BE 49 00:01:53,676 --> 00:01:56,612 RELAYED TO ME FOR THE 50 00:01:56,612 --> 00:01:57,880 INTERROGATION SESSION AT THE 51 00:01:57,880 --> 00:01:58,047 END. 52 00:01:58,047 --> 00:02:01,317 SO IN ANY EVENT, ALL OF THE 53 00:02:01,317 --> 00:02:02,451 PREVIOUS SESSIONS ARE ARCHIVED. 54 00:02:02,451 --> 00:02:04,086 YOU CAN GO IT THAT LINK ON THE 55 00:02:04,086 --> 00:02:06,088 SCREEN TO VIEW THEM AND THERE'S 56 00:02:06,088 --> 00:02:10,826 ADDITIONAL INFORMATION THAT THE 57 00:02:10,826 --> 00:02:11,660 DEMYSTIFYING MEDICINE LINK SHOWN 58 00:02:11,660 --> 00:02:11,861 THERE. 59 00:02:11,861 --> 00:02:14,163 AND OF COURSE, THIS IS A SERIES 60 00:02:14,163 --> 00:02:15,598 THAT BRIDGES SILOS AT THE NIH 61 00:02:15,598 --> 00:02:19,168 AND HAS BEEN DOING SO SINCE 62 00:02:19,168 --> 00:02:19,902 2003. 63 00:02:19,902 --> 00:02:22,338 IN ANY CASE, THE FIRST OF OUR 2 64 00:02:22,338 --> 00:02:26,275 SPEAKERS, IS GOING TO BE 65 00:02:26,275 --> 00:02:32,514 DR. MARIA INES GUYTON AND SHE IS 66 00:02:32,514 --> 00:02:33,482 AN ASSOCIATE RESEARCH PHYSICIAN 67 00:02:33,482 --> 00:02:38,754 AND THE ACTING DIRECTOR OF THE 68 00:02:38,754 --> 00:02:41,156 IMMUNOLOGY CLINIC IN THE 69 00:02:41,156 --> 00:02:41,724 TRANSLATIONAL NEURORADIOLOGY 70 00:02:41,724 --> 00:02:43,392 SECTION OF THE NATIONAL 71 00:02:43,392 --> 00:02:44,927 INSTITUTE FOR NEUROLOGIC 72 00:02:44,927 --> 00:02:45,661 DISEASES AND STROKE. 73 00:02:45,661 --> 00:02:49,098 SHE GOT HER MEDICAL DEGREE WITH 74 00:02:49,098 --> 00:02:51,767 HONORS AT THE BUENOS AIRES 75 00:02:51,767 --> 00:02:53,435 UNIVERSITY SCHOOL OF MEDICINE. 76 00:02:53,435 --> 00:02:55,838 SHE TRAINED IN NEUROLOGY AT THE 77 00:02:55,838 --> 00:02:57,907 INSTITUTE FOR NEUROLOGY 78 00:02:57,907 --> 00:03:00,943 RESEARCH, FLENI, IN BUENOS 79 00:03:00,943 --> 00:03:02,544 AIRES, WAS A POST DOCTORAL 80 00:03:02,544 --> 00:03:05,648 FELLOW IN THE NEUROIMEULOGIOLOGY 81 00:03:05,648 --> 00:03:07,816 BRANCH OF NINDS AND A SENIOR 82 00:03:07,816 --> 00:03:13,722 STAFF CLINICIAN AT FLENI, BEFORE 83 00:03:13,722 --> 00:03:16,158 ASSUMING HER CURRENT POSITION IN 84 00:03:16,158 --> 00:03:18,360 THE NEUROIMMUNOLOGY CLINIC AT 85 00:03:18,360 --> 00:03:19,662 THE NIH. 86 00:03:19,662 --> 00:03:22,331 SHE'S THE RECIPIENT OF A NUMBER 87 00:03:22,331 --> 00:03:24,433 OF AWARDS INCLUDING THE NINDS 88 00:03:24,433 --> 00:03:26,702 CLINICAL DIRECTORS AWARD FOR 89 00:03:26,702 --> 00:03:29,204 CLINICAL EXCELLENCE. 90 00:03:29,204 --> 00:03:31,907 HER RESEARCH GROUP, HER RESEARCH 91 00:03:31,907 --> 00:03:34,677 IS FOCUSED ON DEVELOPING 92 00:03:34,677 --> 00:03:38,213 ADVANCED MRI TECHNIQUES IN 93 00:03:38,213 --> 00:03:41,150 MULTIPLE SCLEROSIS, STUDYING THE 94 00:03:41,150 --> 00:03:45,955 CHRONIC LESIONS IN MS, AND 95 00:03:45,955 --> 00:03:47,423 DEVELOPING IMAGING BIOMARKERS IN 96 00:03:47,423 --> 00:03:47,756 MS. 97 00:03:47,756 --> 00:03:51,593 OUR SECOND SPEAKER IS DR. DANNY 98 00:03:51,593 --> 00:03:52,861 RYKE, WHO IS A SENIOR 99 00:03:52,861 --> 00:03:55,364 INVESTIGATOR AND CHIEF OF THEA 100 00:03:55,364 --> 00:03:56,098 TRANSLATIONAL NEURAL RADIOLOGY 101 00:03:56,098 --> 00:04:00,502 SECTION IN THE DIVISION OF 102 00:04:00,502 --> 00:04:01,770 NEUROIMMUNOLOGY AND 103 00:04:01,770 --> 00:04:05,741 NEUROVIROLOGY IN NINDS, AND HE'S 104 00:04:05,741 --> 00:04:07,876 AN ADJUNCT PROFESSOR IN 105 00:04:07,876 --> 00:04:14,383 RADIOLOGY, AT YALE AND IN 106 00:04:14,383 --> 00:04:15,084 NEUROLOGY, DIAGNOSTIC RADIOLOGY 107 00:04:15,084 --> 00:04:16,885 AT HOPKINS HE GOT HIS MEDICAL 108 00:04:16,885 --> 00:04:18,854 DEGREE AT CORNELL AND Ph.D. AT 109 00:04:18,854 --> 00:04:19,989 PHYSIOLOGY AT THE ROCKEFELLER 110 00:04:19,989 --> 00:04:22,424 UNIVERSITY AND THEN GOT CLINICAL 111 00:04:22,424 --> 00:04:24,827 TRAIN NOTHING NEUROLOGY, 112 00:04:24,827 --> 00:04:25,961 DIAGNOSTIC RADIOLOGY AND 113 00:04:25,961 --> 00:04:27,930 NEURORADIOLOGY AT HOPKINS, AND 114 00:04:27,930 --> 00:04:31,533 NEUROIMMUNOLOGY ALSO AT HOPKIN. 115 00:04:31,533 --> 00:04:35,771 HE IS THE RECIPIENT OF THE 116 00:04:35,771 --> 00:04:37,706 BARANCIK PRIZE FOR MS RESEARCH, 117 00:04:37,706 --> 00:04:40,376 MEMBER OF THE HENRY KUNKEL 118 00:04:40,376 --> 00:04:42,277 ASSOCIATE, ASSOCIATE OF AMERICAN 119 00:04:42,277 --> 00:04:45,381 PHYSICIANS, AAAS FELLOW AND HAS 120 00:04:45,381 --> 00:04:46,315 RECEIVED MULTIPLE OUTSTANDING 121 00:04:46,315 --> 00:04:49,485 MENTOR AND TEACHER AWARDS. 122 00:04:49,485 --> 00:04:54,857 THE GOALS OF HIS RESEARCH GROUP 123 00:04:54,857 --> 00:04:56,492 ARE UNDERSTANDING HOW MS 124 00:04:56,492 --> 00:04:58,494 INJURIES THE BRAIN AND SPINAL 125 00:04:58,494 --> 00:04:58,827 CORD. 126 00:04:58,827 --> 00:05:02,297 HOW TO STOP THAT YOUR AND HOW TO 127 00:05:02,297 --> 00:05:02,731 PROMOTE REPAIR. 128 00:05:02,731 --> 00:05:08,103 ALSO THE DEVELOPMENT OF NEW MRI 129 00:05:08,103 --> 00:05:08,971 TECHNIQUES WITH STATE-OF-THE-ART 130 00:05:08,971 --> 00:05:11,874 EQUIPMENT AT THE NIH CLINICAL 131 00:05:11,874 --> 00:05:13,809 CENTER AND HIS GROUP USES 132 00:05:13,809 --> 00:05:18,280 PATIENT SAMPLES AND ANIMAL 133 00:05:18,280 --> 00:05:20,682 MODELS TO ELUCIDATE CELLULAR AND 134 00:05:20,682 --> 00:05:21,350 MOLECULAR PATHWAYS. 135 00:05:21,350 --> 00:05:22,718 WELL, WITH ALL THAT HAVING KNOW 136 00:05:22,718 --> 00:05:24,920 SAID, I THINK IT'S TIME NOW TO 137 00:05:24,920 --> 00:05:27,189 TURN THINGS OVER TO MARIA WHO IS 138 00:05:27,189 --> 00:05:30,292 GOING TO GET THINGS GOING. 139 00:05:30,292 --> 00:05:35,597 SO MARIA, PLEASE, TAKE IT AWAY. 140 00:05:35,597 --> 00:05:36,965 >> THANK YOU VERY MUCH FOR THE 141 00:05:36,965 --> 00:05:39,034 INVITATION AND IT'S A PLEASURE 142 00:05:39,034 --> 00:05:42,738 TO BE HERE TODAY AND I'M GOING 143 00:05:42,738 --> 00:05:46,842 TO BRUCE OUR PATIENT MR. CARLOS 144 00:05:46,842 --> 00:05:49,078 CHACON, CARLOS IF YOU WANT TO 145 00:05:49,078 --> 00:05:51,213 TURN ON YOUR CAMERA SO YOU CAN 146 00:05:51,213 --> 00:05:56,752 BE PART OF THE CONVERSATION, SO 147 00:05:56,752 --> 00:05:58,053 FIRST I WILL SHARE A COUPLE OF 148 00:05:58,053 --> 00:05:59,788 SLIDES AND THEN I WILL TALK TO 149 00:05:59,788 --> 00:06:01,490 CARLOS AND THEN I WILL ASK HIM 150 00:06:01,490 --> 00:06:01,890 SOME QUESTIONS. 151 00:06:01,890 --> 00:06:04,760 SO TODAY I WILL TALK ABOUT MS, 152 00:06:04,760 --> 00:06:05,928 THROUGH 2 LENSES, THE CLINICAL 153 00:06:05,928 --> 00:06:08,630 INSIGHT AND THE PATIENT 154 00:06:08,630 --> 00:06:09,331 EXPERIENCE SO THE FIRST THING 155 00:06:09,331 --> 00:06:12,734 WE'RE GOING TO DO IS WE'RE GOING 156 00:06:12,734 --> 00:06:16,305 TO TALK WITH MR. CHACON, ABOUT 157 00:06:16,305 --> 00:06:19,007 HIS HISTORY OF PRESENT ILLNESS, 158 00:06:19,007 --> 00:06:20,242 SO I WILL STOP SHARING MY SLIDES 159 00:06:20,242 --> 00:06:24,847 AND I WOULD LIKE TO TALK TO 160 00:06:24,847 --> 00:06:25,080 CARLOS. 161 00:06:25,080 --> 00:06:28,016 SO GOOD AFTERNOON, CAN YOU SEE 162 00:06:28,016 --> 00:06:28,383 ME CARLOS? 163 00:06:28,383 --> 00:06:29,718 YEAH, OKAY. 164 00:06:29,718 --> 00:06:30,185 >> YEAH. 165 00:06:30,185 --> 00:06:31,386 >> THANK YOU SO MUCH FOR COMING. 166 00:06:31,386 --> 00:06:34,656 IT'S A PLEASURE TO HAVE YOU 167 00:06:34,656 --> 00:06:34,857 HERE. 168 00:06:34,857 --> 00:06:36,825 SO I WOULD LIKE TO ASK YOU WHAT 169 00:06:36,825 --> 00:06:39,728 WAS THE FIRST SYMPTOM THAT YOU 170 00:06:39,728 --> 00:06:40,162 EXPERIENCED? 171 00:06:40,162 --> 00:06:41,697 >> THANK YOU FOR INVITING ME. 172 00:06:41,697 --> 00:06:44,099 MY PLEASURE TO BE HERE. 173 00:06:44,099 --> 00:06:47,369 THREE YEARS AGO, BASICALLY MY 174 00:06:47,369 --> 00:06:50,105 EYES, THEY STOPPED COORDINATING. 175 00:06:50,105 --> 00:06:52,407 IT WAS KIND OF CRAZY EYE OR 176 00:06:52,407 --> 00:06:53,342 VETERINARY COMMUNITY GO, WHEN I 177 00:06:53,342 --> 00:06:54,843 WOULD LOOK TO THE RIGHT, THE 178 00:06:54,843 --> 00:06:56,211 RIGHT EYE WOULD GO TO THE RIGHT, 179 00:06:56,211 --> 00:06:59,481 BUT THE LEFT EYE WOULD GO UP OR 180 00:06:59,481 --> 00:07:00,782 IT WOULD BE LOOSE AND WHEN I 181 00:07:00,782 --> 00:07:03,285 WOULD LOOK ON THE LEFT EYE, THE 182 00:07:03,285 --> 00:07:05,687 RIGHT EYE WILL BE IN A CRAZY WAY 183 00:07:05,687 --> 00:07:08,357 AND THAT WAS THE FIRST SYMPTOM I 184 00:07:08,357 --> 00:07:11,326 GOT OFFICIAL DIAGNOSED. 185 00:07:11,326 --> 00:07:15,364 >> HOW OLD WERE YOU AT THE TIM? 186 00:07:15,364 --> 00:07:18,467 >> I WAS 29 YEARS OLD, I THINK, 187 00:07:18,467 --> 00:07:18,800 YEAH. 188 00:07:18,800 --> 00:07:21,003 >> AND HOW MANY DAYS DID IT TAKE 189 00:07:21,003 --> 00:07:22,604 FOR YOUR SYMPTOMS TO REACH THEIR 190 00:07:22,604 --> 00:07:25,007 PEAK OR THEIR WORST? 191 00:07:25,007 --> 00:07:26,742 >> I THINK IT WAS 2 OR 3 DAYS 192 00:07:26,742 --> 00:07:29,611 FROM WHEN I STARTED FEELING BAD. 193 00:07:29,611 --> 00:07:34,049 I ALSO HAD A SUPER HUGE HEADACHE 194 00:07:34,049 --> 00:07:35,317 BEFORE THAT. 195 00:07:35,317 --> 00:07:36,618 A HORRIBLE MIGRAINE AND I THINK 196 00:07:36,618 --> 00:07:38,187 3 DAYS AFTER THAT'S WHEN I WAS 197 00:07:38,187 --> 00:07:39,588 ADMITTED INTO THE HOSPITAL AND I 198 00:07:39,588 --> 00:07:42,157 WAS IN THE HOSPITAL FOR 5 DAYS, 199 00:07:42,157 --> 00:07:43,992 IF I AM NOT MISTAKEN. 200 00:07:43,992 --> 00:07:47,095 >> AND DID YOU FULLY RECOVER. 201 00:07:47,095 --> 00:07:47,496 >> YES. 202 00:07:47,496 --> 00:07:49,965 >> DID YOU RECEIVE ANY TREATMENT 203 00:07:49,965 --> 00:07:52,534 FOR THAT AT THE TIME? 204 00:07:52,534 --> 00:07:56,138 >> YES, I RECEIVED A STEROIDS, I 205 00:07:56,138 --> 00:07:58,640 DON'T REMEMBER THE SPECIFIC NAME 206 00:07:58,640 --> 00:08:01,577 FOR 5 DAYS AND YEAH, AND I WAS 207 00:08:01,577 --> 00:08:04,279 PRETTY FINE AFTER THAT. 208 00:08:04,279 --> 00:08:07,683 AND 2 OR 3 MONTHS AFTER, MY EYES 209 00:08:07,683 --> 00:08:16,291 WERE ALMOST BACK TO NORMAL. 210 00:08:16,291 --> 00:08:16,758 >> OKAY, WONDERFUL. 211 00:08:16,758 --> 00:08:18,927 SO NOW I WILL SHOW MY 212 00:08:18,927 --> 00:08:19,761 PRESENTATION AGAIN AND I WILL 213 00:08:19,761 --> 00:08:22,130 COME BACK TO YOU SHORTLY. 214 00:08:22,130 --> 00:08:25,033 ALL RIGHT, SO WHAT MR. CHACON 215 00:08:25,033 --> 00:08:29,504 HAD AT THE TIME WAS WHAT WE CALL 216 00:08:29,504 --> 00:08:31,106 BILATERAL OPHTHALMIC MALAYSIA, 217 00:08:31,106 --> 00:08:37,145 THIS IS CLINICAL PRESENCE OF 218 00:08:37,145 --> 00:08:40,916 DIVERGENCE OR EYE APPEARANCE IN 219 00:08:40,916 --> 00:08:41,483 THE HORIZONTAL PLANE. 220 00:08:41,483 --> 00:08:44,720 SO BASICALLY WITH WEAK AND SLOW 221 00:08:44,720 --> 00:08:46,788 ADDUCTION OF THE AFFECTED EYE 222 00:08:46,788 --> 00:08:51,627 WHICH MAY BE COMBINED BY THE 223 00:08:51,627 --> 00:08:53,362 INTRA LATERAL EYE, THIS IS THE 224 00:08:53,362 --> 00:08:54,429 EYE THAT WAS AFFECTED AND THIS 225 00:08:54,429 --> 00:08:55,897 IS AN EXAMPLE IN THE LITERATURE 226 00:08:55,897 --> 00:08:59,368 AND THIS EYE WAS MOVING WITH IT 227 00:08:59,368 --> 00:09:00,669 AND LOOKING AT THE FRONT IT WAS 228 00:09:00,669 --> 00:09:02,571 OKAY BUT TRYING TO LOOK TO THE 229 00:09:02,571 --> 00:09:04,039 OPPOSITE SIDE, HE WILL HAVE 230 00:09:04,039 --> 00:09:07,009 EXACTLY THE SAME SYMPTOM. 231 00:09:07,009 --> 00:09:10,078 THIS EYE WAS ABLE NOT ABLE TO DO 232 00:09:10,078 --> 00:09:11,446 ADDUCTION AND THIS WOULD HAVE 233 00:09:11,446 --> 00:09:12,848 TROUBLE MOVING WHEN MOVED TO THE 234 00:09:12,848 --> 00:09:13,248 LEFT. 235 00:09:13,248 --> 00:09:16,184 IT IS 1 OF THE MOST LOCALIZED 236 00:09:16,184 --> 00:09:18,220 BRAIN SYNDROMES RESULTING IN A 237 00:09:18,220 --> 00:09:21,890 LESION FROM THE MEDIA, IN THE 238 00:09:21,890 --> 00:09:24,259 MEDIA BRAIN STEM, OF EITHER THE 239 00:09:24,259 --> 00:09:26,128 POINTS OF THE BRAIN BRAIN, SO 240 00:09:26,128 --> 00:09:28,463 THIS IS CONNECTING THE SIXTH AND 241 00:09:28,463 --> 00:09:29,598 THE THIRD NERVE. 242 00:09:29,598 --> 00:09:30,999 >> DOCTOR, REAL QUICK, YOUR CHAT 243 00:09:30,999 --> 00:09:32,200 BOX IS APPEARING IF YOU WANT TO 244 00:09:32,200 --> 00:09:36,271 GO AHEAD AND MINIMIZE THAT 245 00:09:36,271 --> 00:09:36,505 PLEASE? 246 00:09:36,505 --> 00:09:46,248 >> YEAH, SURE. 247 00:09:46,248 --> 00:09:48,050 APOLOGIZE FOR THAT. 248 00:09:48,050 --> 00:09:52,154 >> OKAY LOOKS GOOD, THANK YOU. 249 00:09:52,154 --> 00:09:52,888 >> SORRY FOR THAT. 250 00:09:52,888 --> 00:09:54,022 SO I WOULD LIKE TO GO BACK TO 251 00:09:54,022 --> 00:09:57,025 YOU AND ASK YOU A COUPLE OF 252 00:09:57,025 --> 00:10:01,897 THINGS, AGAIN, IS HOW WAS 253 00:10:01,897 --> 00:10:02,964 DIAGNOSIS MADE? 254 00:10:02,964 --> 00:10:09,304 >> OKAY, YES, SO I WENT FIRST TO 255 00:10:09,304 --> 00:10:11,039 URJEBT CARE, THE DOCTOR WASN'T 256 00:10:11,039 --> 00:10:12,240 CONVINCED I HAD ANYTHING MORE 257 00:10:12,240 --> 00:10:17,779 THAN VETERINARY COMMUNITY -- 258 00:10:17,779 --> 00:10:20,315 VERTIGO, AND SHE GOT SCARED AND 259 00:10:20,315 --> 00:10:22,384 SHE SAID WE NEED TO TRANSFER YOU 260 00:10:22,384 --> 00:10:23,085 IMMEDIATELY TO A HOSPITAL 261 00:10:23,085 --> 00:10:25,053 BECAUSE THIS MAY BE MS, AND THEN 262 00:10:25,053 --> 00:10:27,422 I WAS TRANSFERRED TO A HOSPITAL 263 00:10:27,422 --> 00:10:29,691 AT YORK TOWN AND SEVERAL DOCTORS 264 00:10:29,691 --> 00:10:31,326 DID SEVERAL EXAMINATIONS FOR A 265 00:10:31,326 --> 00:10:34,496 COUPLE HOURS AND THAT NIGHT, 3 266 00:10:34,496 --> 00:10:39,835 AMOR SO I HAD AN MRI AND 2 OR 3 267 00:10:39,835 --> 00:10:42,304 HOURS AFTER THE MRI, I GOT THE 268 00:10:42,304 --> 00:10:42,871 RESULTS. 269 00:10:42,871 --> 00:10:45,640 WELL THE, DOCTOR, THE RESIDENTS 270 00:10:45,640 --> 00:10:46,775 AND THE TREATING DOCTOR CAME AND 271 00:10:46,775 --> 00:10:50,612 THEY TOLD ME THAT THEY FOUND IT 272 00:10:50,612 --> 00:10:53,348 WASN'T THAT I HAVE MS. 273 00:10:53,348 --> 00:10:55,350 IT WAS NOT TO HAVE THE -- THE 274 00:10:55,350 --> 00:11:00,055 THING ON THE BACK, I FORGOT THE 275 00:11:00,055 --> 00:11:00,489 NAME. 276 00:11:00,489 --> 00:11:00,822 >> PUNCTURE? 277 00:11:00,822 --> 00:11:03,091 >> YEAH, IT WAS NOT NECESSARY 278 00:11:03,091 --> 00:11:04,259 BECAUSE THEY FOUND A LESION AND 279 00:11:04,259 --> 00:11:08,497 THATIA HOW I WAS DIAGNOSED. 280 00:11:08,497 --> 00:11:15,370 >> AND HOW DID YOU FEEL AT THE 281 00:11:15,370 --> 00:11:15,570 TIME? 282 00:11:15,570 --> 00:11:19,441 >> WELL, I WAS SCARED OF COURSE, 283 00:11:19,441 --> 00:11:22,110 BECAUSE YOU SEE A LOT OF MOVIES 284 00:11:22,110 --> 00:11:24,946 ON TV, AND I WAS SCARED BUT ALSO 285 00:11:24,946 --> 00:11:27,048 I THINK THE DOCTORS DID A 286 00:11:27,048 --> 00:11:28,650 TERRIFIC JOB EXPLAINING TO ME 287 00:11:28,650 --> 00:11:30,752 HOW MUCH SCIENCE HAS ADVANCED 288 00:11:30,752 --> 00:11:33,855 ESPECIALLY IN THE LAST 20 YEARS 289 00:11:33,855 --> 00:11:36,324 AND THEY WERE REALLY GOOD AT 290 00:11:36,324 --> 00:11:38,894 TEACHING ME THAT A DIAGNOSIS 291 00:11:38,894 --> 00:11:41,797 WELL, OR WELL, 3 YEARS AGO, IS 292 00:11:41,797 --> 00:11:44,332 NOT THE SAME AS IN THE 90S OR 293 00:11:44,332 --> 00:11:46,401 80S OR EVEN A FEW DECADES AGO 294 00:11:46,401 --> 00:11:48,570 AND THOU MUCH MEDICINE 295 00:11:48,570 --> 00:11:50,472 PROGRESSED AND THAT MY PROGNOSIS 296 00:11:50,472 --> 00:11:53,041 WAS VERY POSITIVE ESPECIALLY 297 00:11:53,041 --> 00:11:53,942 BECAUSE THEY FOUND THE LESION 298 00:11:53,942 --> 00:11:55,610 AND EVEN THOUGH I HAD A FEW 299 00:11:55,610 --> 00:11:57,112 SPOTS AND LESIONS IN MY BRAIN 300 00:11:57,112 --> 00:12:01,783 AND MY SPINE, IT WAS VERY EARLY. 301 00:12:01,783 --> 00:12:04,052 SO IT WAS A BITTER SWEET 302 00:12:04,052 --> 00:12:06,221 FEELING, LIKE BITTER THAT I HAVE 303 00:12:06,221 --> 00:12:08,924 A CONDITION BUT ALSO SOME RELIEF 304 00:12:08,924 --> 00:12:15,297 THAT IT WAS CAUGHT ON TIME. 305 00:12:15,297 --> 00:12:17,666 >> OKAY, AND DO YOU HAVE ANY 306 00:12:17,666 --> 00:12:18,967 OTHER MEDICAL CONDITIONS. 307 00:12:18,967 --> 00:12:24,272 >> YES, I HAVE AN AUTOIMMUNE 308 00:12:24,272 --> 00:12:25,874 DISEASE, PSORIASIS, AND IT'S 309 00:12:25,874 --> 00:12:26,241 SKIN CONDITION. 310 00:12:26,241 --> 00:12:28,109 >> DO YOU HAVE IT FROM BEFORE 311 00:12:28,109 --> 00:12:28,510 MS. 312 00:12:28,510 --> 00:12:30,145 >> BEFORE. 313 00:12:30,145 --> 00:12:36,017 I WAS DIAGNOSED AROUND 10 YEARS 314 00:12:36,017 --> 00:12:36,585 AGO, OR O. 315 00:12:36,585 --> 00:12:36,852 >> OKAY. 316 00:12:36,852 --> 00:12:38,987 AND DO YOU HAVE ANY OTHER 317 00:12:38,987 --> 00:12:39,821 MEDICAL CONDITION? 318 00:12:39,821 --> 00:12:40,255 >> NO. 319 00:12:40,255 --> 00:12:43,058 >> DID YOU EVER HAVE -- DID YOU 320 00:12:43,058 --> 00:12:44,326 EVER SMOKE? 321 00:12:44,326 --> 00:12:44,726 >> NO. 322 00:12:44,726 --> 00:12:49,498 >> WERE YOU OVERWEIGHT DURING 323 00:12:49,498 --> 00:12:49,798 ADOLESCENCE? 324 00:12:49,798 --> 00:12:50,665 >> SLIGHTLY, MAYBE. 325 00:12:50,665 --> 00:12:52,901 SOME OVERWEIGHT, NOT OBESITY, 326 00:12:52,901 --> 00:12:54,503 BUT SOME SLIGHT OVERWEIGHT, 327 00:12:54,503 --> 00:12:55,604 YEAH. 328 00:12:55,604 --> 00:13:00,976 NAND DID YOU HAVE MONONUCLEOSIS? 329 00:13:00,976 --> 00:13:06,748 >> MOST LIKELY I HAD IT, YEAH. 330 00:13:06,748 --> 00:13:07,449 I THINK. 331 00:13:07,449 --> 00:13:09,084 >> AND DOES ANYONE IN YOUR 332 00:13:09,084 --> 00:13:11,086 FAMILY HAVE MS OR ANY OTHER 333 00:13:11,086 --> 00:13:11,953 AUTOIMMUNE DISEASE IN. 334 00:13:11,953 --> 00:13:14,356 >> NO, I'M THE ONLY 1 WITH 335 00:13:14,356 --> 00:13:15,790 AUTOIMMUNE DISEASE IN GENERAL IN 336 00:13:15,790 --> 00:13:16,057 MY FAMILY. 337 00:13:16,057 --> 00:13:17,626 AT LEAST THAT HAS BEEN 338 00:13:17,626 --> 00:13:17,893 DIAGNOSED. 339 00:13:17,893 --> 00:13:18,693 MAYBE THERE WAS SOMETHING BUT 340 00:13:18,693 --> 00:13:20,896 THEY WERE NOT DIAGNOSED. 341 00:13:20,896 --> 00:13:21,496 >> I SEE. 342 00:13:21,496 --> 00:13:22,831 ALL RIGHT, SO, NOW I'M GOING 343 00:13:22,831 --> 00:13:24,132 BACK TO MY PRESENTATION, I WILL 344 00:13:24,132 --> 00:13:31,540 BE BACK TO YOU SHORTLY. 345 00:13:31,540 --> 00:13:32,974 THANK YOU. 346 00:13:32,974 --> 00:13:37,045 ALL RIGHT, SO YOU SEE MY SCREEN 347 00:13:37,045 --> 00:13:42,284 I THINK, YES, SO IN BILATERAL, 348 00:13:42,284 --> 00:13:42,817 SO INTERNUCLEAR OPERATING 349 00:13:42,817 --> 00:13:43,451 GLOBALLY THAT WILLETRY, IS 350 00:13:43,451 --> 00:13:45,887 CAUSED BY MS IN ONE-THIRD OF THE 351 00:13:45,887 --> 00:13:47,389 CASES AND MS IS THE MOST COMMON 352 00:13:47,389 --> 00:13:49,558 CAUSE IN YOUNG PERSONS 353 00:13:49,558 --> 00:13:50,926 PARTICULARLY PERSONS THAT ARE 354 00:13:50,926 --> 00:13:51,793 YOUNGER THAN 45 YEARS OLD, 355 00:13:51,793 --> 00:13:57,065 THAT'S THE CASE OF OUR PATIENT 356 00:13:57,065 --> 00:14:00,735 THAT WAS 29. 357 00:14:00,735 --> 00:14:05,373 DEFICIT IN THESE CASES IS 358 00:14:05,373 --> 00:14:07,309 BILATERAL IN MOST MS, AND THE 359 00:14:07,309 --> 00:14:10,078 MOST COMMON EYE MOVEMENT 360 00:14:10,078 --> 00:14:11,246 ABNORMALITY IN MS, AND MOST 361 00:14:11,246 --> 00:14:14,983 PATIENTS HAD LESIONS IN THE 362 00:14:14,983 --> 00:14:15,650 PONTINE MLF REGION. 363 00:14:15,650 --> 00:14:17,552 SO THIS IS 1 SCREEN, THIS IS T-2 364 00:14:17,552 --> 00:14:19,688 AND THIS IS FLARE AND YOU CAN 365 00:14:19,688 --> 00:14:24,659 SEE A SMALL MEDIUM LESION. 366 00:14:24,659 --> 00:14:28,263 SO AS A BRIEF INTRODUCTION MS A 367 00:14:28,263 --> 00:14:31,199 CHRONIC INFLAMMATORY DEBIL 368 00:14:31,199 --> 00:14:32,367 BAITING AND NEURODEGENERATIVE 369 00:14:32,367 --> 00:14:35,837 DISEASE OF THE NERVOUS SYSTEM, 370 00:14:35,837 --> 00:14:39,307 IT'S MOST OFTEN CHRONIC AND 371 00:14:39,307 --> 00:14:40,108 HETEROGENEOUS, MULTIFACTORIAL 372 00:14:40,108 --> 00:14:42,143 AND IMMUNE MEDIATED AND GOES BY 373 00:14:42,143 --> 00:14:44,779 A COMPLEX GENE ENVIRONMENTAL 374 00:14:44,779 --> 00:14:46,281 ENTERACTIONS AND THE MAIN PATH 375 00:14:46,281 --> 00:14:49,017 LODGE CAM HALLMARK IS THE 376 00:14:49,017 --> 00:14:49,985 ACCUMULATION OF LESIONS IN THE 377 00:14:49,985 --> 00:14:51,019 WHITE MATTER AND THE GRAY MATTER 378 00:14:51,019 --> 00:14:56,157 OF THE BRAIN AND SPINAL CORD. 379 00:14:56,157 --> 00:14:59,361 THE CLINICAL MANIFESTATIONS ARE 380 00:14:59,361 --> 00:15:01,896 REALLY HETEROGENEOUS AND MOST 381 00:15:01,896 --> 00:15:03,798 PATIENTS HAVE REVERSE ABLE 382 00:15:03,798 --> 00:15:05,233 EPISODES OF AS THE 1 OUR 383 00:15:05,233 --> 00:15:06,968 PARTICIPANT, OUR PATIENT HAD 384 00:15:06,968 --> 00:15:08,303 THAT USUALLY LASTS FOR A FEW 385 00:15:08,303 --> 00:15:11,339 DAYS, 2 WEEKS AND OVER THE TIME 386 00:15:11,339 --> 00:15:13,108 DEVELOP MAY DEVELOP PERMANENT 387 00:15:13,108 --> 00:15:15,543 DEFICITS THAT IT'S CALLED 388 00:15:15,543 --> 00:15:18,413 PROGRESSION AND IT'S SECONDARY 389 00:15:18,413 --> 00:15:20,782 PROGRESSIVE MS, A MINOR AMOUNT 390 00:15:20,782 --> 00:15:22,250 OF PATIENTS HOW PROGRESS THIS IS 391 00:15:22,250 --> 00:15:23,585 FROM THE ONSET. 392 00:15:23,585 --> 00:15:31,893 SO THE ONSET IS BETWEEN 20 AND 393 00:15:31,893 --> 00:15:40,468 40 YEARS OF AGE AND IT'S THE 394 00:15:40,468 --> 00:15:42,337 PRIMARY CAUSE OF NONTRAUMATTIC 395 00:15:42,337 --> 00:15:43,438 DISABILITY IN YOUNG ADULTS AND 396 00:15:43,438 --> 00:15:45,740 1 MILLION CASES IN THE U.S., 1 397 00:15:45,740 --> 00:15:48,043 IN 3000 PEOPLE HAS MS AND THE 398 00:15:48,043 --> 00:15:55,583 PREVALENCE BEEN INCREASING SINCE 399 00:15:55,583 --> 00:15:55,817 2013. 400 00:15:55,817 --> 00:15:58,253 SEE THERE ARE MANY FACTORS, NO 1 401 00:15:58,253 --> 00:16:03,992 CAUSE, BUT MANY FACTORS, AND 402 00:16:03,992 --> 00:16:06,695 MOST VARIANTS INVOLVE GENES 403 00:16:06,695 --> 00:16:09,330 REGULATED IMMUNE RESPONSES, HLA 404 00:16:09,330 --> 00:16:11,533 DRB11501 IS THE STRONGEST KNOWN 405 00:16:11,533 --> 00:16:12,534 SUSCEPTIBILITY GENE THAT 406 00:16:12,534 --> 00:16:17,338 INCREASES MS UP TO 3 FOLDS. 407 00:16:17,338 --> 00:16:19,507 SO THE GENETIC RISK IN GENERAL 408 00:16:19,507 --> 00:16:21,342 POPULATION, THE RISK IN 409 00:16:21,342 --> 00:16:22,544 GENTLEMEN POPULATION IS 0.1% AND 410 00:16:22,544 --> 00:16:24,612 THE FIRST DEGREE RELATIVES IS 2 411 00:16:24,612 --> 00:16:31,519 OPINIONED 5 TO 5%. 412 00:16:31,519 --> 00:16:34,956 AND IN IDENTICAL TWINS IT'S UP 413 00:16:34,956 --> 00:16:38,293 TO 30%. 414 00:16:38,293 --> 00:16:41,463 AND THERE ARE OTHER 415 00:16:41,463 --> 00:16:42,931 ASSOCIATIONS, EARLY ADULTHOOD IS 416 00:16:42,931 --> 00:16:46,935 ASSOCIATED WITH THE RISK AND 417 00:16:46,935 --> 00:16:51,339 IT'S ASSOCIATED WITH 32 FOLD 418 00:16:51,339 --> 00:16:52,841 INCREASED RISK, PROTECTED FROM 419 00:16:52,841 --> 00:16:54,242 DEVELOPING MS AND SOME PROTEINS 420 00:16:54,242 --> 00:16:58,680 OF THE VIRUS CAN MIMIC SOME 421 00:16:58,680 --> 00:17:00,582 GLIAL CNS PROTEINS POSSIBLY 422 00:17:00,582 --> 00:17:01,382 LEADING TO AUTOIMMUNITY. 423 00:17:01,382 --> 00:17:06,421 IT'S A HIGHER PREVALENCE IN 424 00:17:06,421 --> 00:17:07,055 CAUSEICATIONIANS AND EUROPEAN 425 00:17:07,055 --> 00:17:09,023 ANCESTRY AND THERE ARE MANY 426 00:17:09,023 --> 00:17:12,026 ENVIRONMENTAL FACTORS SUCH AS 427 00:17:12,026 --> 00:17:14,129 VITAMIN D DEFICIENCY TOBACCO 428 00:17:14,129 --> 00:17:17,632 SMOKING, OBESITY IN ADOLESCENCE 429 00:17:17,632 --> 00:17:19,200 THAT MAY LEAD TO A RISK FACTOR 430 00:17:19,200 --> 00:17:20,001 OF MS. 431 00:17:20,001 --> 00:17:22,737 SO GENETIC AND ENVIRONMENTAL 432 00:17:22,737 --> 00:17:24,506 RISK FACTORS SHIFT IMMUNE 433 00:17:24,506 --> 00:17:26,341 BALANCE TOWARDS MOW PRO 434 00:17:26,341 --> 00:17:28,176 INFLAMMATORY RISK RESPONSES AND 435 00:17:28,176 --> 00:17:29,110 THAT'S PROBABLY THE INTERACTION 436 00:17:29,110 --> 00:17:33,148 OF FACTORS THAT LEAD TO 437 00:17:33,148 --> 00:17:33,681 DEVELOPING MS. 438 00:17:33,681 --> 00:17:36,351 SO THERE ARE -- IT IS CALLED 439 00:17:36,351 --> 00:17:38,086 IMMUNE MEDIATED ATTACK ON THE 440 00:17:38,086 --> 00:17:40,822 MYELIN, THAT IS WHAT OUR PATIENT 441 00:17:40,822 --> 00:17:43,491 HAD, A RELAPSE AND SO THERE IS A 442 00:17:43,491 --> 00:17:44,926 COMBINATION THAT FACTORS BUT 443 00:17:44,926 --> 00:17:46,961 T-CELLS ACTIVATE MOSTLY IN THE 444 00:17:46,961 --> 00:17:48,797 PERIPHERY, ACROSS THE BLOOD 445 00:17:48,797 --> 00:17:50,398 BRAIN BARRIER AND INFLAMMATION 446 00:17:50,398 --> 00:17:52,300 BUT THERE ARE ALSO MANY OTHER 447 00:17:52,300 --> 00:17:55,537 FACTORS THAT PLAY A ROLE LIKE 448 00:17:55,537 --> 00:17:57,005 B-CELLS OR PROINFLAMMATORY AND 449 00:17:57,005 --> 00:17:59,774 THEN THAT SUPPORT IN T-CELL 450 00:17:59,774 --> 00:18:01,442 ACTIVATION, THERE ARE INVOLVING 451 00:18:01,442 --> 00:18:05,079 THE CNS, AND THERE ARE 452 00:18:05,079 --> 00:18:05,580 THERAPEUTIC IMPLICATIONS 453 00:18:05,580 --> 00:18:06,815 ACTUALLY, WE LEARNED A LOT IN 454 00:18:06,815 --> 00:18:08,850 THE LAST YEAR BECAUSE OF THE 455 00:18:08,850 --> 00:18:12,187 HIGH SUCCESS WE SAW OF DEPLETING 456 00:18:12,187 --> 00:18:13,454 THERAPIES HIGHLIGHTING THEIR 457 00:18:13,454 --> 00:18:21,229 CENTRAL ROLE IN THE MASS 458 00:18:21,229 --> 00:18:21,563 PATHOGENESIS. 459 00:18:21,563 --> 00:18:26,067 THESE ARE NICE IMAGES AFTER THE 460 00:18:26,067 --> 00:18:27,435 VENUE AND THEN THE LESIONS 461 00:18:27,435 --> 00:18:29,537 DEVELOPING IN THE BRAIN STEM AS 462 00:18:29,537 --> 00:18:31,773 WELL AS AXONAL DAMAGE DUE TO 463 00:18:31,773 --> 00:18:32,240 LESION INFORMATION. 464 00:18:32,240 --> 00:18:36,211 SO AS I MENTIONED THE HALLMARK 465 00:18:36,211 --> 00:18:39,414 OF FOCAL BRAIN LESIONS AND THIS 466 00:18:39,414 --> 00:18:42,417 IS THE MICROSCOPY OF A FOCAL 467 00:18:42,417 --> 00:18:43,585 MYELIN LESION AND YOU CAN SEE 468 00:18:43,585 --> 00:18:45,820 THAT LESIONS DEVELOP AND HAVE 469 00:18:45,820 --> 00:18:51,593 SOME EDEMA AND THIS IS 470 00:18:51,593 --> 00:18:52,627 INFLAMMATION SURROUNDING THE 471 00:18:52,627 --> 00:18:53,061 BRAIN. 472 00:18:53,061 --> 00:18:55,396 AND SO WE DETECT THEM WITH THE 473 00:18:55,396 --> 00:18:59,734 EYE, IT'S GOOD CORRELATION, THEY 474 00:18:59,734 --> 00:19:02,604 ARE ROUND, THEY DEVELOP IN THE 475 00:19:02,604 --> 00:19:04,906 VENTRICULAR AREA, AND AND WE CAN 476 00:19:04,906 --> 00:19:05,740 ALSO HAVE CORTICALE LESIONS, 477 00:19:05,740 --> 00:19:07,542 THERE ARE MANY TYPES OF 478 00:19:07,542 --> 00:19:08,943 CORTICALE LESIONS AND THEY ARE 479 00:19:08,943 --> 00:19:11,746 VERY DIFFICULT TO DETECT WITH 480 00:19:11,746 --> 00:19:12,614 CURRENT CLINICAL MRIs. 481 00:19:12,614 --> 00:19:14,816 SO EARLY IN THE DISEASE 482 00:19:14,816 --> 00:19:16,217 INFLAMMATION IS COMING MOSTLY 483 00:19:16,217 --> 00:19:19,187 FROM THE PERIPHERY, SO 484 00:19:19,187 --> 00:19:21,489 PERIPHERAL CELLS THAT CROSS THE 485 00:19:21,489 --> 00:19:22,457 BLOOD BRAIN BARRIER, GENERATE 486 00:19:22,457 --> 00:19:25,627 THE LESIONS, THIS IS AN EXAMPLE 487 00:19:25,627 --> 00:19:27,729 OF 1 LESION THAT IS YOU NEW AND 488 00:19:27,729 --> 00:19:29,063 HAS OPENING OF THE BLOOD BRAIN 489 00:19:29,063 --> 00:19:31,366 BARRIER AND WE CAN DETECT IT 490 00:19:31,366 --> 00:19:33,434 BECAUSE IT'S HYPER INTENSITY 1 491 00:19:33,434 --> 00:19:35,370 AND IT'S HYPER INTENSE AFTER WE 492 00:19:35,370 --> 00:19:37,105 PROVIDE CONTRAST TO THE 493 00:19:37,105 --> 00:19:37,505 PATIENTS. 494 00:19:37,505 --> 00:19:41,342 SO THIS IS AN OPEN BLOOD BRAIN 495 00:19:41,342 --> 00:19:42,610 BARRIER AND INFLAMMATORY LESION. 496 00:19:42,610 --> 00:19:45,580 BUT ONLY 1 OR 2 OUT OF THIN 497 00:19:45,580 --> 00:19:47,215 LESIONS ARE SYMPTOMATIC AND 498 00:19:47,215 --> 00:19:48,616 THAT'S WHAT CARLOS IS MENTIONING 499 00:19:48,616 --> 00:19:50,485 THAT HE HAD A LESION, HE HAD AN 500 00:19:50,485 --> 00:19:53,922 EPISODE AND HE HAD A COUPLE OF 501 00:19:53,922 --> 00:19:56,157 OTHER LESIONS IN THE MRI THAT 502 00:19:56,157 --> 00:19:57,759 HOE HAD WHEN HE DEVELOPED THE 503 00:19:57,759 --> 00:19:58,726 FIRST EPISODE. 504 00:19:58,726 --> 00:20:01,362 SO RELAPSE IN PATHOLOGY RECEDES 505 00:20:01,362 --> 00:20:02,964 OVER THE TIME EITHER DUE TO THE 506 00:20:02,964 --> 00:20:09,037 EFFECTS OF THE EMTs OR THROUGH 507 00:20:09,037 --> 00:20:10,004 IMMUNE STAGES. 508 00:20:10,004 --> 00:20:13,541 AT LATER STAGES OF THE DISEASE 509 00:20:13,541 --> 00:20:14,709 AND MORE COMPARTMENTALIZED, 510 00:20:14,709 --> 00:20:17,845 EITHER AS AGGREGATES, FULL OF 511 00:20:17,845 --> 00:20:19,747 B-CELLS, OR CHRONIC ACTIVE 512 00:20:19,747 --> 00:20:21,482 LESIONS OR LESIONS THAT FORM, 513 00:20:21,482 --> 00:20:23,117 THEY DON'T SEAL COMPLETELY, 514 00:20:23,117 --> 00:20:27,121 DON'T REPAIR COMPLETELY AND HAVE 515 00:20:27,121 --> 00:20:27,956 MICROGLIA AND MICROPHAGES 516 00:20:27,956 --> 00:20:30,558 ACTIVATED IN THE BORDER OF THE 517 00:20:30,558 --> 00:20:31,826 LESION OR INNATE IMMUNE 518 00:20:31,826 --> 00:20:34,829 ACTIVATION AND THEN NORMAL WHITE 519 00:20:34,829 --> 00:20:40,768 MATTER DISTRIBUTED ALL AROUND 520 00:20:40,768 --> 00:20:42,236 THE BRAIN. 521 00:20:42,236 --> 00:20:43,638 SO CNS COMPARTMENTALIZE THIS 522 00:20:43,638 --> 00:20:47,241 LESION, AND THIS IS TRIBUTED 523 00:20:47,241 --> 00:20:48,376 THROUGH THE PRODUCTION OF 524 00:20:48,376 --> 00:20:50,845 CHEMOKINES AND OTHER 525 00:20:50,845 --> 00:20:53,114 INFLAMMATORY COMPONENTS. 526 00:20:53,114 --> 00:20:59,954 SO THE FIRST DESCRIPTION OF THIS 527 00:20:59,954 --> 00:21:02,857 WERE MOSTLY FOCUSED ON RELAPSED 528 00:21:02,857 --> 00:21:04,225 PATIENTS, PATIENTS THAT PROGRESS 529 00:21:04,225 --> 00:21:05,526 OVER THE TIME, SECONDARY 530 00:21:05,526 --> 00:21:06,794 PROGRESSIVE BUT THE TRUTH IS 531 00:21:06,794 --> 00:21:10,698 THAT IT'S NOT SO STATIC, IT'S 532 00:21:10,698 --> 00:21:13,668 NOT SO WELL ESTABLISHED. 533 00:21:13,668 --> 00:21:15,303 SO THINGS ARE HAPPENING, SINCE 534 00:21:15,303 --> 00:21:20,208 THE VERY BEGINNING, SO THERE IS 535 00:21:20,208 --> 00:21:21,376 A PRESYMPTOMATIC PHASE WHERE THE 536 00:21:21,376 --> 00:21:22,844 PATIENTS MAY HAVE LESIONS THAT 537 00:21:22,844 --> 00:21:24,345 DO NOT CROSS THE CLINICAL FLESH 538 00:21:24,345 --> 00:21:27,148 HOLD AND THIS IS WHAT WE CALL 539 00:21:27,148 --> 00:21:27,849 REGULARLY ISOLATED SYNDROME AND 540 00:21:27,849 --> 00:21:29,050 THE PATIENT HAS THE FIRST 541 00:21:29,050 --> 00:21:31,019 EPISODE THAT IS THE CLINICAL 542 00:21:31,019 --> 00:21:33,087 ISOLATED SYNDROME AND THEN THE 543 00:21:33,087 --> 00:21:35,623 PATIENT'S ARE -- MAY EVOLVE INTO 544 00:21:35,623 --> 00:21:37,191 RELAPSE AND REMEDIATING MULTIPLE 545 00:21:37,191 --> 00:21:38,259 SCLEROSIS FOR MANY YEARS AND 546 00:21:38,259 --> 00:21:39,527 EVOLVING TO A PROGRESSIVE PHASE 547 00:21:39,527 --> 00:21:46,300 OF THE DEC, -- DISEASE, WHAT IS 548 00:21:46,300 --> 00:21:47,235 CALLED SECONDARY MS, THERE IS 549 00:21:47,235 --> 00:21:50,638 ALSO A FEW PATIENTS THAT MY 550 00:21:50,638 --> 00:21:51,873 DEVELOP PRIMARY MS, PROGRESSION 551 00:21:51,873 --> 00:21:52,340 SINCE THE BEGINNING. 552 00:21:52,340 --> 00:21:55,610 BUT THE TRUTH IS THAT 553 00:21:55,610 --> 00:22:00,014 PROGRESSION IS NOT DICHOTOMOUS, 554 00:22:00,014 --> 00:22:02,717 PATIENTS WITH RELAPSED MS MAY 555 00:22:02,717 --> 00:22:04,852 HAVE REGRESSION FROM RELAPSES SO 556 00:22:04,852 --> 00:22:06,187 BASICALLY MS CLINICAL 557 00:22:06,187 --> 00:22:07,722 PRESENTATIONS REPRESENTS A 558 00:22:07,722 --> 00:22:08,656 CONTINUED SPECTRUM OF MANY 559 00:22:08,656 --> 00:22:12,060 THINGS THAT PLAY TOGETHER LIKE 560 00:22:12,060 --> 00:22:13,828 INFLAMMATION, DEMILENNATION, 561 00:22:13,828 --> 00:22:15,596 AXONAL GENERATION AND THE 562 00:22:15,596 --> 00:22:21,135 CAPACITY OF THE BRAIN, 563 00:22:21,135 --> 00:22:24,072 NEUROPLASTICKITY AND AS WELL AS 564 00:22:24,072 --> 00:22:25,873 AGE AND NEUROBIOLOGICAL AGING. 565 00:22:25,873 --> 00:22:26,941 SO RELAXED PATHOLOGY DOMINATES 566 00:22:26,941 --> 00:22:31,612 IN THE INITIAL PHASES OF MS, AND 567 00:22:31,612 --> 00:22:32,780 RELAPSE ACTIVITY SUBSEQUENTLY 568 00:22:32,780 --> 00:22:35,817 TAKES THE PRIMARY ROAD. 569 00:22:35,817 --> 00:22:37,652 SYMPTOMS MAY BE MANY DIFFERENT 570 00:22:37,652 --> 00:22:40,288 SYMPTOMS, THE MOST IMPORTANT 571 00:22:40,288 --> 00:22:41,823 THING, SO, THE FIRST EPISODE IN 572 00:22:41,823 --> 00:22:48,830 25% OF THE PATIENTS IS OPTIC 573 00:22:48,830 --> 00:22:49,997 NEPHRITIS, AND SEIVET% OF THE 574 00:22:49,997 --> 00:22:51,766 PATIENTS WITH MS DURING THE 575 00:22:51,766 --> 00:22:54,435 COURSE OF THE DEC MAY EXPERIENCE 576 00:22:54,435 --> 00:22:54,936 1. 577 00:22:54,936 --> 00:22:56,637 SO WHAT OUR PARTICIPANT IS 578 00:22:56,637 --> 00:22:59,040 TELLING US IT'S THE PERFECT 579 00:22:59,040 --> 00:23:02,910 DESCRIPTION OF A RELAPSE, IS THE 580 00:23:02,910 --> 00:23:03,845 MODULATION OF SYMPTOMS NEVER 581 00:23:03,845 --> 00:23:05,446 ACUTE THAT LAST MORE THAN 24 582 00:23:05,446 --> 00:23:11,085 HOURS IN THE ABSENCE OF FEVER OR 583 00:23:11,085 --> 00:23:11,352 INFECTION. 584 00:23:11,352 --> 00:23:14,088 SO ACCORDING TO WHERE THE LESION 585 00:23:14,088 --> 00:23:15,356 IS LOCATED, THE SYMPTOM THAT A 586 00:23:15,356 --> 00:23:17,558 PATIENT MAY HAVE AND THESE ARE 587 00:23:17,558 --> 00:23:20,061 ALL POSSIBLE SYMPTOMS THAT MAY 588 00:23:20,061 --> 00:23:21,562 APPEAR IN A REAL LABS. 589 00:23:21,562 --> 00:23:24,065 THERE ARE OTHER SYMPTOMS THAT 590 00:23:24,065 --> 00:23:25,867 ARE NOT TYPICAL FOR RELAPSES BUT 591 00:23:25,867 --> 00:23:27,568 REALLY IMPACT QUALITY OF LIFE. 592 00:23:27,568 --> 00:23:31,405 THE MOST FREQUENT 1 IS FATIGUE, 593 00:23:31,405 --> 00:23:34,075 THAT UP TO 95% OF PARTICIPANT 594 00:23:34,075 --> 00:23:36,844 PATIENTS MAY EXPERIENCE IT, 595 00:23:36,844 --> 00:23:39,313 COGNITIVE IMPAIRMENT, EFFECTIVE 596 00:23:39,313 --> 00:23:44,652 DISTURBANCE, SLEEP DISORDERS AND 597 00:23:44,652 --> 00:23:45,086 PAIN. 598 00:23:45,086 --> 00:23:46,721 SO HOW DO WE DIAGNOSE THAT IS 599 00:23:46,721 --> 00:23:49,123 NOT A SPECIFIC TEST THAT WE CAN 600 00:23:49,123 --> 00:23:53,127 DO SO WE NEED TO SHOW THAT THE 601 00:23:53,127 --> 00:23:53,728 PATIENT HAS DISSEMINATION IN 602 00:23:53,728 --> 00:23:55,997 SPACE AND TIME AND THIS CAN BE 603 00:23:55,997 --> 00:23:58,232 SHOWN WITH MRI, ONCE WE EXCLUDE 604 00:23:58,232 --> 00:23:58,966 OTHER DIAGNOSIS. 605 00:23:58,966 --> 00:24:00,768 SO THE FIRST TIME THAT MRI WAS 606 00:24:00,768 --> 00:24:08,809 INCLUDED IN THE DIAGNOSIS, WAS 607 00:24:08,809 --> 00:24:15,116 IN 2001 WHERE 3 TYPICAL 608 00:24:15,116 --> 00:24:16,284 LOCATION, FRONTAL AND 609 00:24:16,284 --> 00:24:17,218 PERIVENTRICULAR AND WERE 610 00:24:17,218 --> 00:24:18,953 INCLUDED IN THE CRITERIA, LATER 611 00:24:18,953 --> 00:24:20,821 IN 2005, THE SPINAL CORD WAS 612 00:24:20,821 --> 00:24:22,123 INCLUDED AS A PLACE WHERE 613 00:24:22,123 --> 00:24:24,458 LESIONS CAN DEVELOP AND IN 2010, 614 00:24:24,458 --> 00:24:28,296 BOTH LESIONS THAT WERE ENHANCING 615 00:24:28,296 --> 00:24:30,164 AND NONENHANCING COULD COUNT FOR 616 00:24:30,164 --> 00:24:31,699 DISSEMINATION IN TIME. 617 00:24:31,699 --> 00:24:35,636 SO DISSEMINATION AND SPACE TO 618 00:24:35,636 --> 00:24:37,138 AREAS AND DISSEMINATION IN TIME 619 00:24:37,138 --> 00:24:39,574 TO EPISODES OF LESIONS THAT ARE 620 00:24:39,574 --> 00:24:42,343 ENHANCING AND ARE NOT ENHANCING 621 00:24:42,343 --> 00:24:45,012 AND THAT'S WHAT EXACTLY 622 00:24:45,012 --> 00:24:47,448 MR. CHACON HAS AND THAT'S WHY HE 623 00:24:47,448 --> 00:24:48,349 DIDN'T NEED LUMBAR PUNCTURE. 624 00:24:48,349 --> 00:24:52,253 SO WHEN I MENTIONED THE TYPICAL 625 00:24:52,253 --> 00:24:55,923 LESIONS, I'M REFERRING TO THESE 626 00:24:55,923 --> 00:24:57,558 4 AREAS, THE PERIVENTRICULAR, AS 627 00:24:57,558 --> 00:25:01,229 I SHOW YOU, THIS IS I FLIR 628 00:25:01,229 --> 00:25:03,497 SEQUENCE BECAUSE IT INVERTS THE 629 00:25:03,497 --> 00:25:05,933 CONTRAST OF THE CSF, IN THE 630 00:25:05,933 --> 00:25:08,369 LESIONS, WE CAN USE THE SEQUENCE 631 00:25:08,369 --> 00:25:09,270 THAT IS T2. 632 00:25:09,270 --> 00:25:12,440 AND THE FLAIR WHEN IT'S IN 3 633 00:25:12,440 --> 00:25:16,510 DIMENSIONS IS ALSO USEFUL, AND 634 00:25:16,510 --> 00:25:17,712 THE CORTICALE LESIONS THAT 635 00:25:17,712 --> 00:25:20,982 FOLLOW THE U-SHAPE OF THE 636 00:25:20,982 --> 00:25:22,950 FIBERS, AND SPINAL CORD LESIONS, 637 00:25:22,950 --> 00:25:32,760 THE SMALL LESION, LATERAL 638 00:25:32,760 --> 00:25:34,128 LESIONS, SHORT 1S, BUT THE 639 00:25:34,128 --> 00:25:38,232 CORTEX IS ALSO VERY, VERY TOUGH 640 00:25:38,232 --> 00:25:41,402 TO DETECT, SCANNERS WILL DETECT 641 00:25:41,402 --> 00:25:46,173 THEM EASILY AT 17, AND THEY WERE 642 00:25:46,173 --> 00:25:46,974 DEECTOMYOSIN IT INDEED 2017 643 00:25:46,974 --> 00:25:47,241 CRITERIA. 644 00:25:47,241 --> 00:25:48,509 SO LET ME JUST SHOW YOU AN 645 00:25:48,509 --> 00:25:51,545 EXAMPLE OF A BRAIN THAT DOESN'T 646 00:25:51,545 --> 00:25:54,548 SEEM TO HAVE A LOT OF DISEASE 647 00:25:54,548 --> 00:25:55,816 THERE, YOU DON'T SEE WHITE 648 00:25:55,816 --> 00:25:57,018 MATTER LESIONS BUT WHEN YOU LOOK 649 00:25:57,018 --> 00:25:59,487 IN THERE, YOU SEE THERE ARE MANY 650 00:25:59,487 --> 00:26:04,892 LESIONS IN THE BRAIN OF THIS 651 00:26:04,892 --> 00:26:07,261 PARTICIPANT EMPLOY SO THE LUMBAR 652 00:26:07,261 --> 00:26:10,398 PUNCTURE IS SOMETIMES NEEDED FOR 653 00:26:10,398 --> 00:26:11,565 DISDIAGNOSIS, PATIENTS CAN 654 00:26:11,565 --> 00:26:12,366 FULFILL CRITERIA WITHOUT THE 655 00:26:12,366 --> 00:26:16,537 NEED BUT IF THE PARTICIPANT AS A 656 00:26:16,537 --> 00:26:17,672 CLONAL THAT ARE PRESENT, THEY 657 00:26:17,672 --> 00:26:20,675 NEED TO HAVE NEWER LABS OR 658 00:26:20,675 --> 00:26:23,778 ACTIVE LESIONS TO FULFILL THE 659 00:26:23,778 --> 00:26:25,346 CRITERIA IN TIME. 660 00:26:25,346 --> 00:26:26,280 THESE ARE IGG, AND THE 661 00:26:26,280 --> 00:26:29,517 PREVALENCE IS UP TO 90% WITH THE 662 00:26:29,517 --> 00:26:33,154 SENSITIVITY HIGH OF VERY HIGH OF 663 00:26:33,154 --> 00:26:34,889 95%, BUT SPECIFICITY IS NOT AS 664 00:26:34,889 --> 00:26:38,326 HIGH, ON THE ADVANCE, BUT IT'S 665 00:26:38,326 --> 00:26:39,727 ACCELERATE DIAGNOSIS IN PATIENTS 666 00:26:39,727 --> 00:26:40,895 THAT HAVE THE FIRST EPISODE AND 667 00:26:40,895 --> 00:26:45,199 IN PATIENTS THAT HAVE REGULAR 668 00:26:45,199 --> 00:26:45,599 ISOLATED SYNDROME. 669 00:26:45,599 --> 00:26:48,302 SO GOING BACK TO OUR PATIENT, 670 00:26:48,302 --> 00:26:50,204 OUR PATIENT HAD THIS LESION THAT 671 00:26:50,204 --> 00:26:53,374 WAS THE 1 THAT WAS SYMPTOMATIC 672 00:26:53,374 --> 00:26:55,242 IN THE PONTINE AREA, THIS 673 00:26:55,242 --> 00:26:59,547 LESION, SO HE FULFILL THE SPACE 674 00:26:59,547 --> 00:27:01,248 AND HE HAD ENHANCING AND 675 00:27:01,248 --> 00:27:02,450 NONENHANCING LESIONS. 676 00:27:02,450 --> 00:27:04,552 THIS 1 WAS NOT ENHANCING AND 677 00:27:04,552 --> 00:27:07,655 THESE 2 WERE ENHANCING SO HE 678 00:27:07,655 --> 00:27:09,623 FULFILLED CRITERIA FOR 679 00:27:09,623 --> 00:27:10,091 DISSEMINATION IN TIME. 680 00:27:10,091 --> 00:27:11,158 I WILL MENTION A COUPLE OF 681 00:27:11,158 --> 00:27:12,693 THINGS MORE, THERE ARE TYPICAL 682 00:27:12,693 --> 00:27:18,566 FOR MS LESIONS IS THAT A LONG 683 00:27:18,566 --> 00:27:19,867 TIME AGO, DEMONSTRATED THAT 684 00:27:19,867 --> 00:27:20,668 LESIONS DEVELOP SURROUNDING A 685 00:27:20,668 --> 00:27:25,072 VENUE AND THEN THERE IS THE 686 00:27:25,072 --> 00:27:25,906 PERIVASCULAR IMP O SIGHT CALF 687 00:27:25,906 --> 00:27:29,110 AND THEN THE LESION EXTENDS 688 00:27:29,110 --> 00:27:30,344 OUTWARD GENERATING THE 689 00:27:30,344 --> 00:27:31,879 MILENNATION AND MANY, MANY YEARS 690 00:27:31,879 --> 00:27:35,816 AFTER IN 2000, IT WAS ABLE TO BE 691 00:27:35,816 --> 00:27:39,320 DEMONSTRATED AT USING THE STAR 692 00:27:39,320 --> 00:27:42,123 SEQUENCES AND THIS SEQUENCE IS 693 00:27:42,123 --> 00:27:44,592 EXPLORE THE PROPERTIES OF THE 694 00:27:44,592 --> 00:27:48,863 TISSUE AND THE HEMOGLOBIN THAT 695 00:27:48,863 --> 00:27:50,531 IS INSIDE PURTURBING THE 696 00:27:50,531 --> 00:27:51,632 MAGNETIC FIELD AND THE BOXES 697 00:27:51,632 --> 00:27:55,035 THAT ARE WITHIN THAT AREA ARE 698 00:27:55,035 --> 00:27:58,205 SHOWN VERY TARGETS IN THIS 699 00:27:58,205 --> 00:28:01,409 EXAMPLE EMPLOY SO PLAQUES REALLY 700 00:28:01,409 --> 00:28:05,112 FORM AROUND VEINS AND THIS IS 701 00:28:05,112 --> 00:28:06,881 DETECTED AT 70 MRI AS I'M 702 00:28:06,881 --> 00:28:08,916 SHOWING NOW BUT ALSO ONIN 703 00:28:08,916 --> 00:28:09,383 KLF-TWOICAL SCANNERS. 704 00:28:09,383 --> 00:28:11,252 BECAUSE OF THAT THERE ARE INCLUE 705 00:28:11,252 --> 00:28:12,286 CLIEWGZ CRITERIA, SO WE NEED TO 706 00:28:12,286 --> 00:28:15,956 SEE AT LEAST IN 2 PLANES, 1 HAS 707 00:28:15,956 --> 00:28:18,626 TO BE AA LINE, 1 HAS TO BE A 708 00:28:18,626 --> 00:28:21,429 DOT, AND THIS SIDE IS REALLY 709 00:28:21,429 --> 00:28:23,531 VERY IMPORTANT BECAUSE IT HELPS 710 00:28:23,531 --> 00:28:24,665 TO DISCRIMINATE WHITE MATTER 711 00:28:24,665 --> 00:28:25,833 LESIONS AND WHITE MATTER LESIONS 712 00:28:25,833 --> 00:28:28,469 THAT ARE DUE TO MS TO OTHERS 713 00:28:28,469 --> 00:28:33,707 THAT MAY MIMIC MS AND IT'S 714 00:28:33,707 --> 00:28:34,375 REALLY VERY RELIABLE. 715 00:28:34,375 --> 00:28:37,878 SO NOW IN THE NEW CRITERIA THAT 716 00:28:37,878 --> 00:28:41,682 I WILL PROBABLY PUBLISH SHORTLY 717 00:28:41,682 --> 00:28:44,485 ARE THE MITT GAIGDZ OF THE 718 00:28:44,485 --> 00:28:45,653 CRITERIA OF 2024, THEY ARE 719 00:28:45,653 --> 00:28:47,054 PLANNING TO INCLUDE THE OPTIC 720 00:28:47,054 --> 00:28:48,889 NERVE BECAUSE IT'S FREQUENTLY 721 00:28:48,889 --> 00:28:51,859 AFFECTED AS WELL AS A CENTRAL 722 00:28:51,859 --> 00:28:54,628 VEIN SIGN AND OTHER SIGNS THAT 723 00:28:54,628 --> 00:28:59,400 DR. REICH IS PROBABLY GOING TO 724 00:28:59,400 --> 00:29:00,167 DISCUSS LATER. 725 00:29:00,167 --> 00:29:02,036 SO IN OUR PATIENT WE HAVE A FEW 726 00:29:02,036 --> 00:29:02,269 LESIONS. 727 00:29:02,269 --> 00:29:04,538 NOW THEY ARE GETTING VERY SMALL, 728 00:29:04,538 --> 00:29:07,408 BUT THEY WERE ALL CENTRAL VEIN 729 00:29:07,408 --> 00:29:07,775 POSITIVE. 730 00:29:07,775 --> 00:29:09,977 SO WHEN AN MRI HAS MORE THAN 40% 731 00:29:09,977 --> 00:29:12,179 OF THE LESIONS WITH THE CENTRAL 732 00:29:12,179 --> 00:29:19,820 SIGN, WE CAN SAY THAT THAT MRI 733 00:29:19,820 --> 00:29:20,554 IS CENTRAL POSITIVE. 734 00:29:20,554 --> 00:29:22,122 SO IT'S VERY USEFUL BECAUSE 735 00:29:22,122 --> 00:29:23,891 PATIENTS WOULDN'T NEED TO WAIT 736 00:29:23,891 --> 00:29:25,693 FOR ANOTHER MRI TO SHOW 737 00:29:25,693 --> 00:29:26,861 DISSEMINATION AND TIME, AND 738 00:29:26,861 --> 00:29:28,929 WOULDN'T NEED TO HAVE A LUMBAR 739 00:29:28,929 --> 00:29:30,598 PUNCTURE WHEN THEY FULFILL THIS 740 00:29:30,598 --> 00:29:30,998 CRITERIA. 741 00:29:30,998 --> 00:29:31,665 AND IT'S VERY IMPORTANT BECAUSE 742 00:29:31,665 --> 00:29:36,470 IT CAN BE USED ALSO FOR RADIO 743 00:29:36,470 --> 00:29:38,506 LOGICALLY ISOLATED SYNDROME AS I 744 00:29:38,506 --> 00:29:39,473 MENTIONED BEFORE, INCIDENTAL 745 00:29:39,473 --> 00:29:42,776 BRAIN OR SPINAL CORD LESIONS, IN 746 00:29:42,776 --> 00:29:44,812 SYMPTOMATIC PATIENT AND CAN HELP 747 00:29:44,812 --> 00:29:48,516 TO DIAGNOSE THE DISEASE. 748 00:29:48,516 --> 00:29:50,351 SO WITH THAT SAID, I WOULD LIKE 749 00:29:50,351 --> 00:30:00,895 TO GO BACK TO YOU MR. CHACON, I 750 00:30:05,900 --> 00:30:06,300 WILL STOP SHARING. 751 00:30:06,300 --> 00:30:08,869 AND I WILL LIKE TO GO BACK TO 752 00:30:08,869 --> 00:30:09,870 YOU FOR YOUR TREATMENT. 753 00:30:09,870 --> 00:30:10,971 HOW WERE YOU TREATED FOR THIS 754 00:30:10,971 --> 00:30:12,640 DISEASE IN HOW DID YOU MAKE YOUR 755 00:30:12,640 --> 00:30:14,241 DECISION IN, I WOULD LOAMACY 756 00:30:14,241 --> 00:30:16,110 LIKE TO KNOW ABOUT THAT. 757 00:30:16,110 --> 00:30:17,111 >> YES, THANK YOU. 758 00:30:17,111 --> 00:30:19,079 YES, I HAVE BEEN IN TREATMENT 759 00:30:19,079 --> 00:30:21,515 SINCE JANUARY 2022, IF I'M NOT 760 00:30:21,515 --> 00:30:22,716 MISTAKEN. 761 00:30:22,716 --> 00:30:22,950 YEAH. 762 00:30:22,950 --> 00:30:26,587 ONCE I WAS DIAGNOSED, THE 763 00:30:26,587 --> 00:30:30,457 FOLLOWING WEEK I MET WITH A 764 00:30:30,457 --> 00:30:31,725 SPECIALIST, A DOCTOR, AND WE 765 00:30:31,725 --> 00:30:35,362 SPOKE ABOUT THE TREATMENT AND HE 766 00:30:35,362 --> 00:30:38,299 BASICALLY PRESENTED TO ME ALL 767 00:30:38,299 --> 00:30:40,935 THE DIFFERENT OPTIONS FROM 768 00:30:40,935 --> 00:30:42,636 TAKING PILLS TO IMMUNE SUPPRESS 769 00:30:42,636 --> 00:30:46,473 ANTS AND AT THE END WE NARROWED 770 00:30:46,473 --> 00:30:52,246 THE POSSIBILITY TREATMENTS TO 2 771 00:30:52,246 --> 00:30:52,713 OPTIONS. 772 00:30:52,713 --> 00:30:55,349 I CHOSE AN INFUSION THAT'S IT'S 773 00:30:55,349 --> 00:30:57,284 EVERY 6 MONTHS, WELL NOW IT'S 774 00:30:57,284 --> 00:30:58,819 GOING TO BE LIKE WAY EASIER 775 00:30:58,819 --> 00:31:02,289 BECAUSE IT'S GOING TO BE AN 776 00:31:02,289 --> 00:31:03,757 INJECTION INSTEAD OFAIN INFUSION 777 00:31:03,757 --> 00:31:05,659 AND THAT'S THE 1 I'VE BEEN 778 00:31:05,659 --> 00:31:06,594 TAKING SINCE JANUARY 2022 AND 779 00:31:06,594 --> 00:31:08,796 THE REASON I TOOK THAT 1 IS 780 00:31:08,796 --> 00:31:10,230 BECAUSE IT'S EVERY 6 MONTHS 781 00:31:10,230 --> 00:31:13,601 INSTEAD OF AN INJECTION EVERY 782 00:31:13,601 --> 00:31:13,834 MONTH. 783 00:31:13,834 --> 00:31:16,170 >> WONDERFUL SO YOU TOOK PART IN 784 00:31:16,170 --> 00:31:17,738 THE DECISION, RIGHT? 785 00:31:17,738 --> 00:31:18,806 >> YES. 786 00:31:18,806 --> 00:31:20,074 >> THAT'S VERY IMPORTANT. 787 00:31:20,074 --> 00:31:20,574 >> YES. 788 00:31:20,574 --> 00:31:22,142 HE PRESENTED OPTIONS TO ME, I 789 00:31:22,142 --> 00:31:24,445 HAVE ANOTHER FRIEND THAT SHE HAS 790 00:31:24,445 --> 00:31:27,181 MS AS WELL, AND SHE'S TAKING 791 00:31:27,181 --> 00:31:27,381 PILLS. 792 00:31:27,381 --> 00:31:30,918 SHE PREFERRED NOT TO BE AS 793 00:31:30,918 --> 00:31:32,653 AGGRESSIVE AS I WAS. 794 00:31:32,653 --> 00:31:34,021 >> OKAY AND DO YOU EXPERIENCE 795 00:31:34,021 --> 00:31:36,457 ANY ADVERSE EEIVET WHEN YOU HAVE 796 00:31:36,457 --> 00:31:37,057 INFUSIONS? 797 00:31:37,057 --> 00:31:40,194 >> NO, SO FAR, NO ADVERSE EVENTS 798 00:31:40,194 --> 00:31:42,596 AND NOW EVERY TIME I GET AN 799 00:31:42,596 --> 00:31:44,031 INFUSION, IT TENDS TO BE FASTER 800 00:31:44,031 --> 00:31:45,099 THAN THE PREVIOUS TIME, THE 801 00:31:45,099 --> 00:31:48,335 FIRST TIME IT WAS LIKE 4 HOURS 802 00:31:48,335 --> 00:31:50,004 AND SOMETHING, NOW IT'S LESS 803 00:31:50,004 --> 00:31:52,906 THAN 4 HOURS, USUALLY. 804 00:31:52,906 --> 00:31:54,575 SO, YEAH, MY BODY RESPONDS WELL. 805 00:31:54,575 --> 00:31:56,377 I EVEN GET A LOT OF ENERGY THAT 806 00:31:56,377 --> 00:32:02,182 DAY SO I USUALLY GO FOR A RUN 807 00:32:02,182 --> 00:32:02,516 THAT SAME DAY. 808 00:32:02,516 --> 00:32:08,355 >> AND DO YOU KNOW IF THE 809 00:32:08,355 --> 00:32:09,690 TREATMENT IS WORKING? 810 00:32:09,690 --> 00:32:11,525 >> I MEAN I HAVEN'T HAD ANY 811 00:32:11,525 --> 00:32:13,627 SYMPTOMS SINCE I WAS DIAGNOSED 812 00:32:13,627 --> 00:32:14,862 THE FIRST TIME. 813 00:32:14,862 --> 00:32:18,866 I THINK I DON'T HAVE NEW LESIONS 814 00:32:18,866 --> 00:32:19,867 OR, WELL, YOU CAN 815 00:32:19,867 --> 00:32:20,601 COROBSESSIVEERATE THAT BECAUSE 816 00:32:20,601 --> 00:32:24,538 YOU HAVE ACCESS TO MY MRIs, 817 00:32:24,538 --> 00:32:27,307 BUT NO NEW LESIONS AND NO 818 00:32:27,307 --> 00:32:29,009 SYMPTOMS AND NO RELAPSES SO FAR 819 00:32:29,009 --> 00:32:32,146 IN 3 AND HALF YEARS AND KNOCK ON 820 00:32:32,146 --> 00:32:35,349 WOOD BY THE WAY NTHAT'S GOOD. 821 00:32:35,349 --> 00:32:37,418 AND DO YOU DO ANY WORK OUT? 822 00:32:37,418 --> 00:32:38,786 DO YOU EXERCISE REGULARLY IN 823 00:32:38,786 --> 00:32:40,954 WHAT DO YOU DO? 824 00:32:40,954 --> 00:32:43,657 DID YOU CHANGE ANYTHING IN YOUR 825 00:32:43,657 --> 00:32:44,558 RECEIVE AFTER DIAGNOSIS? 826 00:32:44,558 --> 00:32:46,427 >> OH YEAH, THAT'S ANOTHER BIG 827 00:32:46,427 --> 00:32:48,395 COMPONENT SINCE I WAS DIAGNOSED, 828 00:32:48,395 --> 00:32:53,233 I'VE BEEN PRIORITIZE A LOT MORE 829 00:32:53,233 --> 00:32:54,068 SLEEP DURING THE FIRST 20 830 00:32:54,068 --> 00:32:56,170 SOMETHING YEARS OF MY LIFE I 831 00:32:56,170 --> 00:32:58,605 DIDN'T PRIORITIZE SLEEP, SO 832 00:32:58,605 --> 00:33:00,240 MAYBE THAT HAD CONSEQUENCE OR 833 00:33:00,240 --> 00:33:04,611 NOT, BUT NOW I DO PRIORITIZE 834 00:33:04,611 --> 00:33:08,482 SLEEP, I TRY TO GET 7 OR 8 HOURS 835 00:33:08,482 --> 00:33:09,216 EVERY NIGHT. 836 00:33:09,216 --> 00:33:10,250 I CHANGED COMPLETELY. 837 00:33:10,250 --> 00:33:13,020 I EAT BETTER, I TAKE BETTER CARE 838 00:33:13,020 --> 00:33:15,789 OF MY DIET, NOT ALWAYS BUT I EAT 839 00:33:15,789 --> 00:33:16,256 BETTER. 840 00:33:16,256 --> 00:33:20,761 >> BETTER DO YOU MEAN HEALTHIER 841 00:33:20,761 --> 00:33:21,328 >> HEALTHIER, YEAH, YEAH. 842 00:33:21,328 --> 00:33:24,298 I PAY A LOT MORE ATTENTION TO 843 00:33:24,298 --> 00:33:25,833 WHAT I EAT. 844 00:33:25,833 --> 00:33:27,901 I BARELY DRINK ALCOHOL, ONLY ON 845 00:33:27,901 --> 00:33:30,070 SPECIAL OCCASIONS AND YEAH, AND 846 00:33:30,070 --> 00:33:32,039 I DO EXERCISE, AND I LIKE TO RUN 847 00:33:32,039 --> 00:33:38,512 AND I ALSO GO TO GYM 1 OR 2 848 00:33:38,512 --> 00:33:41,148 TIMES A WEEK. 849 00:33:41,148 --> 00:33:41,749 >> WONDERFUL, THAT'S GREAT. 850 00:33:41,749 --> 00:33:44,351 AND DO YOU HAVE ANY SYMPTOM, ANY 851 00:33:44,351 --> 00:33:46,787 FATIGUE DO YOU EXPERIENCE DURING 852 00:33:46,787 --> 00:33:47,354 THE DAY? 853 00:33:47,354 --> 00:33:49,123 >> I MEAN YES, AND THE 854 00:33:49,123 --> 00:33:51,458 CHALLENGES,IME NOT SURE IF IT IS 855 00:33:51,458 --> 00:33:53,327 BECAUSE OF MS OR MY RHYTHM OF 856 00:33:53,327 --> 00:33:55,395 LIFE THAT IS VERY INTENSE BUT I 857 00:33:55,395 --> 00:33:56,463 DO FEEL FATIGUE, NOT EVERY DAY 858 00:33:56,463 --> 00:33:58,532 BUT THERE ARE TIMES IN WHICH I 859 00:33:58,532 --> 00:34:00,400 FEEL VERY, VERY TIRED. 860 00:34:00,400 --> 00:34:04,371 I MEAN I FEEL VERY, VERY TIRED. 861 00:34:04,371 --> 00:34:06,206 AND THAT HAPPENS A LOT. 862 00:34:06,206 --> 00:34:09,309 >> AND WHAT TIME OF THE DAY DOES 863 00:34:09,309 --> 00:34:10,177 IT HAPPEN? 864 00:34:10,177 --> 00:34:13,147 >> USUALLY IN THE AFTERNOON, IN 865 00:34:13,147 --> 00:34:14,047 THE AFTERNOON. 866 00:34:14,047 --> 00:34:15,215 IT'S USUALLY NOT HARD FOR ME TO 867 00:34:15,215 --> 00:34:17,050 WAKE UP IN THE MORNING BUT IN 868 00:34:17,050 --> 00:34:22,122 THE AFTERNOON I GET TIRED, 869 00:34:22,122 --> 00:34:23,590 SOMETIMES AND SOMETIMES, IF IT'S 870 00:34:23,590 --> 00:34:25,559 BEING A VERY, VERY LONG DAY LIKE 871 00:34:25,559 --> 00:34:27,194 AT 7 OR 8:00 P.M., I'M DONE. 872 00:34:27,194 --> 00:34:28,829 I MEAN I REALLY WANT TO GO TO 873 00:34:28,829 --> 00:34:29,296 SLEEP. 874 00:34:29,296 --> 00:34:30,831 IT'S NOT THAT COMMON, BUT WHEN 875 00:34:30,831 --> 00:34:32,900 IT HAPPENS, IT'S VERY BAD, YEAH. 876 00:34:32,900 --> 00:34:34,301 >> AND HOW DO YOU MANAGE? 877 00:34:34,301 --> 00:34:36,370 WHAT DO YOU DO WHEN YOU HAVE 878 00:34:36,370 --> 00:34:38,238 FATIGUE IN THE AFTERNOON? 879 00:34:38,238 --> 00:34:42,476 >> WELL, I TRY TO GO FOR A WALK, 880 00:34:42,476 --> 00:34:45,412 GET ACTIVE, I TRY COFFEE BUT IF 881 00:34:45,412 --> 00:34:46,914 IT IS BEFORE 3:00 P.M. OR SO 882 00:34:46,914 --> 00:34:48,549 BECAUSE THEN IT GETS HARDER FOR 883 00:34:48,549 --> 00:34:49,983 ME TO SLEEP, BUT I USUALLY TRY 884 00:34:49,983 --> 00:34:51,718 TO GET ACTIVE AND ENGAGE IN 885 00:34:51,718 --> 00:34:53,787 SOMETHING, MAYBE I GO FOR A 886 00:34:53,787 --> 00:34:59,693 WALK, MAYBE I TRY TO SPEAK WITH 887 00:34:59,693 --> 00:35:02,329 SOMEONE BUT I NEED TO CHANGE THE 888 00:35:02,329 --> 00:35:04,364 COURSE OF THE DAY BECAUSE IF NOT 889 00:35:04,364 --> 00:35:06,867 I JUST WANT TO NAP. 890 00:35:06,867 --> 00:35:09,169 AND I CANNOT TAKE A NAP, NOT IN 891 00:35:09,169 --> 00:35:09,803 THE OFFICE. 892 00:35:09,803 --> 00:35:12,105 BUT IF I AM AT MY PLACE, I AM 893 00:35:12,105 --> 00:35:14,308 CAN REST NDOES IT WORK, DOES IT 894 00:35:14,308 --> 00:35:16,210 HELP WHEN YOU NAP A LITTLE BIT? 895 00:35:16,210 --> 00:35:17,845 >> YEAH THELPS FOR SURE. 896 00:35:17,845 --> 00:35:21,815 >> WONDERFUL AND HOW IS YOUR 897 00:35:21,815 --> 00:35:22,249 MOOD? 898 00:35:22,249 --> 00:35:22,583 >> GOOD. 899 00:35:22,583 --> 00:35:28,355 THANK EMPLOYLY EMPLOY -- THANKI 900 00:35:28,355 --> 00:35:30,290 HAVEN'T BEEN AFFECTED BY 901 00:35:30,290 --> 00:35:30,791 DEPRESSION. 902 00:35:30,791 --> 00:35:32,059 OF COURSE THERE'S ALWAYS A 903 00:35:32,059 --> 00:35:33,360 LINGERING FEAR OF SOMETHING IN 904 00:35:33,360 --> 00:35:38,232 THE FUTURE BUT OVERALL, I -- AND 905 00:35:38,232 --> 00:35:41,468 I THINK MY WIFE CAN CORROBORATE 906 00:35:41,468 --> 00:35:43,337 BUT MY MOOD IS PRETTY STABLE. 907 00:35:43,337 --> 00:35:46,139 >> AND ARE YOU TAKING ANY 908 00:35:46,139 --> 00:35:47,040 SYMPTOMATIC TREATMENT? 909 00:35:47,040 --> 00:35:48,742 >> WHAT DO YOU MEAN? 910 00:35:48,742 --> 00:35:49,943 >> LIKE FOR THE FATIGUE ARE YOU 911 00:35:49,943 --> 00:35:50,911 TAKE ANYTHING MEDICATION THAT 912 00:35:50,911 --> 00:35:51,712 WILL HELP YOU. 913 00:35:51,712 --> 00:35:52,546 >> NO, NO. 914 00:35:52,546 --> 00:35:54,748 >> HAVE YOU DISCUSSED WITH WITH 915 00:35:54,748 --> 00:35:55,549 YOUR NEUROLOGIST. 916 00:35:55,549 --> 00:35:58,085 >> I HAVE DISCUSSED IT BUT WE 917 00:35:58,085 --> 00:35:59,219 DECIDE THAD IT'S NOT NECESSARY 918 00:35:59,219 --> 00:36:00,053 SO FAR. 919 00:36:00,053 --> 00:36:01,321 NSO CAN YOU REVISIT ANY TIME 920 00:36:01,321 --> 00:36:04,358 THAT YOU WANT AND SEE HOW YOU 921 00:36:04,358 --> 00:36:04,625 ARE DOING. 922 00:36:04,625 --> 00:36:05,759 >> OKAY, WONDERFUL THANK YOU SO 923 00:36:05,759 --> 00:36:07,761 NOW I'M GOING TO GO BACK TO MY 924 00:36:07,761 --> 00:36:08,295 PRESENTATION, TALK ABOUT 925 00:36:08,295 --> 00:36:11,665 TREATMENT AND THEN I WILL GO 926 00:36:11,665 --> 00:36:19,239 BACK TO YOU. 927 00:36:19,239 --> 00:36:19,706 THANK YOU. 928 00:36:19,706 --> 00:36:21,775 ALL RIGHT, SO I WILL TRY TO TALK 929 00:36:21,775 --> 00:36:23,443 A LITTLE BIT ABOUT TREATMENT, 930 00:36:23,443 --> 00:36:24,845 IT'S A VERY COMPREHENSIVE TOPIC 931 00:36:24,845 --> 00:36:27,814 BUT I WOULD LIKE TO SAY A COUPLE 932 00:36:27,814 --> 00:36:29,650 OF THINGS, SO THE TREATMENT 933 00:36:29,650 --> 00:36:32,486 EARLY IN THE DISEASE, IT'S 934 00:36:32,486 --> 00:36:35,889 BASICALLY TO PREVENT OR DELAY 935 00:36:35,889 --> 00:36:40,894 DISABILITY IN THE FUTURE BUT 936 00:36:40,894 --> 00:36:42,996 THERE IS NO TREATMENT, THAT IT'S 937 00:36:42,996 --> 00:36:44,531 AVAILABLE IN THE TREATMENT OF 938 00:36:44,531 --> 00:36:44,831 PROGRESSION. 939 00:36:44,831 --> 00:36:47,935 SO WHEN WE GET TO THE TIME OF 940 00:36:47,935 --> 00:36:49,303 PROGRESSION IT'S WORTH TRYING TO 941 00:36:49,303 --> 00:36:51,705 SLOW OR TO STOP THE PROGRESSION 942 00:36:51,705 --> 00:36:55,409 AND IMPROVE THE QUALITY OF LIFE. 943 00:36:55,409 --> 00:36:57,544 SO THE NATURAL HISTORY OF 944 00:36:57,544 --> 00:36:59,980 PATIENTS UNTREATED WHO HAVE A 945 00:36:59,980 --> 00:37:05,452 HUGE, HUGE DATABASES, SHOWING 946 00:37:05,452 --> 00:37:07,054 THAT AFTER AROUND 50 TO 20 YEAR, 947 00:37:07,054 --> 00:37:09,523 30% OF THE PATIENTS ARE 948 00:37:09,523 --> 00:37:11,992 UNTREATED MAY EVOLVE INTO A 949 00:37:11,992 --> 00:37:13,026 SECONDARY PROGRESSIVE PHASE OF 950 00:37:13,026 --> 00:37:14,895 THE DISEASE OR MORE PROGRESSIVE 951 00:37:14,895 --> 00:37:19,333 PHASE OF THE DISEASE. 952 00:37:19,333 --> 00:37:21,601 BUT CURRENTLY WE HAVE ALL THESE 953 00:37:21,601 --> 00:37:23,437 FDA APPROVED THERAPIES FOR 954 00:37:23,437 --> 00:37:24,471 MULTIPLE SCLEROSIS, THAT ARE 955 00:37:24,471 --> 00:37:28,075 HUGE AND IT'S A VERY LONG LIST 956 00:37:28,075 --> 00:37:30,110 OFF ALL THERAPY INFUSION THERAPY 957 00:37:30,110 --> 00:37:32,279 AND INJECTION THERAPY AND THIS 958 00:37:32,279 --> 00:37:37,117 HAS REALLY CHANGED A LOT, THE 959 00:37:37,117 --> 00:37:38,685 EVOLUTION OF THE DISEASE, SO 960 00:37:38,685 --> 00:37:41,788 THESE ARE THE TREATMENTS, THEY 961 00:37:41,788 --> 00:37:43,890 ARE FDA APPROVED AND MOSTLY THEY 962 00:37:43,890 --> 00:37:45,692 ARE CLASSIFIED AS HIGH EFFICACY, 963 00:37:45,692 --> 00:37:47,861 IT MEANS LIKE HAVING MORE 964 00:37:47,861 --> 00:37:50,364 REDUCTION IN RELAPSE RATE, 965 00:37:50,364 --> 00:37:51,431 MODERATE EFFICACY AND LOW 966 00:37:51,431 --> 00:37:51,698 EFFICACY. 967 00:37:51,698 --> 00:37:53,433 I WILL TRY TO GO A LITTLE BIT IN 968 00:37:53,433 --> 00:37:54,634 DETAIL IN EACH OF THEM BUT I'M 969 00:37:54,634 --> 00:37:56,370 NOT SURE I WILL HAVE TIME. 970 00:37:56,370 --> 00:37:57,637 BUT I THINK IT'S VERY IMPORTANT 971 00:37:57,637 --> 00:38:00,607 TO MENTION IS THAT REALLY THIS 972 00:38:00,607 --> 00:38:02,576 IS MODIFYING THERAPY ARE 973 00:38:02,576 --> 00:38:03,510 EFFECTIVE IN IMPROVING 974 00:38:03,510 --> 00:38:05,812 DISABILITY OUTCOME IN RELAPSING 975 00:38:05,812 --> 00:38:07,948 REPEATING MS OVER THE LONG-TERM. 976 00:38:07,948 --> 00:38:16,623 SO IN THIS STUDY OF MS BASE THAT 977 00:38:16,623 --> 00:38:18,225 HAVE 14,700 PEASHT AND SOME OF 978 00:38:18,225 --> 00:38:23,730 THEM WERE FOLLOWED FOR 1000 WERE 979 00:38:23,730 --> 00:38:25,132 FOLLOWED FOR MORE THAN 15 YEARS 980 00:38:25,132 --> 00:38:30,470 AND MOST WERE TREATED FOR 981 00:38:30,470 --> 00:38:32,672 INTERFERON THAT IS LOW EFFICACY 982 00:38:32,672 --> 00:38:34,541 AND CLASSIFIES AS LOW EFFICACY, 983 00:38:34,541 --> 00:38:36,109 THEY SHOW VERY GOOD EFFECT FOR 984 00:38:36,109 --> 00:38:38,879 REDUCING DISABILITY IN THE 985 00:38:38,879 --> 00:38:41,381 FUTURE, THE RISK OF NEED OF 986 00:38:41,381 --> 00:38:46,119 WALKING AID AND FREQUENCY OF 987 00:38:46,119 --> 00:38:46,586 RELAPSES. 988 00:38:46,586 --> 00:38:47,621 HOWEVER, WHENEVER HIGH THERAPY 989 00:38:47,621 --> 00:38:49,289 EFKASP A R SEINTRODUCED EARLY IN 990 00:38:49,289 --> 00:38:53,060 THE ASSIST, THAT RISK OF 991 00:38:53,060 --> 00:38:53,894 PROGRESSION IS LOWER IN THOSE 992 00:38:53,894 --> 00:38:56,863 THAT ARE TREATED EARLY WITH HIGH 993 00:38:56,863 --> 00:38:58,698 AFFECTIVE THERAPY AS OUR PATIENT 994 00:38:58,698 --> 00:39:01,935 WAS TREATED WITH AND THE SAME IN 995 00:39:01,935 --> 00:39:05,138 TERMS OF DISABILITIES SCALE. 996 00:39:05,138 --> 00:39:07,107 SO I WILL VERY BRIEFLY MENTION 997 00:39:07,107 --> 00:39:17,184 THAT THESE ARE INJECTIONS. 998 00:39:17,184 --> 00:39:21,321 INTERFERON, THEY ARE OLD, THESE 999 00:39:21,321 --> 00:39:24,558 ARE VERY SAFE DURING PREGNANCY, 1000 00:39:24,558 --> 00:39:27,561 AND NURSING AND THEY MAY 1001 00:39:27,561 --> 00:39:30,197 EXPERIENCE INTERFERONS 1002 00:39:30,197 --> 00:39:31,631 PARTICULARLY FLU-LIKE SYMPTOMS 1003 00:39:31,631 --> 00:39:36,837 AND SOME SITE INJECTIONS AND FOR 1004 00:39:36,837 --> 00:39:40,740 THE ACETATE, THEY MAY HAVE 1005 00:39:40,740 --> 00:39:41,908 ATROPOMYOSIN TROPHY IN THE FAT, 1006 00:39:41,908 --> 00:39:45,345 THEY NEED TO BE CHECKED FOR 1007 00:39:45,345 --> 00:39:46,146 HIPOTTIC ENZYMES THAT'S MOST 1008 00:39:46,146 --> 00:39:48,715 IMPORTANT BUT SO FAR ARE VERY 1009 00:39:48,715 --> 00:39:49,616 SAFE. 1010 00:39:49,616 --> 00:39:51,151 ORAL THERAPIES, THERE'S -- THERE 1011 00:39:51,151 --> 00:39:52,986 ARE MANY ORAL THERAPIES. 1012 00:39:52,986 --> 00:39:56,189 THEY REDUCE THE RISK OF RELAPSES 1013 00:39:56,189 --> 00:39:57,958 BETWEEN 30 AND 50% AND THERE IS 1014 00:39:57,958 --> 00:40:01,595 INCREASED RISK OF INFECTIONS AND 1015 00:40:01,595 --> 00:40:04,965 HEPATIC ENZYMES ALSO CAN BE 1016 00:40:04,965 --> 00:40:07,134 AFFECTED AND WHEN THE MOST 1017 00:40:07,134 --> 00:40:09,402 FREQUENT OF THIS TYPE, THE MOST 1018 00:40:09,402 --> 00:40:11,505 USED OF THIS TYPE IS SINGLE 1019 00:40:11,505 --> 00:40:12,906 MODEL THAT MAY HAVE INFECTIONS 1020 00:40:12,906 --> 00:40:19,713 AND MAY NEED TO PREVENT FROM 1021 00:40:19,713 --> 00:40:23,750 MACULAR EDEMA AND SOME 1022 00:40:23,750 --> 00:40:26,052 ARRHYTHMIA, THEN OTHER PEEL THAT 1023 00:40:26,052 --> 00:40:27,654 MAY LEAD TO HAIR THINNING AND 1024 00:40:27,654 --> 00:40:30,724 ALSO RISK OF INFECTIONS BUT THE 1025 00:40:30,724 --> 00:40:32,259 GOOD THING IS THIS DRUG SHOWED 1026 00:40:32,259 --> 00:40:36,263 TO REDUCE THE RISK OF RADIO 1027 00:40:36,263 --> 00:40:38,031 LOGIC ISOLATED SYMPTOMS THAT 1028 00:40:38,031 --> 00:40:42,135 BECOME MS. 1029 00:40:42,135 --> 00:40:44,337 THIS IS THERAPY, IT'S SELECTIVE, 1030 00:40:44,337 --> 00:40:46,306 SO IT DEPLETES THESE CELLS FOR A 1031 00:40:46,306 --> 00:40:48,542 LONG PERIOD OF TIME AND IT HAS 1032 00:40:48,542 --> 00:40:50,410 ONLY 2 CYCLES, THE FIRST YEAR, 5 1033 00:40:50,410 --> 00:40:55,782 DAYS, THE SECOND YEAR, 5 DAYS. 1034 00:40:55,782 --> 00:40:58,518 TWICE DAILY, THEY MAY HAVE A 1035 00:40:58,518 --> 00:41:02,355 SIDE EFFECT, GI SYMPTOMS AND 1036 00:41:02,355 --> 00:41:06,860 FLASHING, AND THIS MAY LEAD TO 1037 00:41:06,860 --> 00:41:08,094 LYMPHPENIA, THESE 3 AND THE 1038 00:41:08,094 --> 00:41:09,062 IMPORTANT THING IS THAT THESE 1039 00:41:09,062 --> 00:41:15,936 ARE NOT ALLOWED TO HAPPEN DURING 1040 00:41:15,936 --> 00:41:17,604 PREGNANCY. 1041 00:41:17,604 --> 00:41:18,772 MONOCLONAL ANTIBODIES DECREASE 1042 00:41:18,772 --> 00:41:23,176 AROUND 70%, RISK OF NEURAL 1043 00:41:23,176 --> 00:41:24,844 RELAPSE AND 45-60 WHEN COMPARED 1044 00:41:24,844 --> 00:41:26,479 TO INTERFERONS SO IT'S REALLY 1045 00:41:26,479 --> 00:41:27,147 MORE EFFECTIVE. 1046 00:41:27,147 --> 00:41:30,183 AND WE HAVE MANY DIFFERENT, 1047 00:41:30,183 --> 00:41:31,384 OBVIOUSLY THE THERAPY THAT IS 1048 00:41:31,384 --> 00:41:35,155 THE TREATMENT THAT MR. CHACON IS 1049 00:41:35,155 --> 00:41:41,761 HAVING, . 1050 00:41:41,761 --> 00:41:44,164 THERE ARE MANY APPROVED AND 1051 00:41:44,164 --> 00:41:45,999 THERE IS ANOTHER THAT CAN ALSO 1052 00:41:45,999 --> 00:41:51,538 BE INFUSIONS EVERY 6 MONTHS, AND 1053 00:41:51,538 --> 00:41:54,574 RITUX MAB IS ALSO USED EVERY 6 1054 00:41:54,574 --> 00:41:56,176 MONTHS, TOO, SO IN THIS CASE, 1055 00:41:56,176 --> 00:42:00,413 THEY NEED TO CHECK FOR 1056 00:42:00,413 --> 00:42:02,048 ANTIBODIES AND UPDATE ALL THE 1057 00:42:02,048 --> 00:42:03,083 VACCINES BEFORE STARTING THE 1058 00:42:03,083 --> 00:42:09,556 TREATMENT AND ONCE THE TREATMENT 1059 00:42:09,556 --> 00:42:10,290 IS STARTED, IMMUNOGLOBULIN 1060 00:42:10,290 --> 00:42:11,758 LEVELS NEED TO BE CHECKED. 1061 00:42:11,758 --> 00:42:16,363 THAT PATIENTS MAY HAVE INFUSION. 1062 00:42:16,363 --> 00:42:18,465 MR. CHACON DIDN'T HAVE ANY 1063 00:42:18,465 --> 00:42:19,733 INFECTION REACTION, AND THEY ARE 1064 00:42:19,733 --> 00:42:21,134 AT HIGHER RISK OF INFECTION SO 1065 00:42:21,134 --> 00:42:23,069 IT'S IMPORTANT TO KEEP UP TO 1066 00:42:23,069 --> 00:42:25,272 DATE BECAUSE ONCE THE TREATMENT 1067 00:42:25,272 --> 00:42:32,879 IS STARTED, THEY -- MOST OF THEM 1068 00:42:32,879 --> 00:42:37,417 CANNOT BE APPLIED. 1069 00:42:37,417 --> 00:42:39,586 UBLITUXIMAB, IT'S AN INJECTION 1070 00:42:39,586 --> 00:42:41,488 EVERY 4 TO 6 WEEKS, 1 CONCERN IS 1071 00:42:41,488 --> 00:42:44,524 THE INDEX THAT NEEDS TO BE 1072 00:42:44,524 --> 00:42:45,692 CHECKED EVERY 6 MONTHS BECAUSE 1073 00:42:45,692 --> 00:42:47,494 OF THE RISK OF PML, THE 1074 00:42:47,494 --> 00:42:49,095 INFECTION OF THE CENTRAL NERVOUS 1075 00:42:49,095 --> 00:42:52,699 SYSTEM, THAT IS INCREASED IN 1076 00:42:52,699 --> 00:42:56,670 PATIENTS THAT HAVE JCV VIRUS 1077 00:42:56,670 --> 00:42:57,470 POSITIVE. 1078 00:42:57,470 --> 00:43:00,907 AND IT'S A CD52 ANTIBODY AND 1079 00:43:00,907 --> 00:43:01,808 ALSO RECONSTITUTION THERAPY AND 1080 00:43:01,808 --> 00:43:04,911 IT ALSO HAS 2 COURSES, IT'S THE 1081 00:43:04,911 --> 00:43:06,279 FIRST YEAR, 5 DAYS, AND THE 1082 00:43:06,279 --> 00:43:10,583 SECOND YEAR 3 DAYS. 1083 00:43:10,583 --> 00:43:15,221 BUT IT NEEDS MONTHLY MONITORING, 1084 00:43:15,221 --> 00:43:16,956 AND SO IT'S REALLY -- IT'S 1085 00:43:16,956 --> 00:43:19,592 CHALLENGING TO DO THE FOLLOW UP. 1086 00:43:19,592 --> 00:43:22,262 BUT BASICALLY WE HAVE MANY 1087 00:43:22,262 --> 00:43:23,997 OPTIONS AND WHEN WE MAKE THE 1088 00:43:23,997 --> 00:43:25,732 DECISION IT HAS TO BE A SHARED 1089 00:43:25,732 --> 00:43:27,033 DECISION BETWEEN THE PATIENT 1090 00:43:27,033 --> 00:43:27,901 ISSUES THE PROVIDER, BECAUSE 1091 00:43:27,901 --> 00:43:30,136 THERE ARE MANY FACTORS THAT 1 1092 00:43:30,136 --> 00:43:34,708 HAS TOO KEEP IN MIND, PERSONAL 1093 00:43:34,708 --> 00:43:37,477 FACTORS, THE JOB, THE FAMILY 1094 00:43:37,477 --> 00:43:43,083 PLAN, AGE, INSURANCE, 1095 00:43:43,083 --> 00:43:44,384 CO-MORBIDITIES, I WILL NOT USE A 1096 00:43:44,384 --> 00:43:48,154 DRUG IN A PATIENT WITH DIABETES, 1097 00:43:48,154 --> 00:43:49,589 ESPECIALLY WHEN INDICATED OR A 1098 00:43:49,589 --> 00:43:50,256 PATIENT THAT'S RECEIVING THERAPY 1099 00:43:50,256 --> 00:43:50,824 AND ACTIVITIES AND PROJECTS 1100 00:43:50,824 --> 00:43:54,260 THAT'S INTERACTING WITH THE DMT. 1101 00:43:54,260 --> 00:43:57,030 SO WE ALSO THINK ABOUT DMS, HOW 1102 00:43:57,030 --> 00:43:58,565 THE PATIENT WILL TOLERATE THE 1103 00:43:58,565 --> 00:44:03,036 SAFETY, OUR PATIENTS ARE MORE 1104 00:44:03,036 --> 00:44:05,972 OPEN TO HAVE MORE EFFICACY THAT 1105 00:44:05,972 --> 00:44:07,574 LESS SAFETY, AND SOME PATIENTS 1106 00:44:07,574 --> 00:44:09,109 WANT TO BE MORE ON THE SECURE 1107 00:44:09,109 --> 00:44:10,577 SIDE AND OF COURSE THE 1108 00:44:10,577 --> 00:44:12,812 INTERACTIONS AND THIS IS 1109 00:44:12,812 --> 00:44:13,813 FACTORS, CLINICAL EVOLUTION, 1110 00:44:13,813 --> 00:44:15,982 EARLY NATURAL HISTORY STUDIES, 1111 00:44:15,982 --> 00:44:16,750 REPORTED FREQUENTLY RELAPSES IN 1112 00:44:16,750 --> 00:44:21,554 THE FIRST 2 YEARS OF ONSET, AND 1113 00:44:21,554 --> 00:44:22,722 SHORTER INTERVALS TO BE 1114 00:44:22,722 --> 00:44:25,558 ASSOCIATE WIDE SHORTER TIMES TO 1115 00:44:25,558 --> 00:44:27,093 LATER DISABILITY. 1116 00:44:27,093 --> 00:44:33,933 AND THE MRI ACTIVITY AS WELL. 1117 00:44:33,933 --> 00:44:35,402 SO EDUCATION, ANTICIPATING 1118 00:44:35,402 --> 00:44:37,937 ADVERSE EVENTS, EASY FOLLOW UP, 1119 00:44:37,937 --> 00:44:39,439 AND REALLY IMPROVES COMPLIANCE 1120 00:44:39,439 --> 00:44:41,274 THE OTHER ENDS OF THE PATIENT 1121 00:44:41,274 --> 00:44:42,175 THAT MOST IMPORTANT BECAUSE ALL 1122 00:44:42,175 --> 00:44:43,543 THE RESULTS OF THE TRIALS ARE 1123 00:44:43,543 --> 00:44:46,246 WHEN PATIENTS ARE TAKING THE 1124 00:44:46,246 --> 00:44:49,849 MEDICATION IN THE RIGHT MANNER. 1125 00:44:49,849 --> 00:44:51,484 SO WHAT DO TREATMENTS DO, HOW DO 1126 00:44:51,484 --> 00:44:52,786 WE KNOW IF THEY WORK? 1127 00:44:52,786 --> 00:44:56,022 THAT'S WHAT I WAS ASKING 1128 00:44:56,022 --> 00:44:58,291 MR. CHACON, TREATMENTS MAKE 1129 00:44:58,291 --> 00:45:01,194 RELAPSES AND CONTRASTING 1130 00:45:01,194 --> 00:45:02,395 ENHANCING LESIONS OR NEW LESIONS 1131 00:45:02,395 --> 00:45:03,630 GO AWAY AND WHEN THE TREATMENT 1132 00:45:03,630 --> 00:45:08,234 IS THAT, WE KNOW THAT IT'S 1133 00:45:08,234 --> 00:45:08,701 WORKING. 1134 00:45:08,701 --> 00:45:11,471 SO DMTs, BASICALLY TARGET 1135 00:45:11,471 --> 00:45:12,405 INFLAMMATORY MECHANISMS THAT 1136 00:45:12,405 --> 00:45:21,448 UNDERLIE RELAPSES AS I MENTIONED 1137 00:45:21,448 --> 00:45:22,582 BEFORE AND MINIMIZE FUNCTION BUT 1138 00:45:22,582 --> 00:45:24,717 THEY ALL WORK HERE IN THE 1139 00:45:24,717 --> 00:45:25,351 PERIPHERY, PREVENTING CELLS TO 1140 00:45:25,351 --> 00:45:27,987 GET IN THE BRAIN. 1141 00:45:27,987 --> 00:45:31,224 THE UNMET THERAPEUTIC NEEDS 1142 00:45:31,224 --> 00:45:32,325 INCLUDE RELAPSING, INDEPENDENT 1143 00:45:32,325 --> 00:45:32,992 PROGRESSIVE MECHANISMS AND 1144 00:45:32,992 --> 00:45:38,231 REPAIR OF THE CNS INJURY THAT 1145 00:45:38,231 --> 00:45:38,898 HAS ALREADY OCCURRED. 1146 00:45:38,898 --> 00:45:41,134 THERE ARE OTHER FACTORS THAT 1147 00:45:41,134 --> 00:45:42,869 IMPACT INFLAMMATION AND THE 1148 00:45:42,869 --> 00:45:47,574 GENERATION THAT INCLUDE VITAMIN 1149 00:45:47,574 --> 00:45:50,276 D LEVELS, OBESITY, 1150 00:45:50,276 --> 00:45:51,211 CO-MORBIDITIES, SMOKING. 1151 00:45:51,211 --> 00:45:53,613 SO THE EFFECT OF SMOKING 1152 00:45:53,613 --> 00:45:55,582 CESSATION IN MS WAS SHOWN IN 1153 00:45:55,582 --> 00:45:58,852 MANY STUDIES, ACTUALLY, THOSE 1154 00:45:58,852 --> 00:46:03,089 THAT QUIT, THEY HAVE THE RISK OF 1155 00:46:03,089 --> 00:46:05,525 CONVERGENT TO SPMS, IT 1156 00:46:05,525 --> 00:46:05,892 DECREASES. 1157 00:46:05,892 --> 00:46:09,729 AND THEN IN PATIENTS WITH CIES, 1158 00:46:09,729 --> 00:46:12,265 VITAMIN D, WAS AN EARLY PREDICT 1159 00:46:12,265 --> 00:46:13,900 ONER OF MS ACTIVITY AND 1160 00:46:13,900 --> 00:46:15,201 PROGRESSION. 1161 00:46:15,201 --> 00:46:17,237 AND PATIENTS THAT HAVE VASCULAR 1162 00:46:17,237 --> 00:46:20,206 CO-MORBIDITIES FOR EXAMPLE, MAY 1163 00:46:20,206 --> 00:46:20,974 EXPERIENCE MORE RAPID DISABILITY 1164 00:46:20,974 --> 00:46:23,676 PROGRESSION AND THE NEED OF 1165 00:46:23,676 --> 00:46:24,844 UNILATERAL OR BILATERAL 1166 00:46:24,844 --> 00:46:27,714 ASSISTANCE, SO TREATING AND 1167 00:46:27,714 --> 00:46:28,281 PREVENTING VASCULAR 1168 00:46:28,281 --> 00:46:31,117 CO-MORBIDITIES IS VERY 1169 00:46:31,117 --> 00:46:31,384 IMPORTANT. 1170 00:46:31,384 --> 00:46:34,554 EXERCISE MAY IMPROVE SYMPTOMS, 1171 00:46:34,554 --> 00:46:36,256 LIKE PHYSIOLOGICAL FITNESS, 1172 00:46:36,256 --> 00:46:37,190 FATIGUE, DEPRESSIVE SYMPTOMS, 1173 00:46:37,190 --> 00:46:39,359 PAIN, BUT IT'S NOT CLEARLY 1174 00:46:39,359 --> 00:46:41,828 CHANGING THE EVOLUTION OF THE 1175 00:46:41,828 --> 00:46:42,529 DISEASE. 1176 00:46:42,529 --> 00:46:44,831 WITH THAT I WOULD LIKE TO GO 1177 00:46:44,831 --> 00:46:52,572 BACK TO YOU, MR. CHACON AND ASK 1178 00:46:52,572 --> 00:46:55,308 YOU A LITTLE BIT -- OOPS -- I 1179 00:46:55,308 --> 00:46:55,808 MADE A MISTAKE. 1180 00:46:55,808 --> 00:46:56,209 HERE WE GO. 1181 00:46:56,209 --> 00:47:00,413 AND I WOULD LIKE TO ASK YOU A 1182 00:47:00,413 --> 00:47:02,515 LITTLE BIT ABOUT WHAT YOU THINK 1183 00:47:02,515 --> 00:47:03,950 ABOUT THE FUTURE, WHAT ARE YOU 1184 00:47:03,950 --> 00:47:05,218 SCARED OF, IF THERE IS ANYTHING 1185 00:47:05,218 --> 00:47:14,027 THAT YOU WANT TO SHARE WITH US? 1186 00:47:14,027 --> 00:47:14,494 >> YES. 1187 00:47:14,494 --> 00:47:16,396 I'M GOING ABOUT THE FUTURE, I 1188 00:47:16,396 --> 00:47:17,463 FEEL VERY GRATEFUL BECAUSE FROM 1189 00:47:17,463 --> 00:47:21,100 THE MOMENT THAT I WAS DIAGNOSED 1190 00:47:21,100 --> 00:47:23,069 AND THEN I BEGAN SEEING MY 1191 00:47:23,069 --> 00:47:25,038 NEUROLOGIST AND THEN GOING TO 1192 00:47:25,038 --> 00:47:26,706 NIH, MOST PEOPLE THEY HAVE SAID 1193 00:47:26,706 --> 00:47:28,408 THAT THEY THINK THAT MY QUALITY 1194 00:47:28,408 --> 00:47:31,144 OF LIFE IS GOING TO BE PRETTY 1195 00:47:31,144 --> 00:47:34,347 SIMILAR IN THE NEXT 30, 40, 50 1196 00:47:34,347 --> 00:47:35,381 YEARS AND SOME DOCTORS HAVE EVEN 1197 00:47:35,381 --> 00:47:38,685 SAID THAT THEY THINK THAT I 1198 00:47:38,685 --> 00:47:42,522 WOULD LIVE TO SEE THE CURE OF 1199 00:47:42,522 --> 00:47:44,223 THE CONDITION, SO THAT'S VERY 1200 00:47:44,223 --> 00:47:45,758 HOPEFUL ON 1 HAND. 1201 00:47:45,758 --> 00:47:47,860 FEARS, YEAH, THERE ARE FEARS, 1202 00:47:47,860 --> 00:47:51,264 THERE ARE 3 MAIN FEARS, 1 IS A 1203 00:47:51,264 --> 00:47:54,334 LONG-TERM EFFECTS OF THE 1204 00:47:54,334 --> 00:47:56,736 MEDICATION AND I AM ALSO TAKING 1205 00:47:56,736 --> 00:47:58,838 MEDICATION FOR MY PSORIASIS, SO 1206 00:47:58,838 --> 00:48:01,140 BOTH MEDICATIONS WERE PRETTY NEW 1207 00:48:01,140 --> 00:48:01,841 SO THAT'S A FEAR. 1208 00:48:01,841 --> 00:48:02,675 I'M NOT THAT CONCERNED ABOUT IT 1209 00:48:02,675 --> 00:48:05,044 BUT WE WILL SEE IN A FEW 1210 00:48:05,044 --> 00:48:05,945 DECADES. 1211 00:48:05,945 --> 00:48:09,782 ALSO, THERE'S A FEAR THAT I CAN 1212 00:48:09,782 --> 00:48:11,951 SUFFER FROM DEPRESSION, BUT THE 1213 00:48:11,951 --> 00:48:15,054 MOST -- THE FEAR THAT IT'S 1214 00:48:15,054 --> 00:48:16,255 ALWAYS LINGERING AROUND US, I 1215 00:48:16,255 --> 00:48:19,292 MENTIONED BEFORE IS THAT I CAN 1216 00:48:19,292 --> 00:48:21,461 START HAVING SYMPTOMS AGAIN AND 1217 00:48:21,461 --> 00:48:26,199 BASICALLY DEVELOP THE 1218 00:48:26,199 --> 00:48:28,401 PROGRESSIVE MS, AND WITHOUT 1219 00:48:28,401 --> 00:48:29,669 LOOSING COGNITIVE ABILITY OR 1220 00:48:29,669 --> 00:48:32,138 OTHER CAPABILITIES IN MY BODY. 1221 00:48:32,138 --> 00:48:34,073 I MEAN THAT'S LIKE THE BIGGEST 1222 00:48:34,073 --> 00:48:36,209 FEAR THEY DO FEEL AND IT'S 1223 00:48:36,209 --> 00:48:37,276 ALWAYS LINGERING AROUND. 1224 00:48:37,276 --> 00:48:40,480 I CAN LIVE WITH IT BUT YOU'RE 1225 00:48:40,480 --> 00:48:43,349 ALWAYS THINKING ABOUT IT AND AT 1226 00:48:43,349 --> 00:48:44,617 THE SAME TIME IT KIND OF HELPS 1227 00:48:44,617 --> 00:48:45,685 YOU TO APPRECIATE WHAT YOU HAVE 1228 00:48:45,685 --> 00:48:47,620 AND IT ALSO FORCES ME TO -- IF I 1229 00:48:47,620 --> 00:48:49,922 SAY THAT I AM NOT EATING WELL, 1230 00:48:49,922 --> 00:48:55,194 OR I AM NOT SLEEPING WELL, OR 1231 00:48:55,194 --> 00:48:56,696 NOT EXERCISING, IT FORCES ME TO 1232 00:48:56,696 --> 00:48:58,398 GOING BACK INTO THAT. 1233 00:48:58,398 --> 00:49:01,668 >> AND WHY ARE YOU SCARED ABOUT 1234 00:49:01,668 --> 00:49:02,101 DEPRESSION? 1235 00:49:02,101 --> 00:49:04,904 DO HAVE YOU ANY LIKE SYMPTOMS? 1236 00:49:04,904 --> 00:49:07,106 IS THERE ANYTHING -- 1237 00:49:07,106 --> 00:49:07,340 >> NO. 1238 00:49:07,340 --> 00:49:10,877 I DON'T HAVE SYMPTOMS, 1239 00:49:10,877 --> 00:49:15,181 THANKFULLY, BUT I HAVE -- YOU 1240 00:49:15,181 --> 00:49:16,916 WHEN GET DIAGNOSED, USUALLY A 1241 00:49:16,916 --> 00:49:19,819 LOT OF YOUR FRIENDS AND FAMILY, 1242 00:49:19,819 --> 00:49:22,221 THEY KNOW PEOPLE WHO HAVE MS, 1243 00:49:22,221 --> 00:49:24,757 AND YOU TALK WITH THEM AND THEY 1244 00:49:24,757 --> 00:49:26,859 SAY THAT A LOT OF THEM HAVE 1245 00:49:26,859 --> 00:49:30,096 DEVELOPED DEPRESSION EXPRK 1246 00:49:30,096 --> 00:49:31,597 THAT'S THE REASON I AM SCARED 1247 00:49:31,597 --> 00:49:33,700 BECAUSE I KNOW 6 OR 7 PEOPLE WHO 1248 00:49:33,700 --> 00:49:36,002 HAVE MS OR FAMILIES WITH MS AND 1249 00:49:36,002 --> 00:49:37,603 THAT'S SOMETHING THEY MENTION 1250 00:49:37,603 --> 00:49:40,206 AND I TAKE IT VERY SERIOUSLY IN 1251 00:49:40,206 --> 00:49:41,040 CASE IT HAPPENS. 1252 00:49:41,040 --> 00:49:42,475 >> IT MAY HAPPEN AND IT COULD BE 1253 00:49:42,475 --> 00:49:45,011 DUE TO MS ITSELF, DUE TO THE 1254 00:49:45,011 --> 00:49:49,816 DIAGNOSIS, AND YOUR REACTION, 1255 00:49:49,816 --> 00:49:51,584 AND IT'S IMPORTANT THAT YOU TALK 1256 00:49:51,584 --> 00:49:52,885 TO YOUR PRIMARY NEUROLOGIST AND 1257 00:49:52,885 --> 00:49:54,821 WITH US IF YOU HAVE ANY DOUBTS. 1258 00:49:54,821 --> 00:49:58,558 SO THAT SAID I WOULD LIKE TO 1259 00:49:58,558 --> 00:50:01,194 SHIFT TO DR. REICH, THAT HE'S 1260 00:50:01,194 --> 00:50:02,295 GOING TO PROBABLY ANSWER A 1261 00:50:02,295 --> 00:50:04,797 COUPLE OF YOUR QUESTIONS AND WE 1262 00:50:04,797 --> 00:50:08,468 CAN DISCUSS MORE LATER. 1263 00:50:08,468 --> 00:50:11,404 THANK YOU. 1264 00:50:11,404 --> 00:50:12,338 >> THANK YOU. 1265 00:50:12,338 --> 00:50:15,074 >> THANK YOU DOCTOR, AND THANK 1266 00:50:15,074 --> 00:50:19,512 YOU MR. CHACON, FOR SHARING YOUR 1267 00:50:19,512 --> 00:50:21,280 STORY WITH US AND YOUR FEARS AND 1268 00:50:21,280 --> 00:50:23,416 YOUR HOPES. 1269 00:50:23,416 --> 00:50:27,286 I HOPE WE DO SEE THE CURE OF THE 1270 00:50:27,286 --> 00:50:30,156 DISEASE AS YOU SAID IN YOUR 1271 00:50:30,156 --> 00:50:33,960 LIFETIME AND IN MY LIFETIME. 1272 00:50:33,960 --> 00:50:39,165 AND I HOPE THAT WE CAN, THROUGH 1273 00:50:39,165 --> 00:50:40,633 RESEARCH, REDUCE THE CHANCE TO 1274 00:50:40,633 --> 00:50:42,168 YOU KNOW AS CLOSE TO 0 AS 1275 00:50:42,168 --> 00:50:43,136 POSSIBLE THAT PEOPLE IN YOUR 1276 00:50:43,136 --> 00:50:45,872 SITUATION WHO ARE DOING SO WELL, 1277 00:50:45,872 --> 00:50:51,711 GO ON TO DEVELOP WHAT WE CALL 1278 00:50:51,711 --> 00:50:53,980 PROGRESSIVE MS WHICH IS WHERE 1279 00:50:53,980 --> 00:50:55,281 DISABILITY JUST CONTINUES TO GET 1280 00:50:55,281 --> 00:50:55,648 WORSE AND WORSE. 1281 00:50:55,648 --> 00:50:59,085 SO WHAT I WOULD LIKE TO DO 1282 00:50:59,085 --> 00:51:00,119 TODAY, IS TO DESCRIBE 1 AREA 1283 00:51:00,119 --> 00:51:03,856 WHERE I THINK WE MADE SOME 1284 00:51:03,856 --> 00:51:06,759 PROGRESS AGAINST PROGRESSION AND 1285 00:51:06,759 --> 00:51:12,465 I'M GOING TO SHARE MY SCREEN. 1286 00:51:12,465 --> 00:51:13,299 HOPEFULLY THAT WORKS. 1287 00:51:13,299 --> 00:51:15,201 IF YOU CAN GIVE ME A THUMBS UP 1288 00:51:15,201 --> 00:51:17,637 IF YOU SEE MY SCREEN. 1289 00:51:17,637 --> 00:51:17,937 GREAT. 1290 00:51:17,937 --> 00:51:19,806 OKAY, THANK YOU. 1291 00:51:19,806 --> 00:51:22,208 OKAY, PERFECT. 1292 00:51:22,208 --> 00:51:23,843 SO SOME DISCLOSURES REGARDING 1293 00:51:23,843 --> 00:51:24,644 FUNDING BUT MOST OF THE WORK 1294 00:51:24,644 --> 00:51:26,846 THAT I'M GOING TO TALK ABOUT HAS 1295 00:51:26,846 --> 00:51:29,048 BEEN FUNDED BY THE NATIONAL 1296 00:51:29,048 --> 00:51:30,883 INSTITUTES OF HEALTH AND IN 1297 00:51:30,883 --> 00:51:32,418 PARTICULAR THE NATIONAL 1298 00:51:32,418 --> 00:51:33,920 INSTITUTE OF NEUROLOGICAL 1299 00:51:33,920 --> 00:51:39,058 DISORDERS AND STROKE, NINDS, 1300 00:51:39,058 --> 00:51:41,561 WHERE BOTH OF US WORK AND THE 1301 00:51:41,561 --> 00:51:42,895 CLINICAL TRUSTEES WHERE WE SEE 1302 00:51:42,895 --> 00:51:45,064 PEOPLE WHO VOLUNTEER FOR OUR 1303 00:51:45,064 --> 00:51:49,268 RESEARCH STUDIES LIKE 1304 00:51:49,268 --> 00:51:50,336 MR. CHACON. 1305 00:51:50,336 --> 00:51:52,004 SO I AM A NEUROLOGIST. 1306 00:51:52,004 --> 00:51:54,073 I WAS TRAINED AS A NEUROLOGIST 1307 00:51:54,073 --> 00:51:57,376 BUT THESE DAYS I PRACTICE 1308 00:51:57,376 --> 00:51:58,211 CLINICAL NEURAL RADIOLOGY SO 1309 00:51:58,211 --> 00:52:00,613 INSTEAD OF HAVING THE GOOD 1310 00:52:00,613 --> 00:52:03,449 FORTUNE OF TALKING TO PATIENTS 1311 00:52:03,449 --> 00:52:05,084 EVERY DAY LIKE MY COLLEAGUE 1312 00:52:05,084 --> 00:52:06,953 DOES, I TALK TO COMPUTER SCREENS 1313 00:52:06,953 --> 00:52:10,957 AND LOOK AT PICTURES MOSTLY OF 1314 00:52:10,957 --> 00:52:12,925 PEOPLE WHO ARE LIVING WITH 1315 00:52:12,925 --> 00:52:13,593 MULTIPLE SCLEROSIS AND YOU'VE 1316 00:52:13,593 --> 00:52:15,595 ALREADY SEEN A LOT OF MRI SCANS 1317 00:52:15,595 --> 00:52:19,632 BUT HERE'S 1 EXAMPLE OF A SCAN 1318 00:52:19,632 --> 00:52:21,067 FROM SOMEBODY WHO HAD BEEN 1319 00:52:21,067 --> 00:52:23,769 VOLUNTEERING FOR A LONG TIME 1320 00:52:23,769 --> 00:52:28,941 ABOUT A QUARTER OF A CENTURY IN 1321 00:52:28,941 --> 00:52:30,543 THE CLINICAL PROTOCOLS, THE SAME 1322 00:52:30,543 --> 00:52:33,079 PROTOCOL THAT MR. CHACON 1323 00:52:33,079 --> 00:52:34,647 VOLUNTEERS FOR AND HAD OVER THAT 1324 00:52:34,647 --> 00:52:40,786 TIME ACCUMULATED A LOT OF YOUR 1325 00:52:40,786 --> 00:52:43,556 TO THE BRAIN CAUSED BY MULTIPLE 1326 00:52:43,556 --> 00:52:46,058 SCLEROSIS AND IN LARGE MEASURE 1327 00:52:46,058 --> 00:52:47,426 BECAUSE SHE STARTED 1328 00:52:47,426 --> 00:52:48,394 PARTICIPATING AND SHE'S OLDER 1329 00:52:48,394 --> 00:52:51,063 AND STARTED BEFORE WE HAD THESE 1330 00:52:51,063 --> 00:52:52,365 VERY EFFECTIVE TREATMENTS. 1331 00:52:52,365 --> 00:52:53,699 SO THIS IS AFTER ALL THOSE 1332 00:52:53,699 --> 00:52:57,737 YEARS, AND WHAT YOU CAN SEE ON 1333 00:52:57,737 --> 00:53:00,106 THIS SCAN ARE THESE WHITE SPOTS 1334 00:53:00,106 --> 00:53:02,408 IN THE MIDDLE OF THE BRAIN. 1335 00:53:02,408 --> 00:53:05,678 THOSE REPRESENT THE PLAQUES OR 1336 00:53:05,678 --> 00:53:07,046 LESIONS THAT YOU HEARD ABOUT 1337 00:53:07,046 --> 00:53:09,682 BEFORE AND IN THE CENTER HERE, 1338 00:53:09,682 --> 00:53:11,484 CAN YOU SEE THESE BLACK SPACES 1339 00:53:11,484 --> 00:53:13,986 WHICH ARE THE FLUID FILLED 1340 00:53:13,986 --> 00:53:16,255 SPACES OF THE BRAIN. 1341 00:53:16,255 --> 00:53:18,124 THEY CONTAIN THE CEREBRAL SPINAL 1342 00:53:18,124 --> 00:53:20,459 FLUID AND THEY ARE CALLED THE 1343 00:53:20,459 --> 00:53:21,527 LATERAL VENTRICLES AND THEY ARE 1344 00:53:21,527 --> 00:53:23,229 LARGER THAN THEY SHOULD BE, SO 1345 00:53:23,229 --> 00:53:25,097 THERE ARE THESE WHITE SPOTS, 1346 00:53:25,097 --> 00:53:27,433 LESIONS AND FLUID SPILLED SPACES 1347 00:53:27,433 --> 00:53:29,168 OF THE LATERAL VENTRICLES THAT 1348 00:53:29,168 --> 00:53:32,171 ARE LARGER THAN THEY SHOULD BE 1349 00:53:32,171 --> 00:53:33,873 AND THAT'S BECAUSE THEY TAKE UP 1350 00:53:33,873 --> 00:53:35,074 SPACE WHERE THERE USED TO BE 1351 00:53:35,074 --> 00:53:39,045 BRAIN AND NO LONGER HIS. 1352 00:53:39,045 --> 00:53:40,413 AND THIS ACCUMULATED OVER A GOOD 1353 00:53:40,413 --> 00:53:41,347 LONG TIME BECAUSE THIS IS 1354 00:53:41,347 --> 00:53:43,149 SOMEBODY WHO HAD BEEN COMING FOR 1355 00:53:43,149 --> 00:53:46,152 MANY, MANY YEARS TO THE NIH, 1356 00:53:46,152 --> 00:53:48,321 GETTING LOTS OF MRI SCANS AND 1357 00:53:48,321 --> 00:53:50,089 THIS SHOWS YOU THE CUMULATIVE 1358 00:53:50,089 --> 00:53:50,456 EFFECTIVE THAT. 1359 00:53:50,456 --> 00:53:54,794 BUT HERE IS A MOVIE THAT IS MORE 1360 00:53:54,794 --> 00:53:56,595 THAN A HUNDRED 50 MRI SCANS 1361 00:53:56,595 --> 00:53:57,930 TAKEN AT THE SAME LEVEL, THE 1362 00:53:57,930 --> 00:54:00,166 SAME PART OF THE BRAIN, THAT ARE 1363 00:54:00,166 --> 00:54:01,434 PUT TOGETHER OVER THAT PERIOD SO 1364 00:54:01,434 --> 00:54:04,670 YOU SEE IT RUNNING OVER THE 1365 00:54:04,670 --> 00:54:05,838 COURSE OF A MINUTE OR SO AND YOU 1366 00:54:05,838 --> 00:54:08,140 WILL SEE IT WILL REPEAT AND 1367 00:54:08,140 --> 00:54:11,877 EARLY ON, YOU CAN SEE WELL, I 1368 00:54:11,877 --> 00:54:20,853 THINK IT WILL REPEAT, I HAVE TO 1369 00:54:20,853 --> 00:54:21,487 START IT AGAIN. 1370 00:54:21,487 --> 00:54:25,191 AND YOU SEE THESE BRIGHT FLASHES 1371 00:54:25,191 --> 00:54:26,926 AND IT REPRESENTS AREA AS YOU 1372 00:54:26,926 --> 00:54:27,960 HEARD BEFORE THESE ARE OPENING 1373 00:54:27,960 --> 00:54:29,261 IN THE BLOOD VESSEL OF THE 1374 00:54:29,261 --> 00:54:30,796 BRAIN, AND THESE ARE AREAS OF 1375 00:54:30,796 --> 00:54:33,232 WHAT WE CALL BLOOD BRAIN BARRIER 1376 00:54:33,232 --> 00:54:35,067 DAMAGE, IT'S ACTUALLY JUST A 1377 00:54:35,067 --> 00:54:36,736 TRANSIENT OPENING OF THE BLOOD 1378 00:54:36,736 --> 00:54:38,137 BRAIN BARRIER, THE CONTRAST DIE 1379 00:54:38,137 --> 00:54:40,239 THAT WE INJECT WHICH HAS A HEAVY 1380 00:54:40,239 --> 00:54:42,975 METAL IN IT CALLED GATTA LYNNIUM 1381 00:54:42,975 --> 00:54:44,243 LEAKS OUT THROUGH THAT OPEN 1382 00:54:44,243 --> 00:54:45,544 BLOOD VESSEL INTO THE BRAIN JUST 1383 00:54:45,544 --> 00:54:47,546 FOR A COUPLE OF WEEKS, 1 OR 2 1384 00:54:47,546 --> 00:54:50,883 FRAMES OF THIS MOVIE AND THEN IT 1385 00:54:50,883 --> 00:54:51,217 RESOLVES. 1386 00:54:51,217 --> 00:54:52,985 SO THE FLASH GOES AWAY, BUT EACH 1387 00:54:52,985 --> 00:54:54,387 TIME THAT HAPPENS THERE'S BEEN 1388 00:54:54,387 --> 00:54:55,654 DAMAGE THAT OCCURS AND THAT'S 1389 00:54:55,654 --> 00:54:57,289 WHAT SHOWS UP AS THE BRIGHT 1390 00:54:57,289 --> 00:54:59,625 SPOTS IN THE OTHER IMAGE AND YOU 1391 00:54:59,625 --> 00:55:03,796 CAN SEE OVER TIME, THERE ARE 1392 00:55:03,796 --> 00:55:07,199 MORE AND MORE OF THESE FLASHES 1393 00:55:07,199 --> 00:55:07,666 OCCUR. 1394 00:55:07,666 --> 00:55:10,870 THE CENTRAL AREA, THE 1395 00:55:10,870 --> 00:55:11,937 VENTRICLES, THE SPACES ARE 1396 00:55:11,937 --> 00:55:13,205 GETTING LARGER AND LARGER AND AS 1397 00:55:13,205 --> 00:55:14,840 THE PATIENT GETS OLDER, YOU CAN 1398 00:55:14,840 --> 00:55:16,675 SEE THE FLASHES LEAVE BEHIND 1399 00:55:16,675 --> 00:55:18,644 THESE DARK SPOTS AND THOSE 1400 00:55:18,644 --> 00:55:20,513 REPRESENT AREAS OF DAMAGE TO THE 1401 00:55:20,513 --> 00:55:23,382 BRAIN THAT REALLY IS 1402 00:55:23,382 --> 00:55:23,716 IRREVERSIBLE. 1403 00:55:23,716 --> 00:55:25,251 EARLY ON IT TENDS TO REPAIR AND 1404 00:55:25,251 --> 00:55:27,653 THEN LATER ON IT BECOMES MORE 1405 00:55:27,653 --> 00:55:28,621 IRREVERSIBLE AND THROUGH STUDIES 1406 00:55:28,621 --> 00:55:31,690 LIKE THIS, WE HAVE LEARNED A LOT 1407 00:55:31,690 --> 00:55:35,127 ABOUT WHAT WE CALL TD NATURAL 1408 00:55:35,127 --> 00:55:36,729 HISTORY OF MULTIPLE SCLEROSIS. 1409 00:55:36,729 --> 00:55:38,497 WE'VE LEARNED AS WAS MENTIONED 1410 00:55:38,497 --> 00:55:40,699 BEFORE THAT THESE NEW LESIONS 1411 00:55:40,699 --> 00:55:43,269 OCCUR MUCH MORE FREQUENTLY THAN 1412 00:55:43,269 --> 00:55:44,970 THE CLINICAL SYMPTOMS LIKE YOU 1413 00:55:44,970 --> 00:55:47,073 HEARD DESCRIBED BEFORE AND SO IT 1414 00:55:47,073 --> 00:55:48,140 WAS REALIZED ACTUALLY HERE AT 1415 00:55:48,140 --> 00:55:50,609 THE NIH IN THE 1990S THAT IF YOU 1416 00:55:50,609 --> 00:55:54,814 USE THE MRI SCANS, YOU COULD 1417 00:55:54,814 --> 00:55:58,117 MUCH MORE RAPIDLY SCREEN NEW 1418 00:55:58,117 --> 00:55:58,717 MEDICATIONS, ANTIINFLAMMATORY 1419 00:55:58,717 --> 00:56:00,820 MEDICATIONS THAT MIGHT BE 1420 00:56:00,820 --> 00:56:01,687 EFFECTIVE IN MULTIPLE SCLEROSIS 1421 00:56:01,687 --> 00:56:03,422 AND SEE WHETHER THEY STOPPED 1422 00:56:03,422 --> 00:56:07,660 THESE NEW LESIONS FROM FORMING 1423 00:56:07,660 --> 00:56:09,395 AND AS YOU ALREADY HEARD, WE 1424 00:56:09,395 --> 00:56:12,832 HAVE MANY, MANY, MORE THAN 2 1425 00:56:12,832 --> 00:56:14,266 DOZEN SUCH ANTIINFLAMMATORY 1426 00:56:14,266 --> 00:56:15,768 DISEASE MODIFYING THERAPIES OR 1427 00:56:15,768 --> 00:56:18,170 DMTs THAT ARE AVAILABLE FOR 1428 00:56:18,170 --> 00:56:19,672 MULTIPLE SCLEROSIS, SOME OF THEM 1429 00:56:19,672 --> 00:56:21,006 INFUSIONS, SOME OF THEM PILLS, 1430 00:56:21,006 --> 00:56:29,615 AS YOU HEARD, AND SOME OF THEM 1431 00:56:29,615 --> 00:56:37,890 EXTREMELY EFFECTIVE, SINCE HIS 1432 00:56:37,890 --> 00:56:38,624 SYMPTOMS OCCURRED. 1433 00:56:38,624 --> 00:56:39,892 THE PROBLEM IS WHILE WE'VE BEEN 1434 00:56:39,892 --> 00:56:41,527 ABLE TO STOP THESE NEW LESIONS 1435 00:56:41,527 --> 00:56:43,262 FROM OCCURRING AND THESE NEW 1436 00:56:43,262 --> 00:56:46,932 RELAPSES FROM OCCURRING, THESE 1437 00:56:46,932 --> 00:56:48,801 CLINICAL EVENTS, WE HAVEN'T 1438 00:56:48,801 --> 00:56:49,835 ACTUALLY CURED MULTIPLE 1439 00:56:49,835 --> 00:56:55,341 SCLEROSIS BECAUSE WE CAN STILL 1440 00:56:55,341 --> 00:56:56,642 SEE, ALBEIT IN A PROPORTION OF 1441 00:56:56,642 --> 00:56:58,344 PEOPLE AND STILL A SIZABLE 1442 00:56:58,344 --> 00:57:00,980 PROPORTION OF PEOPLE WHO GO TO 1443 00:57:00,980 --> 00:57:03,282 DEVELOP THIS DREADED PROGRESSIVE 1444 00:57:03,282 --> 00:57:05,117 MULTIPLE SCLEROSIS WHERE PEOPLE 1445 00:57:05,117 --> 00:57:05,851 LOSE NEUROLOGICAL FUNCTIONING 1446 00:57:05,851 --> 00:57:08,287 AND CAN END UP FOR EXAMPLE 1447 00:57:08,287 --> 00:57:09,889 LOSING THE ABILITY TO WALK AND 1448 00:57:09,889 --> 00:57:12,291 SO THAT'S WHAT WE REALLY WANT TO 1449 00:57:12,291 --> 00:57:15,161 PREVENT AND THE GOAL HERE IS TO 1450 00:57:15,161 --> 00:57:17,163 TAKE THIS EARLY INFLAMMATION 1451 00:57:17,163 --> 00:57:21,066 THAT WE CAN DETECTOT MRI AND 1452 00:57:21,066 --> 00:57:22,601 FIGURE OUT NOT JUST HOW TO 1453 00:57:22,601 --> 00:57:23,769 PREVENT THAT BUT HOW TO TREAT 1454 00:57:23,769 --> 00:57:28,674 THAT SO THAT WE CAN PREVENT THIS 1455 00:57:28,674 --> 00:57:29,375 NEURODEGENERATION MANIFESTED BY 1456 00:57:29,375 --> 00:57:35,314 A LOSS OF BRAIN TISSUE AND 1457 00:57:35,314 --> 00:57:36,749 ENLARGEMENT OF THE FLUID FILLED 1458 00:57:36,749 --> 00:57:39,151 SPACES AND HERE YOU CAN SEE THE 1459 00:57:39,151 --> 00:57:41,353 SCHEMATIC, SHOWING THE 1460 00:57:41,353 --> 00:57:42,188 INFLAMMATORY INJURY, FOCAL 1461 00:57:42,188 --> 00:57:45,424 LESIONS THAT DEVELOP THOSE 1462 00:57:45,424 --> 00:57:47,259 FLASHES, BRIGHT FLASHES ON THE 1463 00:57:47,259 --> 00:57:48,227 MRI SCAN, BECAUSE IT'S COMING 1464 00:57:48,227 --> 00:57:50,462 FROM THE IMMUNE SYSTEM, OF THE 1465 00:57:50,462 --> 00:57:54,300 BLOOD, THE BRAIN IS CENTRAL AND 1466 00:57:54,300 --> 00:57:56,068 THE BLOOD IS PERIPHERAL IN THIS 1467 00:57:56,068 --> 00:58:00,973 CASE, AND WE CAN STOP THOSE BUT 1468 00:58:00,973 --> 00:58:01,874 NONETHELESS, THERE STILL 1469 00:58:01,874 --> 00:58:05,211 ACCUMULATES WHAT WE CALL CNS, OR 1470 00:58:05,211 --> 00:58:09,648 CENTRAL NERVOUS SYSTEM 1471 00:58:09,648 --> 00:58:10,349 COMPARTMENTALIZED INFLAMMATORY 1472 00:58:10,349 --> 00:58:13,285 INJURY THAT CAN ACCUMULATE. 1473 00:58:13,285 --> 00:58:15,187 THERE'S A VARIETY IT MEN FASTS, 1474 00:58:15,187 --> 00:58:17,590 1 IS AT THE EDGE OF THOSE FOCAL 1475 00:58:17,590 --> 00:58:19,692 LESIONS, 1 IS DIFFUSELY 1476 00:58:19,692 --> 00:58:21,527 THROUGHOUT THE BRAIN, AND WE CAN 1477 00:58:21,527 --> 00:58:22,494 ALSO SEE INFLAMMATION NOT JUST 1478 00:58:22,494 --> 00:58:25,998 IN THE BRAIN, BUT AROUND THE 1479 00:58:25,998 --> 00:58:30,502 BRAIN IN THE MENINGS WHICH ARE 1480 00:58:30,502 --> 00:58:31,937 THE THING AREAS WHERE THEY COVER 1481 00:58:31,937 --> 00:58:33,172 AND PROTECT THE BRAIN WHERE 1482 00:58:33,172 --> 00:58:34,907 THERE'S A LOT OF IMMUNE 1483 00:58:34,907 --> 00:58:36,575 SURVEILLANCE BUT YET CAN 1484 00:58:36,575 --> 00:58:38,410 ACCUMULATE INFLAMMATION IN THE 1485 00:58:38,410 --> 00:58:40,346 CONTEXT OF MULTIPLE SCLEROSIS. 1486 00:58:40,346 --> 00:58:42,448 THESE ARE THE 3 MAIN WAYS WE 1487 00:58:42,448 --> 00:58:46,318 TEND TO HAVE THIS CNS CENTRAL 1488 00:58:46,318 --> 00:58:47,820 NERVOUS SYSTEM COMPARTMENTALIZED 1489 00:58:47,820 --> 00:58:48,254 INFLAMMATORY INJURY. 1490 00:58:48,254 --> 00:58:49,188 AND WHEY WILL FOCUS THE REST OF 1491 00:58:49,188 --> 00:58:51,557 THE TIME IN SORT OF DO A DEEP 1492 00:58:51,557 --> 00:58:58,998 DIVE ON IS THIS IRON RIM OR 1493 00:58:58,998 --> 00:58:59,898 PERIPHERAL PARAMAGNETIC RIM 1494 00:58:59,898 --> 00:59:01,066 LESION I WILL EXPLAIN THOSE AND 1495 00:59:01,066 --> 00:59:03,269 HOW THEY ARE AND HOW THEY RELATE 1496 00:59:03,269 --> 00:59:05,671 TO MS AND UP TILL ABOUT 10 YEARS 1497 00:59:05,671 --> 00:59:09,842 AGO THE ONLY WAY WE REALLY KNEW 1498 00:59:09,842 --> 00:59:11,143 ABOUT THIS KIND OF INFLAMMATION 1499 00:59:11,143 --> 00:59:12,978 AT THE EDGE OF THE LESIONS WAS 1500 00:59:12,978 --> 00:59:15,581 THROUGH STUDIES OF BRAIN TISSUE 1501 00:59:15,581 --> 00:59:16,715 AFTER DEATH, AFTER AUTOPSIES 1502 00:59:16,715 --> 00:59:19,518 WHERE PEOPLE HAD DONATED THEIR 1503 00:59:19,518 --> 00:59:22,021 BRAIN TO SCIENCE AND 1 COULD DO 1504 00:59:22,021 --> 00:59:22,288 ANALYSIS. 1505 00:59:22,288 --> 00:59:24,590 YOU COULDN'T TRACK IT, DURING 1506 00:59:24,590 --> 00:59:27,126 THE COURSE OF THE DISEASE, BUT 1507 00:59:27,126 --> 00:59:28,761 YOU CAN MAKE INFERENCES AT THE 1508 00:59:28,761 --> 00:59:29,962 END BY LOOKING AT MANY, MANY 1509 00:59:29,962 --> 00:59:32,231 BRAINS AND SOME OF THEM HAD A 1510 00:59:32,231 --> 00:59:35,000 SHORT TIME WITH MS, SOME HAD A 1511 00:59:35,000 --> 00:59:37,169 LONG TIME WITH MS, SOME WERE 1512 00:59:37,169 --> 00:59:38,971 YOUNG, SOME WERE OLD AND YOU CAN 1513 00:59:38,971 --> 00:59:40,706 TRY TO RECONSTRUCT WHAT MAY HAVE 1514 00:59:40,706 --> 00:59:45,844 HAPPENED AND HERE IS STILL THE 1515 00:59:45,844 --> 00:59:49,481 MOST COMPREHENSIVE STUDY DONE BY 1516 00:59:49,481 --> 00:59:51,884 CLAUDIA AT THE MAYO CLINIC, AND 1517 00:59:51,884 --> 00:59:54,653 IT'S 120 AUTOPSIES BRAINS, 1518 00:59:54,653 --> 00:59:57,523 ALMOST 2500 LESIONS AN LIZED 1519 00:59:57,523 --> 00:59:58,357 CAREFULLY UNDER THE MICROSCOPE 1520 00:59:58,357 --> 01:00:00,392 AND WHAT WE'RE TALKING ABOUT 1521 01:00:00,392 --> 01:00:03,362 HERE ARE THESE LESIONS THAT ARE 1522 01:00:03,362 --> 01:00:05,431 IN THIS SORT OF SALMON COLOR AND 1523 01:00:05,431 --> 01:00:07,166 YOU CAN SEE THEM IN THE BAR 1524 01:00:07,166 --> 01:00:09,468 GRAPHS ON TOP THAT THE 1525 01:00:09,468 --> 01:00:11,070 PROPORTION OF LESIONS THAT 1526 01:00:11,070 --> 01:00:12,838 ANALYZE THAT HAD THIS FEATURE, 1527 01:00:12,838 --> 01:00:14,773 THEY CALL TODAY SMOLDERING, WE 1528 01:00:14,773 --> 01:00:18,911 NOW CALL IT CHRONIC ACTIVE 1529 01:00:18,911 --> 01:00:20,279 LESIONS, TEND TO INCREASE 1530 01:00:20,279 --> 01:00:21,447 ROUGHLY IN PROPORTION AS PEOPLE 1531 01:00:21,447 --> 01:00:22,848 LIVE LONGER AND LONGER WITH THE 1532 01:00:22,848 --> 01:00:27,920 DISEASE BEFORE THEY CAME TO 1533 01:00:27,920 --> 01:00:28,387 AUTOPSIES. 1534 01:00:28,387 --> 01:00:29,288 ALTHOUGH INTERESTINGLY THAT MAY 1535 01:00:29,288 --> 01:00:31,056 DROP A LITTLE BIT IN THE LONGEST 1536 01:00:31,056 --> 01:00:31,423 SPAN PATIENT. 1537 01:00:31,423 --> 01:00:33,792 SO THAT'S SORT OF WHAT WE KNEW 1538 01:00:33,792 --> 01:00:35,728 BUT PEOPLE WHO HAD VERY EARLY 1539 01:00:35,728 --> 01:00:36,795 DISEASE DID NOT TEND TO HAVE 1540 01:00:36,795 --> 01:00:40,432 VERY MANY OF THESE AT ALL OR 1541 01:00:40,432 --> 01:00:40,632 NONE. 1542 01:00:40,632 --> 01:00:42,735 SO TO MAKE A LONG STORY SHORT, 1543 01:00:42,735 --> 01:00:44,703 WE'RE FACE WIDE THE TASK OF 1544 01:00:44,703 --> 01:00:46,739 TRYING TO UNDERSTAND HOW TO 1545 01:00:46,739 --> 01:00:48,874 IDENTIFY WHETHER AN INDIVIDUAL 1546 01:00:48,874 --> 01:00:51,443 MAY HAVE HAD THESE -- MAY HAVE 1547 01:00:51,443 --> 01:00:53,479 THESE CHRONICALLY INFLAMED 1548 01:00:53,479 --> 01:00:54,880 LESIONS AS MUCH AS AFTER THEY 1549 01:00:54,880 --> 01:00:58,384 DIE BUT WHILE THEY'RE ALIVE AND 1550 01:00:58,384 --> 01:00:59,685 DOING WELL, AND THIS WAS ABOUT 1551 01:00:59,685 --> 01:01:01,320 10 YEARS OF WORK IN OUR GROUP 1552 01:01:01,320 --> 01:01:03,389 AND ALSO IN OTHER GROUPS TO 1553 01:01:03,389 --> 01:01:04,590 FIGURE OUT WHAT THIS WAS AND I 1554 01:01:04,590 --> 01:01:06,992 WILL TRY TO SUMMARIZE THAT IN 1 1555 01:01:06,992 --> 01:01:09,228 SLIDE, HOW DO WE IDENTIFY THESE 1556 01:01:09,228 --> 01:01:10,195 SMOLDERING OR CHRONIC ACTIVE 1557 01:01:10,195 --> 01:01:13,365 LESIONS SO WHAT YOU SEE HERE IS 1558 01:01:13,365 --> 01:01:14,666 AN IMAGE, OF A BRAIN SECTION, A 1559 01:01:14,666 --> 01:01:17,403 SMALL SECTION AND JUST FOR 1560 01:01:17,403 --> 01:01:18,570 ORIENTATION, ON THE LEFT SIDE, 1561 01:01:18,570 --> 01:01:21,206 IS THE EDGE OF THE BRAIN, YOU 1562 01:01:21,206 --> 01:01:23,242 HAVE THE OUTSIDE OF THE BRAIN, 1563 01:01:23,242 --> 01:01:24,443 THAT'S THE CEREBRAL CORTEX WHERE 1564 01:01:24,443 --> 01:01:26,178 THE CELL BODIES OF THE NERVE 1565 01:01:26,178 --> 01:01:27,913 CELLS, THE NEURONS LIVE, AND 1566 01:01:27,913 --> 01:01:29,748 THEN THE DARKER BROWN AREA, IS 1567 01:01:29,748 --> 01:01:32,618 THE WHITE MATTER, THESE ARE THE 1568 01:01:32,618 --> 01:01:33,352 FIBERS THAT CONNECT 1 AREA OF 1569 01:01:33,352 --> 01:01:35,821 THE BRAIN TO THE NEXT, 1 CELL TO 1570 01:01:35,821 --> 01:01:36,255 THE NEXT. 1571 01:01:36,255 --> 01:01:37,856 ON THE FAR RIGHT AT THE BOTTOM, 1572 01:01:37,856 --> 01:01:40,559 IS THAT THE FLUID SPILLED SPACE, 1573 01:01:40,559 --> 01:01:42,861 IT'S BLACK HERE BECAUSE THE 1574 01:01:42,861 --> 01:01:44,263 FLUID IS GONE WHEN WE PREPARE 1575 01:01:44,263 --> 01:01:45,330 THE TISSUE AND THEN YOU HAVE 1576 01:01:45,330 --> 01:01:53,972 THESE AREAS WHERE THERE IS NO 1577 01:01:53,972 --> 01:01:55,641 STAINING -- LET ME SEE IF I CAN 1578 01:01:55,641 --> 01:01:57,075 GET A LACER POINTER, SO THESE 1579 01:01:57,075 --> 01:01:58,510 AREAS OVER HERE WHERE THERE'S NO 1580 01:01:58,510 --> 01:02:00,779 BROWN AT ALL, THE BROWN IN THIS 1581 01:02:00,779 --> 01:02:03,682 CASE IS A STAIN FOR MELYN, THAT 1582 01:02:03,682 --> 01:02:04,883 IS THE FATTY SUBSTANCE THAT HAS 1583 01:02:04,883 --> 01:02:07,786 PROTEINS IN IT THAT ENSUEALATES 1584 01:02:07,786 --> 01:02:10,088 THE NERVE FIBERS AND WIRES. 1585 01:02:10,088 --> 01:02:12,090 AND THE MILEIN IS ACTUALLY THE 1586 01:02:12,090 --> 01:02:14,126 TARGET OF THE IMMUNE ATACT IN 1587 01:02:14,126 --> 01:02:18,931 MS, SO THESE ARE LESIONS AND 1588 01:02:18,931 --> 01:02:20,232 THERE'S NO MYELIN, THIS SHOULD 1589 01:02:20,232 --> 01:02:21,033 ALL BE BROWN. 1590 01:02:21,033 --> 01:02:22,401 SO THESE HAVE BEEN HERE FOR 1591 01:02:22,401 --> 01:02:24,036 QUITE A LONG TIME IN THIS 1592 01:02:24,036 --> 01:02:24,336 INDIVIDUAL. 1593 01:02:24,336 --> 01:02:26,405 AND IF YOU LOOK IN DETAIL AT THE 1594 01:02:26,405 --> 01:02:28,507 EDGE OF 1 OF THESE NOW WE'RE 1595 01:02:28,507 --> 01:02:30,876 STAINING FOR A PROTEIN CALLED 1596 01:02:30,876 --> 01:02:33,111 CD68. 1597 01:02:33,111 --> 01:02:34,847 CD68 IS A PROTEIN THAT IS 1598 01:02:34,847 --> 01:02:37,950 PRESENT IN CELLS THAT ARE EATING 1599 01:02:37,950 --> 01:02:39,551 DEBRIS FOR EXAMPLE, AND YOU CAN 1600 01:02:39,551 --> 01:02:42,955 SEE THAT AT THE EDGE OF THIS 1601 01:02:42,955 --> 01:02:44,723 LESION, ARE FULL OF THESE SMALL 1602 01:02:44,723 --> 01:02:46,091 CELLS THAT ARE PRESENT AND THESE 1603 01:02:46,091 --> 01:02:48,060 ARE CELLS OF THE IMMUNE SYSTEM, 1604 01:02:48,060 --> 01:02:49,695 SO EVEN THOUGH IT LOOKS SORT OF 1605 01:02:49,695 --> 01:02:51,430 BENIGN HERE ON THE LEFT OR 1606 01:02:51,430 --> 01:02:52,865 QUIET, YOU CAN ACTUALLY SEE 1607 01:02:52,865 --> 01:02:55,033 THERE'S LOTS OF IMMUNE CELLS 1608 01:02:55,033 --> 01:02:55,968 PRESENT AROUND THE EDGE OF THIS 1609 01:02:55,968 --> 01:02:58,070 LESION AND IF YOU LOOK IN MORE 1610 01:02:58,070 --> 01:03:00,839 DETAIL, THIS IS NOW A STAIN FOR 1611 01:03:00,839 --> 01:03:03,242 LIPID, AND PROTEIN LIPID FATTY 1612 01:03:03,242 --> 01:03:05,210 SUBSTANCE THAT'S IN THE MYELIN, 1613 01:03:05,210 --> 01:03:07,379 YOU CAN SEE THAT THAT SUBSTANCE 1614 01:03:07,379 --> 01:03:10,115 IN BLUE AND PURPLE IS INSIDE 1615 01:03:10,115 --> 01:03:12,050 THESE CELLS AT THE EDGE OF THE 1616 01:03:12,050 --> 01:03:13,952 LESION AND THAT MEANS THAT 1617 01:03:13,952 --> 01:03:17,756 THERE'S ACTIVE EATING OF MYELIN 1618 01:03:17,756 --> 01:03:18,924 GOING ON. 1619 01:03:18,924 --> 01:03:21,460 BUT THAT'S QUITE -- SORRY SO 1620 01:03:21,460 --> 01:03:22,995 SOME FRACTION OF THOSE CELLS 1621 01:03:22,995 --> 01:03:24,162 ACTUALLY HAVE IRON IN THEM, AND 1622 01:03:24,162 --> 01:03:25,864 WE CAN TALK ABOUT THE IRON A 1623 01:03:25,864 --> 01:03:28,133 LITTLE BIT LATER, WE WILL 1624 01:03:28,133 --> 01:03:29,535 ACTUALLY TALK ABOUT A LITTLE 1625 01:03:29,535 --> 01:03:30,068 MORE. 1626 01:03:30,068 --> 01:03:31,370 AND THAT'S REMARKABLE BECAUSE WE 1627 01:03:31,370 --> 01:03:33,572 CAN SEE IRON ON THE MRI SCAN, ON 1628 01:03:33,572 --> 01:03:36,942 A SPECIFIC KIND OF MRI SCAN, 1629 01:03:36,942 --> 01:03:38,510 CALLED A SUSCEPTIBILITY 1630 01:03:38,510 --> 01:03:39,912 SENSITIVE MRI, AND THIS IS AN 1631 01:03:39,912 --> 01:03:43,515 IMAGE OF THAT SAME LESION, RIGHT 1632 01:03:43,515 --> 01:03:44,683 OVER HERE EMPLOY THIS LESION 1633 01:03:44,683 --> 01:03:46,084 OVER HERE THAT I'M OUTLINING AND 1634 01:03:46,084 --> 01:03:47,586 YOU CAN SEE A DARK LINE AT THE 1635 01:03:47,586 --> 01:03:49,454 EDGE OF THAT LESION, THAT 1636 01:03:49,454 --> 01:03:50,656 REPRESENTS THE AREA WHERE 1637 01:03:50,656 --> 01:03:51,189 THERE'S IRON. 1638 01:03:51,189 --> 01:03:55,294 THIS HAPPENS TO BE AN IMAGE OF 1639 01:03:55,294 --> 01:03:57,162 THE BRAIN BEFORE YOU CUT IT TO 1640 01:03:57,162 --> 01:03:59,665 PUT IT UNDER A MICROSCOPE BUT WE 1641 01:03:59,665 --> 01:04:01,967 CAN ACTUALLY SEE THIS IN LIVING 1642 01:04:01,967 --> 01:04:03,802 PEOPLE AS WELL, WITH RELATIVE 1643 01:04:03,802 --> 01:04:04,102 EASE. 1644 01:04:04,102 --> 01:04:05,871 AND IN THIS INDIVIDUAL, CAN YOU 1645 01:04:05,871 --> 01:04:07,606 ACTUALLY SEE THAT OVER THE 7 1646 01:04:07,606 --> 01:04:11,677 YEARS, THAT WE FOLLOWED THEM, 1647 01:04:11,677 --> 01:04:13,712 BEFORE THEY DIED, THE SIZE OF 1648 01:04:13,712 --> 01:04:16,148 THESE LESIONS RIGHT UP AGAINST 1649 01:04:16,148 --> 01:04:17,382 THE VENTRICLE, THESE ARE SCANS 1650 01:04:17,382 --> 01:04:18,784 TAKEN WHILE HE WAS ALIVE, CAN 1651 01:04:18,784 --> 01:04:21,219 YOU SEE THERE'S BEEN SUBSTANTIAL 1652 01:04:21,219 --> 01:04:22,120 ENLARGEMENT OF THOSE SCANS AND 1653 01:04:22,120 --> 01:04:23,522 THAT MAKES A LOT OF SENSE WHEN 1654 01:04:23,522 --> 01:04:26,024 YOU THINK ABOUT THE FACT THAT 1655 01:04:26,024 --> 01:04:27,192 THERE'S ACTIVE EATING BREAK DOWN 1656 01:04:27,192 --> 01:04:29,361 OF THE MILEN THAT'S OCCURRING. 1657 01:04:29,361 --> 01:04:30,796 SO THE LESIONS WOULD ENLARGE. 1658 01:04:30,796 --> 01:04:33,332 SO HOW DO WE IDENTIFY THESE 1659 01:04:33,332 --> 01:04:35,233 SMOLDERING LESIONS, WE LOOK FOR 1660 01:04:35,233 --> 01:04:36,702 THIS PARAMAGNETIC OR IRON OR 1661 01:04:36,702 --> 01:04:38,604 DARK RIM, AND WHEN WE SEE THAT, 1662 01:04:38,604 --> 01:04:42,441 ON THE MRI, WE CAN INFER THAT 1663 01:04:42,441 --> 01:04:44,276 THERE'S CHRONIC INFLAMMATION, 1664 01:04:44,276 --> 01:04:45,644 MYELIN DESTRUCTION AND LESION 1665 01:04:45,644 --> 01:04:46,011 EXPANSION. 1666 01:04:46,011 --> 01:04:47,312 SO WITH THIS TOOL IN HAND WE 1667 01:04:47,312 --> 01:04:50,716 WERE ABLE TO GO BACK AND SAY, 1668 01:04:50,716 --> 01:04:52,985 OKAY, WE CAN NOW IDENTIFY IT, 1669 01:04:52,985 --> 01:04:55,988 HOW DO THESE KINDS OF LESIONS OR 1670 01:04:55,988 --> 01:04:57,656 PLAQUES ARISE IN AND THIS 1671 01:04:57,656 --> 01:05:01,627 ACTUALLY GOES BACK TO WORK THAT 1672 01:05:01,627 --> 01:05:07,232 THE DOCTOR DID WHEN HE WAS A 1673 01:05:07,232 --> 01:05:09,034 TRAINEE IN OUR LAB. 1674 01:05:09,034 --> 01:05:10,869 SHE DID EXPERIMENTS AND STUDIES 1675 01:05:10,869 --> 01:05:13,805 LOOKING AT THE EARLIEST STAGES 1676 01:05:13,805 --> 01:05:16,775 OF LESION DEVELOPMENT WHERE SHE 1677 01:05:16,775 --> 01:05:18,243 INJECTED THE GATTA LYNNIUM 1678 01:05:18,243 --> 01:05:19,411 CONTRAST MATERIAL AND VERY EARLY 1679 01:05:19,411 --> 01:05:20,612 ON WHEN A LESION DEVELOPS, CAN 1680 01:05:20,612 --> 01:05:22,481 YOU SEE THAT THE BRIGHT SPOT 1681 01:05:22,481 --> 01:05:25,617 HERE, SO THIS A MOVIE OVER ABOUT 1682 01:05:25,617 --> 01:05:27,953 AN HOUR OR SO, MAYBE SHORTER 1683 01:05:27,953 --> 01:05:30,355 THAN THAT, CAN YOU SEE THERE'S 1684 01:05:30,355 --> 01:05:31,723 LEAKAGE FROM THE DYE FROM THE 1685 01:05:31,723 --> 01:05:33,792 CENTER OF THE DARK AREA HERE AND 1686 01:05:33,792 --> 01:05:36,128 IT SPREADS OUT OVER TIME. 1687 01:05:36,128 --> 01:05:37,462 ABOUT HALF OF THE TIME IF YOU 1688 01:05:37,462 --> 01:05:38,864 WAIT A FEW DAYS, BRING THE 1689 01:05:38,864 --> 01:05:40,032 PERSON BACK AND SCAN THEM AGAIN, 1690 01:05:40,032 --> 01:05:42,134 WHAT YOU CAN SEE IS ABOUT HALF 1691 01:05:42,134 --> 01:05:45,570 OF THOSE LESIONS HAVE A 1692 01:05:45,570 --> 01:05:47,039 DIFFERENT BEHAVIOR. 1693 01:05:47,039 --> 01:05:47,673 LET ME SEE. 1694 01:05:47,673 --> 01:05:48,840 I LOST THE VIDEO. 1695 01:05:48,840 --> 01:05:50,475 LET ME TRY IT AGAIN. 1696 01:05:50,475 --> 01:05:51,843 YES, CAN YOU SEE THAT THE 1697 01:05:51,843 --> 01:05:53,578 CONTRAST IS NOW LEAKING FROM THE 1698 01:05:53,578 --> 01:05:55,947 EDGE AND FILLING OUT THE CENTER 1699 01:05:55,947 --> 01:05:57,816 AS THIS LESION EXPANDS. 1700 01:05:57,816 --> 01:06:01,086 AND THOSE WERE ABOUT 50% OF THE 1701 01:06:01,086 --> 01:06:02,521 LESIONS THAT WE TRACKED AND THEY 1702 01:06:02,521 --> 01:06:04,156 TENDED TO BE THE LARGER 1S. 1703 01:06:04,156 --> 01:06:06,258 AND SO WHAT WE DID WAS WE 1704 01:06:06,258 --> 01:06:08,193 INVITED THESE PEOPLE BACK TO GET 1705 01:06:08,193 --> 01:06:11,163 REALLY HIGH RESOLUTION DEDICATED 1706 01:06:11,163 --> 01:06:15,000 MRI SCANS, OF THE SAME AREA 1707 01:06:15,000 --> 01:06:17,936 USING OUR ADVANCE 7 TESLA 1708 01:06:17,936 --> 01:06:19,938 SCANNER, THESE ARE AMONG THE 1709 01:06:19,938 --> 01:06:20,872 STRONGEST SCANNERS AVAILABLE, 1710 01:06:20,872 --> 01:06:21,840 FORTUNATELY WE HAVE 3 OF THEM 1711 01:06:21,840 --> 01:06:24,710 HERE AT THE NIH CLINICAL CENTER, 1712 01:06:24,710 --> 01:06:26,478 WHERE WE CAN DO THESE KINDS OF 1713 01:06:26,478 --> 01:06:28,113 STUDIES AND HERE YOU CAN SEE THE 1714 01:06:28,113 --> 01:06:29,815 LEAKAGE OF THE CONTRAST 1715 01:06:29,815 --> 01:06:30,782 MATERIAL, THE OPEN BLOOD BRAIN 1716 01:06:30,782 --> 01:06:31,717 BARRIER AT THE EDGE OF THE 1717 01:06:31,717 --> 01:06:35,253 LESION AND WHEN WE DO THAT, IRON 1718 01:06:35,253 --> 01:06:37,522 SENSITIVE SCAN, YOU CAN SEE A 1719 01:06:37,522 --> 01:06:40,859 DARK RIM AROUND THE EDGE OVER 1720 01:06:40,859 --> 01:06:43,428 HERE YOU CAN ALSO SEE THE 1721 01:06:43,428 --> 01:06:44,963 CENTRAL VEIN THAT THE DOCTOR 1722 01:06:44,963 --> 01:06:45,964 TALKED ABOUT AND YOU CAN SEE HOW 1723 01:06:45,964 --> 01:06:48,467 THE LESION IS FORMING AROUND 1724 01:06:48,467 --> 01:06:49,234 THIS CENTRAL VEIN. 1725 01:06:49,234 --> 01:06:51,770 SO WE WENT ON TO SHOW THAT ABOUT 1726 01:06:51,770 --> 01:06:56,475 A QUARTER OF THE NEW LESIONS 1727 01:06:56,475 --> 01:06:58,143 THAT DEVELOPED HAD THIS REALLY 1728 01:06:58,143 --> 01:06:59,010 INTERESTING FEATURE. 1729 01:06:59,010 --> 01:07:00,212 THEY WERE START SMALL, ABOUT A 1730 01:07:00,212 --> 01:07:01,813 MONTH LATER YOU CAN SEE THIS 1731 01:07:01,813 --> 01:07:04,015 OPEN BLOOD BRAIN BARRIER, A RIM 1732 01:07:04,015 --> 01:07:06,184 IS BEGINNING TO FORM AND THEN IT 1733 01:07:06,184 --> 01:07:08,153 PERSISTS OVER TIME EVEN AS THE 1734 01:07:08,153 --> 01:07:10,689 BLOOD BRAIN BARRIER REPAIRS, SO 1735 01:07:10,689 --> 01:07:11,623 THERE'S THIS CHRONIC 1736 01:07:11,623 --> 01:07:13,258 INFLAMMATION THAT WE CAN DETECT 1737 01:07:13,258 --> 01:07:14,760 AND INFER BY THE PRESENCE OF 1738 01:07:14,760 --> 01:07:17,829 IRON IS REALLY SET UP OVER THE 1739 01:07:17,829 --> 01:07:19,564 FIRST FEW MONTHS AFTER A NEW 1740 01:07:19,564 --> 01:07:21,633 LESION FORMS AND THAT REALLY 1741 01:07:21,633 --> 01:07:24,469 WASN'T UNDERSTOOD AT THE TIME. 1742 01:07:24,469 --> 01:07:26,338 ARE THESE -- WE COULD ALSO ASK 1743 01:07:26,338 --> 01:07:27,606 QUESTIONS ABOUT, YOU KNOW WHY 1744 01:07:27,606 --> 01:07:29,908 AND HOW THESE KINDS OF LESIONS 1745 01:07:29,908 --> 01:07:31,243 MAY BE MORE DESTRUCTIVE THAN 1746 01:07:31,243 --> 01:07:33,078 OTHER SORTS OF LESIONS, SO 1747 01:07:33,078 --> 01:07:34,813 HERE'S AN EXAMPLE, THIS IS JUST 1748 01:07:34,813 --> 01:07:37,415 A ZOOMED IN MRI, SO I'M SORRY IT 1749 01:07:37,415 --> 01:07:38,416 DOESN'T ACTUALLY SHOW SORT OF 1750 01:07:38,416 --> 01:07:39,484 THE CONTEXT OF WHERE IT IS IN 1751 01:07:39,484 --> 01:07:41,820 THE BRAIN BUT HERE YOU CAN SEE, 1752 01:07:41,820 --> 01:07:44,589 IN THIS KIND OF MRI, THE LESION 1753 01:07:44,589 --> 01:07:46,558 IS DARK, AND HERE, I THINK IT 1754 01:07:46,558 --> 01:07:48,560 PROBABLY DOESN'T PROJECT VERY 1755 01:07:48,560 --> 01:07:50,962 WELL, BUT THERE IS A DARK RIM AT 1756 01:07:50,962 --> 01:07:52,798 THE EDGE OF THAT LESION. 1757 01:07:52,798 --> 01:07:55,600 THIS IS A LESION THAT ACTUALLY 1758 01:07:55,600 --> 01:07:59,471 CAUSED THE SYMPTOM AND THAT 1759 01:07:59,471 --> 01:08:01,973 SYMPTOM WAS A LOSS OF ABILITY TO 1760 01:08:01,973 --> 01:08:05,911 SEE PART OF THE WORLD BECAUSE 1761 01:08:05,911 --> 01:08:06,978 THIS LESION AFFECTED A PATHWAY 1762 01:08:06,978 --> 01:08:09,281 IN THE BRAIN CALLED THE OPTIC 1763 01:08:09,281 --> 01:08:11,416 RADIATION TOWARD THE BACK OF THE 1764 01:08:11,416 --> 01:08:14,953 BRAIN WHICH IS WHERE THE VISUAL 1765 01:08:14,953 --> 01:08:16,021 PROCESSING HAPPENS AND EVEN 1766 01:08:16,021 --> 01:08:17,656 THOUGH IT'S A REALLY TINY LITTLE 1767 01:08:17,656 --> 01:08:21,660 LESION BECAUSE IT WAS SUCH A 1768 01:08:21,660 --> 01:08:23,028 DAMAGING LESION, THE INVOLVEMENT 1769 01:08:23,028 --> 01:08:26,431 OF THAT FUNCTIONAL PATHWAY WAS 1770 01:08:26,431 --> 01:08:27,833 QUITE SIGNIFICANT AND HERE'S 1 1771 01:08:27,833 --> 01:08:29,134 WAY OF LOOKING AT THAT. 1772 01:08:29,134 --> 01:08:31,536 THIS IS WHAT WE DID HERE IS WE 1773 01:08:31,536 --> 01:08:33,438 TOOK 2 SCANS, 1 BEFORE THE 1774 01:08:33,438 --> 01:08:34,105 OCCURRED BECAUSE THIS IS 1775 01:08:34,105 --> 01:08:35,740 SOMEBODY WE WERE FOLLOWING OVER 1776 01:08:35,740 --> 01:08:38,043 TIME AND 1 AFTER AND WE JUST 1777 01:08:38,043 --> 01:08:38,844 OVERLAID THEM AND SUBTRACTED 1778 01:08:38,844 --> 01:08:40,946 THEM AND YOU CAN SEE, THE VERY 1779 01:08:40,946 --> 01:08:42,214 BRIGHT SPOT WHICH IS WHERE THE 1780 01:08:42,214 --> 01:08:44,649 LESION IS, BUT YOU CAN SEE A 1781 01:08:44,649 --> 01:08:46,218 MUCH MORE SUBTLE, WE DIDN'T -- 1782 01:08:46,218 --> 01:08:47,919 YOU CAN'T SEE IT ON THE ORIGINAL 1783 01:08:47,919 --> 01:08:49,654 SCANS BUT ON THE SUBTRACTION, 1784 01:08:49,654 --> 01:08:51,323 CAN YOU ACTUALLY SEE THE WHOLE 1785 01:08:51,323 --> 01:08:53,592 PATHWAY OF THE OPTIC RADIATION 1786 01:08:53,592 --> 01:08:55,493 IS LIEDING UP HERE TELLING US 1787 01:08:55,493 --> 01:08:58,029 THIS LITTLE LESION HERE WHICH 1788 01:08:58,029 --> 01:09:01,233 WAS DESTRUCTIVE AND HAD THIS 1789 01:09:01,233 --> 01:09:03,301 CHRONIC INFLAMMATION ATTRIBUTE 1790 01:09:03,301 --> 01:09:04,436 COULD ACTUALLY AFFECT UPTREME 1791 01:09:04,436 --> 01:09:05,937 AND DOWN STREAM THROUGHOUT THE 1792 01:09:05,937 --> 01:09:11,109 PATHWAY AND CAUSINGED REALLY 1793 01:09:11,109 --> 01:09:11,810 SIGNIFICANT SYMPTOMS. 1794 01:09:11,810 --> 01:09:13,578 WE HAVE LOOKED NOW AT 500 1795 01:09:13,578 --> 01:09:14,679 PEOPLE, THE SCAN, THIS SLIDE IS 1796 01:09:14,679 --> 01:09:16,314 A FEW YEARS OLD, SO WE'RE CLOSER 1797 01:09:16,314 --> 01:09:17,716 TO A THOUSAND PEOPLE NOW, AND WE 1798 01:09:17,716 --> 01:09:22,621 ARE ABLE TO SHOW THAT THESE 1799 01:09:22,621 --> 01:09:24,356 PRLs, THESE PARAMAGNETIC RIM 1800 01:09:24,356 --> 01:09:27,325 LESIONS, THESE LESIONS WE CAN 1801 01:09:27,325 --> 01:09:30,428 DETECT ON MRI, ARE OCCURRING IN 1802 01:09:30,428 --> 01:09:33,932 ROUGHLY 50-60% OF INDIVIDUALS 1803 01:09:33,932 --> 01:09:36,167 WITH MS, THEY ARE A BIT MORE 1804 01:09:36,167 --> 01:09:38,336 FREQUENT IN PEOPLE WITH 1805 01:09:38,336 --> 01:09:38,703 PROGRESSIVE MS. 1806 01:09:38,703 --> 01:09:43,642 BUT WHEN YOU SEE THEM, THEY TEND 1807 01:09:43,642 --> 01:09:45,010 WHEN THERE ARE POWER OR MORE IN 1808 01:09:45,010 --> 01:09:47,178 THE BRAIN THEY TEND TO PREDICT A 1809 01:09:47,178 --> 01:09:48,246 WORSE DISEASE COURSE BECAUSE 1810 01:09:48,246 --> 01:09:49,714 THERE'S ALL THIS INFLAMMATION 1811 01:09:49,714 --> 01:09:51,416 GOING ON IN THE BRAIN AND ACTIVE 1812 01:09:51,416 --> 01:09:52,417 DAMAGE TO TISSUE. 1813 01:09:52,417 --> 01:09:53,919 AND THESE LESIONS OCCUR VERY, 1814 01:09:53,919 --> 01:09:56,888 VERY RARELY IN PEOPLE WHO DO NOT 1815 01:09:56,888 --> 01:09:58,657 HAVE MULTIPLE SCLEROSIS, EVEN IF 1816 01:09:58,657 --> 01:10:00,425 CLINICALLY, THEY MIGHT APPEAR TO 1817 01:10:00,425 --> 01:10:02,694 POSSIBLY HAVE MULTIPLE 1818 01:10:02,694 --> 01:10:04,296 SCLEROSIS, IT'S VERY RARE TO SEE 1819 01:10:04,296 --> 01:10:07,732 1 OF THESE AND AS SUCH THE 1820 01:10:07,732 --> 01:10:08,767 PRESENCE OF PARAMAGNETIC RIM 1821 01:10:08,767 --> 01:10:11,069 LESIONS IF THEY OCCUR IN 50 OR 1822 01:10:11,069 --> 01:10:13,371 60% OF PEOPLE OVERALL ARE HIGHLY 1823 01:10:13,371 --> 01:10:16,141 SPECIFIC FOR MS AND WILL ENTER 1824 01:10:16,141 --> 01:10:19,277 THE DIAGNOSTIC CRITERIA VERY 1825 01:10:19,277 --> 01:10:22,380 SHORTLY. 1826 01:10:22,380 --> 01:10:24,049 THIS IS A SECOND STUDY FROM 1827 01:10:24,049 --> 01:10:26,318 COLLEAGUES IN SWITZERLAND WHO 1828 01:10:26,318 --> 01:10:30,021 ALSO LOOKED AT PARAMAGNETIC RIM 1829 01:10:30,021 --> 01:10:31,089 LESIONS USING TECHNOLOGY WE 1830 01:10:31,089 --> 01:10:33,625 BUILT HERE AT THE NIH AND 1831 01:10:33,625 --> 01:10:34,459 REPLICATE FINDING SHOWING THAT 1832 01:10:34,459 --> 01:10:36,428 PEOPLE WHO HAD SUCH LESIONS OR 1833 01:10:36,428 --> 01:10:37,696 PLAQUES IN THE BRAIN WERE MORE 1834 01:10:37,696 --> 01:10:40,665 LIKELY TO HAVE PROGRESSIVE 1835 01:10:40,665 --> 01:10:42,634 MULTIPLE SCLEROSIS AND 1836 01:10:42,634 --> 01:10:43,234 PROGRESSION, WORSENING OF 1837 01:10:43,234 --> 01:10:44,869 DISABILITY EVEN IN THE ABSENCE 1838 01:10:44,869 --> 01:10:50,508 OF RELAPSES, THAT'S WHAT WE CALL 1839 01:10:50,508 --> 01:10:52,811 PROGRESSION INDEPENDENT RELAPSE 1840 01:10:52,811 --> 01:10:53,445 ACTIVITY. 1841 01:10:53,445 --> 01:10:53,645 PIRA. 1842 01:10:53,645 --> 01:10:55,880 I SHOWED YOU AT THE EDGE OF THE 1843 01:10:55,880 --> 01:10:59,584 LESIONS 1 CAN SEE MYELIN, THE 1844 01:10:59,584 --> 01:11:00,518 INSULATION OF NERVES INSIDE 1845 01:11:00,518 --> 01:11:01,853 CELLS THAT ARE EATING THEM AND 1846 01:11:01,853 --> 01:11:03,722 CLEANING IT UP. 1847 01:11:03,722 --> 01:11:05,256 YOU CAN ALSO SEE THE AXONS, 1848 01:11:05,256 --> 01:11:09,094 THESE ARE THE NERVE FIBERS 1849 01:11:09,094 --> 01:11:10,428 THEMSELVES, ARE BEING CUT AT THE 1850 01:11:10,428 --> 01:11:12,831 EDGES OF HE'S LESIONS WHERE THE 1851 01:11:12,831 --> 01:11:13,965 INFLAMMATION IS OCCURRING, AND 1852 01:11:13,965 --> 01:11:16,334 THAT'S SHOWN HERE ON THE TOP 1853 01:11:16,334 --> 01:11:18,570 LEFT IN BROWN AT THE EDGE OF A 1854 01:11:18,570 --> 01:11:19,704 CHRONIC ACTIVE LESION, CAN YOU 1855 01:11:19,704 --> 01:11:23,775 SEE THESE BROWN SPOTS WHICH 1856 01:11:23,775 --> 01:11:25,343 REPRESENT RECENT CUTTING OF 1857 01:11:25,343 --> 01:11:25,577 AXONS. 1858 01:11:25,577 --> 01:11:27,212 AXONS ARE THE HIGHWAYS OF THE 1859 01:11:27,212 --> 01:11:27,879 BRAIN. 1860 01:11:27,879 --> 01:11:29,447 THIS IS WHERE THE COMMUNICATION 1861 01:11:29,447 --> 01:11:32,050 IS OCCURRING, WHEREAS IN A 1862 01:11:32,050 --> 01:11:33,084 CHRONIC INACTIVE LESION, WE 1863 01:11:33,084 --> 01:11:37,422 STILL HAVE A LESION WITH NO 1864 01:11:37,422 --> 01:11:38,590 MYELIN, WITHOUT STANDING HERE IN 1865 01:11:38,590 --> 01:11:39,657 THE BOTTOM, WITHOUT THE BLUE 1866 01:11:39,657 --> 01:11:45,130 STAINING BUT YOU DON'T HAVE THE 1867 01:11:45,130 --> 01:11:45,563 BROWN DOTS PRESENT. 1868 01:11:45,563 --> 01:11:47,966 AND SO THIS IS REALLY OLD DAMAGE 1869 01:11:47,966 --> 01:11:50,135 WHEREAS THIS IS REALLY ONGOING 1870 01:11:50,135 --> 01:11:51,302 AND INTERESTINGLY WE CAN NOW 1871 01:11:51,302 --> 01:11:54,973 DETECT 1 OF THE PROTEINS INSIDE 1872 01:11:54,973 --> 01:11:56,674 AXONS CALLED NEUROFILAMENT, NOT 1873 01:11:56,674 --> 01:11:58,209 JUST IN THE SPINAL FLUID BUT 1874 01:11:58,209 --> 01:12:00,412 ALSO IN THE BLOOD. 1875 01:12:00,412 --> 01:12:03,314 AND WHAT WE WERE ABLE TO SHOW IN 1876 01:12:03,314 --> 01:12:05,517 COLLABORATION WITH OUR 1877 01:12:05,517 --> 01:12:07,519 COLLEAGUES, IN EUROPE, IS THAT 1878 01:12:07,519 --> 01:12:11,623 PEOPLE WHO HAD 1 TO 3 OF THESE 1879 01:12:11,623 --> 01:12:12,457 PARAMAGNETIC RIM LESIONS 1880 01:12:12,457 --> 01:12:14,726 COMPARED TO 0 HAD A 15%ILE 1881 01:12:14,726 --> 01:12:16,594 INCREASE IN THE LEVELS OF THIS 1882 01:12:16,594 --> 01:12:20,765 BLOOD PROTEIN, THAT DETECTS AXON 1883 01:12:20,765 --> 01:12:21,966 NEURON NERVE FIBER DAMAGE AND 1884 01:12:21,966 --> 01:12:26,671 THOSE WHO HAD 4 OR MORE SUCH 1885 01:12:26,671 --> 01:12:28,640 LESIONS HAD A 30 PERCENTILE 1886 01:12:28,640 --> 01:12:29,474 INCREASE, SO GOING ALONG WITH 1887 01:12:29,474 --> 01:12:31,209 THE IDEA THAT AS THE BRAIN IS 1888 01:12:31,209 --> 01:12:33,645 BEING DAMAGED BY THIS CHRONIC 1889 01:12:33,645 --> 01:12:35,613 INFLAMMATION ACCIDENT WE MAY 1890 01:12:35,613 --> 01:12:36,748 ACCUMULATE A DISABILITY AND WE 1891 01:12:36,748 --> 01:12:38,516 ARE ALSO ABLE TO SHOW THAT IF 1892 01:12:38,516 --> 01:12:40,552 YOU LOOK OVER TIME, THAT THESE 1893 01:12:40,552 --> 01:12:43,354 KINDS OF LESIONS ISSUE THESE 1894 01:12:43,354 --> 01:12:44,722 PRLs, CAN ACTUALLY EXPAND 1895 01:12:44,722 --> 01:12:46,791 SLOWLY AS I SHOWED YOU EARLIER 1896 01:12:46,791 --> 01:12:49,794 WITH THE PATIENT WHOSE BRAIN WE 1897 01:12:49,794 --> 01:12:52,297 LOOKED AT AND HERE YOU CAN SEE 1 1898 01:12:52,297 --> 01:12:53,298 CLEEGZ JUST GRADUALLY EXPANDING 1899 01:12:53,298 --> 01:12:54,566 OVER TIME IN THE FRAMES OF THIS 1900 01:12:54,566 --> 01:12:54,799 MOVIE. 1901 01:12:54,799 --> 01:12:56,768 THIS IS SOMEBODY WHO HAD MS FOR 1902 01:12:56,768 --> 01:13:00,305 ALMOST 30 YEARS AND IT'S 118 1903 01:13:00,305 --> 01:13:01,506 SCANS THAT GO INTO THIS MOVIE 1904 01:13:01,506 --> 01:13:05,076 AND HERE YOU SEE A FEW 1905 01:13:05,076 --> 01:13:07,479 SNAPSHOTS, AGE 35, 40, 45, 55 1906 01:13:07,479 --> 01:13:09,013 ISSUEs AS THIS LESION IS 1907 01:13:09,013 --> 01:13:09,981 EXPANDING OVER TIME. 1908 01:13:09,981 --> 01:13:11,649 YOU CAN SEE IT'S RIM AT THE 1909 01:13:11,649 --> 01:13:11,883 EDGE. 1910 01:13:11,883 --> 01:13:16,821 THIS IS NOW A SCAN. 1911 01:13:16,821 --> 01:13:18,123 AND THIS PATIENT IS VERY MUCH 1912 01:13:18,123 --> 01:13:19,390 STILL ALIVE. 1913 01:13:19,390 --> 01:13:24,529 THIS JUST QUANTIFIES WHAT I JUST 1914 01:13:24,529 --> 01:13:25,363 SHOWED YOU ACROSS 54 LESIONS 1915 01:13:25,363 --> 01:13:28,433 THAT TEND TO HAVE THIS RIM GET 1916 01:13:28,433 --> 01:13:30,268 LARGER BY 2 PERCENT PER YEAR ON 1917 01:13:30,268 --> 01:13:31,102 AVERAGE WHEREAS THOSE THAT DO 1918 01:13:31,102 --> 01:13:33,872 NOT TEND TO GET SMALLER OVER 1919 01:13:33,872 --> 01:13:35,373 TIME, NOT SO MUCH BECAUSE 1920 01:13:35,373 --> 01:13:37,175 THEY'RE REPAIRING BUT BECAUSE 1921 01:13:37,175 --> 01:13:38,676 THERE'S SORT OF SLOW CLEAN UP 1922 01:13:38,676 --> 01:13:40,211 THAT OCCURS AND 2% PER YEAR MAY 1923 01:13:40,211 --> 01:13:41,946 NOT SEEM LIKE A LOT BUT IF YOU 1924 01:13:41,946 --> 01:13:44,315 ADD THAT YEAR AFTER YEAR, IT 1925 01:13:44,315 --> 01:13:45,150 BECOMES QUITE SUBSTANTIAL AND 1926 01:13:45,150 --> 01:13:46,918 THE WAY THE BRAIN IS WIRED UP, 1927 01:13:46,918 --> 01:13:49,053 THAT KIND OF EXPANSION CAN HAVE 1928 01:13:49,053 --> 01:13:50,121 REALLY IMPORTANT DOWN STREAM 1929 01:13:50,121 --> 01:13:50,455 CONSEQUENCES. 1930 01:13:50,455 --> 01:13:54,993 SO THIS IS NOT THE ONLY REASON 1931 01:13:54,993 --> 01:13:57,228 WHY SOMEBODY MAY DEVELOP MS 1932 01:13:57,228 --> 01:13:59,631 PROGRESSION BUT IT MAKES SENSE, 1933 01:13:59,631 --> 01:14:00,932 STANDS TO REASON THAT IT MIGHT. 1934 01:14:00,932 --> 01:14:03,134 SO ARE WE ABLE TO TREAT THESE 1935 01:14:03,134 --> 01:14:05,937 WITH OUR CURRENT DISEASE 1936 01:14:05,937 --> 01:14:06,738 MODIFYING THERAPIES, THE 2 DOZEN 1937 01:14:06,738 --> 01:14:08,206 THERAPIES THAT WE HAVE? 1938 01:14:08,206 --> 01:14:11,075 WELL OUR EARLY CLUE IS THAT WE 1939 01:14:11,075 --> 01:14:13,678 ACTUALLY SAW SUCH LESIONS ON 1940 01:14:13,678 --> 01:14:15,113 BASIC -- PEOPLE WHO WERE TAKING 1941 01:14:15,113 --> 01:14:16,881 ALL THE DIFFERENT KINDS OF 1942 01:14:16,881 --> 01:14:17,782 DISEASE MODIFYING THERAPIES THAT 1943 01:14:17,782 --> 01:14:19,851 ARE AVAILABLE FOR US. 1944 01:14:19,851 --> 01:14:21,486 SO IT DIDN'T REALLY SEEM, EVEN 1945 01:14:21,486 --> 01:14:22,654 THOUGH THESE WERE NOT TRIALS 1946 01:14:22,654 --> 01:14:23,488 WHERE WE FOLLOWED PEOPLE OVER 1947 01:14:23,488 --> 01:14:26,257 TIME TO SEE WHETHER THE LESIONS 1948 01:14:26,257 --> 01:14:27,659 WOULD RESULT, NONE THE LESS, WE 1949 01:14:27,659 --> 01:14:30,495 CAN INFER FROM THIS LOOK, THAT 1950 01:14:30,495 --> 01:14:33,131 EVEN IF THERE IS SOME EFFICACY 1951 01:14:33,131 --> 01:14:35,433 OF OUR MEDICATIONS, IT'S NOT 1952 01:14:35,433 --> 01:14:37,802 PERFECTLY EFFECTIVE BECAUSE WE 1953 01:14:37,802 --> 01:14:40,238 CAN SEE IRON RIM, THE 1954 01:14:40,238 --> 01:14:40,939 PARAMAGNETIC RIM LESIONS ON 1955 01:14:40,939 --> 01:14:42,473 PATIENT WHO IS ARE TAKING ALL 1956 01:14:42,473 --> 01:14:44,309 THE DIFFERENT THERAPIES THAT WE 1957 01:14:44,309 --> 01:14:44,509 HAVE. 1958 01:14:44,509 --> 01:14:45,843 SO OVERTIME WE HAVE OTHER VS 1959 01:14:45,843 --> 01:14:50,682 STARTED TO LOOK AT WHETHER OR 1960 01:14:50,682 --> 01:14:53,751 NOT THE THERAPIES CHANGE THE 1961 01:14:53,751 --> 01:14:55,353 APPEARANCE OF THESE IRON RIM 1962 01:14:55,353 --> 01:14:57,121 LESIONS OVER TIME, THIS IS 1 OF 1963 01:14:57,121 --> 01:14:58,957 THE MOST EFFECTIVE THERAPIES, 1964 01:14:58,957 --> 01:15:03,194 THE 1 THAT MR. CHACON IS TAKING, 1965 01:15:03,194 --> 01:15:05,296 WHERE IT REMOVES THE B-CELLS 1966 01:15:05,296 --> 01:15:07,599 FROM THE CIRCULATION, WE WERE 1967 01:15:07,599 --> 01:15:13,171 ABLE TO TRACK 70 PATIENTS OVER 1968 01:15:13,171 --> 01:15:14,305 TIME, ABOUT 350 LESIONS OVER THE 1969 01:15:14,305 --> 01:15:16,140 COURSE OF 2 YEARS IN PATIENT WHO 1970 01:15:16,140 --> 01:15:19,744 IS ARE TAKING THIS THERAPY WHERE 1971 01:15:19,744 --> 01:15:21,312 PEOPLE HAVE OFTEN NO NEW 1972 01:15:21,312 --> 01:15:22,880 LESIONS, NO SYMPTOMS AND YET WE 1973 01:15:22,880 --> 01:15:24,315 SAW NO CHANGE IN THE APPEARANCE 1974 01:15:24,315 --> 01:15:25,984 OF THESE LESIONS WHEN WE TRACK 1975 01:15:25,984 --> 01:15:29,554 THEM BY MRI OVER TIME. 1976 01:15:29,554 --> 01:15:30,955 SO WE REALIZE WE WILL NEED TO 1977 01:15:30,955 --> 01:15:37,195 LOOK FOR OTHER MEDICATIONS THAT 1978 01:15:37,195 --> 01:15:37,795 TREAT THIS. 1979 01:15:37,795 --> 01:15:39,897 AND SO HOW DO WE DO THAT? 1980 01:15:39,897 --> 01:15:41,499 SO WE'VE BEEN FOCUSING ON AND 1981 01:15:41,499 --> 01:15:48,172 OTHERS ARE FOCUSING ON AS WELL 1982 01:15:48,172 --> 01:15:51,209 IS THE CELLS THAT ARE PRESENT AT 1983 01:15:51,209 --> 01:15:52,143 THESE LESIONS. 1984 01:15:52,143 --> 01:15:54,012 THE MAIN CELL WE'VE BEEN 1985 01:15:54,012 --> 01:15:57,081 FOCUSING ON ARE MICROGLIA. 1986 01:15:57,081 --> 01:15:58,483 MICROGLIA ARE A BRAIN CELL 1987 01:15:58,483 --> 01:15:59,417 THAT'S PRESENT IN EVERYBODY, 1988 01:15:59,417 --> 01:16:01,152 THEY HAVE LOTS AND LOTS MUCH 1989 01:16:01,152 --> 01:16:01,486 ROLES. 1990 01:16:01,486 --> 01:16:03,888 THEY HAVE ROLES IN NORMAL 1991 01:16:03,888 --> 01:16:05,490 DEVELOPMENT OF THE BRAIN. 1992 01:16:05,490 --> 01:16:07,959 THEY'RE INVOLVED IN MAKING AND 1993 01:16:07,959 --> 01:16:09,560 MATURING SYNAPSES WHICH ARE HOW 1994 01:16:09,560 --> 01:16:13,531 NERVE CELLS ARE CONNECTED TO 1 1995 01:16:13,531 --> 01:16:16,567 ANOTHER, AND THEY'RE INVOLVED IN 1996 01:16:16,567 --> 01:16:18,636 SURVEILLANCE OF THE BRAIN AND 1997 01:16:18,636 --> 01:16:20,338 PROTECTING FROM INFECTION, EVEN 1998 01:16:20,338 --> 01:16:22,373 WHEN THERE'S NOTHING WRONG AT 1999 01:16:22,373 --> 01:16:22,540 ALL. 2000 01:16:22,540 --> 01:16:24,142 AND THEY ARE ALSO INVOLVED IN 2001 01:16:24,142 --> 01:16:25,910 LOTS AND LOTS OF DIFFERENT DECS, 2002 01:16:25,910 --> 01:16:27,111 THEY'RE INVOLVED IN MULTIPLE 2003 01:16:27,111 --> 01:16:28,713 SCLEROSIS AND THE WAY THEY'RE 2004 01:16:28,713 --> 01:16:31,816 DRIEBED ARE INVOLVED IN STROKE 2005 01:16:31,816 --> 01:16:34,919 AND ALZHEIMER'S DISEASE, IN 2006 01:16:34,919 --> 01:16:35,787 PSYCHIATRIC DISORDERS, LIKE 2007 01:16:35,787 --> 01:16:37,755 SCETS FRENNIA AND AUTISM AND 2008 01:16:37,755 --> 01:16:40,124 THEY ARE REALLY 1 OF THE KEY 2009 01:16:40,124 --> 01:16:41,426 CELLS INVOLVE CELL TYPES OF THE 2010 01:16:41,426 --> 01:16:42,760 BRAIN INVOLVED IN INFLAMMATION, 2011 01:16:42,760 --> 01:16:44,529 AND SO, YOU KNOW THEY CAN HAVE 2 2012 01:16:44,529 --> 01:16:46,564 FACES, THEY CAN BE VERY HELPFUL, 2013 01:16:46,564 --> 01:16:48,166 BUT THEY CAN ALSO BE DAMAGING 2014 01:16:48,166 --> 01:16:50,835 AND SO WE NEED TO UNDERSTAND HOW 2015 01:16:50,835 --> 01:16:55,106 THAT OCCURS IN ORDER TO TREAT T 2016 01:16:55,106 --> 01:16:56,140 WHEN THINGS ARE NOT GOING WELL 2017 01:16:56,140 --> 01:16:57,675 AND 1 OF THE WAYS WE'VE DONE 2018 01:16:57,675 --> 01:16:59,210 THAT IS TO ANALYZE TISSUE IN A 2019 01:16:59,210 --> 01:17:02,647 WAY THAT WAS INFORMED BY THE MRI 2020 01:17:02,647 --> 01:17:05,049 SCANS THAT WE DO SO WE WERE ABLE 2021 01:17:05,049 --> 01:17:06,484 TO USE THE MRI KAN--KANAS TO GO 2022 01:17:06,484 --> 01:17:07,552 RIGHT TO THE EDGE OF THESE 2023 01:17:07,552 --> 01:17:12,290 LESIONS IN THE BRAIN WHERE THE 2024 01:17:12,290 --> 01:17:13,558 IRON WAS PRESENT TO TAKE. 2025 01:17:13,558 --> 01:17:14,926 THIS IS LOOKING AT POST 2026 01:17:14,926 --> 01:17:16,461 AUTOPSIES BRAINS BUT WE'RE ABLE 2027 01:17:16,461 --> 01:17:19,430 TO TAKE BIOPSIES OF THOSE POST 2028 01:17:19,430 --> 01:17:21,399 AUTOPSIES BRAINS, REALLY 2029 01:17:21,399 --> 01:17:23,234 DIRECTED BYOPSYS AND SUBJECT THE 2030 01:17:23,234 --> 01:17:24,736 CELLS ACTUALLY THE NUCLEI OF 2031 01:17:24,736 --> 01:17:27,505 THOSE CELLS TO A TECHNIQUE 2032 01:17:27,505 --> 01:17:29,707 CALLED SINGLE NUCLEUS, RNA 2033 01:17:29,707 --> 01:17:31,109 SEQUENCING, THIS TELLS US ALL OF 2034 01:17:31,109 --> 01:17:32,944 THE GENES THAT HAVE BEEN TURNED 2035 01:17:32,944 --> 01:17:35,580 ON IN THAT CELL, AND THAT GIVES 2036 01:17:35,580 --> 01:17:37,749 US THE SIGNATURE OF NOT ONLY 2037 01:17:37,749 --> 01:17:40,451 WHAT CELL TYPE IT IS SO WE CAN 2038 01:17:40,451 --> 01:17:41,419 RECOGNIZE READILY, MICROGLIA AND 2039 01:17:41,419 --> 01:17:42,787 OTHER TYPES OF IMMUNE CELLS AND 2040 01:17:42,787 --> 01:17:44,088 NERVE CELLS AND OTHER TYPES OF 2041 01:17:44,088 --> 01:17:46,057 CELLS IN THE BRAIN AND BLOOD 2042 01:17:46,057 --> 01:17:53,097 VESSEL CELLS, ET CETERA, OR TO 2043 01:17:53,097 --> 01:17:54,732 SOME EXTENT WHO THOSE CELLS ARE 2044 01:17:54,732 --> 01:17:56,300 DOING BECAUSE IF THEY'RE 2045 01:17:56,300 --> 01:17:57,535 INVOLVED IN INFLAMMATION FOR 2046 01:17:57,535 --> 01:17:59,203 EXAMPLE, THEY MAY BE MAKING 2047 01:17:59,203 --> 01:18:00,204 PROTEINS THAT ARE INVOLVED IN 2048 01:18:00,204 --> 01:18:01,372 THE INFLAMMA ARE TOY REINTONS, 2049 01:18:01,372 --> 01:18:04,308 SO THIS IS A LANDSCAPE THIS, IS 2050 01:18:04,308 --> 01:18:06,944 A SORT OF MAP HERE, IN THE 2051 01:18:06,944 --> 01:18:08,413 MIDDLE OF THE DIFFERENT, EACH 2052 01:18:08,413 --> 01:18:11,249 DOT IN THIS MAP REPRESENTS A 2053 01:18:11,249 --> 01:18:11,883 SINGLE CELL. 2054 01:18:11,883 --> 01:18:13,384 AND THESE ARE THE DIFFERENT CELL 2055 01:18:13,384 --> 01:18:14,886 TYPES OF THE BRAIN, THESE ARE 2056 01:18:14,886 --> 01:18:16,387 THE -- BECAUSE WE WERE IN THE 2057 01:18:16,387 --> 01:18:18,022 WHITE MATTER WHERE THE NERVE 2058 01:18:18,022 --> 01:18:19,757 FIBERS ARE CONNECTED WE HAD VERY 2059 01:18:19,757 --> 01:18:22,059 FEW NERVE CELLS ISSUES THE 2060 01:18:22,059 --> 01:18:25,797 NEURONS, NEU BUT LOTS AND LOTS 2061 01:18:25,797 --> 01:18:26,864 OF OLIGO DENDRITES WHICH ARE 2062 01:18:26,864 --> 01:18:28,866 CELLS AND WE HAD THE IMMUNE 2063 01:18:28,866 --> 01:18:30,301 CELLS, BLOOD VESSEL CELLS, ASTRO 2064 01:18:30,301 --> 01:18:32,904 SIGHTS WHICH ARE ALSO VERY 2065 01:18:32,904 --> 01:18:34,038 INTERESTING CELL TYPE AND 2066 01:18:34,038 --> 01:18:35,940 VARIOUS OTHER CELL TYPES. 2067 01:18:35,940 --> 01:18:40,878 WE DID A DEEP DIVE INTO THE 2068 01:18:40,878 --> 01:18:42,013 MICROGLIA COMPARING MICROGLIA IN 2069 01:18:42,013 --> 01:18:45,450 CONTROL WHITE MATTER, SO PEOPLE 2070 01:18:45,450 --> 01:18:47,418 WITHOUT MULTIPLE SCLEROSIS WHO 2071 01:18:47,418 --> 01:18:48,219 ARE NEUROLOGICALLY HEALTHY AND 2072 01:18:48,219 --> 01:18:51,322 THOSE WITH MS AND YOU CAN SEE 2073 01:18:51,322 --> 01:18:52,023 MANY MORE MICROGLIA PRESENT 2074 01:18:52,023 --> 01:18:54,325 WHICH IS NOT SURPRISING, THIS 2075 01:18:54,325 --> 01:18:56,694 WAS ALREADY KNOWN FROM THE 2076 01:18:56,694 --> 01:18:58,663 HISTOLOGY THAT WAS DONE FROM A 2077 01:18:58,663 --> 01:18:59,363 CONVENTIONAL HISTOLOGY BUT NOW 2078 01:18:59,363 --> 01:19:02,200 WE CAN GET MUCH MORE INFORMATION 2079 01:19:02,200 --> 01:19:03,935 ABOUT WHAT THOSE CELL TYPES ARE 2080 01:19:03,935 --> 01:19:06,137 DOING THAT WE WERE ABLE TO SHOW 2081 01:19:06,137 --> 01:19:07,772 THAT THEY PROBABLY ARE 2082 01:19:07,772 --> 01:19:08,806 MICROGLIA, THAT'S ON THE RIGHT. 2083 01:19:08,806 --> 01:19:10,608 WE CAN SHOW THAT THEY'RE 2084 01:19:10,608 --> 01:19:13,611 PROBABLY MICROGLIA, THAT IS THEY 2085 01:19:13,611 --> 01:19:15,580 ARE MOSTLY THE CELLS THAT WERE 2086 01:19:15,580 --> 01:19:18,549 INVOLVED IN THIS DAMAGE THAT ARE 2087 01:19:18,549 --> 01:19:19,951 OCCURRING ARE CELLS THAT 2088 01:19:19,951 --> 01:19:21,352 ORIGINATED IN THE BRAIN, WERE 2089 01:19:21,352 --> 01:19:23,354 CARRYING OUT THEIR NORMAL DUTIES 2090 01:19:23,354 --> 01:19:25,690 BUT GOT INVOLVED IN THE MULTIPLE 2091 01:19:25,690 --> 01:19:26,858 SCLEROSIS ATTACK, BUT IN 2092 01:19:26,858 --> 01:19:28,593 ADDITION THERE WERE ALSO CELL 2093 01:19:28,593 --> 01:19:29,894 TYPES CALLED MACROPHAGE AND 2094 01:19:29,894 --> 01:19:31,362 MONOCYTES THAT WERE ACTUALLY 2095 01:19:31,362 --> 01:19:33,998 COMING FROM THE BLOOD STREAM AS 2096 01:19:33,998 --> 01:19:34,198 WELL. 2097 01:19:34,198 --> 01:19:35,867 BUT WE DON'T THINK THAT THOSE 2098 01:19:35,867 --> 01:19:36,601 WERE ACTUALLY AFFECTING DAMAGE 2099 01:19:36,601 --> 01:19:39,103 FOR A VARIETY OF REASONS. 2100 01:19:39,103 --> 01:19:42,106 AND WHAT WE IDENTIFIED AFTER A 2101 01:19:42,106 --> 01:19:47,178 LOT OF ANALYSIS, ARE 2 TYPES OF 2102 01:19:47,178 --> 01:19:48,145 MICROGLIA THAT WERE PRESENT 2103 01:19:48,145 --> 01:19:49,213 PRETTY SPECIFICALLY AT THE EDGE 2104 01:19:49,213 --> 01:19:51,682 OF THESE CHRONIC ACTIVE OR 2105 01:19:51,682 --> 01:19:53,150 SMOLDERING LESIONS 1 OF WHICH 2106 01:19:53,150 --> 01:19:59,957 CONTAINED THE MACHINERY OF 2107 01:19:59,957 --> 01:20:01,292 INFLAMMATION AS WELL AS PROTEINS 2108 01:20:01,292 --> 01:20:02,560 THAT BIND TO IRON AND THIS MAKES 2109 01:20:02,560 --> 01:20:04,128 A LOT OF SENSE BECAUSE ON THE 2110 01:20:04,128 --> 01:20:05,897 MRI, WE CAN SEE THE EFFECTS OF 2111 01:20:05,897 --> 01:20:08,833 THAT IRON DIRECTLY, THAT'S THAT 2112 01:20:08,833 --> 01:20:09,901 DARK RIM AND ANOTHER TYPE OF 2113 01:20:09,901 --> 01:20:14,739 CELL THAT WE CALLED FOAMY 2114 01:20:14,739 --> 01:20:16,173 BECAUSE THEY CONTAINED MATERIAL 2115 01:20:16,173 --> 01:20:18,442 PROTEINS THAT ARE INVOLVED IN 2116 01:20:18,442 --> 01:20:21,178 CLEAN UP OF DEBRIS AND IN THIS 2117 01:20:21,178 --> 01:20:23,414 CASE THE DEBRIS IS MILEN, MILEN 2118 01:20:23,414 --> 01:20:24,849 IS A FATTY SUBSTANCE AS I 2119 01:20:24,849 --> 01:20:26,918 MENTIONED AND THAT GIVES IT THIS 2120 01:20:26,918 --> 01:20:28,452 FOAMY APPEARANCE SO WE HAVE 2121 01:20:28,452 --> 01:20:29,153 THESE 2 TYPES. 2122 01:20:29,153 --> 01:20:30,421 WE CAN NOW GO BACK INTO THE 2123 01:20:30,421 --> 01:20:33,024 TISSUE AND LOOK AT WHAT'S THERE 2124 01:20:33,024 --> 01:20:34,525 AND 1 OF THE INTERESTING THINGS 2125 01:20:34,525 --> 01:20:36,294 WE FOUND IS THAT THERE WAS 2126 01:20:36,294 --> 01:20:38,629 INCREASE OF PROTEINS RELATED TO 2127 01:20:38,629 --> 01:20:39,564 THE COMPLEMENT SYSTEM. 2128 01:20:39,564 --> 01:20:41,866 THIS IS AN EVOLUTIONARY ANCIENT 2129 01:20:41,866 --> 01:20:47,138 SYSTEM, PART OF THE IMMUNE 2130 01:20:47,138 --> 01:20:51,542 SYSTEM, WHERE PROTEINS ARE 2131 01:20:51,542 --> 01:20:52,843 INVOLVED IN INFECTIONS BUT IN 2132 01:20:52,843 --> 01:20:55,379 THIS CASE, IT'S NOT INVOLVED IN 2133 01:20:55,379 --> 01:20:56,948 AN INFECTION, IT'S AN 2134 01:20:56,948 --> 01:20:58,616 INFLAMMATORY DEC OF THE BRAIN 2135 01:20:58,616 --> 01:21:00,184 AND WE CAN SEE HERE IN YELLOW 2136 01:21:00,184 --> 01:21:02,787 THE INCREASE OF PROTEIN OF A 2137 01:21:02,787 --> 01:21:04,689 COMPLEMENT SYSTEM CALLED C1 Q 2138 01:21:04,689 --> 01:21:05,923 RIGHT AT THE EDGE OF THE LESION 2139 01:21:05,923 --> 01:21:09,126 BUT NOT SO MUCH AT THE CENTER OF 2140 01:21:09,126 --> 01:21:10,361 THE LESION OR IN THE WHITE 2141 01:21:10,361 --> 01:21:10,962 MATTER OUTSIDE. 2142 01:21:10,962 --> 01:21:13,664 SO THEN WE WENT BACK INTO MICE 2143 01:21:13,664 --> 01:21:16,367 AND WE BLOCK THAD PROTEIN, THE 2144 01:21:16,367 --> 01:21:17,969 C1 Q PROTEIN, THE COMPLEMENT 2145 01:21:17,969 --> 01:21:22,073 PROTEIN USING A DRUG AND 2146 01:21:22,073 --> 01:21:22,607 ANTIBODY AGAINST IT. 2147 01:21:22,607 --> 01:21:25,142 AND WE COULD SHOW THAT IN THIS 2148 01:21:25,142 --> 01:21:26,844 CASE, EVEN THOUGH WE DIDN'T 2149 01:21:26,844 --> 01:21:28,012 EFFECT OVER HERE ON THE TOP 2150 01:21:28,012 --> 01:21:30,781 RIGHT THE SEVERITY OF THE 2151 01:21:30,781 --> 01:21:32,617 MULTIPLE SCLEROSIS, ANIMAL MODEL 2152 01:21:32,617 --> 01:21:36,053 THAT WE USED CALL EAE 2153 01:21:36,053 --> 01:21:37,388 EXPERIMENTAL AUTOIMMUNE INSEVERE 2154 01:21:37,388 --> 01:21:38,456 MITRAL LOW MILITEIS, WE WERE 2155 01:21:38,456 --> 01:21:40,691 ABLE TO DECREASE THE LEVEL OF 2156 01:21:40,691 --> 01:21:42,426 INFLAMMATION IN MICROGLIA WITH 2157 01:21:42,426 --> 01:21:44,895 THE STRATEGY. 2158 01:21:44,895 --> 01:21:46,998 WE ALSO COLLABORATED WITH DORI 2159 01:21:46,998 --> 01:21:49,033 SHAVER AT THE UNIVERSITY OF 2160 01:21:49,033 --> 01:21:50,101 MASSACHUSETTS TO SHOW THIS IN A 2161 01:21:50,101 --> 01:21:52,003 DIFFERENT WAY, NOT WITH A DRUG 2162 01:21:52,003 --> 01:21:54,939 ANTIBODY BUT RATHER HERE BY 2163 01:21:54,939 --> 01:21:56,674 USING A GENETIC TRANSGENIC 2164 01:21:56,674 --> 01:21:58,876 STRATEGY IN MICE AND SHOWED VERY 2165 01:21:58,876 --> 01:22:04,982 MUCH THE SAME THING. 2166 01:22:04,982 --> 01:22:08,719 SO HERE WE LEARNED A LOT MORE 2167 01:22:08,719 --> 01:22:09,954 WHERE 1 MECHANISM IS PROPAGATED 2168 01:22:09,954 --> 01:22:12,023 AT THE EDGE OF THESE LESIONS AND 2169 01:22:12,023 --> 01:22:18,896 CAN WE SEE THAT IN PEOPLE, AND 2170 01:22:18,896 --> 01:22:21,098 SO WHAT WE'VE DONE NOW IS WE 2171 01:22:21,098 --> 01:22:23,200 HAVE BEEN COLLECTING FROM OUR 2172 01:22:23,200 --> 01:22:25,036 RESEARCH VOLUNTEERS, SPINAL 2173 01:22:25,036 --> 01:22:27,371 FLUID, THROUGH A LUMBAR PUNCTURE 2174 01:22:27,371 --> 01:22:29,006 AND SUBJECTING IT TO THE CELLS 2175 01:22:29,006 --> 01:22:31,175 THAT WE GET OUT OF THE SPINAL 2176 01:22:31,175 --> 01:22:34,412 FLUID TO THE VERY SAME 2177 01:22:34,412 --> 01:22:36,347 TECHNOLOGY, THE SINGLE CELL RNA 2178 01:22:36,347 --> 01:22:38,282 SEQUENCING, AND HERE YOU CAN SEE 2179 01:22:38,282 --> 01:22:39,817 A SIMILAR MAP OF THE CELL TYPES 2180 01:22:39,817 --> 01:22:41,852 IN THE SPINAL FLUID FROM 33 2181 01:22:41,852 --> 01:22:44,155 PEOPLE LIVING WITH MULTIPLE 2182 01:22:44,155 --> 01:22:45,790 SCLEROSIS AND COMPARISON TO 5 2183 01:22:45,790 --> 01:22:46,991 HEALTHY CONTROLS, AND AGAIN, YOU 2184 01:22:46,991 --> 01:22:49,593 SEE LOTS AND LOTS OF CELL TYPE 2185 01:22:49,593 --> 01:22:51,362 -- DIFFERENT CELL TYPES WHICH WE 2186 01:22:51,362 --> 01:22:53,097 CAN RECOGNIZE BY THE GENES THAT 2187 01:22:53,097 --> 01:22:55,366 ARE TURNED ON, INCLUDING T-CELLS 2188 01:22:55,366 --> 01:22:56,767 AND B-CELLS, THESE ARE CELLS OF 2189 01:22:56,767 --> 01:22:58,302 THE SO CALLED ADAPTIVE IMMUNE 2190 01:22:58,302 --> 01:23:01,739 SYSTEM AS WELL AS MYELOID CELLS 2191 01:23:01,739 --> 01:23:03,574 OF WHICH MICROGLUE MARIOUSA ARE 2192 01:23:03,574 --> 01:23:06,143 1 ALTHOUGH WE DON'T ACTUALLY SEE 2193 01:23:06,143 --> 01:23:08,512 MICROGLIA IN THE BRAIN, BUT WE 2194 01:23:08,512 --> 01:23:09,947 STILL SEE SIMILAR THINGS IN THE 2195 01:23:09,947 --> 01:23:11,082 SPINAL FLUID AND THAT'S WHAT WE 2196 01:23:11,082 --> 01:23:11,682 WANT TO KNOW. 2197 01:23:11,682 --> 01:23:14,285 SO WHAT WE DID WAS WE LOOKED AT 2198 01:23:14,285 --> 01:23:18,689 THE SUBSET OF PEOPLE WHO WERE 2199 01:23:18,689 --> 01:23:20,091 UNTREATED BECAUSE YOU CAN -- YOU 2200 01:23:20,091 --> 01:23:21,559 DON'T WANT TO AFFECT THIS 2201 01:23:21,559 --> 01:23:23,394 ANALYSIS BY THE REALLY PROFOUND 2202 01:23:23,394 --> 01:23:24,128 IMMUNE EFFECTS OF THE TREATMENTS 2203 01:23:24,128 --> 01:23:26,130 THAT PEOPLE ARE TAKING. 2204 01:23:26,130 --> 01:23:30,701 THEY HAD OR THEY DID NOT HAVE 2205 01:23:30,701 --> 01:23:32,103 PARAMAGNETIC RIM LESIONS ON 2206 01:23:32,103 --> 01:23:33,704 THEIR MRI, THEY HAD NOT 2207 01:23:33,704 --> 01:23:34,872 DEVELOPED NEW LESIONS AND HAD 2208 01:23:34,872 --> 01:23:36,874 NOT HAD NEW FOCAL SYMPTOMS, NEW 2209 01:23:36,874 --> 01:23:38,542 RELAPSES IN A FEW YEARS, SO THIS 2210 01:23:38,542 --> 01:23:40,878 IS REALLY TRYING TO COMPARE WHAT 2211 01:23:40,878 --> 01:23:42,379 THE SPINAL FLUID LOOKS LIKE IN 2212 01:23:42,379 --> 01:23:46,951 THESE 2 GROUPS OF PEOPLE. 2213 01:23:46,951 --> 01:23:48,252 SO, WE FOUND SOME INTERESTING 2214 01:23:48,252 --> 01:23:50,254 THINGS, WE FOUND AN INCREASED 2215 01:23:50,254 --> 01:23:51,756 PROPORTION OF DENDRITIC CELLS, 2216 01:23:51,756 --> 01:23:55,893 SO THESE ARE CELLS THAT PRESENT 2217 01:23:55,893 --> 01:23:59,029 PROTEINS RELATED TO THE 2218 01:23:59,029 --> 01:24:00,965 AUTOIMMUNE ATTACK IN PEOPLE 2219 01:24:00,965 --> 01:24:01,799 WITHOUT THE PARAMETTIC RIM 2220 01:24:01,799 --> 01:24:03,367 LESIONS AS WELL AS INCREASES OF 2221 01:24:03,367 --> 01:24:05,469 OTHER KINDS OF CELLS IN PEOPLE 2222 01:24:05,469 --> 01:24:08,639 WHO DO HAVE THE PARAMAGNETIC RIM 2223 01:24:08,639 --> 01:24:10,407 LESIONS SUGGESTING THE IMMUNE 2224 01:24:10,407 --> 01:24:12,009 MILIEU IN THE SPINAL FLUID IS 2225 01:24:12,009 --> 01:24:13,110 QUITE DIFFERENT BETWEEN THE 2. 2226 01:24:13,110 --> 01:24:14,945 WHEN WE DO A DEEPER DIVE AND 2227 01:24:14,945 --> 01:24:16,914 LOOK AT THESE MYELOID CELLS THAT 2228 01:24:16,914 --> 01:24:27,391 ARE SIMILAR IN SOME WAYS TO 2229 01:24:28,025 --> 01:24:31,295 MICROGLIA, WE CAN SUBSET THEM 2230 01:24:31,295 --> 01:24:31,762 INTO DIFFERENT TYPES. 2231 01:24:31,762 --> 01:24:33,597 WE CAN LOOK THEA THE GENES THAT 2232 01:24:33,597 --> 01:24:35,132 ARE PRESENT AND AMONG THESE 2233 01:24:35,132 --> 01:24:37,168 GENES ARE GENES OF THE 2234 01:24:37,168 --> 01:24:38,435 COMPLEMENT SYSTEM WHICH ARE THE 2235 01:24:38,435 --> 01:24:39,870 SAME, THE SAME SYSTEM THAT I 2236 01:24:39,870 --> 01:24:43,040 DESCRIBED AT THE EDGE OF THE 2237 01:24:43,040 --> 01:24:44,208 LESIONS IN THE PATHOLOGY, AND IF 2238 01:24:44,208 --> 01:24:47,645 YOU LOOK AT PEOPLE WHO HAVE 2239 01:24:47,645 --> 01:24:49,246 PARAMAGNETIC RIM LESIONS IN THIS 2240 01:24:49,246 --> 01:24:51,215 SPECIFIC M5 GROUP OF CELLS, YOU 2241 01:24:51,215 --> 01:24:53,951 CAN SEE THAT MANY OF THE GENES 2242 01:24:53,951 --> 01:24:56,020 THAT ARE MOST STRONGLY INCREASED 2243 01:24:56,020 --> 01:25:06,530 RELATE TO THAT SAME COMPLEMENT 2244 01:25:08,732 --> 01:25:08,899 SYSTEM. 2245 01:25:08,899 --> 01:25:11,769 WE THEN WERE ABLE TO TAKE THE 2246 01:25:11,769 --> 01:25:14,171 MAP AND RELATE IT TO THE BRAIN 2247 01:25:14,171 --> 01:25:15,606 CELL MAP AND DIFFERENT PEOPLE, 2248 01:25:15,606 --> 01:25:17,007 -- CELLS FROM DIFFERENT PEOPLE 2249 01:25:17,007 --> 01:25:18,075 BUT NONETHELESS WE CAN MATCH 2250 01:25:18,075 --> 01:25:20,477 THEM UP BY THE GENES THAT ARE 2251 01:25:20,477 --> 01:25:22,112 TURNED ON AND WE FOUND THAT 2252 01:25:22,112 --> 01:25:23,948 THERE REALLY IS AN OVERLAP 2253 01:25:23,948 --> 01:25:27,484 BETWEEN THESE M3 AND M5 CLUSTERS 2254 01:25:27,484 --> 01:25:29,453 AND THE CELL TYPES WE KNEW WERE 2255 01:25:29,453 --> 01:25:30,988 PRESENT AT THE EDGE OF THE 2256 01:25:30,988 --> 01:25:32,256 LESIONS, AGAIN, THESE ARE NOT 2257 01:25:32,256 --> 01:25:34,225 EXACTLY THE SAME CELLS BECAUSE 1 2258 01:25:34,225 --> 01:25:36,360 IS LOOKING IN SPINAL FLUID, 1 2259 01:25:36,360 --> 01:25:37,962 LOOKING IN BRAIN, BUT 2260 01:25:37,962 --> 01:25:42,166 NONETHELESS, THEY SHARE A LOT OF 2261 01:25:42,166 --> 01:25:42,433 FEATURES. 2262 01:25:42,433 --> 01:25:44,201 SO WE NOW HAVE A WAY POTENTIALLY 2263 01:25:44,201 --> 01:25:46,070 OF LOOKING AT THE SPINAL FLUID 2264 01:25:46,070 --> 01:25:47,238 AND ASSESSING WHETHER 2265 01:25:47,238 --> 01:25:50,274 MEDICATIONS THAT WE MIGHT TRY 2266 01:25:50,274 --> 01:25:52,676 MIGHT INFLUENCE THESE CELL TYPES 2267 01:25:52,676 --> 01:25:54,445 AND MAYBE THEY ARE ALSO 2268 01:25:54,445 --> 01:25:55,379 INFLUENCING THE BRAIN AS WELL, 2269 01:25:55,379 --> 01:25:57,481 SO CAN WE DO THESE KINDS OF 2270 01:25:57,481 --> 01:25:57,715 TRIALS? 2271 01:25:57,715 --> 01:26:00,818 WELL IF WE LOOK OVER TIME AT 2272 01:26:00,818 --> 01:26:02,419 PARAMAGNETIC RIM LESIONS, THE 2273 01:26:02,419 --> 01:26:04,421 IRON RIM LESIONS I DRIEBED 2274 01:26:04,421 --> 01:26:05,356 EARLIER, INITIALLY WE THOUGHT 2275 01:26:05,356 --> 01:26:06,624 THEY WOULD STICK AROUND FOR A 2276 01:26:06,624 --> 01:26:07,958 LONG TIME, BUT WHAT WE ACTUALLY 2277 01:26:07,958 --> 01:26:09,693 FOUND AFTER WE STARTED FOLLOWING 2278 01:26:09,693 --> 01:26:11,362 PEOPLE UP FOR 10 YEARS OR SO, IS 2279 01:26:11,362 --> 01:26:13,964 THAT MANY OF THEM ACTUALLY, THE 2280 01:26:13,964 --> 01:26:16,166 RIM STARTS TO RESOLVE THAT IRON 2281 01:26:16,166 --> 01:26:17,601 SIGNATURE WHICH IS PRESENT 2282 01:26:17,601 --> 01:26:19,670 INSIDE OF INFLAMMATORY CELLS. 2283 01:26:19,670 --> 01:26:21,071 SO THIS GIVES US HOPE AND 2284 01:26:21,071 --> 01:26:24,808 ACTUALLY A VERY POWERFUL METHOD 2285 01:26:24,808 --> 01:26:27,077 OF POTENTIALLY TESTING NEW 2286 01:26:27,077 --> 01:26:29,480 MEDICATIONS ON CHRONIC 2287 01:26:29,480 --> 01:26:30,881 INFLAMMATION AND NOT JUST ACUTE 2288 01:26:30,881 --> 01:26:32,549 INFLAMMATION AND IF YOU REMEMBER 2289 01:26:32,549 --> 01:26:34,285 THE VIDEO I SHOWED AT THE 2290 01:26:34,285 --> 01:26:36,053 BEGINNING WITH ALL THE FLASHES, 2291 01:26:36,053 --> 01:26:38,022 NEW LESIONS DEVELOPING, IT WAS 2292 01:26:38,022 --> 01:26:38,889 STOPPING THOSE FLASHES THAT LED 2293 01:26:38,889 --> 01:26:41,358 TO THE DEVELOPMENT OF THE 25 OR 2294 01:26:41,358 --> 01:26:51,435 SO TREATMENTS THAT WE HAVE 2295 01:26:51,435 --> 01:26:52,569 AVAILABLE INCLUDING OCULIZUMAB 2296 01:26:52,569 --> 01:26:56,840 COULD WE USE NEW MEDICATIONS TO 2297 01:26:56,840 --> 01:27:00,511 BLOCK THIS IMPORTANT PART FOR MS 2298 01:27:00,511 --> 01:27:01,845 PROGRESSION. 2299 01:27:01,845 --> 01:27:03,614 SO IF WE DO THAT HOW WOULD WE DO 2300 01:27:03,614 --> 01:27:03,814 THAT? 2301 01:27:03,814 --> 01:27:05,249 WELL IF WE TAKEAUR MASSIVE 2302 01:27:05,249 --> 01:27:06,483 COLLECTION OF INFORMATION WE GET 2303 01:27:06,483 --> 01:27:08,118 FROM THESE HIGH THROUGH PUT 2304 01:27:08,118 --> 01:27:09,620 TECHNIQUES LIKE SINGLE CELL 2305 01:27:09,620 --> 01:27:11,822 SEQUENCING AND DO SOME ANALYSIS, 2306 01:27:11,822 --> 01:27:14,425 MAKE SOME HYPOTHESIS GENERATION, 2307 01:27:14,425 --> 01:27:16,694 WHAT IF WE DELETE A CERTAIN CELL 2308 01:27:16,694 --> 01:27:20,731 TYPE OR CERTAIN GENE FROM THE 2309 01:27:20,731 --> 01:27:21,231 CELL TYPES. 2310 01:27:21,231 --> 01:27:23,534 SO WE CAN LOOK IN FACT OF WHAT 2311 01:27:23,534 --> 01:27:25,002 HAPPENS IF YOU DEPLETE B-CELLS 2312 01:27:25,002 --> 01:27:35,412 WHICH ARE THE TARGET OF 2313 01:27:38,615 --> 01:27:42,219 OCULIZUMAB, AND I CHOSE THIS 2314 01:27:42,219 --> 01:27:43,387 BECAUSE FOR A VARIETY OF REASONS 2315 01:27:43,387 --> 01:27:45,389 IT IS 1 OF THE THERAPYINGS 2316 01:27:45,389 --> 01:27:46,490 TESTED HEAVILY IN MS NOW AND YOU 2317 01:27:46,490 --> 01:27:49,994 CAN SEE THERE'S MANY, MANY MORE 2318 01:27:49,994 --> 01:27:51,795 ABOUT 6 TIMES MORE GENES THAT 2319 01:27:51,795 --> 01:27:55,199 ARE BEING AFFECTED EVEN THOUGH 2320 01:27:55,199 --> 01:27:58,669 BTK AND CD20 ARE GENES THAT ARE 2321 01:27:58,669 --> 01:28:00,004 PRESENT IN SOME OF THE SAME CELL 2322 01:28:00,004 --> 01:28:01,472 TYPES AND MANY OF THOSE GENES 2323 01:28:01,472 --> 01:28:04,641 THAT WE WOULD EXPECT TO BE 2324 01:28:04,641 --> 01:28:08,145 CHANGED BY INHIBITING THIS BTK, 2325 01:28:08,145 --> 01:28:10,114 ARE ACTUALLY GENES OF THE 2326 01:28:10,114 --> 01:28:13,617 COMPLEMENT SYSTEM, THIS C1 Q, C1 2327 01:28:13,617 --> 01:28:15,185 QC, C3, ET CETERA. 2328 01:28:15,185 --> 01:28:16,120 SO POTENTIALLY COULD BE AN 2329 01:28:16,120 --> 01:28:18,622 INTERESTING WAY TO GO. 2330 01:28:18,622 --> 01:28:22,726 NOW BTK IS AN ENZYME THAT'S 2331 01:28:22,726 --> 01:28:24,661 PRESENT, IT'S A SIGNALING 2332 01:28:24,661 --> 01:28:25,963 MOLECULE THAT'S PRESENT INSIDE 2333 01:28:25,963 --> 01:28:28,065 B-CELLS AND WE KNOW THAT 2334 01:28:28,065 --> 01:28:29,700 BLOCKING B-CELLS IS EFFECTIVE IN 2335 01:28:29,700 --> 01:28:31,101 BLOCKING MS RELAPSE BUT IT'S 2336 01:28:31,101 --> 01:28:33,971 ALSO PRESENT IN THESE MYELOID 2337 01:28:33,971 --> 01:28:35,506 CELLS INCLUDING MICROGLIA AND IT 2338 01:28:35,506 --> 01:28:36,673 HAS MANY, MANY FUNCTIONS THAT WE 2339 01:28:36,673 --> 01:28:38,742 DON'T HAVE TIME TO TALK ABOUT SO 2340 01:28:38,742 --> 01:28:40,711 IT'S PLAWSIBLE THIS MIGHT 2341 01:28:40,711 --> 01:28:41,045 ACTUALLY WORK. 2342 01:28:41,045 --> 01:28:42,713 AND IN FACT WE WERE ABLE TO SHOW 2343 01:28:42,713 --> 01:28:45,682 WITH STAINING HERE IN BROWN, 2344 01:28:45,682 --> 01:28:47,117 THAT BTK IS PRESENT AT THE EDGE 2345 01:28:47,117 --> 01:28:48,519 OF THESE CHRONIC ACTIVE LESIONS 2346 01:28:48,519 --> 01:28:53,457 THAT HAVE IRON RIMS AS WELL. 2347 01:28:53,457 --> 01:28:54,691 THERE'S PRECLINICAL WORK THAT 2348 01:28:54,691 --> 01:29:00,464 WAS DONE IN CELL CULTURE BY OUR 2349 01:29:00,464 --> 01:29:02,699 COLLEAGUES AT SENOFI, WHICH IS A 2350 01:29:02,699 --> 01:29:04,968 COMPANY THAT'S DEVELOPING 2351 01:29:04,968 --> 01:29:06,637 INHIBITORS PER DTK FOR MS, 2352 01:29:06,637 --> 01:29:08,038 THERE'S 4 MAJOR COMPANIES IN 2353 01:29:08,038 --> 01:29:09,373 THAT ARE DOING THIS CURRENTLY 2354 01:29:09,373 --> 01:29:14,645 AND YOU CAN SEE THAT IN THEIR 2355 01:29:14,645 --> 01:29:18,348 CELL CULTURES, THEY CAN 2356 01:29:18,348 --> 01:29:20,417 PROFOUNDLY DECREASE THE LEVELS 2357 01:29:20,417 --> 01:29:23,520 OF MANY OF THESE MOLECULES WHICH 2358 01:29:23,520 --> 01:29:24,855 ARE IMPORTANT INFLAMMATORY 2359 01:29:24,855 --> 01:29:26,957 MEDIATORS USING THE INHIBITOR 2360 01:29:26,957 --> 01:29:29,626 THAT THEY HAVE DEVELOPED AND 2361 01:29:29,626 --> 01:29:31,328 OTHER INHIBITORS WORK SIMILARLY. 2362 01:29:31,328 --> 01:29:33,864 AND SO HERE YOU CAN SEE IN A 2363 01:29:33,864 --> 01:29:35,399 TABLE, ALL THE DIFFERENT TRIALS, 2364 01:29:35,399 --> 01:29:37,067 ALL THE DIFFERENT PHASE 3 2365 01:29:37,067 --> 01:29:39,436 CLINICAL TRIALS, THESE ARE THE 2366 01:29:39,436 --> 01:29:43,373 MASSIVE TRIALS THAT CAN GENERATE 2367 01:29:43,373 --> 01:29:45,676 DATA THAT MAY BE USEABLE FOR THE 2368 01:29:45,676 --> 01:29:48,879 FDA TO, PROVE OR DISAPPROVE A 2369 01:29:48,879 --> 01:29:50,814 MEDICATION FOR A PARTICULAR 2370 01:29:50,814 --> 01:29:51,615 DISEASE LIKE MULTIPLE SCLEROSIS 2371 01:29:51,615 --> 01:29:54,151 AND YOU CAN SEE THAT THESE 2372 01:29:54,151 --> 01:29:54,818 DIFFERENT MOLECULES ARE BEING 2373 01:29:54,818 --> 01:29:56,954 TEST INDEED A VARIETY OF MS 2374 01:29:56,954 --> 01:30:05,762 TYPES, THEY'RE RELAPSING TYPE, 2375 01:30:05,762 --> 01:30:07,865 THAT MR. CHACON PRESENTED WITH 2376 01:30:07,865 --> 01:30:08,665 OR OTHER TYPES. 2377 01:30:08,665 --> 01:30:10,367 AND THESE ARE IN VARIOUS TAIJS 2378 01:30:10,367 --> 01:30:12,236 OF PROGRESS AT THIS TIME AND 3 2379 01:30:12,236 --> 01:30:13,770 OF THEM SPECIFICALLY ARE BEING 2380 01:30:13,770 --> 01:30:19,276 USED IN PROGRESSIVE MS. 2381 01:30:19,276 --> 01:30:21,111 THIS IS THE DATA FROM THE FIRST 2382 01:30:21,111 --> 01:30:26,850 RELEASE LAST YEAR, THIS IS A 2383 01:30:26,850 --> 01:30:28,318 MODEL CALLED EVOBRUTINIB, THIS 2384 01:30:28,318 --> 01:30:30,087 WAS ONLY TESTED IN RELAPSES MS 2385 01:30:30,087 --> 01:30:33,023 AND IT HAD NO EFFICACY 2386 01:30:33,023 --> 01:30:37,060 WHATSOEVER COMPARED TO THE 2387 01:30:37,060 --> 01:30:38,662 COMITITTOR DRUG, WHICH IS A 2388 01:30:38,662 --> 01:30:40,664 MEDICATION THAT IS APPROVED FOR 2389 01:30:40,664 --> 01:30:40,831 MS. 2390 01:30:40,831 --> 01:30:50,974 IT TURNED OUT TO BE NO BETTER AT 2391 01:30:50,974 --> 01:30:51,875 ALL. 2392 01:30:51,875 --> 01:30:53,610 HOWEVER WHAT DISTINGUISHES THESE 2393 01:30:53,610 --> 01:30:55,212 FROM OTHERS IS THE ABILITY TO 2394 01:30:55,212 --> 01:31:02,686 GET INSIDE THE BRAIN WHERE 2395 01:31:02,686 --> 01:31:05,589 MICROGLIA LIVE, AND FENEBRUTINIB 2396 01:31:05,589 --> 01:31:07,024 IS NOT ABLE TO GET IN THE BRAIN 2397 01:31:07,024 --> 01:31:08,425 AND THIS IS SHOWN ON THE LEFT 2398 01:31:08,425 --> 01:31:10,594 LOOKING AT THE CONS TRAITIONZ OF 2399 01:31:10,594 --> 01:31:12,329 THE DRUG RELATIVE TO THE 2400 01:31:12,329 --> 01:31:18,268 CONCENTRATION THAT IS NEEDED TO 2401 01:31:18,268 --> 01:31:27,878 ACHIEVE EFFECT FOR TOLEBRUTINIB, 2402 01:31:27,878 --> 01:31:31,882 AND EVOBRUTINIB, AND 2403 01:31:31,882 --> 01:31:35,485 FENEBRUTINIB, AND SO, AS PART OF 2404 01:31:35,485 --> 01:31:36,220 MY CORRELATED FICIAL DUTY HERE 2405 01:31:36,220 --> 01:31:40,324 AT NIESH H I HAVE BEEN WORKING 2406 01:31:40,324 --> 01:31:41,692 WITH SENOFI IN THEIR TESTING OF 2407 01:31:41,692 --> 01:31:42,993 THE THIS DRUG BECAUSE IT WILL 2408 01:31:42,993 --> 01:31:44,561 TEACH US ABOUT MS, I DON'T GET 2409 01:31:44,561 --> 01:31:46,296 PAID FOR THIS WORK, THIS IS PART 2410 01:31:46,296 --> 01:31:49,499 OF MY GOVERNMENT WORK. 2411 01:31:49,499 --> 01:31:50,534 JUST BECAUSE AGAIN, I THINK WE 2412 01:31:50,534 --> 01:31:52,769 CAN LEARN ABOUT HOW TO MOVE 2413 01:31:52,769 --> 01:31:53,904 FORWARD WITH MULTIPLE SCLEROSIS 2414 01:31:53,904 --> 01:31:56,740 TREATMENT AND WE RECENTLY IN 2415 01:31:56,740 --> 01:31:58,275 COLLABORATION WITH THEM REPORTED 2416 01:31:58,275 --> 01:32:02,846 RESULTS AT 3 OF THESE TRIALS AND 2417 01:32:02,846 --> 01:32:04,982 2 TRIALS IN RELAXING MS AND 2418 01:32:04,982 --> 01:32:08,118 THERE WERE 2 TRIALS IN 2419 01:32:08,118 --> 01:32:12,155 NONRELAPSING MS WHERE 2420 01:32:12,155 --> 01:32:15,859 TOLEBRUTINIB WAS COMPARED TO 2421 01:32:15,859 --> 01:32:16,126 PLACEBO. 2422 01:32:16,126 --> 01:32:17,394 AND I WILL SKIP OVER THIS IN THE 2423 01:32:17,394 --> 01:32:22,165 INTEREST OF TIME TO SHOW YOU THE 2424 01:32:22,165 --> 01:32:22,532 END RESULTS. 2425 01:32:22,532 --> 01:32:32,175 THIS WAS IN THE HERCULES TRIA, 2426 01:32:32,175 --> 01:32:36,280 WHERE THE PEASHT HAD A WORSENING 2427 01:32:36,280 --> 01:32:36,980 OF DISABILITY COMPARED TO 2428 01:32:36,980 --> 01:32:38,715 PLACEBO AND YOU CAN SEE THAT 37% 2429 01:32:38,715 --> 01:32:41,118 OF THE PEOPLE TAKING PLACEBO HAD 2430 01:32:41,118 --> 01:32:43,920 SUCH AN EVENT WHEREAS 27% STILL 2431 01:32:43,920 --> 01:32:46,623 A SUBSTANTIAL NUMBER BUT 30% 2432 01:32:46,623 --> 01:32:47,991 ROUGHLY 30% LOWER NUMBER WHO ARE 2433 01:32:47,991 --> 01:32:51,161 TAKING THE DRUG HAD A 2434 01:32:51,161 --> 01:32:54,231 PROGRESSIVE -- HAD AN EVENT OF 2435 01:32:54,231 --> 01:32:56,133 PROGRESSIVE MS, THAT IS THEIR 2436 01:32:56,133 --> 01:32:57,067 DISABILITY WORSENED OVER TIME. 2437 01:32:57,067 --> 01:33:01,505 THIS IS NOW PUBLISHED DATA AND 2438 01:33:01,505 --> 01:33:02,739 IT'S THE FIRST LARGE PHASE 3 2439 01:33:02,739 --> 01:33:06,910 TRIAL TO SHOW REAL EFFICACY, 2440 01:33:06,910 --> 01:33:09,413 EVEN IF ALBEIT SMALL OR ALBETIT 2441 01:33:09,413 --> 01:33:15,485 A FIRST STEP STILL GOOD IN MS. 2442 01:33:15,485 --> 01:33:16,853 AND INTERESTINGLY EVEN THOUGH IN 2443 01:33:16,853 --> 01:33:19,756 THE RELAPSING TRIALS THE GEMIN I 2444 01:33:19,756 --> 01:33:21,625 TRIALS, THERE WAS NO DIFFERENCE 2445 01:33:21,625 --> 01:33:23,126 IN RELAPSE PROTECTION, THERE WAS 2446 01:33:23,126 --> 01:33:24,628 STILL A SMALL BUT SIGNIFICANT 2447 01:33:24,628 --> 01:33:28,532 REDUCTION IN THE RISK OF PEOPLE 2448 01:33:28,532 --> 01:33:29,266 WITH RELAPSING MULTIPLE 2449 01:33:29,266 --> 01:33:30,267 SCLEROSIS, PROGRESSING AND 2450 01:33:30,267 --> 01:33:30,634 GETTING WORSE. 2451 01:33:30,634 --> 01:33:33,070 SO WHAT IS THE BASIS FOR THIS, 2452 01:33:33,070 --> 01:33:35,806 IS IT BECAUSE BTK INHIBITORS, 2453 01:33:35,806 --> 01:33:40,043 CROSS INTO BRAIN AND AFFECT 2454 01:33:40,043 --> 01:33:40,811 MICROGLIA, WELL, 1 THING WE CAN 2455 01:33:40,811 --> 01:33:44,047 DO IS TO LOOK AT THOSE 2456 01:33:44,047 --> 01:33:45,315 PARAMAGNETIC RIM LESIONS THAT'S 2457 01:33:45,315 --> 01:33:46,950 WHAT WE DID, ABOUT A THIRD OF 2458 01:33:46,950 --> 01:33:48,518 PATIENTS IN THIS TRIAL HAD MRI 2459 01:33:48,518 --> 01:33:52,189 SCANS THAT ALLOWED US TO DO THAT 2460 01:33:52,189 --> 01:33:54,291 SO ABOUT A THOUSAND TOTAL OUT OF 2461 01:33:54,291 --> 01:33:55,926 THE 3000 PATIENTS HAD THAT. 2462 01:33:55,926 --> 01:33:59,496 YOU CAN SEE HERE, IN THE 2 2463 01:33:59,496 --> 01:34:01,131 TRIALS, GEMIN I 1 AND 2, THIS IS 2464 01:34:01,131 --> 01:34:06,703 2 TRIALS MERGED TOGETHER AND THE 2465 01:34:06,703 --> 01:34:08,138 HERCULES PROGRESSIVE TRIAL, 2466 01:34:08,138 --> 01:34:09,840 DISDISTRIBUTION OF PATIENTS IN 2467 01:34:09,840 --> 01:34:11,007 THESE TRIALS, YOU WILL RECALL IN 2468 01:34:11,007 --> 01:34:12,209 THE DATA I SHOWED YOU BEFORE 2469 01:34:12,209 --> 01:34:14,745 THAT PEOPLE WITH MORE THAN 4 2470 01:34:14,745 --> 01:34:19,049 PRLs ARE LIKELY TO HAVE A 2471 01:34:19,049 --> 01:34:22,252 WORSE COURSE OF THE DISEASE AND 2472 01:34:22,252 --> 01:34:24,321 THIS RECAPITULATES WHAT WE FOUND 2473 01:34:24,321 --> 01:34:25,889 IN OUR STUDIES IN TERMS OF 2474 01:34:25,889 --> 01:34:26,590 PROPORTIONS. 2475 01:34:26,590 --> 01:34:29,126 IN THE RELAPSES MS TRIAL, 2476 01:34:29,126 --> 01:34:34,231 COMPARING PEOPLE WITH 0-1-3 AND 2477 01:34:34,231 --> 01:34:36,466 MORE THAN 4 PRLs IN TERMS OF 2478 01:34:36,466 --> 01:34:38,068 LIKELIHOOD OF GETTING WORSE AND 2479 01:34:38,068 --> 01:34:47,144 THEIR DISABILITY BY PERCENTAGE, 2480 01:34:47,144 --> 01:34:50,580 IN TOLEBRUTINIB, AND VERSUS THE 2481 01:34:50,580 --> 01:34:51,815 COMPARATOR, EVEN WITH THOSE WITH 2482 01:34:51,815 --> 01:34:54,084 LESIONS 4 OR MORE THE CHANCE OF 2483 01:34:54,084 --> 01:34:56,019 GETTING THAT DISABILITY 2484 01:34:56,019 --> 01:34:57,387 WORSENING WAS REALLY NOT 2485 01:34:57,387 --> 01:35:00,490 DIFFERENT WHEREAS IT WAS WORSE 2486 01:35:00,490 --> 01:35:09,299 AS EXPECTED IN THE TERIFLUNOMIDE 2487 01:35:09,299 --> 01:35:09,499 STUDY. 2488 01:35:09,499 --> 01:35:10,300 PEOPLE WERE ALREADY PROGRESSING 2489 01:35:10,300 --> 01:35:12,269 SO THERE WAS A HIGHER CHANCE OF 2490 01:35:12,269 --> 01:35:13,437 HAVING A WORSENING OF DISABILITY 2491 01:35:13,437 --> 01:35:15,071 TO THE TRIAL, WE SAW VERY MUCH 2492 01:35:15,071 --> 01:35:16,306 THE SAME EFFECT. 2493 01:35:16,306 --> 01:35:18,308 ABOUT A 50% REDUCTION IN THE 2494 01:35:18,308 --> 01:35:19,876 RISK OF HAVING WORSENING IF YOU 2495 01:35:19,876 --> 01:35:21,545 HAVE THIS EVIDENCE OF CHRONIC 2496 01:35:21,545 --> 01:35:24,548 INFLAMMATION IN THE BRAIN. 2497 01:35:24,548 --> 01:35:26,049 AND I WILL JUST VERY QUIEKLY 2498 01:35:26,049 --> 01:35:27,350 BECAUSE I KNOW YEAR RUNNING 2499 01:35:27,350 --> 01:35:29,386 SHORT ON TIME TELL YOU ABOUT A 2500 01:35:29,386 --> 01:35:30,921 TRAIL WE DID, THE DOCTOR AND I 2501 01:35:30,921 --> 01:35:32,889 AND OUR TEAM HERE AT THE NIH TO 2502 01:35:32,889 --> 01:35:35,425 TRY TO GET AT THIS DEEPER. 2503 01:35:35,425 --> 01:35:42,732 AND THIS IS THE NIH CLINICAL 2504 01:35:42,732 --> 01:35:52,375 CENTER WHERE WE WORK BUT WE 2505 01:35:52,375 --> 01:35:54,110 STUDY A FEW PEOPLE IN A DEEP WAY 2506 01:35:54,110 --> 01:35:55,946 SO WE CAN UNDERSTAND WHAT'S 2507 01:35:55,946 --> 01:36:02,219 GOING ON, WE TOOK A SMALLER 2508 01:36:02,219 --> 01:36:05,355 TRIAL AND WE STUDY THEM WITH A 2509 01:36:05,355 --> 01:36:08,124 POWERFUL MRI SCAN, THEY HAD HAD 2510 01:36:08,124 --> 01:36:10,126 THIS PARAMAGNETIC RIM LESION, 2511 01:36:10,126 --> 01:36:14,097 THEY HAD ALL BEEN TAKING B-CELL 2512 01:36:14,097 --> 01:36:24,641 DEPLETION AND ALL WITH THE SAME 2513 01:36:27,878 --> 01:36:28,979 MEDICATION AND WE WILL CONTINUE 2514 01:36:28,979 --> 01:36:30,280 TO FOLLOW SEVERAL OF THESE 2515 01:36:30,280 --> 01:36:31,748 PEOPLE WHO ARE TAKING THE 2516 01:36:31,748 --> 01:36:33,950 MEDICATION AND WE DID IT WITH 2517 01:36:33,950 --> 01:36:36,353 LUMBAR PUNCTURE AND MRI, SO WE 2518 01:36:36,353 --> 01:36:38,889 TRACKED HOW THEIR B-CELLS HAD 2519 01:36:38,889 --> 01:36:41,424 BEEN DEPLETED WITH THE THIS 2520 01:36:41,424 --> 01:36:45,996 BEGAN TO REPOPULATE BUT VERY 2521 01:36:45,996 --> 01:36:47,797 SLOWLY OVER TIME AND SO WHAT DO 2522 01:36:47,797 --> 01:36:48,431 WE FIND. 2523 01:36:48,431 --> 01:36:50,100 WE FOUND I GUESS SOMEWHAT 2524 01:36:50,100 --> 01:36:52,469 DISAPPOINTINGLY AT THE END OF 48 2525 01:36:52,469 --> 01:36:55,071 WEEKS, THAT EVEN WITH THIS 2526 01:36:55,071 --> 01:36:57,007 MEDICATION WE WERE NOT ACTUALLY 2527 01:36:57,007 --> 01:37:00,076 REALLY ABLE TO AFFECT THE 2528 01:37:00,076 --> 01:37:01,444 PARAMAGNETIC RIM LESIONS THAT 2529 01:37:01,444 --> 01:37:03,346 WERE PRESENT AT BASE LINE AND 2530 01:37:03,346 --> 01:37:04,648 THIS WAS DONE BEFORE WE HAD THE 2531 01:37:04,648 --> 01:37:09,920 RESULTS OF THE PHASE 3 AND WHERE 2532 01:37:09,920 --> 01:37:11,288 I SHOWED YOU BEFORE WHERE THERE 2533 01:37:11,288 --> 01:37:12,589 WAS A DISABILITY AFFECT BUT I 2534 01:37:12,589 --> 01:37:16,993 COULD BT SEE IT IN THIS GROUP OF 2535 01:37:16,993 --> 01:37:17,127 7. 2536 01:37:17,127 --> 01:37:18,428 HOWEVER, AND WE LOOKED DEEPER 2537 01:37:18,428 --> 01:37:19,963 AND THAT'S WHAT WE CAN DO HERE 2538 01:37:19,963 --> 01:37:21,965 AT THE NIH AND WE DID THAT SAME 2539 01:37:21,965 --> 01:37:27,904 SEQUENCING OF THE CELLS IN THE 2540 01:37:27,904 --> 01:37:29,839 SPINAL FLUID, AND HERE YOU CAN 2541 01:37:29,839 --> 01:37:31,107 SEE BTK, THE PURPLE DOTS SHOWING 2542 01:37:31,107 --> 01:37:32,943 YOU THE CELLS IN THE B-CELL 2543 01:37:32,943 --> 01:37:35,946 LINEAGE AND THE MYELOID CELLS 2544 01:37:35,946 --> 01:37:37,380 THAT CONTAIN BRUTON'S TYROTEEN 2545 01:37:37,380 --> 01:37:38,848 KINASE, WE FOCUSED ON THE 2546 01:37:38,848 --> 01:37:40,283 MYELOID CELLS WHICH ARE 2547 01:37:40,283 --> 01:37:41,885 MICROGLIA LIKE, SOME OF THEM AND 2548 01:37:41,885 --> 01:37:43,420 WE LOOKED AT HOW THEY MIGHT 2549 01:37:43,420 --> 01:37:51,761 CHANGE EAEVER 48 WEEKS OF 2550 01:37:51,761 --> 01:37:53,697 TOLEBRUTINIB, AND WE LOOKED AT 2551 01:37:53,697 --> 01:37:55,098 EACH CASE BUT THIS M2 CLUSTER 2552 01:37:55,098 --> 01:37:56,266 HAS GENES THAT ARE SIMILAR TO 2553 01:37:56,266 --> 01:37:58,401 THE 1 I SHOWED BEFORE INCLUDING 2554 01:37:58,401 --> 01:38:03,540 COMPLEMENT YEERNS AND AFTER 48 2555 01:38:03,540 --> 01:38:07,611 WEEKS, OF TREATMENT, SHOWS GENES 2556 01:38:07,611 --> 01:38:08,211 WERE SUBSTANTIALLY REDUCED BY 2557 01:38:08,211 --> 01:38:10,380 TREATMENT AND HERE IS JUST 2558 01:38:10,380 --> 01:38:14,084 ANOTHER VERSION OF THAT WITH 2559 01:38:14,084 --> 01:38:15,118 ADDITIONAL MOLECULES FROM THE 2560 01:38:15,118 --> 01:38:17,420 COMPLEMENT SYSTEM AS WELL AS 2561 01:38:17,420 --> 01:38:19,856 OTHER MOLECULES, FOR EXAMPLE, 2562 01:38:19,856 --> 01:38:23,159 APOLIPIE PROTEIN E WHICH IS AN 2563 01:38:23,159 --> 01:38:24,127 IMPORTANT MOLECULE FOR 2564 01:38:24,127 --> 01:38:25,829 MICROGLIAL INFLAMMATION, SO I 2565 01:38:25,829 --> 01:38:27,097 WILL SUMMARIZE, AND JUST TELL 2566 01:38:27,097 --> 01:38:29,165 YOU WHAT I ALREADY TOLD YOU THAT 2567 01:38:29,165 --> 01:38:32,836 CHRONIC ACTIVE WHITE MATTER 2568 01:38:32,836 --> 01:38:34,304 LESIONS ARE DETECTABLE, IN VIVO, 2569 01:38:34,304 --> 01:38:39,442 IN LIVING PEOPLE AS PARAMAGNETIC 2570 01:38:39,442 --> 01:38:41,177 RIM LESIONS AND THEY ARE 2571 01:38:41,177 --> 01:38:42,812 IMPORTANT FOR THE DEVELOPMENT OF 2572 01:38:42,812 --> 01:38:45,582 THESE CHRONIC ACTIVE LESIONS, 2573 01:38:45,582 --> 01:38:47,317 WE'RE STILL WORKING OUT MANY OF 2574 01:38:47,317 --> 01:38:48,551 THE PATHWAYS, MOLECULAR AND 2575 01:38:48,551 --> 01:38:50,787 CELLULAR PATHWAYS THAT ARE 2576 01:38:50,787 --> 01:38:52,789 INVOLVED IN THOSE LESIONS, WE'RE 2577 01:38:52,789 --> 01:38:54,891 DOING THAT USING HIGH THROUGH 2578 01:38:54,891 --> 01:38:56,726 PUT OIMMUNE DYSFUNCTION MICS 2579 01:38:56,726 --> 01:38:58,561 TECHNIQUES TO IDENTIFY GENES OF 2580 01:38:58,561 --> 01:38:59,696 INTEREST OR TARGETS FOR NEW 2581 01:38:59,696 --> 01:39:01,131 DRUGS AND TO TEST OUTCOMES IN 2582 01:39:01,131 --> 01:39:08,938 THE CONTEXT OF THOSE TRIALS, 2583 01:39:08,938 --> 01:39:11,341 THIS IS THE BTK INHIBITOR WHICH 2584 01:39:11,341 --> 01:39:13,443 DID NOT RESOLVE THE RIM LESIONS 2585 01:39:13,443 --> 01:39:15,078 BUT DID STILL HAVE ANTIINFLAMMA 2586 01:39:15,078 --> 01:39:15,912 ARE TOY PROPERTIES AND WE KNOW 2587 01:39:15,912 --> 01:39:18,348 FROM THE LARGE TRIALS HAVE SOME 2588 01:39:18,348 --> 01:39:19,749 INFLUENCE ON DISABILITY AND I 2589 01:39:19,749 --> 01:39:21,584 WOULD SAY WE'RE STILL SEARCHING 2590 01:39:21,584 --> 01:39:23,820 FOR OPTIMIZED PROOF OF CONCEPT 2591 01:39:23,820 --> 01:39:27,891 TRIAL DESIGNS FOR PROGRESSIVE 2592 01:39:27,891 --> 01:39:30,260 MS, BUT I THINK WE'VE HOPEFULLY 2593 01:39:30,260 --> 01:39:32,762 TAKEN THE NEW STEPS. 2594 01:39:32,762 --> 01:39:35,065 MANY, MANY PEOPLE INVOLVED IN 2595 01:39:35,065 --> 01:39:37,300 WORK, MANY OTHER GROUPS AND OUR 2596 01:39:37,300 --> 01:39:39,335 COLLABORATORS, AND HERE'S JUST 2597 01:39:39,335 --> 01:39:40,970 SOME PICTURES OF THE GROUPS 2598 01:39:40,970 --> 01:39:42,439 WONDERFUL PEOPLE I WORK WITH 2599 01:39:42,439 --> 01:39:52,916 HERE AT TD NIH WHO ARE DOING 2600 01:39:56,453 --> 01:39:56,953 THIS WORK. 2601 01:39:56,953 --> 01:39:58,755 >> WHERE WE ARE IN TERMS OF 2602 01:39:58,755 --> 01:40:00,123 CHALLENGES AND OPPORTUNITIES IN 2603 01:40:00,123 --> 01:40:01,791 TERMS OF MULTIPLE SCLEROSIS, CAN 2604 01:40:01,791 --> 01:40:12,001 YOU HEAR ME? 2605 01:40:22,412 --> 01:40:23,012 OR NOT? 2606 01:40:23,012 --> 01:40:25,415 >> I DON'T KNOW WHY MY SPEAKER 2607 01:40:25,415 --> 01:40:25,648 STOPPED. 2608 01:40:25,648 --> 01:40:27,217 >> I CAN HEAR YOU NI CAN HEAR 2609 01:40:27,217 --> 01:40:27,383 YOU? 2610 01:40:27,383 --> 01:40:29,319 I CAN HEAR YOU, TOO NIT WOULD BE 2611 01:40:29,319 --> 01:40:31,855 NICE IF DANNY CAN HEAR ME TOO SO 2612 01:40:31,855 --> 01:40:33,790 THAT I CAN MODERATE A LITTLE BIT 2613 01:40:33,790 --> 01:40:36,993 OF A DISCUSSION AMONGST US. 2614 01:40:36,993 --> 01:40:38,328 >> YES, HE MIGHT BE SIGNING OUT 2615 01:40:38,328 --> 01:40:40,597 AND SIGNING BACK IN, THAT'S MY 2616 01:40:40,597 --> 01:40:45,802 SENSE. 2617 01:40:45,802 --> 01:40:47,070 >> YEAH, YEAH, PERHAPS. 2618 01:40:47,070 --> 01:40:53,009 >> WHILE HERE DOING THAT PERHAPS 2619 01:40:53,009 --> 01:40:55,145 I CAN ASK THE DOCTOR SINCE WE 2620 01:40:55,145 --> 01:40:56,513 HAVE QUITE A FEW QUESTIONS FROM 2621 01:40:56,513 --> 01:41:00,216 THE AUDIENCE AND A FEW THAT HAVE 2622 01:41:00,216 --> 01:41:03,653 OCCURRED TO ME AS WELL, SO 1 OF 2623 01:41:03,653 --> 01:41:04,387 THE INTERESTING QUESTIONS IS 2624 01:41:04,387 --> 01:41:08,925 JUST THIS 1 THAT HAS BEEN RAISED 2625 01:41:08,925 --> 01:41:11,995 BEFORE OF THE EPITEEMIOLOGY OF 2626 01:41:11,995 --> 01:41:16,065 MS AND THE DISTRIBUTION OF 2627 01:41:16,065 --> 01:41:18,301 CASES, COULD YOU POSSIBLY SAY A 2628 01:41:18,301 --> 01:41:21,037 LITTLE BIT MORE DOCTOR ABOUT 2629 01:41:21,037 --> 01:41:21,404 THAT? 2630 01:41:21,404 --> 01:41:28,311 I UNDERSTAND AT LEAST THERE'S 2631 01:41:28,311 --> 01:41:30,113 SOME ASSOCIATION WITH FREQUENCY 2632 01:41:30,113 --> 01:41:32,782 AND INCIDENCE OF MS AND MORE 2633 01:41:32,782 --> 01:41:33,516 NORTHERN LATITUDES. 2634 01:41:33,516 --> 01:41:35,351 IS THAT SO? 2635 01:41:35,351 --> 01:41:43,226 AND IF SO, WHAT MIGHT BE THE 2636 01:41:43,226 --> 01:41:44,227 MECHANISM OF THAT? 2637 01:41:44,227 --> 01:41:45,495 >> YES, IT IS ACTUALLY RIGHT AND 2638 01:41:45,495 --> 01:41:49,966 IT MAY BE SOCKED LESS EXPOSURE 2639 01:41:49,966 --> 01:41:53,870 FOR EXAMPLE AND GENETIC VALID 2640 01:41:53,870 --> 01:41:54,571 AND RELIABLUATION SOPHISTICATED 2641 01:41:54,571 --> 01:41:57,140 OOTH BEEN SHOWN, WHICH IS CLEAR 2642 01:41:57,140 --> 01:42:00,643 AND PROBABLY SOME EXPOSURE, LESS 2643 01:42:00,643 --> 01:42:01,377 EXPOSURE PLUS GENERATEDETEC 2644 01:42:01,377 --> 01:42:04,180 FACTORS ARE RESPONSIBLE FOR 2645 01:42:04,180 --> 01:42:04,614 THAT. 2646 01:42:04,614 --> 01:42:08,318 I SEE, I SEE AND THEN YOU HAD 2647 01:42:08,318 --> 01:42:13,356 MENTIONED VITAMIN D AS BEING 2648 01:42:13,356 --> 01:42:15,625 ANOTHER FACTOR THERE, SO I TAKE 2649 01:42:15,625 --> 01:42:19,362 THAT VITAMIN D AND PROTECTIVE 2650 01:42:19,362 --> 01:42:23,032 FOR MS IS THAT CORRECT? 2651 01:42:23,032 --> 01:42:25,368 >> YEAH, SO THE EFFICIENT OF 2652 01:42:25,368 --> 01:42:28,872 VITAMIN D AND LOW SUN LIGHT 2653 01:42:28,872 --> 01:42:30,173 EXPOSURE ARE BOTH IMPORTANT IN 2654 01:42:30,173 --> 01:42:32,041 MS AND THERE WERE ASSOCIATION 2655 01:42:32,041 --> 01:42:34,377 SO, PATIENTS WITH HIGHER LEVEL 2656 01:42:34,377 --> 01:42:39,549 OF VITAMIN D FOR EXAMPLE AT THE 2657 01:42:39,549 --> 01:42:41,484 TIME OF THE FIRST CLINIC EPISODE 2658 01:42:41,484 --> 01:42:47,223 HAVE LESS RISK OF RELAPSING, SO 2659 01:42:47,223 --> 01:42:49,058 HIGHER LEVELS OF VITAMIN D AT 2660 01:42:49,058 --> 01:42:51,427 THE TIME OF EPISODE ARE 2661 01:42:51,427 --> 01:42:53,496 ASSOCIATE WIDE LESS RISK FOR 2662 01:42:53,496 --> 01:42:55,365 EVOLUTION OF LESS RELAPSE IN MS, 2663 01:42:55,365 --> 01:42:58,501 AS WELL THERE WERE OTHER STUDIES 2664 01:42:58,501 --> 01:43:00,003 THAT SHOW LOWER LEVELS OF 2665 01:43:00,003 --> 01:43:03,006 VITAMIN D WERE ASSOCIATE WIDE 2666 01:43:03,006 --> 01:43:04,741 NEUROLESIONS OR ENHANCED LESIONS 2667 01:43:04,741 --> 01:43:06,009 HOWEVER, THE REPLACEMENT WITH 2668 01:43:06,009 --> 01:43:09,879 VITAMIN D IS NOT SHOWING ANY 2669 01:43:09,879 --> 01:43:12,081 BENEFIT, SO TAKING RL IS NOT 2670 01:43:12,081 --> 01:43:13,449 SHOWING A CHANGE IN THE 2671 01:43:13,449 --> 01:43:17,287 EVOLUTION OR IN THE MRI. 2672 01:43:17,287 --> 01:43:18,788 >> YES, I WAS ABOUT TO ASK YOU 2673 01:43:18,788 --> 01:43:20,323 THAT QUESTION GIVEN WHAT YOU HAD 2674 01:43:20,323 --> 01:43:22,292 SAID AND WHAT YOU SAID ABOUT SUN 2675 01:43:22,292 --> 01:43:23,493 LIGHT AND SO FORTH IS WOULD 2676 01:43:23,493 --> 01:43:28,131 THERE BE SOME SORT OF SUPPLEMENT 2677 01:43:28,131 --> 01:43:30,199 THAT MIGHT BE BENEFICIAL. 2678 01:43:30,199 --> 01:43:31,734 ARE THERE ANY SUPPLEMENTS THAT 2679 01:43:31,734 --> 01:43:32,635 MIGHT BE BENEFICIAL. 2680 01:43:32,635 --> 01:43:33,836 >> YEAH, WE SUGGEST PATIENTS TO 2681 01:43:33,836 --> 01:43:40,510 HAVE LEVELS OF VITAMIN D ABOVE 2682 01:43:40,510 --> 01:43:43,646 14 NANO GRAMS, SO IT'S VERY 2683 01:43:43,646 --> 01:43:45,848 THERE AT THE COUNTER, SO IT'S 2684 01:43:45,848 --> 01:43:53,690 VERY STRAIGHT FORWARD TO GET THE 2685 01:43:53,690 --> 01:43:54,257 VITAMIN D REPLACEMENT. 2686 01:43:54,257 --> 01:43:56,459 MAYBE I SHOULD REPEAT THE CME 2687 01:43:56,459 --> 01:43:57,994 CODE NOW THAT WE'RE ENGAINLING 2688 01:43:57,994 --> 01:43:58,928 IN THIS DISCUSSION FOR THOSE WHO 2689 01:43:58,928 --> 01:44:02,432 WANT TO GET CONTINUING MEDICAL 2690 01:44:02,432 --> 01:44:12,942 EDUCATION CREDIT, IT IS 58794. 2691 01:44:14,010 --> 01:44:14,410 AGAIN THAT'S 58794. 2692 01:44:14,410 --> 01:44:16,779 LET ME SEE IF I CAN FIND A 2693 01:44:16,779 --> 01:44:17,680 COUPLE MORE QUESTIONS. 2694 01:44:17,680 --> 01:44:20,149 SOMEONE IS CATEGORY GO THE 2695 01:44:20,149 --> 01:44:21,784 DEVELOPMENT OF BI-SPECIFIC 2696 01:44:21,784 --> 01:44:22,919 ANTIBODIES FOR THE THERAPY OF 2697 01:44:22,919 --> 01:44:23,853 MS. 2698 01:44:23,853 --> 01:44:25,321 IN OTHER WORDS ANTIBODIES WHERE 2699 01:44:25,321 --> 01:44:27,857 1 ARM OF THE ANTIBODY MOLECULE 2700 01:44:27,857 --> 01:44:28,858 MIGHT BE DIRECTED AGAINST 2701 01:44:28,858 --> 01:44:31,327 B-CELLS AND THE OTHER HARM MIGHT 2702 01:44:31,327 --> 01:44:37,467 BE DIRECTED AT LEAST BASED ON 2703 01:44:37,467 --> 01:44:39,736 DR. REICH'S PRESENTATION MAYBE 2704 01:44:39,736 --> 01:44:43,106 TOWARDS MICROGLIAL CELLS OR 2705 01:44:43,106 --> 01:44:43,473 WHATEVER? 2706 01:44:43,473 --> 01:44:45,241 >> YEAH, SO THESE, THESE, 2707 01:44:45,241 --> 01:44:46,509 ANTIBODIES ARE IN DEVELOPMENT 2708 01:44:46,509 --> 01:44:49,645 FOR MANY CONDITIONS AND MS IS NO 2709 01:44:49,645 --> 01:44:50,413 EXCEPTION TO THAT. 2710 01:44:50,413 --> 01:44:54,384 THEY ARE IN VERY EARLY STAGES OF 2711 01:44:54,384 --> 01:45:01,324 TREATMENT -- SORRY OF TESTING. 2712 01:45:01,324 --> 01:45:04,160 ONE OF THE -- SO 1 OF THE 2713 01:45:04,160 --> 01:45:04,894 TREATMENTS IN QUESTION IN 2714 01:45:04,894 --> 01:45:05,695 PARTICULAR IS WHETHER IT WILL 2715 01:45:05,695 --> 01:45:07,663 GET INTO THE BRAIN IN SUFFICIENT 2716 01:45:07,663 --> 01:45:10,733 AMOUNTS TO BE EFFECTIVE BECAUSE 2717 01:45:10,733 --> 01:45:12,735 ANTIBODIES ARE LARGE PROTEINS 2718 01:45:12,735 --> 01:45:14,704 AND THEY DON'T READILY ACROSS 2719 01:45:14,704 --> 01:45:16,105 THE BLOOD BRAIN BARRIER, 2720 01:45:16,105 --> 01:45:20,543 PROBABLY 1 PART IN A THOUSAND OR 2721 01:45:20,543 --> 01:45:22,045 SO, GETS ACROSS OF NORMAL ASPECT 2722 01:45:22,045 --> 01:45:23,713 BODIES, THERE ARE NORMAL 2723 01:45:23,713 --> 01:45:24,981 TECHNOLOGIES TWEPPED TO TRY TO 2724 01:45:24,981 --> 01:45:27,183 INCREASE THAT USING SHUTTLE 2725 01:45:27,183 --> 01:45:29,886 SYSTEMS FOR EXAMPLE, REALLY SORT 2726 01:45:29,886 --> 01:45:33,022 OF CLEVER, MOLECULAR TRICKS TO 2727 01:45:33,022 --> 01:45:35,158 GET INTO THE BRAIN OR TO NOT GET 2728 01:45:35,158 --> 01:45:36,392 SHUTTLED OUT OF THE BRAIN BUT 2729 01:45:36,392 --> 01:45:40,730 THAT ALSO IS AN EARLY STAGES 2730 01:45:40,730 --> 01:45:43,199 MUCH SO IDEALLY I THINK FOR MUCH 2731 01:45:43,199 --> 01:45:45,301 OF WHAT IS BEING DONE IN THE 2732 01:45:45,301 --> 01:45:46,436 BRAIN, SMALL MOLECULES WHICH CAN 2733 01:45:46,436 --> 01:45:47,837 GET ACROSS THE BLOOD BRAIN 2734 01:45:47,837 --> 01:45:49,338 BARRIER OR EVEN CELL THERAPY 2735 01:45:49,338 --> 01:45:51,674 BECAUSE CELLS CAN GET INTO THE 2736 01:45:51,674 --> 01:45:54,710 BRAIN, THROUGH VARIOUS 2737 01:45:54,710 --> 01:45:57,346 MECHANISMS, MAY PROVE MORE 2738 01:45:57,346 --> 01:46:00,083 PROMISING BUT NONETHELESS, IT'S 2739 01:46:00,083 --> 01:46:02,318 BEEN SURPRISING THAT ANTIBODIES, 2740 01:46:02,318 --> 01:46:05,521 EVEN IF THEY DON'T GET IN MUCH 2741 01:46:05,521 --> 01:46:06,422 CAN SOMETIMES HAVE EFFICACY AND 2742 01:46:06,422 --> 01:46:08,057 I THINK WE ARE GOING TO LEARN A 2743 01:46:08,057 --> 01:46:13,162 LOT MORE ABOUT THAT AS THESE NEW 2744 01:46:13,162 --> 01:46:14,764 BI-SPECIFIC ANTIBODIES ARE BEING 2745 01:46:14,764 --> 01:46:15,031 DEVELOPED. 2746 01:46:15,031 --> 01:46:16,866 >> AND MAYBE JUST TO FOLLOW UP A 2747 01:46:16,866 --> 01:46:18,501 LITTLE BIT ON THIS THOUGHT WITH 2748 01:46:18,501 --> 01:46:25,441 REGARD TO POSSIBLE CONNECTIONS 2749 01:46:25,441 --> 01:46:28,077 BETWEEN B-CELL TARGETING AND 2750 01:46:28,077 --> 01:46:30,880 MICROGLIAL OR MYELOID TARGETING, 2751 01:46:30,880 --> 01:46:35,551 WHAT EXACTLY FOR PLASMA CELLS, 2752 01:46:35,551 --> 01:46:38,321 WHAT ARE THE B-CELLS DOING WHY 2753 01:46:38,321 --> 01:46:40,723 ARE THEY THE BAD GUYS IN THIS 2754 01:46:40,723 --> 01:46:42,892 AND THERE'S BENEFIT IN KNOCKING 2755 01:46:42,892 --> 01:46:43,659 THEM OFF? 2756 01:46:43,659 --> 01:46:47,697 >> YEAH, I MEAN B-CELLS HAVE 2757 01:46:47,697 --> 01:46:49,432 MANY FUNCTIONS. 2758 01:46:49,432 --> 01:46:50,466 THE ANTIBODY PRODUCTION FUNCTION 2759 01:46:50,466 --> 01:46:52,068 EVEN THOUGH YOU KNOW WE DO SEE 2760 01:46:52,068 --> 01:46:53,236 ANTIBODIES IN THE SPINAL FLUID 2761 01:46:53,236 --> 01:46:55,238 WHEN WE TEST THIS, 1 OF THE 2762 01:46:55,238 --> 01:46:57,306 TESTS WE USE FOR MULTIPLE 2763 01:46:57,306 --> 01:47:00,710 SCLEROSIS, IT'S PROBABLY NOT THE 2764 01:47:00,710 --> 01:47:01,744 ANTIBODIES, THERE'S SOME DEBATE 2765 01:47:01,744 --> 01:47:02,945 BUT IT'S PROBABLY NOT THE 2766 01:47:02,945 --> 01:47:07,650 ANTIBODIES THAT ARE THE MAJOR 2767 01:47:07,650 --> 01:47:10,720 CAUSE OF THE MS DISEASE, BUT 2768 01:47:10,720 --> 01:47:13,189 B-CELLS HAVE OTHER FUNCTIONS. 2769 01:47:13,189 --> 01:47:15,725 THEY CAN FUNCTION FOR EXAMPLE, 2770 01:47:15,725 --> 01:47:16,792 AS ANTIGEN PRESENTING CELLS 2771 01:47:16,792 --> 01:47:19,428 WHERE THEY CAN TAKE PROTEINS AND 2772 01:47:19,428 --> 01:47:21,430 SHOW THEM TO OTHER CELLS OF THE 2773 01:47:21,430 --> 01:47:24,233 IMMUNE SYSTEM THAT MAY CAUSE 2774 01:47:24,233 --> 01:47:27,670 DAMAGE, THEY CAN FUNCTION IN 2775 01:47:27,670 --> 01:47:29,539 WORKING WITH OTHER IMMUNE CELLS 2776 01:47:29,539 --> 01:47:31,140 INCLUDING T-CELLS WHICH FOR MANY 2777 01:47:31,140 --> 01:47:33,009 YEARS, PEOPLE HAVE OCCURRED THE 2778 01:47:33,009 --> 01:47:35,978 MAJOR CELL TYPE INVOLVED IN 2779 01:47:35,978 --> 01:47:38,281 MULTIPLE SCLEROSIS, SO B-CELLS 2780 01:47:38,281 --> 01:47:40,816 CAN GIVE HELP TO T-CELLS IN 2781 01:47:40,816 --> 01:47:42,318 CARRYING OUT THE AUTOIMMUNE 2782 01:47:42,318 --> 01:47:43,920 ATTACK AND B-CELLS 2783 01:47:43,920 --> 01:47:44,587 INTERESTINGLY, AND IMPORTANTLY 2784 01:47:44,587 --> 01:47:47,957 ARE, YOU KNOW THE TARGET 2785 01:47:47,957 --> 01:47:50,193 EPI-BLAST STEIN BARRE VIRUS 2786 01:47:50,193 --> 01:47:52,161 WHICH IS A VERY COMMON, IT WAS 2787 01:47:52,161 --> 01:47:54,096 MENTIONED IN THE DOCTOR'S 2788 01:47:54,096 --> 01:47:58,501 PRESENTATION, A VERY COMMON 2789 01:47:58,501 --> 01:48:00,369 VIRUS TYPE OF HERPES VIRUS THAT 2790 01:48:00,369 --> 01:48:03,039 IS THE CAUSE OF MONONUCLEOSIS 2791 01:48:03,039 --> 01:48:06,442 AND EVEN THOUGH IT AFFECTS -- 2792 01:48:06,442 --> 01:48:10,279 INFECTS 90% OR MORE OF PEOPLE, 2793 01:48:10,279 --> 01:48:12,815 IT VERY, VERY FEW PEOPLE IF ANY 2794 01:48:12,815 --> 01:48:14,750 WHO HAVE MULTIPLE SCLEROSIS HAVE 2795 01:48:14,750 --> 01:48:17,186 BEEN UNINFECTED BY IT SO THERE'S 2796 01:48:17,186 --> 01:48:18,321 A STRONG EPIDEMIOLOGICAL 2797 01:48:18,321 --> 01:48:20,656 ASSOCIATION BETWEEN THE 2 2798 01:48:20,656 --> 01:48:22,525 MR. CHACON MENTIONED THAT HE 2799 01:48:22,525 --> 01:48:24,060 THINKS HE HAD MONONUCLEOSEIS AND 2800 01:48:24,060 --> 01:48:26,829 WE GET THAT HISTORY MOST OF THE 2801 01:48:26,829 --> 01:48:34,203 TIME AND IT MAY BE THAT THE 2802 01:48:34,203 --> 01:48:35,705 B-CELL INFECTION BY THE VIRUS IS 2803 01:48:35,705 --> 01:48:38,140 1 OF THE REASONS WHY B-CELL 2804 01:48:38,140 --> 01:48:40,409 THERAPY IS EFFECTIVE IN THIS 2805 01:48:40,409 --> 01:48:41,177 DISEASE NYES AND ACTUALLY ALONG 2806 01:48:41,177 --> 01:48:46,816 THE LINE OF THE EBV, 1 OF OUR 2807 01:48:46,816 --> 01:48:48,551 MEMBERS OF THE AUDIENCE ASKS THE 2808 01:48:48,551 --> 01:48:51,320 QUESTION WHETHER IT COULD BE 2809 01:48:51,320 --> 01:48:53,556 THAT MONONUCLEOSIS VIRAL 2810 01:48:53,556 --> 01:48:54,523 INFECTION WHICH MIMICS GLIAL 2811 01:48:54,523 --> 01:48:57,026 CELLS AND CAUSES AN AUTOIMMUNE 2812 01:48:57,026 --> 01:48:59,262 RESPONSE AGAINST THE MYELIN 2813 01:48:59,262 --> 01:49:01,330 SHEATH COULD BE HIDING IN THE 2814 01:49:01,330 --> 01:49:02,431 IMMUNE RESPONSE AND EVEN THOUGH 2815 01:49:02,431 --> 01:49:03,966 THE SYMPTOMS OF THE VIRUS ARE 2816 01:49:03,966 --> 01:49:07,436 GONE, THE VIRUS COULD PERSIST IN 2817 01:49:07,436 --> 01:49:11,741 THE BRAIN AND BE THE TARGET OF 2818 01:49:11,741 --> 01:49:12,908 IMMUNE ACTIVITY. 2819 01:49:12,908 --> 01:49:14,910 >> WELL THIS IS 1 OF THE RAGING 2820 01:49:14,910 --> 01:49:19,815 DEBATES AND I WOULD SAY EVERY 2821 01:49:19,815 --> 01:49:21,484 CONFERENCE WE GO TO THIS IS 1 OF 2822 01:49:21,484 --> 01:49:24,186 THE -- 1 OF THE QUESTIONS THAT 2823 01:49:24,186 --> 01:49:27,790 PEOPLE SEPARATE INTO THEIR CAMPS 2824 01:49:27,790 --> 01:49:28,858 ABOUT WHETHER THAT'S THE CASE OR 2825 01:49:28,858 --> 01:49:38,401 NOT, THERE ARE PEOPLE WHO HAVE 2826 01:49:38,401 --> 01:49:39,201 REPORTED EPSTEIN BARRE VIRUS 2827 01:49:39,201 --> 01:49:40,936 WHEN THEY LOOK IN THE BRAIN, NO 2828 01:49:40,936 --> 01:49:42,104 MATTER HOW HARD THEY LOOK, THERE 2829 01:49:42,104 --> 01:49:44,073 ARE PEOPLE WHO DESCRIBED NORMAL 2830 01:49:44,073 --> 01:49:46,942 PROEN TEES OF THE BRAIN THAT 2831 01:49:46,942 --> 01:49:49,712 LOOK LIKE OR MIMIC EPSTEIN BARRE 2832 01:49:49,712 --> 01:49:52,748 VIRUS PROTEINS AND THAT'S AN 2833 01:49:52,748 --> 01:49:54,050 EASY TO UNDERSTAND WAY IN WHICH 2834 01:49:54,050 --> 01:49:59,188 THE IMMUNE SYSTEM MAY BE TRICKED 2835 01:49:59,188 --> 01:50:00,856 INTO ATTACKING THE BRAIN BUT 2836 01:50:00,856 --> 01:50:02,358 WHILE THESE FINDINGS -- YOU YOU 2837 01:50:02,358 --> 01:50:03,993 CAN COME UP WITH THEM IN A 2838 01:50:03,993 --> 01:50:06,929 HANDFUL OR 1 OR ANOTHER, THEY 2839 01:50:06,929 --> 01:50:08,130 DON'T REALLY TWHAI HAVEN'T BEEN 2840 01:50:08,130 --> 01:50:09,165 CONVINCING IN THAT IS THAT A 2841 01:50:09,165 --> 01:50:17,173 SORT OF EXPLAIN ALL OF THE 2842 01:50:17,173 --> 01:50:18,908 SCREKS OF SYMPTOMS AND ALL THE 2843 01:50:18,908 --> 01:50:20,209 EPIDEMIOLOGY OF THE DISEASE AND 2844 01:50:20,209 --> 01:50:24,046 EVERYTHING YOU WILL LIKE TO SEE 2845 01:50:24,046 --> 01:50:29,185 FOR EXAMPLE, YOU KNOW THAT STORY 2846 01:50:29,185 --> 01:50:30,119 IS TANTALIZING, YOU KNOW THERE'S 2847 01:50:30,119 --> 01:50:35,358 A LOT OF PEOPLE WHO BELIEVE THAT 2848 01:50:35,358 --> 01:50:37,426 PREVENTING EPSTEEN BARRE VIRUS 2849 01:50:37,426 --> 01:50:39,061 WITH A VACCINE MAY PREVENT MS 2850 01:50:39,061 --> 01:50:40,162 FROM OCCURRING IN THE FIRST 2851 01:50:40,162 --> 01:50:42,064 PLACE, YOU WOULD HAVE TO 2852 01:50:42,064 --> 01:50:42,798 VACCINATE CHILDREN IN ORDER TO 2853 01:50:42,798 --> 01:50:48,604 DO THAT AND SO, SPECIAL THAT 2854 01:50:48,604 --> 01:50:52,508 RAISES ALL SORTS OF QUESTIONS OF 2855 01:50:52,508 --> 01:50:56,812 COURSE AND ALSO THE EPSTEIN 2856 01:50:56,812 --> 01:50:58,013 BARRE VIRUS IS 1 WE'VE LIVED 2857 01:50:58,013 --> 01:50:59,749 WITH AS A SPECIES FOR SUCH A 2858 01:50:59,749 --> 01:51:01,317 LONG TIME AND YOU NEVER KNOW 2859 01:51:01,317 --> 01:51:04,653 WHEN YOU ELIMINATE A VIRUS WHAT 2860 01:51:04,653 --> 01:51:08,023 THE UNXEBTED, UNTOURED EFFECTS 2861 01:51:08,023 --> 01:51:08,557 MIGHT BE. 2862 01:51:08,557 --> 01:51:10,226 SO THIS A RAGING DEBATE IN THE 2863 01:51:10,226 --> 01:51:11,460 FIELD. 2864 01:51:11,460 --> 01:51:12,628 I DON'T KNOW WHETHER THE DOCTOR 2865 01:51:12,628 --> 01:51:14,797 HAS SOMETHING TO ADD TO THAT? 2866 01:51:14,797 --> 01:51:18,801 >> I AGREE WITH THAT, I VACCINE 2867 01:51:18,801 --> 01:51:20,336 COULD POTENTIALLY PREVENT OTHER 2868 01:51:20,336 --> 01:51:22,805 DISEE DISEASES THAT MAY BE 2869 01:51:22,805 --> 01:51:24,740 ASSOCIATE WIDE EPSTEIN BARRE, 2870 01:51:24,740 --> 01:51:26,442 NOT ONLY MS. 2871 01:51:26,442 --> 01:51:29,512 >> OKAY, SO, NOW, ANOTHER OF OUR 2872 01:51:29,512 --> 01:51:33,783 AUDIENCE IS ASKING THE QUESTION 2873 01:51:33,783 --> 01:51:35,451 OZ TO WHETHER ARTERIES ARE ALSO 2874 01:51:35,451 --> 01:51:41,157 INVOLVED IN THE MS BRAIN OR IS 2875 01:51:41,157 --> 01:51:48,531 THE PRIMARY LOCUST THE VEINS? 2876 01:51:48,531 --> 01:51:49,865 >> SO LESIONS DEVELOP 2877 01:51:49,865 --> 01:51:52,735 SURROUNDING VEINS IN THE 2878 01:51:52,735 --> 01:51:53,903 PERIVASCULAR SPACE, WHEREAS THE 2879 01:51:53,903 --> 01:51:55,938 ACCUMULATION OF CELLS AND IN THE 2880 01:51:55,938 --> 01:52:00,976 BLOOD BRAIN BARRIER AND THE 2881 01:52:00,976 --> 01:52:03,512 MELINNATION OCCURS AND CYTOKINES 2882 01:52:03,512 --> 01:52:05,948 AND CHEMOKINES ARE GENERATED AND 2883 01:52:05,948 --> 01:52:06,749 THERE'S OPENING OF THE 2884 01:52:06,749 --> 01:52:08,184 CAPILLARIES WITHIN THE LESION SO 2885 01:52:08,184 --> 01:52:09,919 OF COURSE THERE IS A OPENING OF 2886 01:52:09,919 --> 01:52:12,021 THE BLOOD BRAIN BIRRIER 2887 01:52:12,021 --> 01:52:12,822 SURFACESSIER THAT IMPAIRS 2888 01:52:12,822 --> 01:52:13,789 CAPILLARIES BUT THE MAIN 2889 01:52:13,789 --> 01:52:15,391 STRUCTURE THAT IS IMPAIRED IS 2890 01:52:15,391 --> 01:52:18,027 THE VEIN SO IT'S A CENTRAL VEIN. 2891 01:52:18,027 --> 01:52:19,595 YOU NOT ONLY SEE THAT IN WHITE 2892 01:52:19,595 --> 01:52:21,197 MATTER LESIONS BUT WE ARE ALSO 2893 01:52:21,197 --> 01:52:28,337 FINDING THE SAME THING IN 2894 01:52:28,337 --> 01:52:34,343 CORTICALE LESIONS AND WE HAVE 2895 01:52:34,343 --> 01:52:35,878 SOME MODELS SHOWING THIS LESION 2896 01:52:35,878 --> 01:52:37,279 DEVELOPMENT, MAYBE I CAN ADD 1 2897 01:52:37,279 --> 01:52:44,553 PIECE TO THAT, YOU KNOW THE 2898 01:52:44,553 --> 01:52:45,955 BRAIN HAS EVOLVED WAYS OF 2899 01:52:45,955 --> 01:52:47,923 PROTECTING ITSELF IS THAT'S CALL 2900 01:52:47,923 --> 01:52:48,958 IMMUNE SURVEILLANCE BECAUSE THE 2901 01:52:48,958 --> 01:52:50,292 IMMUNE SYSTEM HAS TO KNOW NOT TO 2902 01:52:50,292 --> 01:52:52,795 COME INTO THE BRAIN AND THAT 2903 01:52:52,795 --> 01:52:56,832 HAPPENS IN THE MENNEGES AND 2904 01:52:56,832 --> 01:53:00,302 SURROUNDING SPACES OF THE BRAIN 2905 01:53:00,302 --> 01:53:01,170 AND AROUND SMALL VEINS AND 2906 01:53:01,170 --> 01:53:02,471 THAT'S WHERE THE CELLS OF THE 2907 01:53:02,471 --> 01:53:04,206 IMMUNE SYSTEM HAD THE ABILITY TO 2908 01:53:04,206 --> 01:53:06,509 TRAFFIC AND IN AND OUT OF THE 2909 01:53:06,509 --> 01:53:07,776 BLOOD VESSELS AND SAMPLE THE 2910 01:53:07,776 --> 01:53:10,179 BRAIN AND IN NORMAL 2911 01:53:10,179 --> 01:53:10,646 CIRCUMSTANCES, HEALTHY 2912 01:53:10,646 --> 01:53:11,881 CIRCUMSTANCES TO GET USED TO 2913 01:53:11,881 --> 01:53:14,717 THEM SO THAT THEY DON'T ARK TACK 2914 01:53:14,717 --> 01:53:17,286 THE BRAIN AND THAT'S WHERE IT 2915 01:53:17,286 --> 01:53:19,755 HAPPENS AROUND VEINS BUT IT'S 2916 01:53:19,755 --> 01:53:21,624 VERY UNUSUAL AND YOU KNOW YOU'RE 2917 01:53:21,624 --> 01:53:25,127 A RHEUMATOLOGIST SO YOU CAN -- 2918 01:53:25,127 --> 01:53:27,029 YOU CAN TALK ABOUT THIS AS WELL 2919 01:53:27,029 --> 01:53:31,901 BUT I THINK IT'S RELATIVELY 2920 01:53:31,901 --> 01:53:33,168 UNUSUAL AMONG BLOOD VESSEL 2921 01:53:33,168 --> 01:53:35,337 DISEASES TO HAVE THIS PHENOMENON 2922 01:53:35,337 --> 01:53:36,972 OF THE VEIN BEING THE MAIN 2923 01:53:36,972 --> 01:53:37,172 PLACE. 2924 01:53:37,172 --> 01:53:40,409 MOST OF THE TIME WE ARE TALKING 2925 01:53:40,409 --> 01:53:42,378 AROUND SMALL ARTERIES, 2926 01:53:42,378 --> 01:53:44,113 INFLAMMATION AROUND SMALL 2927 01:53:44,113 --> 01:53:45,080 ARTERIES VASCULITIS, ET CETERA, 2928 01:53:45,080 --> 01:53:48,817 AND WE DO SEE THAT IN THE BRAIN 2929 01:53:48,817 --> 01:53:50,586 AND CLINICALLY IT LOOKS 2930 01:53:50,586 --> 01:53:53,022 DIFFERENT AND CLINICALLY IT 2931 01:53:53,022 --> 01:53:53,923 LOOKS DIFFERENT AS WELL. 2932 01:53:53,923 --> 01:53:58,227 SO MS DOESN'T APPEAR TO DIRECTLY 2933 01:53:58,227 --> 01:54:00,396 AFFECT THE ARTERIES ALTHOUGH WE 2934 01:54:00,396 --> 01:54:02,231 DO KNOW -- WE DO KNOW THAT 2935 01:54:02,231 --> 01:54:05,000 PEOPLE WHO HAVE OTHER DISEASES 2936 01:54:05,000 --> 01:54:06,135 FOR EXAMPLE, HYPERTENSION, HIGH 2937 01:54:06,135 --> 01:54:07,736 BLOOD PRESSURE, DIABETES THAT DO 2938 01:54:07,736 --> 01:54:08,804 AFFECT THE ARTERIES WHEN YOU 2939 01:54:08,804 --> 01:54:10,139 HAVE THAT IN THE SAME PERSON 2940 01:54:10,139 --> 01:54:12,741 WITH MS, THINGS GOT A LOT WORSE. 2941 01:54:12,741 --> 01:54:14,443 AND WE CAN SOMETIMES SEE WHEN WE 2942 01:54:14,443 --> 01:54:19,615 LOOK AT THE MRI SCANS, SPACES 2943 01:54:19,615 --> 01:54:23,686 AROUND THE ARTERIES WHICH ARE 2944 01:54:23,686 --> 01:54:26,155 NORMALLY SPACES FOR FLUID FLOW 2945 01:54:26,155 --> 01:54:28,457 AND WITHIN THE BRAIN CAN GET 2946 01:54:28,457 --> 01:54:30,492 QUITE BIG. 2947 01:54:30,492 --> 01:54:34,697 THOSE ARE CALLED PERIVASCULAR 2948 01:54:34,697 --> 01:54:36,198 SPACES AND WE AND OTHERS ARE 2949 01:54:36,198 --> 01:54:37,666 INVESTIGATING THE ROLE OF THAT 2950 01:54:37,666 --> 01:54:39,401 BECAUSE IT DOES SEEM TO BE 2951 01:54:39,401 --> 01:54:41,236 SOMETHING GOING ON AROUND THE 2952 01:54:41,236 --> 01:54:43,138 ARTERIES, TOO BUT THE PRIMARY 2953 01:54:43,138 --> 01:54:45,774 IMMUNE ATTACK IS CLEARLY AROUND 2954 01:54:45,774 --> 01:54:46,008 VEINS. 2955 01:54:46,008 --> 01:54:47,076 >> ALL RIGHT, SO MAYBE JUST 2956 01:54:47,076 --> 01:54:49,578 FOLLOWING A LITTLE BIT ON THIS 2957 01:54:49,578 --> 01:54:51,413 CONCEPT OF CELLS GETTING INTO 2958 01:54:51,413 --> 01:54:55,084 THE BRAIN, SO OF COURSE, 1 OF 2959 01:54:55,084 --> 01:54:56,118 THE TOPICS THAT'S OF GREAT 2960 01:54:56,118 --> 01:54:58,253 INTEREST IN THE WORLD OF 2961 01:54:58,253 --> 01:54:59,989 RHEUMATOLOGY BUT NOW, EVEN IN 2962 01:54:59,989 --> 01:55:02,858 THE -- I THINK THE WORLD OF MS, 2963 01:55:02,858 --> 01:55:06,428 IS THE WHOLE IDEA OF CAR T-CELLS 2964 01:55:06,428 --> 01:55:09,031 AS A POSSIBLE TREATMENT. 2965 01:55:09,031 --> 01:55:11,133 WOULD YOU WANT TO COMMENT AT ALL 2966 01:55:11,133 --> 01:55:12,868 ON CAR T-CELLS AND AT LEAST 2967 01:55:12,868 --> 01:55:15,771 RIGHT NOW WHAT'S THE REPORT CARD 2968 01:55:15,771 --> 01:55:20,042 ON CAR T-CELLS? 2969 01:55:20,042 --> 01:55:21,877 >> WELL, VERY EXCITING BECAUSE 2970 01:55:21,877 --> 01:55:23,812 YOU CAN MAKE CAR T-CELLS AND 2971 01:55:23,812 --> 01:55:26,181 DIRECT THEM FOR EXAMPLE AGAINST 2972 01:55:26,181 --> 01:55:27,483 B-CELLS THIS THAT'S THE MOST 2973 01:55:27,483 --> 01:55:29,018 COMMON THING THAT'S BEING DONE 2974 01:55:29,018 --> 01:55:31,854 NOW AND TESTED IN AUTOIMMUNE 2975 01:55:31,854 --> 01:55:32,221 DISEASE. 2976 01:55:32,221 --> 01:55:38,327 YOU KNOW WE TALKED ABOUT OCREVIA 2977 01:55:38,327 --> 01:55:40,295 AS AN ANTIBODY TARGETING CD20 2978 01:55:40,295 --> 01:55:42,665 WHICH IS A PROTEINOT SURFACE OF 2979 01:55:42,665 --> 01:55:44,500 THE B-CELLS, THERE'S ANOTHER 2980 01:55:44,500 --> 01:55:46,835 PROTEIN CALLED CD19 WHICH IS ON 2981 01:55:46,835 --> 01:55:48,804 A WIDER SPECTRUM OF B-CELLS IN 2982 01:55:48,804 --> 01:55:52,474 CD20 AND THERE ARE LOTS AND LOTS 2983 01:55:52,474 --> 01:55:55,444 OF COMPANIES, ARE DEVELOPING CAR 2984 01:55:55,444 --> 01:55:56,712 T-CELLS ENGINEERED T-CELLS THAT 2985 01:55:56,712 --> 01:55:58,647 CAN ATTACK THE CELLS THAT HAVE 2986 01:55:58,647 --> 01:56:00,315 CD19 ON THEM AND HOPEFULLY, THE 2987 01:56:00,315 --> 01:56:01,717 IDEA IS THAT THEY WOULD BE ABLE 2988 01:56:01,717 --> 01:56:03,652 TO HAVE THE IMPACT NOT JUST IN 2989 01:56:03,652 --> 01:56:04,453 THE PERIPHERY, IN THE BLOOD 2990 01:56:04,453 --> 01:56:05,854 STREAM AND THE PERIPHERAL IMMUNE 2991 01:56:05,854 --> 01:56:07,856 SYSTEM BUT ALSO TO GET INTO THE 2992 01:56:07,856 --> 01:56:09,591 BRAIN BECAUSE T-CELLS CAN GET 2993 01:56:09,591 --> 01:56:12,695 INTO THE BRAIN AND ATTACK 2994 01:56:12,695 --> 01:56:14,296 WHATEVER B-CELLS MAY STILL BE 2995 01:56:14,296 --> 01:56:15,931 PRESENT AROUND THE EDGES OF 2996 01:56:15,931 --> 01:56:16,765 THESE CHRONIC ACTIVE LESIONS 2997 01:56:16,765 --> 01:56:20,135 WHICH WE DO SEE, OR IN THE 2998 01:56:20,135 --> 01:56:22,738 MENENG ES, IN THE SURROUNDING 2999 01:56:22,738 --> 01:56:24,907 AND TO PROPAGATE INFLAMMATION SO 3000 01:56:24,907 --> 01:56:26,508 I THINK VERY LITTLE HAS BEEN 3001 01:56:26,508 --> 01:56:26,875 DONE. 3002 01:56:26,875 --> 01:56:28,410 THERE ARE A FEW CASE REPORTS 3003 01:56:28,410 --> 01:56:30,379 HERE AND THERE, THERE ARE SAFETY 3004 01:56:30,379 --> 01:56:31,914 CONCERNS WITH T-CELLS, YOU KNOW 3005 01:56:31,914 --> 01:56:33,215 CAR T-CELLS HAVE MOSTLY BEEN 3006 01:56:33,215 --> 01:56:36,785 USED IN CANCER WHERE THE 3007 01:56:36,785 --> 01:56:38,053 TOLERANCE FOR AN ADVERSE EVENT 3008 01:56:38,053 --> 01:56:39,822 MAY BE DIFFERENT THAN IN 3009 01:56:39,822 --> 01:56:41,423 MULTIPLE SCLEROSIS WHERE PEOPLE, 3010 01:56:41,423 --> 01:56:45,027 FOR EXAMPLE, MR. CHACON WHO ARE 3011 01:56:45,027 --> 01:56:45,861 FORTUNATELY DOING REALLY WELL 3012 01:56:45,861 --> 01:56:46,862 WITH THE DISEASE, YOU DON'T WANT 3013 01:56:46,862 --> 01:56:48,864 TO PUT THEM AT RISK. 3014 01:56:48,864 --> 01:56:55,237 SO WE'RE AT VERY EARLY STEAJS. . 3015 01:56:55,237 --> 01:56:57,306 THERE ARE OTHERS THAT ARE 3016 01:56:57,306 --> 01:56:58,307 DEVELOPED, SPECIALIZED T-CELLS 3017 01:56:58,307 --> 01:56:59,975 THAT CAN QUELL INFLAMMATION AND 3018 01:56:59,975 --> 01:57:02,444 MAYBE CONTRIBUTE TO REPAIR. 3019 01:57:02,444 --> 01:57:05,748 AND THERE ARE ALSO COMPANIES 3020 01:57:05,748 --> 01:57:07,015 THAT ACADEMIC INSTITUTIONS THAT 3021 01:57:07,015 --> 01:57:08,350 ARE DEVELOPING THOSE KINDS OF 3022 01:57:08,350 --> 01:57:09,485 APPROACHES AS WELL AND WE DON'T 3023 01:57:09,485 --> 01:57:15,023 KNOW WHAT WILL BE BETTER BUT 3024 01:57:15,023 --> 01:57:16,358 IT'S VERY EXCITING. 3025 01:57:16,358 --> 01:57:17,593 >> YES, INDEED, IT APPEARS WE 3026 01:57:17,593 --> 01:57:19,561 ARE GETTING CLOSE TO THE END OF 3027 01:57:19,561 --> 01:57:19,828 OUR TIME. 3028 01:57:19,828 --> 01:57:24,166 WE'RE JUST 2 MINUTES AWAY FROM 3029 01:57:24,166 --> 01:57:24,867 OUR TIME LIMIT. 3030 01:57:24,867 --> 01:57:26,368 SO AT THIS POINT I THINK I WOULD 3031 01:57:26,368 --> 01:57:28,437 LIKE TO JUST THANK THE BOTH OF 3032 01:57:28,437 --> 01:57:31,406 YOU FOR A REALLY WONDERFUL 3033 01:57:31,406 --> 01:57:36,145 PRESENTATIONS AND TO OUR PATIENT 3034 01:57:36,145 --> 01:57:39,448 WHO REALLY HAS PUT TOTALLY 3035 01:57:39,448 --> 01:57:43,585 IMPORTANT HUMAN FACE ON WHAT'S 3036 01:57:43,585 --> 01:57:45,020 GOING ON HERE AND CERTAINLY 3037 01:57:45,020 --> 01:57:46,522 GIVES AUSA LOT TO THINK ABOUT. 3038 01:57:46,522 --> 01:57:48,457 CERTAINLY WE'RE IN A SITUATION 3039 01:57:48,457 --> 01:57:50,325 IN WHICH AN ENORMOUS AMOUNT HAS 3040 01:57:50,325 --> 01:57:52,928 BEEN DONE AND CERTAINLY A LOT OF 3041 01:57:52,928 --> 01:57:55,264 IT OWING TO STUDIES THAT WERE 3042 01:57:55,264 --> 01:57:57,432 DONE IN THE NIH CLINICAL CENTER 3043 01:57:57,432 --> 01:57:59,902 AND CLEARLY THERE'S A WHOLE NEW 3044 01:57:59,902 --> 01:58:03,238 CHAPTER YET TO BE WRITTEN WHICH 3045 01:58:03,238 --> 01:58:05,407 AGAIN IS BASED ON A LOT OF TOOLS 3046 01:58:05,407 --> 01:58:08,744 THAT HAVE BEEN DEVELOPED IN THE 3047 01:58:08,744 --> 01:58:10,479 NIH CLINICAL CENTER AND STUDIES 3048 01:58:10,479 --> 01:58:12,614 THAT ARE ONGOING. 3049 01:58:12,614 --> 01:58:16,552 AND SO, WE'RE REALLY EXCITED BY 3050 01:58:16,552 --> 01:58:18,887 ALL THIS AND LOOKING FORWARD TO 3051 01:58:18,887 --> 01:58:22,891 THE NEXT ADVANCES IN THE STUDY 3052 01:58:22,891 --> 01:58:25,060 OF AND TREATMENT OF MS. 3053 01:58:25,060 --> 01:58:27,663 SO ANYWAY, THANK YOU BOTH VERY 3054 01:58:27,663 --> 01:58:29,998 MUCH AND THANK OUR PATIENT AS 3055 01:58:29,998 --> 01:58:30,232 WELL. 3056 01:58:30,232 --> 01:58:32,801 >> THANK YOU FOR INVITING US AND 3057 01:58:32,801 --> 01:58:34,536 HOPEFULLY WE CAN COME BACK 3058 01:58:34,536 --> 01:58:35,804 SOMETIME AND REPORT ON MORE 3059 01:58:35,804 --> 01:58:38,574 PROGRESS IN THE FUTURE. 3060 01:58:38,574 --> 01:58:38,874 >> BRAVO. 3061 01:58:38,874 --> 01:58:40,342 >> YES INDEED. 3062 01:58:40,342 --> 01:58:42,177 >> THANK YOU AND WE WILL CALL IT 3063 01:58:42,177 --> 01:58:44,479 TO A CLOSE THEN AND WE WILL LOOK 3064 01:58:44,479 --> 01:58:47,316 FORWARD TO SEEING EVERYONE TO 3065 01:58:47,316 --> 01:58:50,719 TALK ABOUT NUTRIFILL NETS NEXT 3066 01:58:50,719 --> 01:58:50,919 WEEK. 3067 01:58:50,919 --> 01:58:54,056 SO IN ANY CASE, THANK YOU AGAIN 3068 01:58:54,056 --> 01:58:59,027 AND HAVE A GOOD AFTERNOON TO 3069 01:58:59,027 --> 01:59:09,204 EVERYONE.