>> GOOD MORNING, EVERYONE.
HELLO.
WELCOME TO THE RARE DISEASE DAY.
WE'RE MEERA AND AINSLIE HAVE
BEEN PLANNING THE EVENT WITH A
BIG TEAM.
WE'RE WITH THE DIVERSION OF RARE
DISEASES INNOVATION RESEARCH.
WE'RE LOCATED WITHIN THE
NATIONAL CENTER OF
TRANSLATIONAL -- ADVANCING
TRANSLATIONAL SCIENCES OR NCATS
AT THE NIH.
FOR THOSE WHO NEED CLOSED
CAPTIONING YOU CAN TOGGLE THE
OPTION ON THE NIH VIDEOCAST OR
EVENT APP.
FOR THOSE IN PERSON YOU CAN VIEW
LIVE CAPTIONING GOING TO THE
LINK OR SCANNING THE QR CODE AND
ENTERING THE EVENT CODE RDD2024.
IF YOU HAVE ADDITIONAL QUESTIONS
STAFF CAN ANSWER QUESTIONS.
WE WOULD LIKE TO THANK ALL OUR
PARTNERS IN PLANNING THIS YEAR'S
PLANNING COMMITTEE INCLUDED
REPRESENTATIVES FROM MANY
DIVISIONS AND OFFICES ALL OVER
NCATS AS WELL AS CO-SPONSORS
FROM THE NIH CLINICAL CENTER AND
NIAA, NINDS, THE FDA, CHILDREN'S
INN AT NIH, EVERY REACH FOR RARE
DISEASES.
WE HAVE MORE THAN 200
REGISTRANTS IN PERSON AND
VIRTUAL FROM ALL OVER THE WORLD.
WE'RE EXCITED TO BRING YOU AN
AWESOME LINEUP OF SPEAKERS AND
PATIENT STORIES FOR TODAY'S
EVENT.
WE'LL GO THROUGH A FEW LOGISTICS
TOE HELP NAVIGATE YOUR DAY.
THE MAIN AGENDA WILL TAKE PLACE
IN THIS AUDITORIUM AND CAN BE
VIEWED IN THE LOWER LEVEL
CONFERENCE CENTER OR UPPER
LEVELS BALCONIES.
WE HAVE PLENTY OF SPACE.
DO NOT STAND BY THE DOORS THE
FIRE MARSHAL WILL COME AND
FILMING AND PHOTOGRAPHY IS
TAKING PLACE SO IF YOU DO NOT
WISH TO BE PHOTOGRAPHED CHECK IN
AT THE DESK.
WE HAVE OVERFLOW ROOMS SET UP
FOR NETWORKING OR IF YOU FEEL
MORE RFRTABLE VIEWING THE EVENT
FROM THERE.
ROOMS ABD, G AND F2 ARE SET UP
FOR THIS AND BATHROOMS AND
ELEVATORS ON THE SIDES OF BOTH
DOORS.
THIS YEAR HAS IN-PERSON VISITS
AND SCIENTIFIC POSTERS.
WE ARE HOSTING A LITTLE OVER 100
TOTAL EXHIBITS AND POSTERS WHICH
SETS A RECORD FOR RARE DISEASE
DAY AT NIH.
THE CIRCLES ON THE MAP SHOW --
WHERE THEY'RE LOCATED IN THE
UPPER LEVEL ATRIUM, LOWER LEVEL
IN ROOM EF1.
THIS YEAR WE'RE DELIGHTED TO
HAVE SPECIAL ART EXHIBITIONS TO
VISIT IN PERSON AT NATUR AND
THEY'RE DISPLAYED IN ROOM C AND
RARE DISEASES CAN BE VIEWED IN
ROOM G PRESENT THE DISORDER
CHANNEL.
AS MANY REMEMBER LAST YEAR, THIS
YEAR THERE ARE SEVERAL MORE FOOD
OPTIONS AVAILABLE.
THE CONFERENCE CENTER CAFETERIA
IS OPEN FROM 10:00 A.M. TO 1:30
P.M. OFFERING FOOD AND SNACKS
AND COFFEE THROUGHOUT THE DAY.
IF YOU PRE-ORDERED A BOX LUNCH
IT WILL BE AVAILABLE AT THE
REGISTRATION DESK AT THE LOWER
LOBBY LEVEL.
NOW, WE'LL GO THROUGH A FEW
DETAILS ABOUT THIS YEAR'S EVENT
APP.
YOU CAN SEARCH FOR WEBEX IN YOUR
MOBILE APP STORE OR ENTER THE
LINK IN THE WEB BROWSER AND SIGN
USING THE E-MAIL YOU REGISTERED
FOR THE EVENT WITH.
FOR THOSE WOULD ARE REGISTERED
AND VIEWING THIS EVENT ON THE
VIDEOCAST RIGHT NOW, THE LINK TO
THE EVENT APP IS AVAILABLE IN
THE DESCRIPTION BELOW.
I'LL GO INTO DETAILS HOW TO USE
THE NAVIGATION ICONS WITHIN THE
APP.
THIS YEAR VIRTUAL ATTENDEES CAN
VIEW THE LIVE STREAM DIRECTLY
THROUGH THE EVENT APP OR THROUGH
THE WEB BROWSER OR
VIDEOCAST.NIH.gov.
CHOOSE THE MOST CONVENIENT
OPTION FOR YOU.
YOU CAN SUBMIT QUESTIONS LIVE OR
ENTER POLL QUESTIONS AND CONNECT
WITH OTHER ATTENDEES, POST ON
THE SOCIAL WALL AND POST A
VIEWING OF THE EXHIBITS AND
SCIENTIFIC CENTERS.
YOU WANTED TO SHOW PHOTOS OF THE
LIGHT UP CAMPAIGN IN OBSERVANCE
OF RARE DISEASE DISEASE.
SILVER SPRING, MARYLAND WILL BE
ILLUMINATED AND THERE'S LIGHTS
IN RECOGNITION OF RARE DISEASE
DAY.
WE'LL HAVE BUILDING 38A, ACROSS
FROM THE CONFERENCE CENTER
ILLUMINATED THROUGH MONDAY.
WE ALSO LIT UP BUILDING 1 THE
OTHER DAY TO TAKE PHOTOS.
WE WANT TO SAY A SPECIAL THANK
YOU TO JAMES TAYLOR AND NCATS
WHO LED THE COORDINATION OF THIS
INTENSE EFFORT AT NIH ALONG WITH
THE OFFICE OF RESEARCH
FACILITIES.
WE COULD NOT HAVE DONE IT
WITHOUT THEM AND WANTED TO SHARE
A SNEAK PEEK OF THE SPECTACULAR
PHOTO THEY TOOK IN SETTING UP
FOR THE LIGHTS.
MORE PROFESSIONAL PHOTOGRAPHY
WILL BE AVAILABLE SOON.
ALL ATTENDEES BOTH IN PERSON AND
VIRTUAL ARE EXPECTED TO EXERCISE
PROFESSIONALISM AND
CONSIDERATION AND RESPECT IN
YOUR SPEECH, POSTINGS AND OTHER
ACTIONS.
THANK YOU AND LET'S HAVE A GREAT
2024 EVENT.
>> NOW, WE WOULD LIKE TO
INTRODUCE JONI RUTER TO PROVIDE
WELCOMING REMARKS.
AS NCATS REMARKS SHE PRESENTS V
AND TREATMENT OF NEW SOLUTIONS
AND NCATS SUPPORTS NEW TOOLS AND
APPROACHES TO MAKE EACH STEP OF
THE TRANSLATIONAL PROCESS MORE
EFFECTIVE AND EFFICIENT.
A KEY GOAL IS TO SPEED RESEARCH
ACROSS A RANGE OF DISEASES WITH
A PARTICULAR FOCUS ON RARELIEDS
>>> OF COURSE.
VACCINATION THE SCIENCE OF
TRANSLATION, NCATS HELPS TURN
PROMISING RESEARCH DISCOVERIES
INTO REAL WORLD APPLICATIONS TO
IMPROVE PEOPLE'S HEALTH.
LET'S WELCOME DR. RUTTER TO THE
STAGE.
>> THANK YOU, BOTH.
YOU KNOW I CAN'T SEE.
I NEED TO RAISE THE PODIUM UP.
THANK YOU SO MUCH, BOTH OF YOU.
WELL, GOOD MORNING, EVERYONE.
IT'S GREAT TO SEE THOSE OF WHO
WHO ARE HERE IN PERSON AND TO
ALL ONLINE AS WELL.
I KNOW MANY ARE ONLINE ACROSS
THE NATION AND EVEN ACROSS THE
GLOBE.
THANK YOU FOR JOINING TODAY.
WELCOME TO RARE DISEASE DAY
2024.
IT'S LIKE THE ULTRA RARE DAY.
IT'S THE RAREST DAY OF THE YEAR,
THE LEAP YEAR AND THIS IS A
GREAT DAY.
SO I'M JONI RUTTER THE DIRECTOR
OF NCATS AND BEFORE I DIVE INTO
MY REMARKS LET ME TAKE EXPRESS
THE MI GRATITUDE FOR THE EFFORTS
OF AINSLIE AND MEERA AND THE
EVENT TEAM WHO THEY MENTIONED
EARLIER.
THOSE HERE TODAY, STAND UP,
PLEASE, AND TAKE NOTICE.
THIS IS AN EFFORT WITH MANY
PARTNERS AND DOESN'T GO
UNNOTICED.
IT'S SO MUCH APPRECIATED AND A
SPECIAL NOD TO AL IS CHEN OUT ON
MATERNITY LEAVE BUT IS
SYNONYMOUS WITH THE EVENT AND
MISS HER THIS YEAR BUT SHE'LL BE
BACK.
AT NCATS OUR MISSION IS TO TURN
SCIENTIFIC DISCOVERIES INTO
HEALTH SOLUTIONS FASTER.
OVER THE PAST YEAR WE HELD
NEARLY 50 ROUNDTABLE EVENTS TO
DISCUSS AND PLOT OUR COURSE FOR
OUR STRATEGIC PLAN FOR NCATS FOR
THE DECADE AHEAD.
NOW, MANY OF YOU IT'S IMPORTANT
TO NOTE MANY PARTICIPATED IN THE
ROUNDTABLE DISCUSSIONS.
WE SPECIFICALLY HELD THESE
DISCUSSIONS WITH PEOPLE WITH
RARE DISEASES, PATIENT ADVISORY
GROUPS, COMMUNITY LEADERS,
RESEARCHERS, CLINICIANS AND THE
PUBLIC.
WE WANT TO MAKE SURE THAT WE'RE
REFLECTING YOUR IDEAS, YOUR
NEEDS AND YOUR GOALS IN BRINGING
MORE TREATMENTS TO MORE PEOPLE
PERFECTLY.
IT'S IMPORTANT TO HAVE THE
VOICES AT THE TABLE WHEN
DEVELOPING STRATEGIC PLANS AT
THE HEART OF RARE DISEASE
STORIES FROM PATIENTS AND
FAMILIES GUIDE OUR SCIENTIFIC
JOURNEY AND SPUR THE MEANINGFUL
CHANGE WE NEED TO SEE.
THAT NEEDS TO HAPPEN AT THE
START, AT THE BEGINNING OF
PLANNING NOT AT THE END.
AND THE SAME GOES FOR THE
RESEARCH THAT WE DO.
THAT WILL BE A THEME YOU HEAR
TODAY.
LAST NIGHT THE BIDEN-HARRIS
ADMINISTRATION HELD A FIRST OF
ITS KIND EVENT AT THE WHITE
HOUSE SPONSORED BY THE OFFICE OF
SCIENCE AND TECHNOLOGY AND I
HEARD A CLAP AND IT'S A BIG
DEAL.
KUDOS TO THE ADMINISTRATION FOR
HOLDING THE EVENT.
I WAS GRATEFUL TO BE INVITED TO
BE A PANEL DISCUSSANT TO
HIGHLIGHT RECENT RESEARCH
PROGRESS ON RARE DISEASES AND
OUR PRIORITIES FOR RESEARCH THAT
EMPHASIZES THE IDEA OF
PATIENT-PARTNERED RESEARCH AND
HEALTH EQUITY.
I COULDN'T IMAGINE A BETTER WAY
TO SPEND RARE DISEASE EVE AND
THE INITIATIVE IN HOSTING THE
EVENT UNDER SCORE AS A NATIONAL
COMMITMENT TO ADVANCING RARE
DISEASE RESEARCH, FOSTERING
PATIENT-CENTERED APPROACHES AND
PROMOTING HEALTH EQUITY AND
SIGNALS A POWERFUL STEP FORWARD
ON INCLUSIVENESS AND INNOVATIVE
HEALTH CARE SOLUTIONS.
I WAS DELIGHTED TO SEE THIS
HAPPEN AND HOPE IT CONTINUES AS
WELL.
SPEAK OF ALL THESE KINDS OF
ACTIVITIES AND THOSE THEMES,
AGAIN YOU'LL HEAR ABOUT THESE
TODAY.
YOU'LL HEAR ABOUT RECENT TRIUMPH
OF LIKE THE APPROVAL FOR
VAMOROLONE AND WE HAVE PARTNERS
AT OTHER I.C.s FUNDING SOME OF
THE CLINICAL TRIALS.
AND VAMOROLONE AND MAY HELP
WITH JUVENILE MYELOCYTEIS AND
ALREADY THINKING TO USE THIS IN
OTHER APPLICATIONS AND WE LACK
ANIMAL MODELS FOR MANY RARE
DISEASES.
LATER YOU'LL HERE ABOUT A NEW
TISSUE CHIP MODEL ADDRESSING
RARE POLY NEUROPATHY DISORDERS.
THEY SHOW PROMISE FOR SCREENING
REPURPOSE DRUGS AND THERE'S NOW
A CANDIDATE DRUG IN PHASE II.
WE'RE EXCITED ABOUT THE NEW
TECHNOLOGY THIS PLATFORM
PROVIDES AND HOW IT CAN MAYBE
HELP US ADVANCE RESEARCH IN RARE
DISEASES.
PREDICTIVE MODELS ARE CRUCIAL.
WORKING WITH PATIENT CELLS TO
BETTER STIMULATE AND PREDICT HOW
DISEASES MAY PROGRESS TO BETTER
UNDERSTAND HOW DRUGS CAN STOP
THAT PROGRESSION.
ALL WITHOUT RELYING ON THE
TRADITIONAL ANIMAL MODELS THAT
WE HAVE BEFORE.
SO THESE ADVANCEMENTS NOT ONLY
REFINE OUR INFORMATION OF RARE
DISEASES BUT HASTEN THE ARRIVAL
OF SAFE AND EFFECTIVE THERAPIES.
THERE'S A LOT OF HOPE IN THE
TECHNOLOGIES THAT WE'RE BUILDING
FOR THE FUTURE.
AND AS WE MOVE FURTHER, THE
CONVERGENCE OF DATA SCIENCE,
YOU'LL HEAR A LOT ABOUT DATA
SCIENCE TODAY.
THE CONVERGENCE OF DATA SCIENCE
AND ARTIFICIAL SCIENCE FROM
ALGORITHM DEVELOPMENT TO
SHORTENING THE DIAGNOSTIC
ODYSSEY AND RAPID GENETIC DATA
AND PREDICTION OF COMPOUNDS THAT
OF SOMETHING WE MAYBE THOUGHT
WERE UNDRUGGABLE ARE THE POWER
BEHIND A.I. AND M.L. AND WE'LL
TALK ABOUT THE HOPE AND PROMISE
OF PERSONALIZED TREAT
STRATEGIES.
BY POOLING OUR KNOWLEDGE WE
UNCOVERED COMMON GENETIC THREADS
FROM GENE THERAPY APPROACHES AND
MANY GENETIC DISEASES CAN BE
TREATED WITH MORE OF THE
STREAMLINE BASED TECHNOLOGY IN
THE GENETIC APPROACHES.
AND WE CAN ALSO BE THINK HOW WE
CAN DESIGN NEW CLINICAL OR
BASKET TRIALS TO TEST ONE
THERAPY ON MANY DIFFERENT RARE
DISEASES.
IN THIS WAY WE'RE NOT JUST
CHASING TREATMENTS.
WE'RE LEAPFROGGING TOWARDS
CURES.
RARE DISEASE DAY IS A DAY TO
CELEBRATE OUR SUCCESSES, HONOR
THOSE WE HOLD DEAR AND HONOR
THOSE WE'VE LOST.
TODAY WE PAUSE GRANTING
OURSELVES THE SPACE FOR
CREATIVITY AND CONTEMPLATION SO
TOMORROW WE CAN SPEED UP WITH A
RENEWED SENSE OF PURPOSE AND
THAT PURPOSE NEEDS ALL OF YOU.
I'M SO DELIGHTED TO SHARE THIS
EVENT WITH YOU TODAY AND I'M SO
GLAD YOU WERE ABLE TO JOIN
TODAY.
I WANT TO GO AHEAD AND GET TO
IT.
THANK YOU SO MUCH.
>> JIM TOOK THE HELM IN 2017 AND
NOW STEERS ONE OF THE PREMIER
RESEARCH HOSPITALS AT THE NIH ON
CAMPUS AND HIS LEADERSHIP
EMPHASIZES PATIENT SAFETY AND
QUALITY AND CARE AND THE
DEVELOPMENT OF NEW HOSPITAL
OPERATIONS AND POLICIES AND HE
IS DEDICATED TO SUPPORTING THE
RARE DISEASES AND THE RESEARCH
THAT WE DO.
WITH THAT I WANT TO BRING
DR. GILLMAN UP AND DIRECTED
HOSPITALS AN SHAPED POLICY
WITHIN THE SURGEON GENERAL'S
OFFICE BEFORE RETIRING WITH THE
RANK OF GENERAL AND IT'S MY
PLEASURE TO BRING HIM UP TO THE
STAGE.
THANK YOU, DR. GILMAN.
>> GOOD MORNING AND WELCOME BOTH
TO ALL OF YOU THAT ARE HERE IN
THE AUDITORIUM AND THOSE WHO ARE
IN THE VIRTUAL ROOM.
THE NIH CLINICAL CENTER IS THE
HOSPITAL AT THE CENTER OF THE
NATIONAL INSTITUTES OF HEALTH IS
A KEY PARTNER IN RESEARCH INTO
RARE DISEASES.
THIS CONFERENCE GOT TOO BIG TO
HOLD IN BUILDING 10.
IT'S THE PRIDE A PARENT HAS WHEN
THEY WATCH THEIR CHILD GROW UP
AND MOVE OUT IN THE WORLD.
THE CLINICAL CENTER HAS FONDNESS
FOR RARE DISEASE DAY.
THEY DO MORE RARE DISEASE
RESEARCH THAN ANY PLACE ON THE
PLANET.
WE'RE NOT SURE ABOUT THE REST OF
THE UNIVERSE BUT WE HAVE THE
SOLAR SYSTEM DOWN.
THE PARTNERSHIP BETWEEN PATIENTS
AND RESEARCHERS RESULTED IN
MILESTONE.
THE DEVELOPMENT OF CHEMOTHERAPY
AND THE FIRST CURE OF CANCER BY
CHEMOTHERAPY TO PLACE IN THE
CLINICAL CENTER.
THE FIRST USE OF AN IMMUNOTOXIN
TO TREAT A MALIGNANCY.
IDENTIFICATION OF THE GENES THAT
THAT CAUSE KIDNEY CANCER LEADING
TO SIX TARGETED TREATMENTS FOR
ADVANCED KIDNEY ANSWER.
DEMONSTRATING LITHIUM HELPS
TREAT DEPRESSION.
FIRST GENE THERAPIES WERE
APPLIED THERE.
THE FIRST TREATMENT OF AIDS WITH
ANTIRETROVIRALS AND TESTING HIV
AND HEPATITIS VIRUS IN BLOOD
LEADING TO A SAFER BLOOD SUPPLY
NOT ONLY IN THIS COUNTRY BUT
AROUND THE WORLD.
ONE OF OUR SCIENTISTS WAS A
CO-WINNER OF THE 2020 NOBEL
PRIZE FOR HIS WORK ON THE
DISCOVERY OF HEPATITIS C.
CLINICAL RESEARCHERS COME FROM
AROUND THE WORLD AND ABOUT HALF
OUR STUDIES ARE OF THE NATURAL
HISTORY OF DISEASE, ESPECIALLY
RARE DISEASE.
THEY'RE OFTEN NOT STUDIED
ANYWHERE ELSE, BY THE WAY, THERE
NEEDS TO BE MORE TREATMENT
TRIALS OR THE RARE DISEASES AT
THE NIH CLINICAL CENTER AND
DR. RUTTER AND I HAVE RECENTLY
SPENT TIME TRYING TO MAKE THAT
CAN HAPPEN.
NIH UNDIAGNOSED DISEASE PROGRAM
WAS HOUSED AT THE CLINICAL
CENTER AND STILL IS.
THE PROGRAM EXPANDED IN THE
UNDIAGNOSED DISEASES NETWORK
WITH MULTIPLE SITES THROUGHOUT
THE COUNTRY AND STILL HAS A HOME
IN OUR HOSPITAL.
THE UNDIAGNOSED NETWORK FOCUSES
ON RARE DISEASES AND MOST RARE
MEDICAL CASES.
THERE WAS A WONDERFUL WRITE-UP
IN THE ISSUE OF THE WASHING
WASHINGTONIAN MAGAZINE AND
FEATURES THE TEAM OF MEDICAL
DETECTIVES.
THIS WORK HELPS PATIENTS WITH
RARE CONDITIONS AND HELPS THE
HEALTH OF OUR NATION.
SOME PATIENTS WITH RARE DISEASE
TAUGHT US MORE ABOUT COMMON
CONDITIONS SUCH AS OSTEOPOROSIS,
KIDNEY STONES, VIRAL COLLECTIONS
AND CHOLESTEROL METABOLISM.
ADVANCES IN DIAGNOSIS OF RARE
DISEASE ARE GRATIFYING BUT NOT
ENOUGH.
THE 7,000 IDENTIFIED RARE AND
NEGLECTED DISEASES FOR WHICH WE
KNOW THE MOLECULAR CAUSE, ONLY
ABOUT 500 HAVE APPROVED
TREATMENTS.
NIH IS COLLABORATING WITH
MULTIPLE PARTNERS TO SPEED UP
THE DEVELOPMENT OF EFFECTIVE
TREATMENTS AND THE CLINICAL
CENTER IS PROUD TO PLAY AN
IMPORTANT ROLE AND WE UNDERSTAND
FOR US IT'S SCIENTIFICALLY
INTERESTING BUT WE DO UNDERSTAND
THAT FOR MANY OF YOU, THIS IS A
MUCH MORE URGENT MISSION AND WE
APPRECIATE YOUR HELP IN PURSUING
THAT MISSION.
SO WHAT CAN YOU DO?
WELL, IF YOU'RE ON SITE YET, OUR
PATIENT RECRUITMENT STAFF FROM
THE CLINICAL CENTER ARE HERE AND
SHARE YOUR STORY.
WE WANT TO MEET I AND SEE IF WE
CAN HELP.
FOR THOSE AT HOME, THE RARE
DISEASE DAY SITE WILL ALSO HAVE
THE CONTACT INFORMATION.
THANK YOU ALL FOR COMING AND FOR
SUPPORTING RARE DISEASE DAY.
THANK YOU FOR YOUR WORK ON
CAPITOL HILL IN PREPARATION FOR
THIS DAY.
THEY DON'T WANT ME TO GO UP AND
TELL THEM ABOUT BUT REMIND THEM
WE MADE PROGRESS BUT THEY CAN DO
BETTER.
THANK YOU.
>> THAT WAS A GREAT SEGUE
BECAUSE YOU KNOW THERE'S VIDEOS
WE SHOW FROM THE CO-CHAIRS OF
THE CONGRESSIONAL CAUCUS.
WE HAVE SENATOR KLOBUCHAR AND
CONGRESS MATSUI AND
REPRESENTATIVE BILIRAKIS AND
SENATOR WICKER AND THEY HAVE
SENT A VIDEO TO SHARE THE ROLE
THEY PLAY AND THE PROGRESS THEY
HAVE FOR PROGRESS.
WE APPRECIATE THE BICAMERAL
SUPPORT AND I THINK IT REFLECTS
AND EMPHASIZES THE IMPACT ALL OF
YOU ARE HAVING ON THEM.
THE ISSUES FACED BY OUR RARE
DISEASE COMMUNITY ARE RECOGNIZED
AT THE HIGHEST LEVEL OF OUR
GOVERNMENT.
I THANK HERE TO REALLY TELL YOU
THAT.
IN OTHER WORDS, WE SEE THAT.
WITH THAT LET'S ROLL THE TAPE.
WE'LL GO IN ORDER I THINK FROM
SENATOR KLOBUCHAR AND
CONGRESSWOMAN MATSUI AND
REPRESENTATIVE BILIRAKIS AND
SENATOR WICKER.
>> WELCOME TO THE 2024 RARE
DISEASE DAY AT THE NIH AND THANK
YOU TO DR. BERTAGNOLLI AND
DR. RUTTER AND DR. GILMAN FOR
YOUR LEADERSHIP AND EVERYONE
GATHERED TODAY FOR WHAT YOU DO.
I KNOW MY COLLEAGUES AND I KNOW
WE ARE ADVOCATES TO END RARE
DISEASES AS WE KNOW THEM.
I'M IN THE FIGHT BECAUSE OF
PEOPLE LIKE ABBY HOUSER.
A MINNESOTA NATIVE IS ONE OF 30
MILLION AMERICANS LIVING WITH
ONE OF 10,000 KNOWN RARE
DISEASES BUT HER CONDITION
HASN'T STOPPED HER FROM
THRIVING.
THESE A MARATHON FINISHER,
CHAMPION FOR INCLUSIVITY IN
SPORTS AND THE BOARD MEMBER OF
THE EVERY RIGHT FOUNDATION FOR
RARE DISEASES FIGHTING FOR A
RESEARCH WHERE RESEARCH GIVES
EVERYONE A CHANCE TO FIGHT.
I KNOW ABBY THROUGH HER RARE
DISEASE PATIENT ADVOCACY AND
HAVE SEEN HER IN D.C.
INSPIRED BY HER I AM DEDICATED
MAKING SURE NO PATIENT MISSES
OUT ON OR HAS TO FIGHT FOR CARE,
TREATMENTS OR CURES JUST BECAUSE
THEIR CONDITION IS LESS COMMON
THAN SOMEONE ELS.
I'M FOCUSSED ON PUTTING FEDERAL
DOLLARS INTO RESEARCH.
INVESTMENT WE MAKE TODAY WILL
PAVE THE WAY FOR CUTTING EDGE
TREATMENTS AND CURES OF
TOMORROW.
LAST YEAR FOR THE NINTH YEAR
CONGRESS SECURED SIGNIFICANT
FUNDING BOOST FOR THE NIH.
PERSONALIZED MEDICINE INCLUDING
AT MAYO CLIN IN MINNESOTA, IS
REALLY EXCITING.
ALL THE WORK THAT FRANCES
COLLINS AND YOU HAVE DONE ON THE
HUMAN GENOME AND THE SCARY PARTS
OF A.I. BUT THE POTENTIAL TO
HELP WITH RARE DISEASES CAN'T BE
FORGOTTEN.
I ALSO WANT TO EMPOWER PATIENTS
AND FAMILIES TO PLAY A LARGER
ROOM IN THE TREATMENT, RESEARCH
AND APPROVAL PROCESS.
I'M PROUD OF LEGISLATION TO HELP
HOW HOW TO WORK WITH PATIENTS
BECAME LAW AND MORE TO DO.
AS CO-CHAIR OF THE BIPARTISAN
RARE DISEASE CONGRESSIONAL
CAUCUS I'M PUSHING THE FDA TO
IMPROVE RELIABILITY IN HOW THEY
REVIEW APPLICATION FOR RARE
DISEASE THERAPIES.
I HEARD FROM SO MANY ADVOCATES,
PHYSICIANS AND SCIENTISTS,
THERE'S INCONSISTENCIES BETWEEN
PATIENTS AND RECORDS AND MAKE
SURE TREATMENT ARE APPROVED.
THIS IS IMPORTANT FOR KIDS BORN
WITH RARE DISEASES AND RARE
GENETIC CONDITIONS START IN
CHILDHOOD AND WITH COLLEAGUES ON
BOTH SIDES OF THE AISLE I'M
IMPROVING ACCESS TO CARE FOR
RARE DISEASE PATIENTS.
WORKING WITH SO MANY WE MADE
STRIDES IN NEWBORN SCREENINGS TO
EMPOWER THE FAMILIES OF BABIES
BORN WITH RARE DISEASE TO BEGIN
THE MOST EFFECTIVE TREATMENTS AS
SOON AS POSSIBLE.
IN MY OWN STATE OF MINNESOTA WE
WORKED HARD TO OFFER A
COMPREHENSIVE SCREENING PROGRAMS
BUT NEED TO ENSURE FAMILIES IN
EVERY STATE CAN RECEIVE
EFFECTIVE AND AFFORDABLE
SCREENINGS.
WE KNOW EARLY DETECTION AND
DIAGNOSIS CAN MAKE THE WORLD OF
DIFFERENCE.
I'M DEDICATED TO ENSURING EVERY
INFANT HAS ACCESS TO SCREENS
THAT RELIABLY DETECT RARE
CONDITIONS.
I'M ALSO LEADING BIPARTISAN
LEGISLATION TO ENSURE PATIENTS
WITH RARE CANCERS CAN ACCESS
MOLECULAR DIAGNOSTIC TESTING ONE
OF THE MOST POWERFUL TOOLS FOR
TREATING RARE CANCERS AT THEIR
INITIAL DIAGNOSIS.
THERE'S SO MUCH WORK TO DO AND I
KNOW YOU KNOW THAT TOO BUT
THANKS TO THE BREAKS THROUGH AT
THE NIH AND THE WORK EVERYONE
GATHERED TODAY IS DOING I
BELIEVE A FUTURE IS POSSIBLE
WITHOUT RARE DISEASES.
BEFORE I GO I WANT TO SHARE
WORDS OF WISDOM FROM ABBY, SHE
SAID, I REFUSE TO BE DEFINED BY
THE GENETIC MUTATION WEAKENED
THE COLLAGEN HOLDING MY BODY
TOGETHER.
IT WILL ALWAYS BE UNSTABLE BUT
MY LIMITATIONS DO NOT DETERMINE
WHO I AM.
SHE'S RIGHT.
LIMITATIONS DON'T DEFINE US OR
YOU AND YOU'RE BREAKING THROUGH
THOSE LIMITATIONS EVERY DAY.
I KNOW EVERYONE GATHERED TODAY
REFUSE TO LET OBSTACLES STAND IN
THE WAY OF CURING RARE DISEASES.
WORKING TOGETHER WILL DEVELOP
TREATMENTS AND CURES AND SAVE
LIVES.
THANK YOU, KEEP UP THE
INCREDIBLE WORK.
HERE'S TO YOU.
THERE'S A LOT GOING ON.
HAVE FUN TODAY.
>> THANK YOU FOR JOINING US FOR
RARE DISEASE AT NIH.
I WANT TO GIVE A SPECIAL THANK
YOU TO ALL THE NIH STAFF AND THE
PARTNERS WHO MAKE THIS POSSIBLE
EVERY SINGLE YEAR.
I ALSO WANT TO THANK EACH OF YOU
FOR TAKING THE TIME TO BE WITH
US TODAY, PATIENTS, FAMILIES AND
CAREGIVERS IMPACTED BY RARE
DISEASES AND THE RESEARCHERS WHO
HAVE COMMITTED THEIR LIVES TO
FINDING CURES.
YOUR DEDICATION TO IMPROVING THE
LIVES OF THE RARE DISEASE
COMMUNITY IS FOUNDATIONAL TO THE
WORK WE DO IN CONGRESS.
AS CO-CHAIR OF THE RARE DISEASE
CONGRESSIONAL CAUCUS, I DEEPLY
UNDERSTAND THE UNIQUE NEEDS OF
THIS COMMUNITY AND THE
CHALLENGES IN ACCESSING CRUCIAL
CARE.
RARE DISEASE WEEK IS AN
IMPORTANT TIME TO HAVE
DISCUSSIONS LIKE THE ONES WE'RE
HAVING TODAY.
TO LEARN FROM EACH OTHER, THINK
OUTSIDE THE BOX AND CHART A PATH
FORWARD.
LAST YEAR WE CELEBRATED 40 YEARS
OF THE ORPHAN DRUG ACT WHICH HAS
BEEN CRUCIAL TO ENCOURAGING
PHARMACEUTICAL COMPANIES TO
DEVELOP DRUGS FOR THE RARE
DISEASE COMMUNITY.
IT HAS BEEN A KEY DRIVER FOR
DECADES OF INNOVATION THAT
LEGISLATION CONTINUES TO BE
IMPORTANT.
DESPITE THE SUCCESS OF THE
ORPHAN DRUG ACT OUT OF THE 7,000
KNOWN RARE DISEASES, FEWER THAN
10% HAVE A TREATMENT.
THE BASIC SCIENCE RESEARCH ON
RARE DISEASES CONDUCTED BY NIH
AND ITS PARTNERS IS ESSENTIAL TO
DEVELOPING EVIDENCE FOR THOSE
NOVEL THERAPIES.
FOR THE MILLIONS OF RARE DISEASE
PATIENTS THROUGHOUT THE COUNTRY,
WE MUST CONTINUE TO PUSH FORWARD
AND THAT'S WHY DAYS LIKE TODAY
ARE SO IMPORTANT.
TO SHARE OUR STORIES AND ENGAGE
IN PRODUCTIVE DIALOGUE ABOUT THE
FUTURE.
WE KNOW ACCESS TO THE BEST
MEDICAL CARE IS CRUCIAL FOR
PATIENTS LIVING WITH RARE AND
ULTRA RARE DISEASES AND MADE IT
A PRIORITY TO WORK ON POLICY TO
VET THE SCIENCE OF RARE DISEASE
THERAPIES AND EXPAND ACCESS TO
CARE THROUGH CONGRESS I ADVANCED
PATIENT ENGAGEMENT IN THE DRUG
DEVELOPMENT PROCESS.
I'M ALSO PROUD TO LEAD IT
PROTECT RARE ACT WHICH WOULD
SUPPORT PATIENTS WITH RARE AND
ULTRA RARE DISEASES IN GETTING
EVIDENCE-BASED MEDICALLY
NECESSARY CARE COVERED BY HEALTH
INSURANCE.
I ALSO URGED THE FDA TO BRING
MORE RELIABILITY AND CONSISTENCY
OF THE PROCESS OF REVIEWING RARE
DISEASE THERAPIES.
AS 2024 CONTINUES, I LOOK
FORWARD TO CONTINUING TO WORK
TOGETHER WITH MY CAUCUS
COLLEAGUES AND THE RARE DISEASE
COMMUNITY.
WE MUST FOCUS ON HOW WE CAN MAKE
IMPORTANT PROGRESS TOWARD OUR
GOAL TO IMPROVE THE LIVES OF
PATIENTS AND FAMILIES.
TODAY IS ABOUT THE ACTIONS WE'LL
TAKE FOR TOMORROW, THE DAY AFTER
THAT AND IN THE YEARS AHEAD.
TO ADVANCE EFFORTS THAT SUPPORT
INNOVATIVE THERAPIES AND
EVENTUALLY CURES THAT WILL
FOREVER CHANGE THE OUTLOOK OF
THOSE LIVING WITH RARE DISEASES.
I TRULY BELIEVE THE TREMENDOUS
ADVANCEMENTS WE HAVE MADE IN
RESEARCHING AND UNDERSTANDING
THESE DISEASES WILL ONLY
CONTINUE TO GROW.
I LOOK FORWARD TO CONTINUING OUR
WORK TOGETHER AND THANK YOU
AGAIN FOR BEING TO SUPPORT THE
RARE DISEASE COMMUNITY.
THANK YOU.
>> HELLO, MY NAME IS CONGRESS
BILIRAKIS AND I APPRECIATE THE
OPPORTUNITY TO PROVIDE BRIEF
REMARKS FOR RARE DISEASE DAY
2024.
AS A SENIOR MEMBER OF THE
COMMERCE COMMITTEE AND SERVING
AS A CO-CHAIR OF THE RARE
DISEASE CAUCUS I LOOK FORWARD TO
HEARING FROM PATIENTS AND
ADVANCING POLICY TO HELP MY
CONSTITUENTS.
WE KNOW THERE'S AN ESTIMATED
7,000 RARE DISEASES, MOST OF
WHICH HAVE NO TREATMENT OR CURE,
UNFORTUNATELY.
THERE'S SIGNIFICANT CHALLENGES
TO DEVELOP THOSE TREATMENTS WITH
SMALL POPULATIONS AND CLINICAL
RARE DISEASE TRIAL BARRIERS.
BUT I'M GRATEFUL FOR THE WORK
DONE BY THE NATIONAL INSTITUTE
OF HEALTH, SPECIFICALLY THE
NATIONAL CANCER FOR ADVANCING
TRANSLATIONAL SCIENCES OR NCATS.
I'M A STRONG PROPONENT FOR
ADDITIONAL FUNDING THE NIH AND
TO NCATS FOR RESEARCH INTO WAYS
WE CAN TRANSITION BASIC
SCIENTIFIC AND MEDICAL
DISCOVERIES INTO THE MARKET OF
MEDICINES.
THIS WORK IS CRITICAL
PARTICULARLY FOR A NEW ERA OF
CELL AND GENE THERAPIES TO
PROVIDE FOR RARE DISEASE
PATIENTS.
BIOMEDICAL RESEARCH IS THE KEY
TO DISCOVERING CURES AND SAVING
LIVES.
I'M GLAD TO SUPPORT CRITICAL
FUNDING FOR THESE INITIATIVES
HERE IN THE UNITED STATES
CONGRESS.
I'M ALSO VERY INTERESTED IN
ENSURING THE BIO TECHNOLOGY
MANUFACTURING ORGANIZATION HAVE
THE INCENTIVE TO ACCELERATE
TREATMENTS AND BRING THEM TO THE
MARKETPLACE AND INTO PATIENT'S
HANDS.
THAT'S THE ULTIMATE GOAL,
OBVIOUSLY FOR CURES AND
TREATMENTS.
PROGRAMS SUCH AS THE PEDIATRIC
RARE REVIEW VOUCHER AT THE FDA
AND OTHER MARKET BASE INCENTIVES
PROVIDE SIGNIFICANT
OPPORTUNITIES TO BRING MORE SAFE
AND EFFECTIVE THERAPIES TO RARE
DISEASE PATIENTS.
WE MUST ENSURE THE PROGRAMS
CONTINUE AND THE FDA SET UP FOR
SUCCESS TO ACCELERATE APPROVALS
OF THESE THERAPIES.
MANY TREATMENTS BROUGHT TO THE
MARKET FOR RARE DISEASE ARE
FIRST IN KIND.
BREAKTHROUGH TREATMENTS AND I
HOPE WE CAN CONTINUE TO SURE
THEY'RE AVAILABLE AND ACCESSIBLE
FOR PATIENTS IN THE COMMUNITY.
THAT'S THE KEY.
THEY HAVE TO BE ACCESSIBLE AS
WELL FOR PATIENTS WHO ARE NO
OTHER OPTIONS AVAILABLE.
PUBLIC-PRIVATE PARTNERSHIPS HAVE
BEEN PROVEN TO BE A SUCCESSFUL
MODEL TO GET THINGS DONE AND
LEVERAGE EXPERTISE AND
RESOURCES.
I LOOK FORWARD TO WORKING WITH
MY COLLEAGUES ON BOTH SIDES OF
THE AISLE TO DEVELOP SOLUTIONS
THAT WILL ACCELERATE FRAMEWORKS
LIKE THESE AND CONTINUE TO SPUR
INNOVATIVE IDEAS IN THE PUBLIC
AND PRIVATE SECTOR.
IT TAKES BOTH.
IN FACT, ENTITIES SUCH AS THE
ADVANCED RESEARCH PROJECTS
AGENCY FOR HEALTH AND OTHERS CAN
PROVIDE RENEWED HOPE TO FINDING
AND DISCOVERING CURES.
AGAIN, THANK YOU FOR INVITING ME
TO PROVIDE REMARKS FOR RARE
DISEASE DAY 2024.
I ALSO ALWAYS APPRECIATE HEARING
FROM MY CONSTITUENTS AND
PATIENTS IN THE RARE DISEASE
COMMUNITY FROM ALL OVER THE
UNITED STATES.
I HEARD FROM MANY THEM THIS PAST
YEAR ON THE STRUGGLES THEY ARE
FACING AND THEY HAVE IMPACTED ME
GREATLY AND GIVEN ME A REASON TO
BE UP HERE FIGHTING FOR A
CHANGE.
I'VE ALWAYS FOUND THAT PERSONAL
INDIVIDUAL STORIES TRULY MAKE
THE BIGGEST IMPACT.
THEY TRULY INFLUENCE US AND WILL
HELP GARNER THE SUPPORT.
THESE STORIES HELP GARNER THE
SUPPORT WE NEED TO CHANGE POLICY
AND IMPROVE THE LIVES OF PAT
PATIENTS NATIONWIDE.
IT SHOULD BE A PRIORITY.
THANK YOU FOR THE PARTICIPATION
TODAY AND THANK YOU, NIH FOR
HOSTING THIS GREAT EVENT AND
SUPPORTING THIS WORTHWHILE
ENDEAVOR.
>> HELLO, THIS IS U.S. SENATOR
ROGER WICKER FROM MISSISSIPPI.
THANK YOU FOR BEING HERE TODAY.
IT'S AN HONOR TO WORK TOGETHER
TOWARD THE SHARED GOAL.
OVER 25 MILLION AMERICANS SUFFER
FROM RARE DISEASES.
350 MILLION WORLDWIDE.
THEY'RE OUR LOVED ONES AND NEXT
DOOR NEIGHBOR.
MANY ARE OUR CHILDREN.
NATIONAL INSTITUTE OF HEALTH IS
A SOURCE OF HOPE FOR THOSE
LIVING WITH THESE DISEASES
BY INVESTING IN THE NIH WE EQUIP
THE BEST AND BRIGHTEST
SCIENTISTS WORKING TOWARDS LIVE
SAVING TREATMENTS AND CURES TO
OUR MOST CHALLENGING CONDITIONS.
THERE ARE OVER 7,000 RARE
DISEASES BUT WE HAVE TREATMENTS
FOR ONLY 500.
I'M CONFIDENT THE RESEARCH WILL
CONTINUE TO GOES THE GAP.
EVERY DOLLAR COUNTS AND CONTINUE
TO SUPPORT AND ESPECIALLY WITH
AILMENTS WITH NO APPROVED
TREATMENT.
AS CO-CHAIR OF THE RARE DISEASE
CAUCUS, I WILL CONTINUE FIGHTING
THIS FIGHT.
THIS CONGRESS I RE-INTRODUCED
THE BENEFIT ACT TO HELP THE FDA
APPROVAL PROCESS AND FRAMEWORK
AND TAKE PATIENT EXPERIENCE INTO
EXPERIENCE IN NEW WAYS.
I'M COMMITTED TO GETTING THIS
WORK OVER THE FINISH LINE.
WE KNOW ALL TOO WELL THERE'S
CHALLENGES AHEAD BUT THE
PROGRESS WE'VE MADE HOLDS THE
PROMISE OF GREATER BREAKTHROUGHS
TO COME.
THANK YOU ALL FOR YOUR
COMMITMENT TO HELPING BETTER THE
LIVES OF THOSE WHO HAVE RARE
DISEASES.
>> THAT WAS AMAZING.
THANK YOU SO MUCH.
AND NOW NEXT UP ON THE AGENDA IS
ANOTHER INTRODUCTION I WANT TO
MAKE.
IT IS A REAL PLEASURE TO
INTRODUCE DR. DOMINIQUE PICHARD
THE NEW DIRECTOR FOR DRDRI.
I'M SUPER EXCITED FOR HER.
IT WILL BE HER FIRST RARE
DISEASE DAY IN THIS ROLE.
SHE'S NOW LEADING AND
COORDINATING RARE DISEASE
EFFORTS ACROSS NIH, ACROSS NCATS
AND BEFORE HER ROLE AS NCATS SHE
WAS THE CHIEF SCIENCE OFFICER AT
THE NATIONAL SYNDROME FOUNDATION
DRIVING INITIATIVES FOR RETT
SYNDROME A RARE GENETIC
NEUROLOGICAL DISORDER.
HER BACKGROUND IS SHE RECEIVED
HER MEDICAL DEGREE FROM
GEORGETOWN UNIVERSITY SCHOOL OF
MEDICINE AND MASTER'S DEGREE
FROM THE MARYLAND UNIVERSITY
SCHOOL OF MEDICINE AND HAS A
DEPTH OF EXPERTISE IN MEDICINE
AND TRANSLATIONAL RESEARCH AND
IT'S AN HONOR FOR HER TO BE HERE
TODAY AND HAVE HER HON OUR TEAM
WITH HER EXPERIENCE AND HER
PERSONALITY WHICH IS ALSO
WONDERFUL.
I WANT TO WELCOME HER TO THE
STAGE.
>> I'M DOMINIQUE PICHARD AND I
HAVE THE HONOR AND PRIVILEGE OF
LEADING THE RARE DISEASE
RESEARCH INNOVATION DIVISION.
AND BEFORE I TELL YOU ABOUT OUR
DIVISION AND SOME OF THE WORK WE
DO, I WANT TO TELL YOU WHERE MY
STORY STARTED.
THIS IS ME AT MY MEDICAL SCHOOL
GRADUATION WITH MY SUPPORTIVE
HUSBAND AND BEAUTIFUL PERFECT
CHUBBY LITTLE FIRST BORN.
I WAS SETTING UP ON A NEW
ADVENTURE.
THIS WAS MY NEXT PHASE OF LIFE
AND A HAD PLANNED IT DOWN TO THE
MINUTE.
I'M A LITTLE BIT OF A PLANNER SO
I KNEW THE NEXT 50 YEARS OF MY
LIFE EXACTLY HOW THEY WOULD TURN
OUT AND THE ADVENTURE WAS
DIFFERENT THAN I HAD SO
DILIGENTLY PLANNED FOR.
IN MY INTERN YEAR, THIS
BEAUTIFUL LITTLE GIRL ONE NIGHT
LOST HER VERBAL LANGUAGE.
THAT WAS IT.
THE NEXT MORNING WE NO LONGER
HEARD HER WORDS.
SHE WAS NO LONGER SAYING MOM OR
HER WAY OF SAYING DOLL.
I BROUGHT HER TO THE
PEDIATRICIAN AND SAID, I THINK
SHE HAS RETT SYNDROME.
SHE SAID DON'T BE A NEUROTIC
DOCTOR DIAGNOSING YOUR FAMILY.
DIAGNOSE YOUR PATIENTS, LEAVE
YOUR FAMILY ALONE.
SOME HAVE HAD THE SAME FEELING.
I WAS NOT SEEN AND NOT HEARD AND
I KNEW HOW TO GET REFERRALS AND
WAS ABLE TO GET TESTS.
WE HAD GREAT INSURANCE.
I WAS VERY LUCKY.
IT STILL TOOK ALMOST A YEAR
BEFORE A NEUROLOGIST CALLED ME
AND SAID GUESS WHAT, WE HAVE
YOUR DIAGNOSIS.
YOU'RE DAUGHTER HAS RETT
SYNDROME.
I SAID YEAH, I KNOW.
I TOLD YOU THAT A YEAR AGO.
I WAS FORTUNATE TO GET THE EARLY
DIAGNOSIS BUT WE HAD NO EARLY
TREATMENTS.
THE DIVISION OF RARE DISEASE
RESEARCH INNOVATION WORKS HARD
TO ONE DAY FAMILIES DON'T HAVE
TO GO THROUGH THIS OR HAVE TO BE
DOCTORS WITH INSURANCE KNOWING
ALL THE SPECIALISTS AND WHAT
TEST TO ORDER TO GET A DIAGNOSIS
IN LESS THAN A YEAR.
WE GOT OUR FIRST FDA APPROVED
TREATMENT FOR RETT SYNDROME IN
2023.
RETT SYNDROME WAS DIAGNOSED IN
THE '80s AND I DON'T WANT OTHERS
TO HAVE A LONG TREATMENT
ODYSSEY.
SO TO TELL YOU ABOUT THE
DIVISION OF RARE DISEASE
RESEARCH INNOVATION IT'S
IMPORTANT TO KNOW, UNDERSTAND
THAT WE LIVE WITHIN NCATS THE
NATIONAL CENTER FOR ADVANCING
TRANSLATIONAL SCIENCES.
WE DON'T WORK ON THE SPECIFIC
ORGAN SYSTEM OR TYPE OF
CONDITION.
WE'RE DISEASE AGNOSTIC.
THIS IS OUR MISSION.
WE WANT TO TURN THOSE RESEARCH
OPTIONS, THE BASIC SCIENCE
DISCOVERIES INTO HEALTH
SOLUTIONS THROUGH TRANSLATIONAL
SCIENCE AND I LOVE THIS FIGURE
HERE.
WHAT'S AT THE CENTER?
PATIENTS.
PATIENTS ARE THE KEY TO FINDING
TREATMENTS FOR RARE DISEASES.
PATIENTS ARE CRITICAL TO THE
RESEARCH PROCESS BECAUSE IF WE
DON'T HAVE THE PATIENTS
INVOLVED, WE MAY NOT BE
RESEARCHING THE RIGHT THINGS OR
FINDING THE RIGHT TREATMENT AND
THEY MAY PROVIDE SO MUCH
TREATMENT AND GUIDANCE YOU CAN'T
OTHERWISE GET.
IT'S BEEN MENTIONED EARLIER.
I'LL SAY IT AGAIN.
RARE DISEASES HAVE A HOME IN
NCATS.
WE WORK TO CREATE EFFICIENCIES
IN THE SYSTEM AND WITH MORE THAN
7,000 DISEASES WE'LL NEVER GET
TO MOST IF WE GO ONE AT A TIME.
THIS IS AN OVERVIEW OF WHAT WE
DO AND I HOPE YOU VISIT OUR
TABLE TO LEARN MORE ABOUT OUR
RESOURCES AND PROGRAMS AND
WEBSITE TO SEE HOW CAN YOU
BENEFIT THE WORK WE DO AND HOW
CAN YOU HELP INFORM US ON WHAT
WORK NEEDS TO BE DONE.
YOU ARE PART OF THE SOLUTION AND
WE WANT TO HEAR FROM YOU.
I WANT TO MENTION WE HAVE TOOLS
AVAILABLE FOR PATIENTS, THEIR
ADVOCATES, REPRESENTATIVES WHO
NEED TO LEARN ABOUT THE PROCESS
AND LEARN WHAT TO DO NEXT AND
UNDERSTAND ABOUT THE DISEASE.
WE HAVE PROGRAMS FOR RESEARCHERS
LOOKING TO ADVANCE TREATMENTS
AND CURES.
WE HAVE PROGRAMS THAT BUILD
EFFICIENCIES IN THE SYSTEM SO WE
CAN GET TO THOSE TREATMENTS NOT
ONE DISEASE AT A TIME BUT BY
HELPING DERISK THE PROCESS SO
THE FUTURE TREATMENTS COME
FASTER.
WE ALSO CONVENE AND I'LL HAVE A
SLIDE LATER BAY WORKSHOP WE'LL
HOST WITH OUR COLLEAGUES AT THE
FDA.
IT'S IMPORTANT TO CONVENE ALL
THE STAKEHOLDERS WITH THE
PATIENTS BEING AN IMPORTANT PART
OF THAT.
THESE NEXT FEW SLIDES ARE THE
HIGHLIGHTS FROM OUR PROGRAMS.
THIS IS FROM THE BESPOKE GENE
THERAPY CONSORTIUM FOR BTC --
BGTC AND THERE'S A PLAYBOOK
THAT'S BEEN RELEASED INTENDED TO
HELP STREAMLINE PRODUCT
NAVIGATION.
SO LET'S DERISK IT AND NOT ALL
MAKE THE SAME MISTAKES OVER AND
OVER.
THE BGTC MADE A COMMITMENT TO
PUBLISH THE LEARNINGS TO ANY
DEVELOPMENT PROGRAMS CAN LEARN
FROM THEIR SUCCESSES AND THEIR
MISTAKES AND NOT HAVE TO
REINVENT THE WHEEL.
THIS THROUGH OUR SOMATIC CELL
GENOME EDITING PROGRAM.
WE HAVE A TARGETED CHALLENGE.
IT'S A COOL PROGRAM.
THE GOAL IS TO DEVELOP BETTER
TARGETED DELIVERY SYSTEMS TO
DELIVER GENOME EDITORS TO
SOMATIC CELLS.
AND YOU CAN SCAN THE QR CODE.
THERE'S AN OPEN CHALLENGE THAT
WE INVITE RESEARCHERS TO APPLY
FOR.
NEXT THIS IS ABOUT BASKET TRIALS
FOR RARE DISEASES.
THIS IS SOMETHING WE LEARNED
FROM ONCOLOGY AND IT'S BEEN A
SUCCESSFUL MODEL.
YOU CAN HAVE ONE DRUG THAT MAY
BE BENEFICIAL FOR MORE THAN ONE
DISEASE WHICH MANY OF US KNOW
AND WE HAVE TWO FUNDED PROGRAMS
WHERE THEY HIT THEIR FIRST
MILESTONE AND GOT ONE DRUG WITH
MULTIPLE RARE DISEASES AND WITH
THE QR CODE YOU CAN FIND THE
FUNDING OPPORTUNITY FOR A SMALL
BUSINESS GRANT.
AND FINALLY I WANT TO CLOSE AS A
MENTIONED WE'RE HOSTING A
WORKSHOP WITH THE FDA ON NATURAL
HISTORY STUDIES AND RARE DISEASE
DEVELOPMENT AND HOPEFULLY THE QR
CODE WORKS IT LAUNCHED THIS
MORNING.
WE INVITE YOU TO BE THERE AND
LEARN ABOUT HOW NATURAL HISTORY
STUDIOS CAN HELP THE DRUG
DEVELOPMENT PROCESS.
SO WITH THAT, I WILL CLOSE OUT.
AGAIN, THANK YOU TO EVERYONE FOR
BEING HERE AND TO ALL OF NIH FOR
WHAT YOU DO TO SUPPORT THIS
WORK.
NEXT UP I'M GOING TO INTRODUCE
OUR FIRST SPEAKER.
THIS IS RARE STORY NUMBER ONE.
SHORTENING THE DIAGNOSTIC
ODYSSEY.
I INVIDE DR. SEEMA LALANI FROM
BAYLOR COLLEGE OF MEDICINE TO
PLEASE TAKE THE STAGE AND TELL
US ABOUT HER WORK.
>> IT'S A GREAT PLEASURE TO BE
HERE AND YOU WOULD LIKE THE
ORGANIZERS TO ALLOW ME TO TALK
ABOUT THE PROJECT.
I'LL TAKE YOU TO A UNIQUE REGION
IN TEXAS,RIO GRANDE VALLEY AND
THE PROJECT IS GENETIC GIVE BY
VIRTUAL EVALUATION.
I AM A CLINICAL GENETICISTS AT
THE BAYLOR COLLEGE OF MEDICINE
AND HAVE BEEN INVOLVED WITH THIS
PROJECT THE PAST TWO YEARS.
LET ME TAKE YOU TO THIS REGION
AT THE SOUTHERN MOST TIP OF
TEXAS.
YOU CAN SEE THERE IS A HIGH
ENRICHMENT OF HISPANIC
POPULATION IN THE REGION.
IT HAS A POPULATION OF ABOUT 1.3
MILLION RESIDENTS.
ONE-THIRD OF THE POPULATION
UNDER AGE 65 IS UNINSURED AND
THIS REGION WHICH IS AT THE
TEXAS-MEXICO BORDER, IS HOME TO
ONE OF THE POOREST CITIES IN THE
NATION WHICH INCLUDES MISSION
AND McCALHON AND ACCORDING TO
THE BIRTH DE FECTS REGISTRY IT'S
HIGHER THAN OTHER PARTS OF TEXAS
ESTIMATED TO BE OVER 400 PER
10,000 LIVE BIRTHS.
I WORK WITH CHILDREN WITH RARE
DISEASES.
FOR CHILDREN WITH RARE DISEASES
IN THIS REGION THERE'S TONS OF
BARRIERS TO RECEIVING GENOMIC
CARE AND DIAGNOSES.
FIRST THERE IS MINIMAL ACCESS TO
LOCAL GENETICISTS IN THE REGION.
THE FAMILIES TYPICALLY HAVE TO
TRAVEL A DISTANCE TO REACH A
GENETICIST.
HOUSTON IS FIVE HOURS FROM THE
REGION.
THERE'S LACK OF INSURANCE,
LANGUAGE BARRIER, SIGNIFICANT
FRACTION OF THE FAMILIES JUST
SPEAK SPANISH AND NOT JUST THAT,
THERE'S LIMITED PRIMARY CARE
PHYSICIANS IN THIS REGION AND
THE FAMILIARITY OF THESE WITH
GENOMIC DISORDERS HAMPERS ACCESS
TO GENOMIC CARE.
STUDIES AMONG THOSE GROUPS SHOW
HISPANICS ARE LEAST LIKELY TO
GAIN GENETIC TESTING.
PEOPLE ARE WARM AND FRIENDLY AND
THIS REGION IS RICH IN CULTURE
AND TRADITIONS AND YES, YOU SEE
THE URBANIZATION AND STRUCTURE
BUT THERE'S ALSO AREAS OF RURAL
COMMUNITIES LIKE THE FAR RIGHT.
THESE ARE CALLED CLONIAS WHICH
HAVE HORRIBLE WATER, ELECTRICITY
AND SANITATION.
THE COST IS OUT OF REACH FOR
MANY FAMILIES.
REDUCING HEALTH DISPARITIES AND
ACCESS TO CARE SAY PRIORITY FOR
US.
BECAUSE THESE ARE CHILDREN WHO
MAY ENDURE YEARS OF HEALTH
DECLINE WITH NO PROSPECT OF
PREVEN
PREVENTING MORBIDITIES AND
CHRONIC DISEASE AND THE
TREATMENT WOULD BE AVAILABLE IN
OTHER PARTS OF THE COUNTRY
EITHER MEDICATION OR DIETARY
MODIFICATION OR TARGETED
THERAPIES SUCH AS ENZYME
REPLACEMENT.
THESE CHILDREN MAY NEVER HAVE
ACCESS TO CLINICAL TRIALS
WITHOUT A DIAGNOSIS.
MORE IMPORTANTLY, THESE ARE
PARENTS WHO HAVE NO IDEA ABOUT
THE INHERENT GENETIC RISK
FACTORS THEY CARRY AND THEY MAY
GO ON TO HAVE REOCCURRENCE OF
SOMETIMES VERY DEVASTATING
DISEASES.
SO WE WERE FORTUNATE TO BE FUND
NCATS IN EARLY 2022 AND CALLED
THE PROJECT, GIVE.
IT WAS A COLLABORATION BETWEEN
BAYLOR COLLEGE OF MEDICINE AND
COLLEGE OF RIO GRANDE VALLEY.
WE FINISHED RECENTLY AND TODAY
I'LL TALK ABOUT THE PROJECT AND
WHAT WE HAVE ACHIEVED.
THESE ARE THE MAIN AIMS TO BEGIN
WITH.
REDUCE TIME TO DIAGNOSIS AND FOR
THAT WE WANTED TO USE A
MACHINE-ASSISTED VIRTUAL
PLATFORM TO DELIVER STATE OF THE
ART GENETIC EVALUATION IN THE
MEDICALLY UNDER SERVED
POPULATION.
WE ALSO DECIDED THAT WE WANTED
TO DO A WHOLE GENOME SEQUENCING
AS THE FIRST LINE TEST FOR THESE
FAMILIES.
AND WE TARGETED AND SAID WE
WOULD BE ABLE TO ENROLL 100
CHILDREN DURING THIS TWO-YEAR
PERIOD.
AT THE SAME TIME WE KNEW WE HAD
TO CONCENTRATE ON EDUCATION IS
AND INCREASE GENOMIC COMPETENCY
OF THE FRONT LINE PROVIDERS AND
THESE CHILDREN NEEDED TO BE
REFERRED AS SOON AS POSSIBLE
SUSPECT WITH RARE DISEASES.
THERE WERE SEVERAL CHALLENGE.
HOW DO WE SIMPLIFY THE PATIENT
PATHWAY WHERE THEY MAY NOT HAVE
ACCESS TO LOCAL GENETICISTS.
HOW DO WE REDUCE THE TIME TO
DIAGNOSIS AND INCREASE ACCESS TO
CARE AND HOW DO WE INCREASE THE
GENOMIC COMPETENCY OF THE FRONT
LINE HEALTH CARE PROVIDERS IN
THE REGION TO REDUCE THE
DIAGNOSTIC ODYSSEY.
THERE'S A WEB BASED PLATFORM
DESIGN BY BAYLOR COLLEGE OF
MEDICINE PRIOR TO THE COVID
PANDEMIC.
THE MAIN PURPOSE FOR THIS
PLATFORM WAS TO PROVIDE
EDUCATIONAL RESOURCES AND
SERVICES SUCH AS GENTIC
COUNSELING AND PEER-TO-PEER
CONSULTATIONS.
WE DECIDED TO USE CULT AGENE FOR
THIS PURPOSE WHAT WE DECIDED TO
DO EARLY WAS TO EXPAND THE
REFERRAL BASE SO IT WASN'T JUST
A PHYSICIAN FOR A NURSE
PRACTITIONER TO REFER AND WANTED
THEM TO GO TO PHYSICAL AND
OCCUPATIONAL THERAPISTS IN THE
REGION ESPECIALLY THOSE SEEING
THE PATIENTS 0 TO 3 TO EXPEDITE
THE REFERRAL PROCESS.
THIS IS WWW.CONSULTAGENE.org AND
YOU CAN REQUEST A PEER-TO-PEER
CONSULTATION.
THEY'RE ENCOURAGED TO CREATE AN
ACCOUNT.
AND ONCE THEIR ACCOUNT IS SET UP
THEN WE ASK THEM TO UPLOAD SOME
DEMOGRAPHIC INFORMATION ABOUT
THE PATIENTS THEY WOULD LIKE TO
REFER.
WE ALSO ASK THEY SEND US AT
LEAST ONE CLINIC NOTE THAT HELPS
US UNDERSTAND THE MAIN PROBLEMS
FOR THE CHILD.
OUR STUDY SITE IS PART OF THE
UNIVERSITY OF TEXASRIO GRANDE
VALLEY A SPECIALTY CLINIC IN
TEXAS ABOUT 20 MILES FROM THE
MEXICO BORDER.
WE DID THIS WORK UNDER THE
LEADERSHIP DR. ROBERT NELSON WHO
WAS THE CHAIR OF PEDIATRICS
DEPARTMENT AT THAT TIME.
OUR MODEL WAS TO WORK CLOSELY
WITH THE CLINICIANS IN THE AREA
TO REFER.
IT'S A YOUNG INSTITUTION AND THE
SCHOOL OF MEDICINE WAS FOUNDED
IN 2015.
WE DECIDED THAT THIS WOULD BE A
GREAT PARTNER FOR THIS WORK.
AS SOON AS WE STARTED WE KNEW WE
HAD TO MAKE A LIST OF
INDICATIONS FOR OUR REFERRERS TO
CONSIDER POSSIBLE GENETIC
DIAGNOSIS AND MADE THIS FOR THEM
AND CONCENTRATED ON THE
DEVELOPMENT PART AND THERE'S
OTHER INDICATIONS ON THE SLIDE
WE MADE SURE REFERRERS KNEW WHEN
TO REFER.
WE DECIDED UTRG WOULD BE OUR
MAIN BASE FOR SENDING THESE
PATIENTS OUR WAY BUT WE HAD TO
REACH OUT TO COMMUNITY
COLLABORATORS AND THE FIRST WAS
EASTER SEALS AND THEY WERE
SEEING CHILDREN 0 TO 3 AND WE
PARTNERED WITH THEM AND ANOTHER
SYSTEM CALLED DHR HEALTH AND
COLLABORATED WITH THE
ENDOCRINOLOGISTS TO SEND US
PATIENTS WITH SYNDROMES AND
SHORT STATURE AND WE
CONCENTRATED ON THE THERAPISTS
GIVING SERVICES TO CHILDREN WITH
COMPLEX DISEASES.
AND COMMUNITY PEDIATRICIANS.
FOOD IS AN IMPORTANT PART OF
HISPANIC CULTURE AND WE WANTED
TO BUILD RELATIONSHIPS BY
SHARING MEALS WITH THEM AND THAT
WAS A GREAT WAY TO KNOW THEM
WELL AND FOR THEM TO KNOW US
WELL.
WE ALSO LEVERAGED THIS GREAT
FACILITY.
IT'S A PUBLIC LIBRARY.
IT HAS A GREAT AUDITORIUM AND WE
DESIGN TWO CME CONFERENCES FOR
PHYSICIANS AND OTHER HEALTH CARE
PROVIDERS IN THE REGION TO TALK
ABOUT GENETICS AND GENETIC
DIAGNOSES.
SO IN THE LAST TWO YEARS WE
RECRUITED PATIENTS FROM ALL
THESE PLACES I JUST MENTIONED
PLUS WE ALSO USED TEXAS BIRTH
DEFECTS REGISTRY ONE OF THE
WORLD'S LARGEST POPULATION-BASED
SURVEILLANCE SYSTEM TO FIND
PATIENTS IN THE REGION.
THIS IS OUR TEAM, THE TOP LINE
ARE THE PEDIATRICIAN WE
PARTNERED WITH AT UTRG AND BELOW
IS OUR TEAM AT BAYLOR COLLEGE OF
MEDICINE.
THIS WORK WOULD NOT HAVE BEEN
POSSIBLE WITHOUT A GENETIC
NAVIGATOR ON SITE AND SHE'S
BILINGUAL AND IS A SOCIAL WORKER
AND KNOWS THE FAMILIES REALLY
WELL.
WE ESTABLISHED A CONSULT AGENE
KIOSK TO SEE THE FAMILIES AT THE
SITE.
THIS IS ONE EXAMPLE HOW WE SEE
THE PATIENTS.
WE LOOK ON TO ZOOM AND OUR
GENETIC NAVIGATOR BRINGS
FAMILIES ON SITE AND SEE VIDEOS
THROUGH CONSULTA GENE, WHAT TO
EXPECT AT THE GENETICS
APPOINTMENT AND THEY COMPLETE A
SURVEY AND WE COMPLETE OUR
REMOTE EVALUATION.
ONCE THAT IS COMPLETED, SAMPLES
ARE COLLECTED AT THE STUDY SITE
AND SENT TO BAYLOR GENETICS IN
HOUSTON FOR WHOLE GENOME
SEQUENCING.
ONCE THAT'S DONE WE MEET WITH
THE FAMILY AND PROVIDE A
COMPREHENSIVE COUNSELING AND
GUIDELINE IF THEY HAVE A
DIAGNOSIS AND FOLLOW THE
PATIENTS LONGITUDINALLY FOR A
YEAR.
AT DIFFERENT TIME POINTS WE USED
THESE ARE SURVEYS TO COLLECT
DATA.
AND WITH THE TARGET ENROLLMENT
OF 100 PATIENTS WE HAD OVER 200
PATIENTS REFERRED TO US THROUGH
CONSULT A GONE.
THIS WAS AMAZING AND WOULD NOT
HAVE BEEN POSSIBLE IF WE HAD NOT
EXPANDED OUR REFERRAL BASE.
WE WERE ABLE TO ACCEPT 80% OF
THE PATIENTS REFERRED TO US, 109
PATIENTS HAVE BEEN ENROLLED TO
DATE AND 61 FAMILIES HAVE
RECEIVED THEIR WHOLE GENOME
SEQUENCING RESULTS.
SO FAR WE HAVE RESOLVED
DIAGNOSES FOR 17 FAMILIES AND
PARTIALLY RESOLVED DIAGNOSIS FOR
TWO FAMILIES WITH OVER ALL
DIAGNOSTIC RATE OF ABOUT 71%.
WE HAD ONE CHILD WHO DEVELOPED
MENTAL DELAY WITH A SYNDROME
THAT CAN CAUSE SIGNIFICANT
ARRHYTHMIA.
LOOKING AT THE DEMOGRAPHICS OF
THESE FAMILIES, YOU CAN SEE 98%
OF OUR FAMILIES WERE HISPANIC
AND.
ABOUT 30% TO 40% HAD SPANISH AS
THEIR PRIMARY LANGUAGE.
YOU CAN SEE MOST OUR FAMILIES GO
TO LOWER SOCIAL ECONOMIC GROUP
AND SHOWS THE HIGHEST EDUCATION
LEVEL OF OUR FAMILIES.
THESE ARE SOME OF THE GENETIC
DISORDERS WE ASCERTAINED AND THE
SECOND CHILD WAS DIAGNOSED WITH
VITAMIN D DEPENDENT RICKETS AND
MAKING PROGRESS IN HIS
DEVELOPMENT.
THESE ARE OTHER DISORDERS.
YOU CAN TELL MANY OF THESE ARE
IN THE NEURODEVELOPMENT
CATEGORY, BRAIN MALFORMATION
DEVELOPMENTAL DELAY.
WE HAD ONE PATIENT ON THE FAR
LEFT WITH DUAL GENETIC DIAGNOSES
AND COLLECTING THE SURVEYS WE
WANTED TO ASSESS HOW THE
FAMILIES WERE LOOKING AT PROJECT
GIVE AND THE PRESENCE OF
RESEARCHERS IN THAT REGION.
AND YOU CAN SEE MOST FAMILIES
APPRECIATED THESE GENETIC TEST
RESULTS.
AND ALSO IT WAS GRATIFYING TO
SEE THEY WERE ALSO ABLE TO
UNDERSTAND THESE GENETIC RESULTS
WHEN WE WENT BACK TO VISIT.
MORE IMPORTANTLY, THEY FELT
THEIR DOCTORS COULD USE THE
RESULT TO IMPROVE THEIR
CHILDREN'S HEALTH.
I THINK THIS WAS VERY IMPORTANT.
AND ALL ACROSS THE BOARD THEY
FELT HOPE.
AND THESE ARE THE RESULTS.
WE HAVE STARTED TREATMENT AND
CREATED A HEALTH PLAN.
IT'S BEEN VERY GRATIFYING TO GET
THESE CARDS FROM PARENTS AND THE
SAME THEME AND THERE'S YEARS IN
TRYING TO FIND APE ANSWER.
-- AN ANSWER AND I THINK HAVING
THE WEB BASED TOOL CONSULTING
GENE THAT OPENED UP THE REFERRAL
PROCESS WAS CRUCIAL AND HAVING A
BILINGUAL NAVIGATOR ON SITE WAS
IMPORTANT AND BUILD STRONG
RELATIONSHIP WITH THE COMMUNITY
PARTNERS AND SHOWING UP IS
IMPORTANT.
WE MADE MULTIPLE AND IN PERSON
SITE VISITS.
WE PROMOTED THE STUDY ANY CHANCE
WE GOT, PEDIATRIC GRAND ROUND
WHETHER FACULTY MEETING OR
TEACHING SESSION WITH ECI AND
TREATING PARTNERS WELL.
THEY'VE BEEN DOING GREAT WORK
FOR A LONG TIME SO JUST
APPRECIATING THE WORK THEY'RE
DOING, RESPECTING THEIR WORK
JUST BEING HUMBLE AS YOU ENTER
THIS COMMUNITY.
IT WORKS BOTH WAYS.
IT HAS TO BENEFIT THE FAMILIES.
EVERY TIME WE HAD AN ENCOUNTER
WEDGE OUR FAMILIES WE MADE SURE
THERE WERE NOTES THAT COULD GO
BACK TO REFERRING PHYSICIANS.
THE CHALLENGES WERE MANY TIMES
WE DON'T HAVE A COMPLETE
CLINICAL INFORMATION AS WE
ACCEPT THESE PATIENTS.
BUT AS WE SAW WE ACCEPTED 80% OF
THESE PATIENTS.
IN SUMMARY THEY'VE ALLOWED A
PLATFORM FOR GENTETIC --
GENETIC ASSESSMENT AND WHOLE
GENOME ASSESSMENT AND I BELIEVE
THESE EFFORTS CAN BE REPLICATED
UP OTHER MEDICALLY UNDER SERVED
REGIONS.
I HAVE A LOT OF PEOPLE TO THANK
AND AGAIN THANK YOU FOR HAVING
ME HERE.
>> HI, I'M SUSIE SCHELLER AND
WORK WITH MITOACTION SO OUR
PATIENTS DEPEND ON GENETIC
TESTING TO CONFIRM MANY NOT ALL
THE DIAGNOSES.
I'M WORKING HARD.
[SPEAKING SPANISH]
I'M WORKING HARD TO LEARN
SPANISH AS FAST AS I CAN.
I HAVE PATIENTS IN THE ZONE YOU
DESCRIBED, EL PASO TOO AND WHAT
IS HEARTBREAKING IS WHEN I
RECEIVE ASKS FOR HELP FROM
PEOPLE FROM MEXICO WHO HAVE AN
APPOINTMENT AT UNIVERSITY OF
TEXAS AT HOUSTON AND THEY CAN'T
GET ACROSS THE BORDER BECAUSE
YOU HAVE TO HAVE A CERTAIN
AMOUNT OF MONEY SECURED.
THEY MAY BE HAVE RAISED WHAT IS
EQUIVALENT TO THOUSANDS OF
U.S. DOLLARS AND IT'S NOT ENOUGH
AND THEY WILL NOT LESS THEM
CROSS THE BORDER FOR THE
APPOINTMENT.
I'M SO GLAD FOR THE WORK THAT
YOU'RE DOING IN TEXAS BUT MY
HEART BLEEDS FOR THOSE WHO
CANNOT ACCESS IT.
AND I WONDER WHAT YOU WOULD SAY
FOR TO HELP ME WITH MY PATIENTS
FROM MEXICO WHO NEED SUPPORT.
>> THANK YOU SO MUCH.
I TRULY UNDERSTAND THESE
BARRIERS EVEN FOR PEOPLE WHO
LIVE IN THE VALLEY SOMETIMES
BECAUSE OF MULTIPLE CHECK POINTS
THEY'RE UNABLE TO GET TO OUR
CENTERS FOR CARE.
SO YES, I'LL BE HAPPY TO TALK TO
YOU MORE.
THANK YOU VERY MUCH.
>> ALL RIGHT.
I'D LIKE TO INTRODUCE OUR NEXT
SPEAKER, SHE'LL BE PROVIDING
ANOTHER RARE STORY.
I'D LIKE TO INVITE JESSICA
SWANSON SO TO THE STAGE.
JESSICA ALONG WITH BEING A RARE
DISEASE CAREGIVER AND MOM IS A
CO-CHAIR OF THE UNDIAGNOSED
DISEASES NETWORK PARTICIPANT
ENGAGEMENT AND EMPOWERMENT
RESOURCE.
JESSICA.
>> HI.
I STAND BEFORE YOU TODAY HUMBLED
BY THE OPPORTUNITY TO SHARE OUR
FAMILY'S JOURNEY THROUGH THE
LANDSCAPE OF RARE DISEASE
COURTESY OF NIH.
OUR STORY, WHILE UNIQUE, REFLECT
AS A COMMON NARRATIVE IN THIS
COMMUNITY.
CHALLENGING THE NOTION OF WHAT
IS CONSIDERED NORMAL, OUR NORMAL
AND A TYPICAL NORMAL
ENCAPSULATES A LIFE
UNCONVENTIONAL BY MANY BUT OUR
EVERYDAY REALITY.
OUR JOURNEY BEGAN WITH THE BIRTH
OF OUR DAUGHTER IN 2012 SHADOWED
BY THE KNOWLEDGE OF A FAMILY
DISPOSITION OFF SEA7.
DESPITE POSITIVE TEST RESULTS
FOR THE CONDITION SHE WAS NOT
EXPECTED TO EXHIBIT SYMPTOMS FOR
DECADES THANKS TO HER LOWER CAG
REPEAT COUNTY.
SHE MET MILESTONES AND FILLING
OUR HEARTS WITH JOY.
LITTLE DID WE KNOW OUR
INFORMATION OF RARE WOULD BE
PROFOUNDLY WHEN AT 7 MONTHS OLD
SHE BEGAN DISPLAYING UNUSUAL
MOVEMENTS.
WHAT WE INITIALLY DISMISSED AS
BABY REFLEXES WERE RECOGNIZED AS
SOMETHING MORE SERIOUS.
LED US TO THE HOSPITAL AND
BATTERY OF TESTS REVEALED
INFANTILE SPASMS, SEA7 WAS NOT
THE CAUSE AND THE ACTUAL CAUSE
WE MAINED ELUSIVE.
-- REMAINED ELUSIVE.
OVER THE NEXT NINE YEAR WE
CONSULTED WITH NUMEROUS
NEUROLOGISTS AND SPECIALISTS IN
PURSUIT OF AN EXPLANATION OF HER
CONDITION.
DESPITE COMPREHENSIVE TESTING, A
DIAGNOSIS REMAINED OUT OF REACH.
CAN OUR QUEST FOR ANSWERS WAS
COMPOUNDED BY A DIAGNOSIS OF
AUTISM AT 2 YEARS OLD.
HER QUALITY OF LIFE WAS LOW AND
WE LOOKED ON HELPLESSLY AS HE
SUFFERED THROUGH EIGHT SEIZURES
A DAY AND WE EXHAUSTED ALL
ANTI-EPILEPTIC MEDICATIONS
AVAILABLE AT THAT TIME, FAILED A
KETO GENIC DIET AND NERVE
STIMULATOR.
OUR LAST HOPE FOR SEIZURE
CONTROL WAS A MEDICATION THAT
BROUGHT HER SEIZURE TO A HALT.
TODAY THE REMAINS TONIC CONNICK
SEIZURE FREE AND ONLY HAS A FEW
A YEAR.
THIS IS NOT SOMETHING WE TAKE
FOR GRANT AND THANK FOL FOR THE
FDA APPROVAL OF THE DRUG THAT
SAVED HER LIFE.
DESPITE THE SIGNIFICANT
IMPROVEMENT IN HER CONDITION THE
ABSENCE OF A DIAGNOSIS SX
EXASPERATE THE EMOTIONAL TOLL.
I KNOW MANY PARENTS CAN RELATE.
THE RARE DISEASE COMMUNITY
HOWEVER, TAUGHT US RARE DOES NOT
EQUATE ALONE AND THERE IS
STRENGTH IN SHARED EXPERIENCES.
OUR JOURNEY WAS NOT WITHOUT
BENEFITS.
THE CONSTANT RELOCATION OF A
MILITARY LIFE OFFERED FRESH
PERSPECTIVES AND TREATMENTS WITH
EACH MOVE ALLOWING PARTICIPATE
IN THE STUDY WHEN SHE WAS 3 WAS
ONE OF THOSE.
YET THE CHALLENGE OF CONVEYING
YEARS OF MEDICAL HISTORY IN MERE
MINUTES TO NEW DOCTORS THE
WEIGHT OF THE FOUR-INCH MEDICAL
BINDER AND TRUST PLACED IN NEW
HANDS NEVER GOT EASIER.
IN 2021 MY FAMILY EMBARKED ON A
PATH WITH THE UNDIAGNOSED
DISEASE NETWORK AS A RESOURCE
FOR A POSSIBLE DIAGNOSIS.
IT WAS THROUGH THE EFFORTS OF
THIS NETWORK WE RECEIVED A
DIAGNOSIS BEFORE HER 10th
BIRTHDAY.
THE DIAGNOSIS WAS CDKL5.
A SURPRISE TO US AS THIS
CONDITION WAS PREVIOUSLY RULE
OUT MULTIPLE TIMES WITH HER
GENOME SEQUENCE TWICE WHEN SHE
WAS 2 AND 4 YEARS OLD.
ADDITIONALLY, SHE WAS
SPECIFICALLY TESTED FOR CDKL5 AT
14 MONTHS OLD
DESPITE THIS, THE DIAGNOSIS WAS
A REVELATION AND CONFIRMATION
CHANGING EVERYTHING AND NOTHING.
IT PROVIDED A LABEL, A COMMUNITY
AND HOPE FOR THE FUTURE YET SHE
REMAINED THE SAME VIBRANT CHILD
WE ALWAYS NEW.
THE DIAGNOSIS OF CDD WAS A
SIGNIFICANT TURNING POINT AND
WHILE A CHALLENGING RARE
DIAGNOSIS IT OPENED DOORS TO
BECOMING PART OF A UNIQUE AND
SUPPORTIVE COMMUNITY.
THIS HAS PROVIDED A STRONG
FOUNDATION OF SUPPORT, RESOURCES
AND ILLUMINATED MOMENTS OF HOPE.
THROUGH THE COLLECTIVE EFFORT OF
THOSE AFFECTED BY THIS PRIOR TO
THE DIAGNOSIS WE DID NOT KNOW
WHERE WE BELONGED IN THE
COMMUNITY.
WITH EXCITING POSSIBLE MEDICAL
TREATMENTS FOR CDKL5 IN THE
IMMEDIATE PIPELINE WE WOULD HAVE
THE OPPORTUNITY TO IMPROVE HER
LIFE BECAUSE WE DIDN'T HAVE THE
DIAGNOSIS UNTIL THE END.
THIS BRINGS ME TO THE HEART OF
THE MESSAGE TODAY.
HER STORY IS A TESTAMENT TO THE
COMPLEXITIES OF RARE DISEASES.
THE LIMITATION OF CURRENT
MEDICAL SYSTEMS AND THE PROFOUND
IMPACT OF COMMUNITY AND
COLLABORATION.
THE NEED FOR A UNIFIED MEDICAL
SYSTEM AND MORE COLLABORATIVE
APPROACHES TO PATIENT CARE IS
EVIDENT.
OUR EXPERIENCE UNDER SCORE THE
IMPORTANCE OF NOT JUST LOOKING
BUT SEEING, NOT JUST TESTING BUT
INFORMATION AND NOT JUST
TREATING BUT EMPATHIZING.
AS RESEARCHERS, HEALTH CARE
PROVIDERS AND ADVOCATES LET US
TAKE HER STORY AS A CALL TO
ACTION.
LET US STRIVE FOR A FUTURE WHERE
THE RARE ARE NOT JUST RECOGNIZED
BUT UNDERSTOOD.
WHERE OUR MEDICAL SYSTEMS ARE AS
INTERCONNECTED AS OUR SHARED
EXPERIENCES AND WHERE EVERY
INDIVIDUAL REGARDLESS OF THEIR
CONDITION FINDS A PLACE OF
BELONGING AND HOPE.
TOGETHER, WE CAN TURN THE TIDE
FOR FAMILIES LIKE OURS
NAVIGATING THE TURBULENT WATERS
OF RARE DISEASE TOWARDS A
BRIGHTER MORE INCLUSIVE FUTURE.
THANK YOU.
I'LL BE HAPPY TO TAKE ANY
QUESTIONS BEFORE OUR BREAK.
>> THANK YOU FOR THE STORY.
I LOVE THE PHOTOS.
THEY'RE SO BEAUTIFUL.
MY QUESTION ESPECIALLY SINCE WE
HEAR ABOUT THE OF THE ODYSSEY
NOT REALLY A JOURNEY.
WOULD YOU INCLUDE SPEECH AND
THERAPY EVEN WHILE YOU'RE NOT
GETTING A DIAGNOSIS?
WHAT WOULD YOU DO DIFFERENTLY
BECAUSE I KNOW THERE'S PARENTS
THAT MUST BE EXPERIENCING THIS
AND MAYBE THAT'S WHAT WE SAY.
UNTIL YOU GET IT MAYBE SOME OF
THESE ARE THINGS YOU CAN DO
UNTIL YOU GET THE CONFIRMED
DIAGNOSIS.
>> GREAT QUESTION.
DO ALL THOSE THINGS.
AS MUCH TREATMENT AS POSSIBLE.
SOME BARRIERS PARENTS COME TO IS
NOT HAVING A MEDICAL LABEL FOR
TREATMENT FOR INSURANCE.
I'M A BEHAVIOR ANALYST BY TRADE
SO I TREAT THOSE WITH AUTISM
WITH ADA THERAPY WHICH IS AN
EFFECTIVE THERAPY FOR MANY
DEVELOPMENT DELAYS BUT IF YOU
DON'T HAVE THE CODING, INSURANCE
WON'T COVER IT.
WE WERE LUCKY TO HAVE A PARTIAL
DIAGNOSIS OF AUTISM WHICH IS
PART OF THIS AND I'M GLAD YOU
BROUGHT THAT UP.
I DON'T KNOW WHAT THE ANSWER IS
BUT MAYBE WE CAN FIGURE IT OUT
TOGETHER.
>> PERFECT, THANK YOU.
>> THANK YOU FOR SHARING YOUR
STORY.
THAT WAS AMAZING AND I
APPRECIATE IT.
I KNOW YOUR DAUGHTER'S YOUNGER
AND MANY IN THE RARE DISEASE
COMMUNITY HAVE A LONG, LONG
PERIOD BEFORE THEY GET A
DIAGNOSIS EVEN IF THEY DO.
WHAT WE'VE BEEN SEEING AND I
DON'T KNOW IF THAT'S A
REFLECTION OF OUR HEALTH CARE
SYSTEM RIGHT NOW IS THAT THOSE
WITH RARE DISEASES ESPECIALLY
WHEN THEY GET ON THE CUSP OF
ADULTHOOD OFTEN FIND THEMSELVES
BEING TOLD IT'S PSYCHOLOGICAL OR
IN YOUR HEAD OR -- AND AGAIN, I
BELIEVE IN MENTAL HEALTH WHEN
HAVE YOU A DIAGNOSIS IN YOUR
FAMILY AS A CAREGIVER OR A CHILD
BECAUSE THAT'S VERY HEAVY BUT
AGAIN I SEE MORE AND MORE
INDIVIDUALS WITH RARE DISEASES
BEING DISMISSED.
WHAT ARE YOUR THOUGHTS ON THAT?
>> THANKS FOR THAT QUESTION.
THAT'S A GOOD POINT.
THAT'S SOMETHING WE HAVE TALKED
ABOUT AS PART OF MY WORK WITH
THE UNDIAGNOSED DISEASE NETWORK
FOUNDATION.
THE STATISTICS SHOW
AND WE KNOW ONE IN 10 PEOPLE
HAVE A RARE DISORDER SO IT IS
COMMON.
IT'S NOT UNCOMMON.
YEAH.
GREAT QUESTION.
>> I KNOW I'M NOT THE ONLY
PERSON WITH THIS QUESTION IF
THEY'RE DOING IT.
FURTHER BACK.
THERE.
MAA, CBS, WHAT ARE THOSE?
>> I'M A BOARD CERTIFIED
BEHAVIOR ANALYST AND CERTIFIED
AUTISM SPECIALIST WITH MY
MASTER'S.
>> THANK YOU.
>> WHILE WE'RE WAITING FOR A
MEDICAL DIAGNOSIS WHILE SHE WAS
DIAGNOSED WITH AUTISM I DECIDED
TO DEVOTE MY LIFE TO HELPING
THOSE WITH AUTISM IN THE BEST
WAY I COULD WAS BECOME AN EXPERT
IN THE FIELD SO THAT'S WHAT I
DID TO SUPPORT HER AND NOW ALL
OF HER FRIENDS.
THANK YOU.
>> BEFORE WE LEAVE I WANT TO
WELCOME A PROCLAMATION OF THANKS
TO DR. RUTTER.
>> HELLO, EVERYONE.
MY NAME IS JAMES BEST.
I HAVE JUVENILE MYO-CYTIS AND
HAD SYMPTOMS AT 4 YEARS OLD AND
NOT DIAGNOSED UNTIL I WAS 4.
I'VE BEEN BATTLING THIS DISEASE
MY WHOLE LIFE AND MY LIFE
RESOLVES AROUND TREATMENTS.
IN ADDITION TO THOUSANDS OF
PILLS OVER THE YEARS ANYWAY,
WEEKLY, CHEMO SHOTS, 25
TREATMENT DAYS A YEAR.
I HAVE AN ALL DAY INFUSION AND
PUT ME UNDER WITH ANESTHESIA OR
SOMETHING OF THE SORT AND A
MONTH EVERY YEAR I LOSE BECAUSE
THERE HASN'T BEEN MUCH OUT THERE
FOR JM AND OTHER RARE DISEASES
IN TERMS OF TREATMENTS.
IDEAL WITH EXTREME WEAKNESS
PROJECTS ARE TRADE AND PROJECTS
GIVE ME HOPE THE NEWLY DIAGNOSED
WHO COME AFTER ME WILL NOT HAVE
TO DEAL WITH ALL THE CONCERNS I
HAVE.
ON BEHALF OF THE CURE JM COUNCIL
AND RARE DISEASE COMMUNITY IT'S
MY HONOR TO GIVE THIS TO
DR. RUTTER AND THE NCATS TEAM.
THANK YOU FOR YOUR COMMITMENT
AND DEDICATION TO RARE DISEASES
AND YOUR WORK MEANS EVERYTHING
TO PATIENTS LIKE ME.
>> HU THU -- THANK YOU FOR
PRESENTING THAT AND THE TEAM.
WE'LL BE ON BREAK TO 10:55 AND
SEE ART AND EXHIBITS AND TALK
AMONGST YOURSELVES AN WE'LL KEEP
IT GOING.
WE'LL SEE YOU SOON.
>> WE'RE GOING GET STARTED.
IT'S A PLEASURE TO ANNOUNCE
ANOTHER FIRST.
WE HAVE DR. MONICA BERTAGNOLLI
HERE TODAY THE DIRECTOR OF THE
NIH.
SHE'S THE 17th DIRECTOR OF THE
NIH.
SHE IS THE FIRST SURGEON AND
SECOND WOMAN TO HOLD THE
POSITION.
SHE WAS NOMINATED BY PRESIDENT
BIDEN AND TOOK OFFICE OF
NOVEMBER 2023.
HER PREVIOUS SERVICE WAS AT THE
NIH.
SHE WAS THE 16th DIRECTOR OF THE
NATIONAL CANCER INSTITUTE AND
PRIOR TO THAT THE PROFESSOR OF
AND SURGICAL ONCOLOGY AT HARVARD
MEDICAL SCHOOL AND PART OF THE
SARCOMA CENTER AT DANA FAR BER
INSTITUTE.
SHE'S BEEN AT THE FOREFRONT OF
THE FIELD OF CLINICAL ONCOLOGY
AND SHE IS NO STRANGER TO RARE
DISEASES AND TO PEOPLE WITH
DEBILITATING DISORDERS.
SHE HAD A LAB IN CANCER AND THE
RESEARCH OF CANCER GROWTH AND
TRANSFORMED THE DATA
INFRASTRUCTURE FOR CLINICAL
RESEARCH AND WAS THE FOUNDING
CHAIR OF THE MINIMAL COMMON
ONCOLOGY GROUP ON THE EXECUTIVE
COMMITTEE.
SHE SERVED IN A VARIETY OF
CAPACITIES, HAS A GREAT DEPTH OF
TRANSLATIONAL SCIENCE AND DATA
SCIENCE.
SHE'S ALSO THE DAUGHTER OF FIRST
GENERATION OF IMMIGRANT AND
GRADUATED FROM PRINCETON WITH A
BACHELOR OF SCIENCE AND
ENGINEERING AND ATTEND MEDICAL
SCHOOL AT THE UNIVERSITY OF YOU
IT AND TRAINED IN SURGERY AT
BRIGHAM AND WOMEN'S HOSPITAL AND
WAS A RESEARCH FELLOW IN
IMMUNOLOGY AT THE DANA FARBER
INSTITUTE AND WE'VE BEEN ABLE TO
COAX HER IT BETHESDA AND IT'S MY
PLEASURE TO WELCOME HER TO THE
STAGE TODAY.
>> THANK YOU.
I CAN'T TELL YOU HOW THRILLED I
AM TO BE HERE.
I WANT TO JOIN OUR HOST IN
WELCOMING YOU TO RARE DISEASE
TODAY 2024 AND THANK YOU TO
DR. RUTTER AND GILMAN THE
DIRECTOR OF THE CLINICAL CENTER
HERE FOR THE WORK YOU AND YOUR
COLLEAGUES DO AT THE NATIONAL
CENTER FOR ADVANCING
TRANSLATIONAL SCIENCES AND AT
THE NIH CLINICAL CENTER TO
BETTER UNDERSTAND AND TREAT THE
WIDE RANGE OF RARE DISEASES.
WE BELIEVE IN CARING FOR PEOPLE
WITH RARE DISEASES IS AT THE
HEART OF EVERYTHING WE DO
BECAUSE NIH CAN BE A FOCAL POINT
FOR THIS INCREDIBLY DIVERSE AND
CHALLENGING COMMUNITY OF PEOPLE
WITH RARE DISEASES.
I'D ALSO LIKE TO RECOGNIZED
DR. DOMINIQUE PICHARD AND
DR. CHEN AND FOR THEIR WORK IN
COORDINATING THE EVENT.
I WANT TO ACKNOWLEDGE THE
CO-CHAIRS OF THE RARE DISEASE
CAUCUS WHO HAVE PROVIDE D
LEADERSHIP AND THANK YOU FOR
YOUR PARTICIPATION AND YOUR
CARING AND YOUR SUPPORT.
ON A PERSONAL NOTE, I AM A RARE
DISEASE DOCTOR.
WHEN I DID MY SURGICAL TRAINING
I CAME INTO CONTACT WITH A
BEAUTIFUL MAN WHO WAS SUFFERING
FROM TA RARE TUMOR SUSCEPTIBILIY
SYNDROME THAT CAUSES DUODENAL
CANCERS AND THIS WONDERFUL
GENTLEMAN I CARED FOR AS A
SENIOR RESIDENT WAS SUFFERING
FROM THE LATE STAGES OF
TREATMENT FOR DESMOID
DEMOYMA
DEMOYMATROSIS.
A DOCTOR IN COLORADO WAS
TREATING AN A PATIENT WITH THIS
DISEASE AND THEY LOOK LIKE AN
INFLAMMATORY REACTION AND
TREATED HIS PATIENT WITH A
NON-STEROIDAL ANTIINFLAMMATORY
DRUG AND DIDN'T DO A THING TO
THE DESMOID BUT ALL THEIR
INTESTINAL POLYPS WENT AWAY AND
HE TREATED A COUSIN AND THEN
THAT COUSIN'S AND GOT THE SAME
RESULT AND THE FIRST TIME THEY
SAW IT COWS INHIBIT INFLAMMATION
IN THE INTESTINE.
THAT'S WAS AN INSPIRATION TO ME
AND I JUST FINISHED MY POSTDOC
IN IMMUNOLOGY AND I STUDIED
FAMILIAL POLYPOSIS AND HOW IT
COULD REVERSE EFFECTS AND CARE
FOR FAMILIES WITH FAP.
LATER IN MY CAREER BECAUSE THERE
WERE MANY PEOPLE WHO TOOK CARE
OF PATIENTS WITH COLON CANCER
AND DODEAL CANCERS I TREATED
THESE TUMORS.
I SPENT MY BASIC SCIENCE CAREER
TAKING CARB OF THESE FAMILIES
WITH THIS RARE DISEASE.
AND HOW COURAGEOUS AND DEDICATED
ALL THOSE WONDERFUL PEOPLE WERE
IN HELPING US HAVE AN INCREDIBLE
UNDERSTANDING AND THIS IS THE
POINT, OF COMMON DISEASES.
WE KNOW THEY HAD IT BECAUSE OF A
GERM LINE MUTATION AND EVERYBODY
ELSE GETS IT AS A RESULT OF
OTHER SOMATIC INSULTS BUT
EVERYTHING WE LEARNED FROM
PEOPLE WITH FAP ENDED UP HELPING
EVERYBODY IN UNDERSTANDING HOW
TO TREAT A DEADLY CANCER.
I JUST THOUGHT I'D START WITH
THE RARE EXPERIENCE AND LET YOU
KNOW WHAT AN INCREDIBLE HONOR IT
IS TO WORK WITH THE RARE DISEASE
FAMILIES AND HOW FORTUNATE I AM
TO BE HERE TODAY.
OKAY, YOU PROBABLY KNOW RARE
DISEASES ARE COLLECTIVELY NOT
RARE.
I DON'T NEED TO TELL ALL OF YOU
THIS.
THEY ARE SO COMMON.
WE HAVE SO MUCH TO DO AND SO
MUCH TO LEARN TOGETHER TO MAKE
LIFE BETTER PEOPLE WITH RARE
DISEASES OFTEN STRUGGLE FOR
YEARS TO RECEIVE AN ACCURATE
DIAGNOSIS AND WHEN THEY DO THEY
FIND FEW TREATMENTS ARE
AVAILABLE.
LET'S TALK ABOUT LINKING THE
DIAGNOSIS AND LINKING TO
TREATMENTS AND LINKING TO
OPPORTUNITIES FOR RESEARCH.
I WILL ALSO TELL YOU ONE OF THE
THINGS CERTAINLY NOT PUBLIC YET
THAT I AM ALSO DEDICATED TO DO,
I WANT TO MAKE IT POSSIBLE FOR
EVERY SINGLE PERSON WHO WALKS
INTO A CLINIC AND INTO A
DOCTOR'S OFFICE, ANY LOCATION
WITH AN ELECTRONIC HEATH RECORD
IN THE UNITED STATES TO BE ABLE
TO SAY, I GIVE MY PERMISSION FOR
MY DATA TO USE FOR RESEARCH AND
MORE IMPORTANT, I WANT YOU TO
RECONTACT ME IF SOMETHING
RELEVANT TO ME OR MY FAMILY
BECOMES AVAILABLE.
TO HAVE THAT AVAILABLE TO THE
ENTIRE CLINICAL CARE AND
RESEARCH COMMUNITY TO BE ABLE TO
IDENTIFY PEOPLE WHO ARE REACHING
OUT BECAUSE THEY HAVE A SPECIAL
NEED.
AND THINK ABOUT WHAT THIS WOULD
DO FOR THE RARE DISEASE
COMMUNITY AND NIH, FOR INSTANCE,
WOULD SAY WE HAVE A BRAND NEW
PROTOCOL FOR DUCHESNE'S MUSCULAR
DYSTROPHY AND PEOPLE SAID YES, I
WANT YOU TO LET ME KNOW WHAT'S
GOING ON.
I'LL FINISH BY SAYING AMAZON
KNOWS WHAT KIND OF SHAMPOO I USE
FOR CRYING OUT LOUD, WHY CAN'T
WE MAKE IT POSSIBLE FOR THOSE
PEOPLE WHO NEED US TO STAND UP
AND SAY, HEY, I'M HERE?
OKAY, THANK YOU FOR THAT AND I
HOPE TO MOVE THIS IT'S MY BIG
AGENDA AS DIRECT AND WE'RE
GETTING HELP ACROSS HEALTH AND
HUMAN SERVICES.
IT WILL PUSH HARD AND WE NEED
SOME TWEAKS IN LEGISLATION FROM
CONGRESS TO MAKE IT MANDATORY
BUT WE'RE DETERMINED.
OKAY, A FEW FINISHING COMMENTS.
AT NIH WE'RE COMMITTED TO TAKING
ON THE CHALLENGE OF RARE
DISEASES.
ONE OF MY GUIDING PRINCIPLES I
TOLD YOU ABOUT MY OWN
RELATIONSHIP WITH PEOPLE WHO ARE
LIVING WITH RARE DISEASE IS THAT
WHEN IT COMES TO RESEARCH, WE
CAN DO NOTHING POUT THE PEOPLE
WE SERVE.
NOTHING ABOUT US WITHOUT US THIS
FROM THE ADVOCATE COMMUNITY IS A
GUIDING PRINCIPLE FOR US.
CERTAINLY FOR ME PERSONALLY AND
FOR US.
YOU NEED TO BE AT THE TABLE FOR
EVERYTHING.
THE PATIENT COMMUNITY IS A
CRITICAL PART AND THE PATIENT --
REMEMBER, WHEN I TALK ABOUT THE
PATIENT COMMUNITY I DON'T OFTEN
REMEMBER TO SAY IT BUT THE MOMS
AND DAD AND SISTERS AND BROTHERS
AND COMMUNITY MEMBERS AND ALL
THOSE OTHER PEOPLE WHO MIGHT NOT
HAVE THE DISEASE BUT THEY'RE
INCREDIBLY CRITICAL PART OF THE
COMMUNITY.
REMEMBER, I ENCOMPASS THE
CAREGIVERS OF ALL TYPES IN THAT
DISCUSSION.
NIH IS DOING SOME THINGS WE
THINK ARE STARTING TO CRACK SOME
CODES.
ONE, IS TO ENGAGE THE PATIENT
COMMUNITY WRIT LARGE THROUGH THE
RARES CLINICAL NETWORK AND 10 OF
THE INSTITUTES AND CENTERS
PARTICIPATE IN THIS NETWORK
RIGHT NOW WHICH CONNECTS
SCIENTIST TO RARE DISEASE
ORGANIZATIONS AND PATIENT
ADVOCACY GROUPS, HOPING TO GET
ALL.
COMMUNICATION AND NETWORKING IS
KEY.
NIH ALSO SUPPORTS THE
ACCELERATING MEDICINES
PARTNERSHIP, BESPOKE GENE
THERAPY CONSORTIUM.
I KNOW WE'RE ALL LOOKING FOR THE
NEW PLATFORMS, THE NEW
APPROACHES, THE NEW ATTORNEY
GENERALS THAT ARE GOING TO START
TO YEEL -- REALLY MOVE THE
NEEDLE AND HAVE A SINGLE
MUTATION DEFECT AND WE'RE PROUD
TO BE PART OF A PROGRAM THAT'S A
PARTNERSHIP BETWEEN NIH,
INDUSTRY, PHARMACEUTICALS AND
MULTIPLE OTHER NON-PROFIT AND
PROFESSIONAL ORGANIZATIONS TO
MOVE FORWARD BESPOKE GENE
THERAPIES FOR EACH GENETIC
DEFECT THAT CAN PRODUCE DISEASE.
THIS IS ACTIVELY WORKING TO
ADVANCE TREATMENT THERAPIES FOR
EIGHT RARE DISEASES.
THAT IS JUST THE TIP OF THE
ICEBERG.
WE HOPE TO SEE MANY MANY MORE
SOON.
WE'RE NOT DONE.
WE HAVE SO MUCH MORE TO DO.
WE'LL CONTINUE TO LOOK FOR WAYS
TO WORK WITH EVERYONE IT TAKES
AS RESEARCH PARTNERS TO MAKE
LIFE BETTER.
EQUITY IS THE THEME OF RARE
DISEASE DAY 2024 NATIONALLY AND
SOMETHING WE ALSO ABS --
ABSOLUTELY CANNOT FORGET.
I CAN'T FORGET THE PATIENTS WHO
SAW ME AT THE MAJOR CENTERS IN
BOSTON AND I HAD SOME THAT HAD
FUND RAISERS TO FLY TO BOSTON TO
SEE ME FOR THEIR CARE.
THAT'S TOUGH.
THAT'S REALLY TOUGH.
WHEN YOU THINK ABOUT THE ENTIRE
MEDICAL SYSTEM, PEOPLE WITH RARE
DISEASES HAVE TO GO WHERE THE
SPECIAL EXPERTS ARE AND SO IT
CAN BE RECOGNIZING THE DOUBLE
CHALLENGE.
EQUITY IS OUR THEME THIS YEAR
AND BY EQUITY WE MEAN WE HAVE TO
BE PART OF THE SOLUTION
INVOLVING THE PROBLEMS FOR THOSE
INDIVIDUAL WHO'S NEED EXTRA HELP
GETTING WHERE THE EXPERTS ARE.
I'LL CALL OUT AGAIN OUR CLINICAL
CENTER.
I THINK WORLDWIDE TREASURE IN
THIS REGARD WHEN WE HAVE
PROTOCOLS HERE FOR PATIENTS OF
ALL KINDS.
OF COURSE WITH A HUGE FOCUS ON
RARE DISEASES, WE CAN MAKE IT
POSSIBLE FOR THEM TO COME AND
RECEIVE THEIR CARE FREE OF
CHARGE.
OBVIOUSLY THIS DEPENDS ON OUR
FEDERAL FUNDING AND ON THE
AVAILABILITY OF RESEARCH
PROJECTS BUT WE WILL REMAIN
DEDICATED TO THIS AND TAKE THIS
AS FAR AS WE POSSIBLY CAN.
OKAY.
WE NEED TO DISCOVER NEW
TREATMENTS AND HOW TO MAKE THEM
WIDELY AVAILABLE TO EVERYONE WHO
NEEDS THEM.
SICKLE CELL DISEASE WOW.
NOT GOOD ENOUGH YET.
ALMOST A YEAR IN THE HOSPITAL
AND CHALLENGING TREATMENT AND I
KNOW FOR THE SPECIAL PEOPLE WHO
HAVE SICKLE CELL DISEASE IT'S
WORTH IT WHEN YOU THINK OF THE
SUFFERING WITH THE DISEASE BUT
IT'S STILL WAY TOO MUCH TO
RECEIVE TREATMENT FOR THE
DISEASE.
IT'S THE BEGINNING.
WE'RE DETERMINED FOR THAT TO BE
AVAILABLE TO EVERYBODY AND
NUMBER TWO, SO MUCH BETTER THAN
IT IS TODAY.
WE HAVE A BREAKTHROUGH, NOW
LET'S RUN WITH IT AND MAKE THAT
BETTER.
I'M GOING TO END BY SAYING THAT
WE INTEGRATE RARE DISEASE
RESEARCH AND TREATMENT INTO ALL
OF OUR BROADER HEATH
INITIATIVES.
WE REMIND PEOPLE THAT THE
LEARNING WE GET FROM THE RARE
DISEASE COMMUNITY LIKE THAT OF
PATIENTS WITH FAP HELP
EVERYBODY.
SO THERE ARE ENUMERABLE REASONS
TO FOCUS ON TAKING ON THESE
CHALLENGES.
FINALLY, MY SLOGAN AS NIH
DIRECTOR IS THE FOLLOWING.
OUR WORK AT NIH IS NOT FINISHED
WHEN WE MAKE SCIENTIFIC
DISCOVERIES.
OUR WORK AT NIH IS ONLY FINISHED
WHEN ALL PEOPLE ARE LIVING LONG
AND HEALTHY LIVES.
SO, THANK YOU FOR BEING OUR
PARTNERS IN MAKING THIS HOPE A
REALITY AND I HOPE YOU ENJOY
THIS WONDERFUL DAY PUT TOGETHER
BY OUR FOLKS AT NCATS AND THE
CLINICAL CENTER.
THANK YOU.
>> ALL RIGHT, MOVING ALONG WE
HAVE OUR FIRST SESSION OF THE
DAY, LIKED TO INTRODUCE OUR
MODERATOR FOR THE SESSION,
CHRISTINE CUTILLO WITHIN THE
OFFICE OF THE DIRECTOR AT NIH.
>> HI, ALL.
IT'S GREAT TO BE HERE TODAY.
I'M CHRISTINE CUTILLO AND HEALTH
DATA SCIENTIST FOR A.I. ETHICS
IN THE OFFICE DATA SCIENCE
STRATEGY FOR ODSS.
IT'S PART OF THE OFFICE OF THE
DIRECTOR.
WE WORK WITH ALL 27 INSTITUTES
AND CENTERS AND LOOK ACROSS THE
FULL WATERFRONT OF THE NIH
MISSION SPACE.
THERE'S MANY A.I. ACTIVITIES
ACROSS NIN.
AND ODSS TRIES TO FIND WAYS TO
LIFT ALL BOATS IN THE SPACE.
ONE OF OUR FOCUS AREAS IS
ENHANCING TRANSPARENCY ACROSS
THE ECO SYSTEM FOR DATA AND
MODEL DEVELOPMENT.
AS A FIRST STEP TOWARDS BUILDING
RESPONSIBLE AND ETHICAL A.I.
PRACTICES.
ENHANCING TRANSPARENCY COULD
HELP PATIENTS AND PROVIDERS
ANSWER QUESTIONS LIKE HOW WELL
DOES THIS A.I. DIAGNOSTIC TOOL
PERFORM FOR PATIENTS LIKE ME.
TRANSPARENCY IS ALSO A FIRST
STEP TO ENCOURAGING AND HELPING
RESEARCHERS WANTING TO MAKE A.I.
TOOLS MORE INCLUSIVE AND
EQUITABLE.
WHAT WE DON'T STOP THERE.
MYSELF AND THE WHOLE PANEL ARE
EXCITED TO SPEAK WITH YOU ABOUT
THAT NOW.
FIRST, YOU'LL HEAR ABOUT A.I. AT
A HIGH LEVEL AND HOW IT CAN BE
LEVERAGED TO BENEFIT PATIENTS
AND YOU'LL HEAR ABOUT PROJECTS
AIMED AT REDUCING THE DIAGNOSTIC
ODYSSEY, IDENTIFYING PATIENTS
FOR CLINICAL TRIALS AND BUILDING
TOOLS FOR REPURPOSING DRUGS.
AFTERWARD, WE'LL HAVE A Q&A
PANEL DISCUSSION AND YOU'LL BE
ABLE TO ASK QUESTIONS.
SO NOW I'D LIKE TO INTRODUCE OUR
FIRST PANELIST TODAY, KIM MORAN
IS THE HEAD OF U.S. RARE
DISEASES AT UBC.
COME ON UP, KIM.
GO
>> GOOD MORNING, EVERYONE.
CAN WE DO THAT AGAIN?
GOOD MORNING, EVERYONE.
THANK YOU FOR NCATS FOR THIS DAY
AND WE'RE CELEBRATING THE WORLD
OF RARE DISEASE.
TODAY MY JOB IS TO HELP
DEMYSTIFY ARTIFICIAL
INTELLIGENCE.
MY MOM'S NAME IS CINDY SO WE'RE
GOING TO USE THE CINDY FACTOR
AND TRY TO BRING A.I. DOWN SO WE
CAN ALL UNDERSTAND IT NOT BE SO
SCARED OF IT THOUGH IT IS A
LITTLE SCARY WHEN YOU LOOK AT
SOME OF THE DEFINITIONS.
WHAT IS A.I.?
ARTIFICIAL INTELLIGENCE I FOUND
IT BY GOOGLING.
IT'S A MACHINE'S ABILITY TO
PERFORM THE COGNITIVE FUNCTIONS
WE USUALLY ASSOCIATE WITH HUMAN
MINDS.
IS THAT SCARY?
YES AND FASCINATING TOO.
LET'S BREAK IT DOWN.
THERE'S A FIELD OF ARTIFICIAL
INTELLIGENCE AND BELOW THAT A
TOPIC OF MACHINE LEARNING AND
USE MATH TO LOOK FOR PATTERNS
AND USE COMPUTER TO DO THINGS
HUMANS DON'T NEED TO DO LIKE THE
CALCUL
CALCULATOR.
WE HAVE ALEXA AND SYRI IN OUR
HOMES FOR ENABLING OUR LIVES BUT
IT GETS SCARY WHEN A COMPUTER IS
RECOMMENDING THINGS ABOUT YOUR
HEALTH CARE, YOUR DIAGNOSIS.
HOW CAN WE USE A.I. FOR GOOD?
DATA.
HEALTH CARE IS ONE OF THE
RICHEST DATA ENABLERS IN THE
WORLD.
SO HOW CAN WE UNLOCK THE SECRETS
OF HUNDREDS OF THOUSAND OF
MILLIONS OF BILLIONS DATA POINTS
TO CREATE A BETTER EXPERIENCE
SPECIFICALLY FOR RARE DISEASE?
THE MATH COMPONENT.
IF YOU LOOK AT MACHINE LEARNING
THEY USE ALGORITHMS TO DETECT
PATTERNS IN PILES AND PILES OF
DATA.
THIS HAPPENS EVERY DAY IN OUR
LIVES.
I'M SURE THERE'S A LOT OF
NETFLIX SUN -- SUBSCRIBERS.
YOU SEE THE SUGGESTIONS FOR YOU.
THEY TAKE ALL THE USERS THAT ARE
LOOKING AT ALL THE DIFFERENT
FILMS AND THEN LOOKING AND DOING
WHAT IS KNOWN AS A LOOK ALIKE
ANALYSIS.
BUT YOU SEE YOUR SUGGESTIONS
CHANGE WEEKLY, MONTHLY, DAILY.
SO WHY IS THAT HAPPENING?
THE DATA'S CHANGING.
WE HAVE THE MATH AND THE DATA.
THE DATA IN HEALTH CARE, YOUR
PERSONAL RECORDS.
EVERY TIME YOU DING THE HEALTH
CARE SYSTEM.
I WENT TO CVS AND PICKED UP A
SCRIPT.
I WENT TO MY DOCTOR AND THEY RAN
X, Y AND Z.
ALL THOSE DATA POINTS TIMES THE
MI
MILLIONS OF PEOPLE IN THE UNITED
STATES GROWS BY THE SECOND.
IT'S A BALANCE BETWEEN THE MATH
LEARNING THE DATA PILES AND THE
DATA PILE GETTING BIGGER AND
BIGGER.
SO WHAT ARE THE EXCITING THINGS?
WE'RE LEARNING MORE ABOUT THE
DIAGNOSTIC ODD SPIP THIS SIMPLE
LINE IS LAYERS OF DATA LOOKING
FOR KEY POINTS IN A PATIENT'S
JOURNEY.
THINK OF THE SYSTEMS AND THE
FIRST SEIZURE AND CLINICAL
EVENT.
THERE'S TO MANY SYMPTOMS THAT
OCCUR WE DON'T ALWAYS AS LAY
PEOPLE ALWAYS UNDERSTAND OR EVEN
NOTE.
WHAT IF THE SYMPTOMS WERE
REPORTED EARLIER OR WERE ABLE TO
CAPTURE THEM QUICKER?
COULD THE MACHINE LEARNING
EVENTS BE ABLE TO DETECT THINGS
EARLIER.
SEND A FLAG TO A PHYSICIAN?
EVEN A NOTIFICATION TO YOURSELF.
OR HELP IN THE DIAGNOSTIC
JOURNEY.
INFINITY LOOPS ARE WHERE
PATIENTS GET STUCK AND A GET A
SYMPTOM, GO TO THE HOSPITAL AND
GO BACK.
HOW CAN WE PROTECT AND IDENTIFY
THOSE MOMENTS AND BREAK THOSE
MOMENTS?
I'LL SHARE A COUPLE EXAMPLES OF
THINGS WE'RE DOING DOING TODAY
AND SHARE HOW WHY HAVING A
COMPUTER ACT WITH ETHICS IS
GOOD.
FIRST CASE, PATIENT FINDING.
YOU HEARD ABOUT THE DIAGNOSTIC
ODDITY VOOECH WITH DOMINIQUE IT
TOOK A YEAR.
THIS IS THE MOST EQUIPPED PERSON
IN THE WORLD TO HAVE A CHILD
WITH A RARE DISEASE AND I
COULDN'T BE FASTER.
WE UTILIZE THE HEALTH CARE DATA
AND THE LOOK ALIGN ANALYSES.
GOING BACK TO THE DEFINITION OF
A LOOK ALIKE ANALYSIS.
I BUY A PURPLE DRESS AND GO ON
AMAZON AND PURPLE DRESS YOU'LL
SEE CUSTOMERS LIKE YOU ALSO
BOUGHT.
THEY'RE TAKING ALL MY BACKGROND
DATA, AGE, BUYING PATTERNS,
WHERE I LIVE MOM OF WHO KIDS AND
LIVE IN GEORGIA AND THERE'S A
BUNCH OF OTHER WOMEN LIKE ME
LOOK AGENT PURPLE DRESSES.
IT TACKS THEM UP AND RECOMMENDS
AND RANKS THOSE MISTAKE LIKELY
I'D WANT TO BUY.
HOW DO WE USE THIS IN HEALTH
CARE?
WE TAKE A COHOST PATIENTS.
I WORK IN A COHORT MICE AND WE
USE DIAGNOSTIC CODES AND CREATE
A DATA COHORT OF ALL THE
PATIENTS IN THE UNITED STATES.
WHAT DO THEY LOOK LIKE TODAY?
WHAT DO ALL THEIR DINGS IN THE
HEALTH CARE SYSTEM LOOK LIKE?
LAYER THAT UP AND GET IT TO THE
COMPUTER WITH THE MATH AND
MACHINE LEARNING UNDER THE A.I.
UMBRELLA AND GIVE ME PATTERNS
HERE.
HOW CAIN BREAK THIS UP TO
SMALLER COHORTS.
SAY WE LOOK AT WOMEN LOOKING AT
A SUBSEFT A POPULATION WHICH IS
MUSK.
SEVERAL THOUSAND PATIENTS IN THE
UNITED STATES.
WE HAVE THAT GROUP AND TEMPLATE
AND TAKE THE MATH THAT NOW NOU
KNOWS HOW TO IDENTIFY AND IT
DOESN'T JUST INCLUDE THESE
PATIENTS BUT ALL IN THE
PATIENTS.
IT CAN START TO LOOK AT PATIENTS
HAVING SYMPTOMS BEFORE THEY HIT
THE DIAGNOSIS.
THEY HAD MUSCLE WEAKNESS OR
UNABLE TO BREATHE AND THE MATH
IS LEARNING FROM ALL THE OTHER
PATIENTS THAT WENT THROUGH THAT
DIAGNOSTIC ODYSSEY.
SOME ARE USING CLINICAL SUPPORT
AND THE MATH IS HELPING US
SHORTEN TIME TO DIAGNOSIS,
SHORTEN TIME TO THE RIGHT
TREATMENT AND GET RID OF SOME OF
THOSE INFINITY LOOPS.
THE SECOND IS PREDICTION.
HOW MIGHT WE PREDICT?
HOW MIGHT WE PREDICT IF MAYBE
YOU'LL HAVE A BAD DAY WITH
SYMPTOMS?
OR MIGHT WE PREDICT THAT YOU AS
A PATIENT MAY HAVE AN EASIER
PATH OF THE DISEASE OR HARDER
PATH?
AND IF WE KNOW AHEAD OF TIME
THAT MAYBE YOU'RE THE ONE WITH
THE HARDER PATH, THEN WE CAN
ACCELERATE THEY'LL NEW
TREATMENTS, TARGETED THERAPIES
EARLY FOR PATIENTS.
SO WE'RE USING THE MATH TO DO
THINGS LIKE THIS.
WE TAKE A SAME COHORT OF
PATIENTS WE LOOK FOR PATTERNS,
THEY GIVE US SIGNALS TO ALERT
THAT PERHAPS THIS PATIENT'S
GOING HAVE A HARDER JOURNEY.
THOSE TYPES OF ANALYSES CAN BE
PUT IN SYSTEMS AND IN THE HANDS
OF YOU AS PATIENTS AND
CAREGIVERS AND PEOPLE IN OUR
COMMUNITY.
THIS IS MY APPLE WATCH.
IT DOES DETECT A WHOLE LOT OF
THINGS.
SO WHAT WE'RE SEEING NOW IS THAT
REAL LIVE DATA YOU ARE
GENERATING AS A LIVING HUMAN
BEING CAN BE USED ALSO TO
IDENTIFY PREDICTORS.
IT'S FASCINATING.
WORKING AGAIN IN THIS CONDITION
THE PHONE CAMERA CAN LOOK FOR
CHANGE IN EYELIDS OR VOICE
CHANGES TO ALERT A PATIENT THAT
MAYBE TOMORROW WON'T BE A GREAT
DAY.
MAYBE YOU WANT TO STAY AWAY FROM
HEAT AND HUMIDITY, HELLO,
ATLANTA, GEORGIA AND STAY INSIDE
BECAUSE YOU'RE AT A HIGH RISK
FOR A CRISIS OR AN EXACERBATION.
SO WE'RE UTILIZING ALL THESE
THINGS.
I DON'T IF YOU HEARD THE TARGET
STORY.
YEARS BACK TARGET WAS USING A.I.
TO SEND COUPONS TO HOUSEHOLDS.
THEY STARTED TO FIGURE OUT
BUYING PATTERNS OF WOMEN BEFORE
THEY TOOK A PREGNANCY TEST.
SO PARENTS WERE GETTING LEAFLETS
ABOUT BABY STUFF AND THEIR
DAUGHTERS MAY HAVE BEEN PREGNANT
AND THEY DIDN'T KNOW IT.
NOT A GREAT EXAMPLE WHEN A.I.
WAS USED AND LED TO DIFFICULT
DISCUSSIONS IN THE HOUSEHOLD.
A.I. CAN BE USED FOR GOOD BUT WE
ALSO HAVE TO HAVE THE RIGHT
CONSTRAINTS AND RIGHT DATA, THE
RIGHT VALIDATION FOR IT TO
ENABLE FORAY BETTER DIAGNOSTIC
TREATMENT FOR THOSE IN RARE
DISEASE.
THANK YOU AND I'LL PASS TO IT
OUR NEXT PANELIST.
NEXT WE'LL HAVE MANISHA BALWANI
A PROFESSOR AND CHIEF DIVISION
OF THE MEDICAL GENETICS AND
GENOMICS DEPARTMENT OF GENETICS
AND GENOMIC SCIENCES ICAHN
SCHOOL OF MEDICINE AT MOUNT
SINAI.
>> WE'LL TALK ABOUT SHORTENING
THE DIAGNOSTIC ODYSSEY FOR
PATIENTS WITH RARE DISEASES.
I'LL HIGHLIGHT THE CHALLENGES
AND SUCCESSES AND WHAT WE
LEARNED FROM THE PROCESS.
THERE WAS WORK IN DEVELOPING A
PEDIATRIC MACHINE-ASSISTED
ALGORITHM.
AS PART OF THE UG3 PHASE OF THE
GRANT WE PILOTED THE ALGORITHM
IN A STUDY WITH 200 PATIENTS AND
AS A SECONDARY AIM, WE WANTED TO
TRAIN AND CONTINUE TO IMPROVE
THE ALGORITHM.
THE NEXT PHASE OF THE STUDY IS
THE UH3 PHASE WHERE WE AIM TO
DEPLOY THIS IMPROVED ALGORITHM
AT A COMMUNITY HOSPITAL WITHIN
THE MOUNT SINAI SYSTEM AND AIM
TO ADOLESCENTS AND ADULTS.
IT WAS BASED ON THE PRINCIPLE
INFANTS AND TODDLERS WOULD BE
ENRICHED FOR PATIENTS WITH RARE
DISORDERS.
A MODEL WAS TRAINED ON THE
ELECTRONIC HEALTH RECORD NOTES
OF THE CHILDREN.
THIS NATURAL LANGUAGE BASE
ALGORITHM WENT FOR THE TESTING
AND THE PROCESS WAS REPEATED FOR
OLDER CHILDREN FROM 3 TO 12.
WE DEPLOYED THE RULES AND
NATURAL LANGUAGE BASED RECORD TO
GENERATE A LIST OF PATIENTS WHO
COULD BE TRIAGED FOR GENETIC
DISORDERS.
THERE WERE 0-3, 3-4 AND 4 AND
OLDER.
DURING THE DEVELOPMENT OF THE
ALGORITHM IN A REVIEW OF 450
CASES, PHYSICIANS WERE LIKELY TO
ORDER TESTING IN 78% OF CASES.
THE POSITIVE WAS 15 TIMES MORE
THAN STANDARD OF CARE.
YOU CAN SEE A PATIENT PREDICTED
TO NEED A REFERRAL TO GENETICS
AND ON THE VERTICAL LINE YOU CAN
SEE THE AGE OF THE PATIENT YOU
CAN SEE IT LIST FROM THE MEDICAL
RECORD AND THERE'S A COUPLE
DIAGNOSES OF CONGENITAL HEART
DISEASE DIAGNOSED AFTER BIRTH.
ON THE RIGHT YOU CAN SEE
MULTIPLE TOUCH POINTS WITH THE
HEALTH SYSTEM.
YOU CAN SEE MULTIPLE SPECIALTY
VISITS AND E.R. AND YOU COULD
SEE THE GENETIC CONSULTATION.
YOU CAN SEE THE PATIENT HAS A
LOW SICKNESS CORE AND FEWER
TOUCH POINTS WITH THE HEALTH
CARE SYSTEM.
SO AS PART OF THE PROJECT WE
RECRUITED PHYSICIANS AND
PRACTICES WITHIN OUR HEALTH CARE
SYSTEM AND WE RECRUITED
PRACTICES WHICH WERE PART OF OUR
HOSPITAL-BASED CLINICS AS WELL
AS PRACTICE GROUPS AND PRIMARY
CARE AND ALSO A CARDIOLOGY
PRACTICE AND WE SAW A MIX OF
PATIENTS ON GOVERNMENT AND
PRIVATE PLAN AND SAW A DIVERSE
POPULATION REFLECTIVE OF THE
AREA OF MOUNT SINAI.
AS PART OF THE PROJECT, THE
PHYSICIANS RECEIVED AN
EDUCATIONAL TRAINING AND SPOKE
ABOUT THE DIAGNOSTIC ODYSSEY AND
CURRENT STATE OF GENETIC TESTING
AND THEN REVEALED THE STUDY
OVERVIEW AND DEFINED CLEARLY
THAT ALL THE PATIENTS IDENTIFIED
THROUGH THIS ALGORITHM WOULD
QUALIFY FOR A STANDARD OF CARE
CLINICAL GENETICS REFERRAL AND
IF TREATED AS A STANDARD
REFERRAL THEY'D BE OFFERED AN
OPTION TO PARTICIPATE IN
RESEARCH STUDIES AT THE END.
SIMULTANEOUSLY THEY SET UP A
SEPARATE CLINIC, A SEPARATE
PIPELINE FOR REFERRAL OF THE
PATIENTS THE MOUNT SINAI GENETIC
OUTREACH CLINIC IN THE DIVISION
OF MEDICAL GENETICS AND GENOMICS
AND CREATED RESERVED APPOINTMENT
SLOTS FOR THE PATIENTS.
TO GIVE AN IDEA, GENETICS
CONSULTATIONS USUALLY HAVE A
LONG WAIT TIME NATIONALLY.
THEY CAN BE UPWARDS OF SIX
MONTHS BUT OUR GOAL WAS TO SEE
THE PATIENTS WITHIN A COUPLE
WEEKS OF REFERRAL.
THE REFERRAL INFORMATION ONCE
THE PATIENTS WERE IDENTIFIED WAS
SENT TO THE PEDIATRICIAN ALONG
WITH THE INDICATIONS WHY WE
THOUGHT THE PATIENT SHOULD BE
REFERRED AND HIGHLIGHTED THE
PATIENTS WOULD BE REFERRED AS
FOR STANDARD OF CARE AND
EVALUATED AS STANDARD OF CARE
AND RECRUITMENT IN A RESEARCH
STUDY AND WOULD HAVE A STANDARD
OF CARE FOLLOW UP FOR RELATES OF
MANAGEMENT AND WOULD PROVIDE THE
PHYSICIAN WITH A CONSULTATION
AND SUMMARY OF RESULTS.
SO HERE'S A FLOAT CHART SHOWING
OUR PROCESS AGAIN.
SO THE MOUNT SINAI WAREHOUSE
SCREENED AND IDENTIFIED THE
PATIENTS AND CONDUCTED MANUAL
CHART REVIEWS ON EACH OF THE
MEDICAL RECORDS.
TWO CLINICIANS REVIEWED THE
MEDICAL RECORDS AND EVERY
DIFFERENCE OF OPINION WAS
ADJUDICATED BY THE GROUP
INCLUDING A THIRD PHYSICIAN.
WE WANTED TO MAKE SURE WE MADE
AN UNBIASSED DECISION AND THEY
WERE SHOPLIFTED FOR REFERRAL.
IN ADDITION TO IDENTIFYING WHICH
PATIENT SHOULD BEING REFERRED,
WE ALSO IDENTIFIED IF WE THOUGHT
THE ALGORITHM WORKED OR NOT AND
IF WE FELT IT DID NOT WORK WE
MADE NOTES TO SHARE THAT WITH
THE DEVELOPER TO KEEP IMPROVING
THE ALGORITHM.
WE PROVIDED PEDIATRIC PROVIDERS
AND REFERRED PATIENTS.
THE TWO PARTS OF THE PROCESS
WERE CLINICAL CARE, AGAIN,
GENETICS CONSULTATION WITH
ROUTINE GENETIC TESTING AS
CLINICALLY INDICATING BUILD TO
INSURANCE AND FOLLOW UP
APPOINTMENT AND AT THE END A
RESEARCH COORDINATOR ON SITE TO
ENROLL THE PATIENTS IN THE STUDY
AND AS PART OF THE STUDY THEY
WOULD GIVE INFORMED CONSENT FOR
ACCESS TO THE ELECTRONIC HEALTH
RECORD.
HERE ARE SOME OF THE COMMON
REFERRALS FOR THE CLINIC.
THESE ARE PREDOMINANTLY IN THREE
BUCKETS.
THIS IS MY NO MEANS A
COMPREHENSIVE LIST BUT THEY WERE
ANOMALIES, NEURAL DEVELOPMENT
DISORDERS OR CARDIOVASCULAR
DISEASE.
WE REVIEWED 431 CHARTS AS A
GROUP.
102 PATIENTS WERE SHORT LISTED
FOR REFERRAL.
64 PATIENTS RESOURCED REFERRALS.
OF THESE, 29 PATIENTS DID NOT
COME TO CLINIC.
I'LL TALK ABOUT SOME OF THE
BARRIERS IN GETTING THE PATIENT
TO CLINIC.
22 PATIENT SEEN AT THE CLINIC
AND OF THESE 17 ENROLLED IN THE
STUDY AND 13 PATIENTS ARE IN
PROCESS OF BEING SEEN.
WE ALSO HAD 82 REFERRALS PENDING
AND I'LL TALK ABOUT THE
CHALLENGES ON THE PEDIATRIC
PROVIDER IN AND THERE WERE
LOGISTIC CONCERNS INCLUDING
MOVING OUT OF THE AREA.
SO THERE WERE HUMAN FACTORS.
IT'S STRIKING THAT DESPITE ALL
THE EFFORTS TO MAKE IT EASY
POSSIBLE FOR PATIENTS WE WERE
NOT ABLE TO GET ALL THE PATIENTS
INTO CLINIC.
THIS CLINIC HAD AN EXTREMELY
HIGH NO-SHOW RACE OR LAST-MINUTE
CANCELLATION.
THE PATIENT GETS THREE TOUCH
POINTS TO CONFIRM AN APPOINTMENT
BUT DESPITE THAT WE HAD AN
ALMOST 50% NO-SHOW OR
CANCELLATION RATE.
SOMETIMES THE REFERRED FAMILIES
DECLINED THE APPOINTMENT AND
THERE WAS CONFUSION ABOUT WHAT
WAS CLINICAL AND RESEARCH.
SOMETIMES THERE WAS AN ACUTE OR
CHRONIC ILLNESS LIMITING
SCHEDULING AND INSURANCE-RELATED
ISSUES, FAMILY CRISIS OR
PATIENTS IN FOSTER CARE AND WE
COULDN'T GET CONSENT OR PATIENTS
COME IN WITH A SIBLING OR
CAREGIVER INSTEAD OF A PARENT.
SIMILA
SIMILARLY THERE WERE CHALLENGE
FOR PROVIDERS, BUSY
PEDIATRICIANS AND ITS WAS HARD
TO CALL THE PATIENTS AND SAY I
THINK YOU NEED A GENETICS
CONSULT.
MOST PROVIDERS PREFER TO DISCUSS
THE STUDY AT THE REGULARLY
SCHEDULED WELL VISIT FOR THE
PATIENT.
EVEN EVEN WHEN THEY APPROACHED
THE FAMILY THE FAMILY DECLINED
THE REFERRAL OR WANTED TO FOCUS
OR FOCUS ON THE MORE IMMEDIATE
NEEDS OF ACUTE ILLNESS AND TIME
LIMITATIONS.
OUR STUDY TEAM TRIED TO SUPPORT
PROVIDERS AND ONE-ON-ONE AS PART
OF A NEWSLETTER, E-MAIL
COMMUNICATION.
WE PROVIDED LANGUAGE DISCUSSIONS
AND TRACKED THE REFERRALS
CLOSELY.
WE WERE DETERMINED TO GET AS
MANY PATIENTS TO CLINIC AS
POSSIBLE.
THERE WAS A 9-YEAR-OLD PATIENT
PREMATURE WITH A HISTORY OF
CONGENITAL HEART DISEASE WITH
SOME DEVELOPMENTAL DELAY AND VP
SHUNT.
IT APPEARS THE PATIENT WAS BEING
FOLLOWED BY THE CARD YOL IOLOGYP
AND SOME SYSTEMS WERE SUGGESTIVE
OF A DISORDER OF PROMINENT EYES
AND DROOPING EYELIDS AND HAD TOE
WALKING AND INCREASED DOME OF
THE LOWER LIMBS AND IT
IDENTIFIED TWO ABNORMALITIES
HERE.
THE AND THERE WAS ANOTHER GENE
AND THIS CHANGES THE MANAGEMENT
OF A PATIENT WHO IS NOW 9 YEARS
AT THE TIME OF DIAGNOSIS.
THEY NEEDED A RENAL ULTRASOUND
AND NEUROLOGY REFERRAL TO MON
FOR FOR SIGNS OF HEREDITARY
MOTOR NEUROON THE.
NEUROP
NEUROPATHY.
AND RESEARCHERS AMONG OTHER
MEMBERS WHICH COULD INCLUDE
COMMUNITY LEADERS AN ADVOCACY
GROUPS.
I'LL TYPE THE THOUGHT UP CHAT
GPT AND ASKED FOR A GRAPHIC AND
THIS IS WHAT IT CAME UP WITH.
WE HAVE A WAY TO GO BUT IT'S
GREAT TO HAVE A START WITH THE
PROJECTS.
THANK YOU.
>> NEXT WE HAVE EWY MATHE THE
DIRECTOR OF INFORMATICS DIVISION
OF PRECLINICAL INNOVATION AT
NCATS.
>> THANK YOU TO THE ORGANIZERS
FOR GIVING ME THE OPPORTUNITY
AND TALKING HOW WE'RE USING A.I.
TO EMPOWER US IN MAKING RESEARCH
DISCOVERIES.
THERE'S DIFFERENT WAYS IN WHICH
WE USE A.I. FOR DIFFERENT
PURPOSES.
SOME ARE LISTED HERE ON THE LEFT
AND THESE INCLUDE PREDICTING THE
EFFECTS OF TREATMENTS,
DIAGNOSTICS, THERAPIES AND
MATCHING PATIENTS TO THE RIGHT
TREATMENT AND A SYSTEMS VIEW
POINT.
THAT'S RELEVANT FOR THIS
COMMUNITY BECAUSE IT ENABLES US
TO LOOK AT MANY DISEASES AT ONCE
NOT JUST A SINGLE RARE DISEASE.
AND ON THE RIGHT YOU CAN SEE
WHAT POWERS OUR ABILITY TO DO
ANYTHING WITH A.I. AND THAT'S
DATA.
SO WITHIN NCATS WE HAVE A NUMBER
OF RESOURCES WHICH WE CURATE AND
MAKE AVAILABLE TO THE PUBLIC.
AND THEY'RE LISTED HERE.
THERE'S THERE'S DATA ANNOTATIONS
ON DISEASE.
THERE'S EXPERIMENTAL DATA, IN
VITRO ASSAYS AND DRUG SUBSTANCES
AND METABOLISM.
MAYBE YOU RECOGNIZE SOME
RESOURCES UP HERE.
ALL THIS DATA IS AT THE CORE OF
WHAT WE CAN DO WITH A.I.
TODAY I WANT TO TALK ABOUT HOW
WE'VE BEEN PUTTING A.I. TO WORK.
I'LL START BY USE CASES AND HOW
WE APPLY A.I. AND THEN I'LL END
WITH OF AN EXAMPLE OF HOW WE
BUILD UP THE DATA FOR A.I.
IN TERMS OF THE APPLICATIONS,
I'LL TALK ABOUT HOW WE IDENTIFY
DRUG CANDIDATES WITH HIGH
POTENCY AND REPURPOSE DRUGS AND
BIOLOGICAL MECHANISMS THAT CAN
BE TREATED.
SO BEFORE I GET INTO THE USE
CASES, I WANT TO GIVE YOU A VERY
BASIC VIEW OF HOW WE APPROACH
A.I.
IT'S ALL ABOUT THE INPUT, MODELS
AND OUTPUT AND VALIDATION.
THE INPUT DATA HAS TO BE A.I.
READY AND CAN BE AS SIMPLE AS
DATA TABLES.
MAYBE YOU HAVE DESCRIPTIONS
ABOUT DRUGS OR DISEASES OR
TARGETS.
THEN A FEWER WAY IS GRAPHS.
GRAPHS ARE NOTES AND EDGES.
YOU CAN SEE A COMPOUND GRAPH,
CAFFEINE, MAYBE SOME OF US NEED
A LITTLE BIT RIGHT NOW.
HAVE YOU EACH ATOM AND THEY HAVE
A PHYSICAL INTERACTION.
THOSE THE EDGES.
YOU CAN REPRESENTATIVE THOUSAND
OF MILLIONS OF MOLECULES IN THAT
WAY.
YOU CAN SEE A MORE ACCOMPLISHED
GRAPHING A HAIR BALL, IT
INCLUDES MANY SOURCES OF
INFORMATION, MAYBE CLINICAL,
INFORMATION FROM THE LITERATURE
OR GENOMIC INFORMATION.
WHEN YOU HAVE SUCH COMPLEX
GRAPHS OR HUMAN MIND THAT'S
WHERE THE MODEL COMES IN AND TWO
MAIN TYPES.
ONE ARE THE PREDICTION MODELS.
WITH THIS YOU NEED SOME TYPE OF
DATA YOU TRAIN THE MODEL ON.
YOU HAVE DRUG AND THEIR ACTIVITY
AND TRAIN THE ACTIVITY OF NEW
DRUGS.
ANOTHER TYPE IS A DISCOVERY
MODEL.
TAKE A COMPLEX GRAPH AND THERE'S
ALGORITHMS THAT WILL LOOK
THROUGH AND FIND PATTERNS.
NOW WE'RE GOING TO THE RESULTS
AND VALIDATION.
IN TERMS OF PREDICTION MODELS
THEY GIVE PREDICTIONS.
ARE THE DRUGS ACTIVE?
INACTIVE?
YOU WANT TO VALIDATE THIS MORE
AND MAY WANT TO LOOK AT THE
ACCURACY PREDICTING THE ACCESS
OR INACCESS.
THEY'RE JUST PREDICTIONS.
SOMETIMES THEY'RE WRONG SO YOU
HAVE TO VALIDATE THE MODELS.
FOR DISCOVERY YOU FIND AREAS OF
THE GRAPH THAT MAYBE YOU CAN
INVESTIGATE MORE INTO.
I'VE NOTED SOME EXAMPLES AND
MAYBE THERE'S A CLUSTER OF DRUGS
LOW ACTIVITY WOULD BE WORTH
LOOKING INTO.
LET ME GIVE YOU REAL EXAMPLES.
YOU IDENTIFY COMPOUNDS THAT
PREVENTS SARS COV2 FROM ENTERING
THE CELLS.
THE THERE WERE 170,000 COMPOUNDS
AND THERE WAS A GRAPH
CONVOLUTION NETWORK A DEEP
LEARNING MODEL THAT PREDICT THE
ACTIVITY OF THE DRUGS.
USING THIS WE WERE ABLE TO NA
NAFRO -- NARROW 2,000 COMPOUNDS
AND FROM THOSE 27 UNDERWENT A
MORE SPECIFIC ASSAY.
THIS SHOWS HOW A.I. IS A FAST
AND NOVEL APPROACH AND GOING
FROM 170,000 TO 27 AND TOP HITS
SHOWED HIGH EFFICIENT.
ANOTHER EXAMPLE IS USING A.I. TO
IDENTIFY ANOTHER REPURPOSED
DRUGS.
THERE WERE INFORMATION ABOUT
DRUG TARGETS AND BIO CHEMICAL
PATHWAYS MERGED TO A COMPLEX
GRAPH AND FROM THIS WE APPLIED
NATURAL LANGUAGE PROCESSING
METHODS TO IDENTIFY CLUSTERS OF
RARE DISEASES.
WE FOUND 35.
ONE WE WERE SUPER INTERESTED IN
INCLUDING GLIAL BLASTOMA.
ON THE BOTTOM LEVEL YOU CAN SEE
HOW WE LOOKED MORE INTO THE
CLUSTER WITH ENRICHING
INFORMATION FROM A RARE DISEASE
NETWORK BUILT INCLUDING
INFORMATION ON PUBLICATIONS AND
GRANTS AND MORE.
SOME FROM THE RARE DISEASE ALERT
SYSTEM PRESENTED HERE.
WE CAN LOOK FOR THE AREAS MOST
INTERESTING.
FROM THIS THERE'S ONE CANDIDATE,
VK0214 THAT IS DESIGNATED AS AN
ORPHAN DRUG BY THE FDA FOR
TREATING ASLD AND IDENTIFIED AS
A CANDIDATE.
IT'S UNDERGOING EXPERIMENTAL
VALIDATION AND THE RESULTS LOOK
GOOD SO STAY TUNED AS THE STORY
CONTINUES TO UNFOLD.
THE LAST USE CASE IS IDENTIFYING
NOVEL MECHANISMS.
OUR GOAL WAS TO UNDERSTAND THE
MECHANISM UNDERSTAND IGE.
THEY'RE IMPORTANT BECAUSE HIGH
LEVELS ARE ASSOCIATED WITH
POORER CLINICAL OUTCOMES IN
PEDIATRICAGES MA PATIENTS AND
TREATING PATIENTS WITH ANTI-IGE
HAS HETEROGENOUS EFFECTS.
WE HAD GENOMIC DATA AND
METABOLOMIC DATA.
THE MODELS HAD TO SIFT THROUGH
12 MILLION PAIRED INTERACTIONS.
WHAT WE FOUND IS THAT GAU
GAUNINOASSETIC ACID WERE
CONSISTENT THE RESULTS ARE QUITE
ROBUST.
AND WE WANTED TO TALK ABOUT HOW
TO ADVANCE THERAPEUTIC
DEVELOPMENT.
THIS IS AN ONGOING EFFORT WE'RE
TRYING TO TAKE OFF AND THERE'S A
LOT OF MODEL AND DATA GENERATION
INVOLVED HERE.
INCLUDING GENERATING AND
DEVELOPING PATIENT DERIVED
MODELS AND A.I. AND M.L.
PREDICTIONS AND IT WILL CREATE A
RICH DATA SET FOR THE RARE
DISEASE COMMUNITY TO IDENTIFY
NEW TREATMENTS.
NOW I'M GOING SWITCH GEARS A
LITTLE BIT AND TALK ABOUT DATA.
IT'S AT THE CORE OF ALL OF THIS.
I'D LIKE TO HIGHLIGHT THE M CATS
TRANSLATOR PROGRAM A PLATFORM TO
ENRICH RESEARCHERS WITH
KNOWLEDGE.
IT COMBINES INFORMATION FROM
COMPLEMENTARY SOURCES OF
INFORMATION THAT SPAN THE WIDE
RANGE OF TRANSLATIONAL RESEARCH.
FROM BASIC PRE CLINICAL TO
CLINICAL RESEARCH.
IN ORDER TO DO THIS THERE'S
STANDARDIZATIONS INVOLVED.
LOT OF NITTY-GRITTY CURATION
INVOLVED AND EMPHASIS PLACED ON
THE DETAILS AND TRUST.
WHERE DOES THE INFORMATION COME
FROM?
IS IT TRUSTWORTHY?
THIS IS A LARGE CONSORTIUM
EFFORT.
ONE PRODUCT THAT CAME FROM THE
TOP RIGHT IS A WEB APPLICATION.
YOU CAN CHECK IT OUT.
FROM THIS APPLICATION ONE CAN
ASK QUESTIONS OF THE DATA.
ONE INTERESTING QUESTION THAT
CAN BE ASKED IS WA CHEMICALS MAY
UPREGULATE WHAT GENE?
I WANT TO GIVE AN EXAMPLE ON THE
USE CASE WITH SHINE SYNDROME.
IT'S ALSO CALLED DLG4 AND IT
LOSES ITS FUNCTION IN THESE
PATIENTS.
SO TRANSLATOR WAS USED TO ASK
WHAT CHEMICALS CAN UP REGULATE
DLG4 TO GO BACK TO NORMAL
LEVELS.
THE RESULTS WERE EVALUATED BY
PHYSICIANS AND EXPERTS AND
GAUNFACINE WAS DEEMED WORTH
TRYING.
AND A PATIENT WAS TREATED WITH
THIS AND HAD IMPROVEMENTS AND ON
THE RIGHT YOU CAN SEE THIS
BEAUTIFUL DRAWING.
EVERYTHING'S NICELY DRAWN.
ANOTHER LARGE DATA COLLECTION
EFFORT IS CURE I.D.
HERE THIS PLATFORM IS ABOUT
CAPTURING NOVEL USES OF EXISTING
DRUGS MAINLY FOR DRUG
REPURPOSING EFFORTS.
THERE'S NEW FRAME WORKS I'D LIKE
TO HIGHLIGHT RECENTLY THERE
WAS -- YOU CAN GO TO THE
APPLICATION AND SEE ON THE
BOTTOM LEFT ALSO FOR THE SITE
BUT PATIENTS CAN INPUT THEIR
TREATMENTS FOR LONG COVID.
WE'RE TRYING TO GET TO 1,000
ENTRIES.
IF I OR ANYONE YOU KNOW HAS
SUFFERED FROM LONG COVID,
CONSIDER FILLING OUT THE FORM.
I WANT TO HIGHLIGHT WHILE THIS
IS SPECIFIC TO LONG COVID RIGHT
NOW THE STRUCTURE IS NOW IN
PLACE.
THIS PROJECT WE'RE STARTING TO
FOCUS MORE ON RARE CANCERS AND
RARE GENETIC DISORDERS AS WELL.
THIS IS AN AREA TO LOOK FOR
HERE.
I WANT TO END WITH THIS SLIDE
BUZ I THINK A.I. IS VERY
PROMISING.
HOWEVER, IT REQUIRES US TO HAVE
TRUST IN BOTH THE DATA AND
MODELS.
SO WHAT I'M SHOWING HERE WITH
THIS PLOT ON THE Y AXIS YOU SEE
THE DATA AND THE MODELS.
YOU HAVE HIGHER QUALITY DATA AND
APPROPRIATENESS OF THE DATA AND
INTEROPERABILITY AND MACHINE
LEARNING AND READINESS AND
DIVERSITY.
DIVERSITY HERE IS IMPORTANT.
THE RARE DISEASE PATIENTS HAVE
TO BE REPRESENTED IN THE DATA
FOR US TO BE ABLE TO MAKE
MEANINGFUL PREDICTIONS FROM THE
COMMUNITY.
ON THE X WE WANT ROBUSTNESS TO
INCREASE AND MODELS TO BE
VALIDATED AND APPROPRIATE.
THE IDEA IF YOU START ON THE
BOTTOM LEFT YOU GET A BLURRY
PICTURE.
YOU GO TO THE UPPER RIGHT
QUADRANT YOU GET A CLEAR PICTURE
OF WHAT THE DATA IS TELLING YOU
AND PREDICTIONS YOU CAN MAKE.
I'LL END THERE.
THANK YOU FOR YOUR ATTENTION.
I'VE TALKED A LITTLE ABOUT MANY
PROJECTS.
THESE ARE LARGE PROGRAMS
INCLUDING COLLABORATORS WITHIN
NCATS AND FDA AND A LOT OF
ACADEMIC INSTITUTIONS AND I WANT
TO HIGHLIGHT WE HAVE POSTERS AND
BOOTHS FOR THE RARE DISEASE
ALERT SYSTEM, CURE I. AND
TRANSLATORS.
CHECK THEM OUT.
THANK YOU.
>> THANK YOU, ALL PANELISTS AND
BRIEF REMINDER FOLKS CAN COME UM
TO THE MICS AND ASK QUESTIONS AS
WELL.
THANK YOU ALL SO MUCH.
THOSE WERE GREAT PRESENTATIONS.
YOU TALKED ABOUT THE CONCEPT OF
DEMYSTIFYING A.I.
IT SEEMS LIKE IT'S KEY TO HAVE
MEANINGFUL CONVERSATIONS AND
CONNECTIONS WITH A WIDE RANGE OF
AUDIENCES.
HOW DO YOU ALL MEANINGFULLY
ENGAGE WITH PATIENTS IN YOUR
WORK AND INCREASE THE
UNDERSTANDING OF A.I. SO
PATIENTS CAN MAKE THE BEST
DECISIONS FOR THEMSELVES?
>> IT'S A GREAT QUESTION.
FIRST AND FOREMOST PARTNERING,
INCREASING AWARENESS AND
EDUCATION ABOUT YOUR DATA.
WE HEARD FROM THE NIH TALKING
ABOUT VOLUNTEERING YOUR DATA
THOSE ARE CHOICES YOU NEED TO
MAKE IN THE FUTURE AND BEING
EDUCATED AS POSSIBLE KNOWING THE
GOOD THAT CAN COME FROM THE
TALKS KNOWING WE FOUND NEW
GENETIC DISEASES AND PATIENTS
STRUGGLING WITH THE DIAGNOSIS
AND WE FOUND A TREATMENT THAT
WORKED.
IT'S SCARY KNOWING A COMPUTER IS
SEARCHING BUT IT'S VALIDATED THE
DATA NEEDS TO BE ROW BEST AND
MATH IS CHECKED AND IF IT'S
CHECK AND ACCURATE IT'S GIVING
PREDICTS AND PREDICTIONS, IF THE
MATH IS RIGHT, CAN PREDICT
THINGS IN A GOOD WAY BUT IF THE
MATH ISN'T BAD GOOD IT CAN MAKE
YOU WORRY.
THIS TYPE OF EDUCATION WILL TAKE
THE COMMUNITY TO BE EDUCATED AND
LITERAL IN TERMS OF DATA AND
UNDERSTANDING THE POWER.
WE SEE THE RARE DISEASE
COMMUNITY TWOIL GIVE THEIR DATA.
THERE'S A NUMBER OF GROUPS THAT
HOUSE THIS DATA TO UNDERSTAND
MORE.
>> WE NEED TO DO WORK IN THE
TRUST OF THE PATIENTS.
A.I. DOESN'T MEAN YEAR
ELIMINATING HUMANS WE'RE JUST
ENHANCING HUMAN CAPABILITIES.
TO TRUST PATIENT THE PROCESS CAN
WORK IS ENGAGING WITH COMMUNITY
STAKEHOLDERS.
>> IT'S ALSO IMPORTANT FOR
PATIENTS TO CONTINUE ASKING HOW
THE DATA IS BEING USED.
WHAT'S IT MEAN, ARE THERE
DIFFERENT WAYS THE DATA COULD BE
PROVIDED FOR A.I. AND DEMAND A
LITTLE BIT.
AT THE END OF THE DAY IF
PATIENTS ARE GIVING SOMETHING
AND I VIEW IT AS A GIFT TO HAVE
ACCESS TO ALL THE DATA, WELL,
WHAT IN RETURN ARE YOU GETTING?
THE MORE DATA WE'LL GO FROM THE
POPULATION VIEW TO THE
INDIVIDUAL IMPACT AND SOMETIMES
THAT'S CHALLENGING TO MAKE.
>> HOW YOUR DATA IS BEING USED
AND THERE'S WORK IN THAT SPACE.
GOING INTO THAT AREA GIVEN THE
CRITICAL NATURE OF A.I. USE IN
RARE DISEASE RESEARCH AND M
MEDICAL ISSUES WHERE YOU HAVE
SAFETY AND URGENCY, HOW DO YOUR
GROUPS TEST OR ASSESS THE
ALGORITHMS BEFORE PUTTING THEM
INTO PRACTICE?
>> THE ALGORITHM PROCESS NEEDS
IT TAKE TIME AND WE NEED TO KEEP
TRAINING THE ALGORITHM AND
VALIDATING THE ALGORITHM.
WE HAVE USED HUMANS TO TRIAGE
WHAT THE ALGORITHM IS PINGING UP
QUE NEED TO KEEP IMPROVING THEAL
RIDGES.
-- ALGORITHM.
.
>> THESE ARE PREDICTIONS AND
YOUR HEALTH CARE PRACTITIONER
NEEDS TO USE IT AS A SUPPLEMENT
IN CASE VALIDATIONS, LOOKING DO
WE AGREE WITH WHAT THE COMPUTER
SUGGESTED?
WE'LL SEE IF IT PREDICTS AND
THEY'RE ESSENTIAL BEFORE IT'S
NOT WILD.
THE TESTING AND VALIDATION IS
ESSENTIAL TO BUILD THAT TRUST AT
THE MATH CAN WORK AND IT STILL
NEEDS THE HUMAN TO SAY DOES THIS
MAKE SENSE.
>> USING OUR HUMAN BRAINS AT THE
END IS THE MOST IMPORTANT THING.
AT THE END OF THE DAY, HEALTH IS
MORE IMPORTANT THEN PURPLE
DRESS.
QUESTIONING THE RESULTS AND
MAKING SURE IT MAKES SENSE.
THERE'S IMPACT FROM THE
ENVIRONMENT AND AGAIN HAVING
ACCESS TO ALL THIS INFORMATION
IS REALLY DIFFICULT.
MAKING SURE TO VALIDATE THE MATH
BUT ALSO VALIDATE THE MEANING
DOES IT MAKE SENSE FOR MY
CONTEXT IS IMPORTANT.
>> TALKING ABOUT THE DATA AND
THE QUESTION BEING ASKED.
>> APOLOGIZE.
I CAME IN LATE AND I'M GOING
APOLOGIZE BECAUSE -- MANISHA
BALWANI, IT IMMEDIATELY CAME TO
MY MIND AND A MISSED PART OF
YOUR PRESENTATION YOU MUST BE
USING E RECORDS AS PART OF THE
SEARCH.
I'VE BEEN DEALING WITH THE
NEWBORN SCREENING
REAUTHORIZATION WITH THE GENETIC
COMPONENT.
THE USE OF PRIOR DATA AND
CONSENT IS A HUGE ISSUE.
I LOVE WHAT YOU'RE DOING BUT
WHERE IN YOUR PROCESS WITH E
RECORDS ON PAST INFORMATION DID
YOU GET CONCEPT FROM PATIENTS?
>> AS PART OF THE PROCESS IRB
GAVE US PERMISSION AND WE HAD TO
CONSENT PATIENTS IN ORDER TO USE
THE INFORMATION IN THE
ELECTRONIC HEALTH RECORDS.
I THINK YOU BRING UP AN
IMPORTANT POINT WHICH IS IT WAS
GREAT WE RECEIVED PERMISSION TO
REVIEW THE RECORDS BUT WE CAN
SEE THESE BEING IMPORTANT IN THE
SPACE.
>> WE'RE TALKING ABOUT TRUST.
BEING FROM A LIBERTARIAN STATE
AND EXPOSED TO LIBERTARIAN
THINKING PART IS A DID TRUST OF
GOVERNMENT.
IF THE CONSENT IS AT THE
BEGINNING, LIKELY THEY WON'T
GRANT IT BUT IF THEY DIDN'T
GRANT IT YOU'RE PROBABLY IN A
BETTER POSITION BECAUSE THE
TRUST STARTS AT THE BEGINNING IF
THAT MAKES SENSE.
>> THAT MAKES SENSE AND NEEDS TO
BE AT THE CENTER AND NEEDS TO BE
A CONTINUED CONVERSATION.
>> IT BRINGS UP OTHER ETHICAL
ISSUES IN THE SPACE.
BEFORE WE GET TO ONE I WANT TO
MAKE SURE WE TOUCH ON THIS, WHAT
ARE SOME ETHICAL ISSUES FRONT OF
MIND FOR EACH OF YOU IN THE
PROJECTS THAT YOU'VE BEEN
DISCUSSING TODAY?
>> MUCH OF THE PHARMACEUTICAL
SIDE IS DE-IDENTIFIED DATA BUT
IF YOU GET TO VERY ULTRA RARE
SPACES, THIS BECOMES A BIG
CONCERN BECAUSE IT'S HARD TO
KEEP THE DATA DEIDENTIFIED.
I WORK IN RARE MITOCHONDRIAL
DISEASE WHERE THERE'S 75
PATIENTS IDENTIFIED IN THE
U.S. AND THAT PATIENT PRIVATE
PROTECTION IS HARD.
>> THERE'S A HUGE RESPONSIBILITY
TO VALIDATE AND TAKE RUNNING OF
THE DATA AND SAY HERE'S
PREDICTIONS.
LET'S RUN WITH IT.
THERE'S A HUGE RESPONSIBILITY TO
VALIDATE AND THINK ABOUT THE
RESULTS.
>> MANISHA.
THE ISSUE IS CONTENT AND HOW DO
WE ENGAGE AND HOW DO WE EXECUTE
A PROJECT LIKE THIS WITH
INDIVIDUAL CONSENT?
WE NEED A BROADER MODEL AND A
LOVE WHAT WAS BROUGHT UP THIS
MORNING WHICH IS SHARING OF
ELECTRONIC MEDICAL RECORDS WITH
A PATIENT'S CONSENT WHICH SURELY
WOULD BE AN ENORMOUS STEP
FORWARD IN THIS.
>> THANK YOU VERY MUCH.
>> ONE MORE QUESTION.
>> JAMES PATTERSON.
I HAVE TWO KIDS WITH BATON'S
DISEASE.
IT'S A FAIRLY SMALL POPULATION
BUT WE'RE ACTIVE IN TRIALS AND
THINGS ONGOING AT NIH.
HOW DO WE SHARE THE DATA TO MAKE
SURE IT'S IN THE BROADER
COLLECTION BEING USED WITHOUT
HAVING TO GO THROUGH ALL THOSE
PROCESSES A WEEK AT A TIME EACH
YEAR.
IT'S A LOT OF DATA AND SEEMS IT
WOULD BE VALUABLE.
>> THERE'S EFFORTS GOING ON TO
TRY TO CONNECT THESE DIFFERENT
DATA ECO SYSTEMS BUT MORE STILL
TO BE DONE.
I DON'T KNOW IF THERE'S ANYONE
ON THE PANEL THAT WANTS TO
DISCUSS THAT.
>> I CAN SPEAK TO THE ODYSSEY
MODELS BEING ONE EXAMPLE TO TRY
TO INGEST DATA FROM DIFFERENT
SOURCES.
I'M NOT SURE THAT'S THE QUESTION
YOU'RE ASKING BECAUSE I'M
ANSWERING MORE ON THE TECHNICAL
SIDE.
YOU MAY BE ASKING WHERE CAN YOU
GO TO GET THE DATA SUBMITTED?
>> HAVING THIS PART OF THE
LARGER DATA MODELS.
INTERESTING IT CONTRIBUTE TO THE
LARGER DATA SETS.
>> YOU BRING A GREAT POINT.
IF IT'S AN ONGOING CLINICAL
TRIAL THE ABILITY TO RELEASE
DATA AS IT'S ONGOING BECAUSE IT
COULD BE VERY MEANINGFUL TO THE
COMMUNITY BUT IN A SAFER
ENVIRONMENT.
>> THANK YOU FOR BRINGING THAT
UP.
>> WE'RE OUT OF TIME BUT YOU
HAVE GREAT ENTHUSIASM.
PLEASE FIND US.
WE'RE ABOUT TO GO TO A BREAK --
NO, FIND US AFTER THE BREAK.
THANK YOU ALL SO MUCH.
>> UP NEXT WE HAVE JAMES
HICKMAN, PROFESSOR UNIVERSITY OF
CENTRAL FLORIDA, CO-FOUNDER AND
CHIEF SCIENTIFIC OFFICER OF
HESPEROS.
>> I AN UNDIAGNOSED NEUROPATHY
SO I UNDERSTAND THE FRUSTRATION
AND THERE'S HOPE IN PROJECTS AND
SYSTEMS WE'RE BEING ABLE TO
DEVELOP.
MY CO-FOUNDER AND I FORMED THE
COMPANY EIGHT YEARS AGO AND I
WANT TO HIGHLIGHT THE COMPANY
BECAUSE EVERYTHING I'M GOING TO
SHOW YOU IS COMMERCIALLY
AVAILABLE AS PART OF A CRI.
THESE AREN'T JUST LANTRY THINGS
SAYING YOU MIGHT HAVE
APPLICATION IN 10 YEARS.
THEY'RE ALL COMMERCIALLY
AVAILABLE RIGHT NOW.
THE COMPANY WAS FOUNDED ABOUT
EIGHT YEARS AGO AND WE LICENSED
PATENTS FROM CORNELL AND GOT
GREAT SUPPORT FROM NIH AND
ESTABLISHED INTERNATIONAL AND
NATIONAL CONTRACTS WITH MANY
RARE DISEASE DEVELOPERS AND HAVE
A 14,000 SQUARE FOOT IN ORLANDO,
FLORIDA AND ARE THE FIRST
COMPANY TO GET A DRUG REPURPOSED
INTO A CLINICAL TRIAL USING ONLY
DATA FROM ONE OF OUR SYSTEMS.
I'LL GO THROUGH THAT.
WHEN YOU GO TO A DOCTOR'S OFFICE
THEY DON'T IMMEDIATELY TAKE OUT
FLUID.
THEY ASK HOW YOU'RE WALK AN
TALKING AND HE'S LOOKING FOR
CLINICALLY RELEVANT FUNCTIONAL
READOUTS.
WE CKCAN REPRODUCE THEM BY
BASICALLY PUTTING YOU CAN PUT
SKELETAL MUSCLE ACUTELY AND
CHRONICALLY NON-INVASIVELY
WITHOUT CELL DEATH AND NOT USING
DEATH MARKERS AND GET
MECHANISTIC INSIGHT.
WE CAN TAKE CELLS AND ON A DISK
AND PUT IT IN A MEDIA AND A TOP
ON IT AND PUT IT TOGETHER TO
MONITOR THE SYSTEMS UP TO A
MONTH.
AND THE WHOLE SYSTEM IS THIS,
THAT PLATFORM IS IN THE PALM OF
MY HAND.
THERE'S NO EXTRA TUBING.
THERE'S NO EXTRA PUMPS, NO HUGE
COMPARTMENTS TO MAKE THIS RUN.
WE USE GRAVITY TO PUMP IT BUT
THIS IS WHAT I'M HOLDING IN MY
HAND.
WE CAN TAKE MOTOR NEURONS FROM
ALS PATIENTS AND DIFFERENTIATE
THEM FROM MUSCLE AND SCHWAN'S
CELLS AND INNERVATE MUSCLE ON
THE OTHER SIDE AND DO MOTION
CAPTURE AND LOOK IN TERMS OF
STIMULATION LOOK AT MUSCLE
CONTRACTION AND FOR ALS YOU GET
SKIPPING AND WE CAN WITH
THERAPEUTICS SHOW WE CAN REVERSE
THAT.
YOU CAN SEE WHEN THEY LOSE GRIP
STRENGTH.
WE CAN STIMULATE THE MOTOR
NEURONS FASTER AND FASTER,
THAT'S JITTERS.
IF WE SEE LOSS OF TETANUS IT'S
LOSS OF GRIP STRENGTH.
YOU CAN GET MORE DETAILS FROM
THE POSTER AND PUBLISH THIS.
YOU CAN SEE THE TETANUS AND THE
CLINICAL TRIAL OF THE FATIGUE
INDEX AN IT GOES UP FOR THE
DIFFERENT MUTATIONS.
YOU DON'T SEE THE LOSS OF IF IT
FIDELITY BUT THIS IS THE JITTERS
THEY SEE IN THE CLINICAL TRIALS
AND PARTIAL AN TOTAL LOSS OF
TETANUS AND KNOW IT WAS AT THE
MUSCULAR JUNCTION TO GIVE US A
CHANCE TO TREAT THIS.
WE MAKE THE SCHWAN'S CELLS TAKE
THE MUTATIONS FROM THEM AS WELL
AND DID A TRIAL WITH A RARE
DISEASE COMPANY THEY SAID COULD
YOU BUILD IN THE IMMUNE SYSTEM.
WE PUT THE MICROGLIA ON THE
MOTOR NEURON SIDE AND PUT THE
SCHWAN'S CELLS ON THE ACTIVATED
MONOCYTES ON THE OTHER SIDE AND
LOOKED AT THE RESULTS.
THIS IS THE UNACTIVE BETA
MONOCYTES AND WHEN YOU ADD IN
THE COMPLIMENT PART OF THE
INNATE IMMUNE SYSTEM YOU SEE THE
DEFICIT AND THE DRUG CORRECTED
IT.
IN INFLAMMATION YOU SEE A LARGE
DEFICIT AND NOT MUCH CHANGE WITH
THE UNACTIVATED MONOCYTE S BUT
YOU'VE SEEN THE BIOMARKER YOU
CAN SEE HERE A DECREASE.
THE DATA WAS USED TO GET A DRUG
FOR AN ORPHAN DRUG STATUS.
YOU CAN USE THE SAME PLATFORM.
AS YOU KNOW ABOUT MICE MY AS YA
GRAPH IS AND YOU GET RECEPTORS
ON THE MUSCLE WHICH BLOCKS THE
SIGNALS FROM THE AX OONS WE SAW
THE DIFFERENCES BETWEEN THE
BLOCKING BLOCKING OR
INTERNALIZATION EFFECT.
IN THE UNTREATED WE SEE A DOWN
REGULATION BUT ON THE INSIDE
HIGH CONCENTRATIONS OF ANTIBODY
AND THIS WAS USED FOR A NUMBER
OF CLINICAL TRIALS.
ONE JUST GOT APPROVED FOR
DIANTHIS GETTING INTO A PHASE 2
CLINICAL TRIAL.
ALL THE DATA IS PUBLISHED IN
FRONTIERS AND CELL BIOLOGY.
WE'RE VALIDATING THIS BY GETTING
IT THROUGH CLINICAL TRIALS AND
VALIDATING IT BY PUBLISHING
EVERYTHING FROM THE COMPANY.
WHEN YOU HAVE RARE DISEASES YOU
HAVE RARE VARIANTS OF THE RARE
DISEASE.
THIS WAS A CLINICAL TRIAL
WORKING WITH VANDA
PHARMACEUTICALS TAKING A
FIBROBLAST FROM A CHILD WITH THE
DISEASE AND DIFFERENTIATE FROM
THE STEM CELL THE NOTER NEURONS
AND FROM THE MUSCULAR JUNCTION
PLATF
PLATFORMS.
AND WE DIDN'T SEE AS MUCH AS THE
JITTERS BUT THAT'S ALSO YOU
DON'T SEE THAT CLINICALLY FOR
CHACOT DISEASE AND YOU CAN SEE
THE TETANUS IN THE WILD TYPE
CHANGES.
WE SAW WITH THE DISEASE.
IF WE TRACKED IT IN TERMS OF
CLASSICAL TETANUS FOR THE WILD
TYPE YOU HAVE UNCLASSICAL
TETANUS AND YOU'RE GETTING
SPORADIC TETANUS.
WE SEE A SINGLE AXON GOING
THROUGH A SINGLE MUSCLE.
WHAT HAPPENS IF YOU'RE IN
CHARCOT DISEASE NOW KNOWS ARE
CLINICAL SYSTEMS FOR -- THESE
ARE CLINICAL SYMPTOMS FOR THIS
DISEASE.
WE TREAT WITH AN NUCLEOTIDE AND
IT SMOOTHED IT OUT.
NOW WE HAVE AN NUCLEOTIDE NOR
PATIENT NOW APPROVED TO GO INTO
A CLINICAL TRIAL.
WE CAN LOOK AT THE SYSTEMS.
THE WHOLE PROCESS FROM GETTING
THE PATIENT'S CELLS THROUGH TO
GETTING THE ASO DOSING WAS LESS
THAT.
A YEAR.
A FRACTION OF THE COST IT WOULD
TAKE FOR AN ANIMAL MODEL TO
DEVELOP.
WE'RE ALSO DEVELOPING
MYELINATION MODELS AND A COMPANY
SAW THIS AN SAID CAN YOU CREATE
A MODEL FOR THIS NEUROPATHY IN
CLDP.
WE SAID OKAY, YOU GET ANTIBODIES
THE AMPLIFICATION POINT ALONG
THE MYELINATION AND WE SAID WE
CAN DO THAT.
THEY'RE TRYING TO PREVENT PART
OF THE INNATE IMMUNE SYSTEM FROM
DEPOSITING.
WE'RE USING THE PATIENT'S SAMPLE
AND YOU SEE COMPLIMENT
DEPOSITION FROM TWO PATIENTS.
THE MOLECULE PREVENTED IT.
WE WANTED TO BUILD A MODEL TO
LOOK AT THE VELOCITY.
WHAT OUR TEAM OF ENGINEERS,
DR. LONG IS THE CHIEF ENGINEER
AND IN THE AUDIENCE, HE RETURN
THE MODEL 90 DEGREES AND WE HAVE
THE ELECTRODES GOING THROUGH THE
TUNNELS TO CONDUCT THE VELOCITY
IN THE SYSTEM.
WE ARE WILLING TO SEE OVER THE
DIFFERENT ELECTRODES AND SUM
THAT TOGETHER AND THIS WAS THE
KEY EXPERIMENT WHERE AGAIN WHAT
WE HAVE IS UNTREATED VELOCITY,
UNTREATED WITH THE SERUM CONTROL
AND THE MOLECULE AND YOU SEE FOR
THE CONTROL YOU GET NICE
APPLICATION BUT WITH THE
MOLECULE IT WAS MAINTAINED.
THIS WAS PUT INTO AN IND WHICH
ENABLED THIS CLINICAL TRIAL
ONGOING NOW AND THIS IS
PUBLISHED WITH SANOFI IN
ADVANCED THERAPEUTICS.
AGAIN ALL THE MODELS BEING DONE
WITHOUT CELL DEATH.
WE'RE NOT LOCKING AT DEATH
MARKERS BUT WHAT A CLINICIAN
WOULD WANT TO OBSERVE FROM A
PATIENT WHEN THEY CAME INTO
THEIR OFFICE.
WE ARE ALSO LOOKING FOR
LONG-TERM APPLICATION FOR
ALZHEIMER'S DISEASE AND ALSO
APPLICABLE FOR FRONTAL TEMPORAL
DEMENTIA AND WE -- REDUCED THE
ANIMAL TISSUE AND WE TOOK HUMAN
CORTICAL NEURONS OVER
ELECTRODES, PATTERN THEM TO
RECORD ON THE UNSTIMULATED
ELECTRODES OVER HERE TO BE ABLE
TO REPRODUCE WHAT THEY SEE WITH
THE ANIMAL SLICE DATA IN A HIGH
THROUGHPUT SYSTEM.
THIS WAS PUBLISHED IN SYSTEM
STEM CELL REPORTS AND WE BLOCKED
THE TWO MAIN RECEPTORS TO THE
SHOW THIS AND TO PROVE IT WE
TOOK THE SCRAMBLE WITH THE
PHYSIOLOGY AND A BETA 42 ONE OF
THE KEY THINGS FOR ALZHEIMER'S
AND SHOWN WE COULD REVERSE THAT
AND REPRODUCE THAT DATA ON THE
MEAs.
SHOWING WE CAN GET REVERSAL.
WE HAVE FRONTAL TEMPORAL
DEMENTIA THERE'S A TAOOPATHY AND
IT'S INVOLVED IN LOOKING AT FOR
OTHER RARE DISEASES IN THE
BRAIN.
YOU CAN SEE WE CAN ALSO SEE THIS
IN TAO BEING ABOLISHED.
THIS WAS PUBLISH END ALZHEIMER'S
AND DEMENTIA.
WE CAN DUE THE MUTATION AND
THERE'S THREE DIFFERENT
MUTATIONS IN AB.
APOE 4 AND SAW IT IN MUTATION
FOR TAO FOR FRONTAL TEMPORAL
DEMENTIA.
IT'S A BUSY SLIDE.
IT SHOWS THE WHOLE PROGRESSION.
IT'S ONE OF THE MORE ADVANCED
ORGAN SYSTEMS HERE AND WE'RE
LOOKING AT OPIOID OVERDOSE AND
RECOVERY IN TOXICITY MODELLED AN
CAN CREATE THE MODELS FOR MANY
ORGAN TYPES AND RECONFIGUREABLE.
OUR PHILOSOPHY IS WE CUSTOM
BUILD WHAT PEOPLE WANT FOR THEIR
DISEASE.
THIS IS A SLOW ACTION SYSTEM AND
CAN SEE THE METABOLITE IN THE
SYSTEM.
WE SAW THIS IN A PROJECT WITH
ASTRAZENECA AND NOT ONLY DO YOU
NEED A PLATFORM TO SHOW THE
THERAPEUTIC IS WORK AND YOU HAVE
TO USE ANIMALS.
WE'RE TRYING TO GET RID OF THAT
PORTION OF IT TOO.
WE LOOKED AT THIS THAT CALLED
PROM YOU WILL -- PROMULGATION
AND SAW THE MICROMOLAR AND WE
SAW EFFECT ALL WITHOUT CELL
DEATH.
WE CAN CREATE THE MODELS.
HOW LONG DOES THE DRUG LAST UP
YOUR BODY AND WHAT DOES IT DO IN
THE ORGANS WHERE YOU NEED TO
HAVE AN EFFECT.
WE NEED THE MODELS WE DID IN THE
MODELS WITH ASTRAZENECA TO LOOK
AT PHARMO DYNAMICS AND WE
REPRODUCED THAT AT THE GATE
FOUNDATION FOR MALARIA AND WHAT
WOULD BE THE DOSING IN HUMANS
AND THERE'S A POSTER UPSTAIRS
YOU CAN GET MORE DETAILS AS
WELL.
LAST I WANT TO TALK ABOUT A
CANCER SYSTEM.
WE WERE CHALLENGED BY ROCHE TO
TAKE THE MODEL AND A MULTIDRUG
MODEL AND ANOTHER VARIATION OF
THE PLATFORM TO RECONFIGURE THIS
IN MANY WAYS.
WE LOOKED AT TOMOXIN AND FOR THE
NON MULTI-DRUG CANCER WE SAW
DECREASES IN PROLIFERATION AND
WHEN WE BLOCKED THE CHANNEL
WHICH PUMP THE THERAPEUTIC WE
SAW THE DEPROLIFERATION.
FOR CANCER DRUG-DRUG
COMBINATIONS ARE THE WAY TO GO
AND FOR CONDUCTION VELOCITY YOU
GOT DECREASE FOR TAMOXFEN AND
REDUCTION IN RECOVER
I.
FOR THE COMBINATION YOU SAW A
DECREASE BUT NO RECOVERY FOR
FORCE AND IMPARTIAL WITH THE
FREQUENCY BUT AGAIN WE WEREN'T
KILLING THE CELLS.
WE CAN TAKE THE CANCER AND LOOK
AT NOT ONLY THE EFFICACY BUT THE
OFF-TARGET TOXICITY WHICH WILL
NEED TO BE APPROVED FOR PATIENTS
AND IN SCIENCE TRANSLATIONAL
MEDICINE IN ROCHE AND FEATURED
IN FRANCIS COLLINS' BLOG.
LAST, WE CAN CREATE AN INNATE
IMMUNE SYSTEM ON THE CHIP AND
IT'S BEEN HIGHLIGHTED IN
FINANCIAL TIMES AND MANY
PUBLICATIONS.
I'D LIKE TO THANK YOU ALL FOR
LISTENING.
THANK YOU FOR THE INVITATION.
THANK YOU ALL WHO WORKED WITH
ME.
AND EMPHASIZE ONE OF THE BIGGEST
PROBLEMS ONE OF THE SPEAKERS HAS
SAID IS WE HAVE 7,000 RARE
DISEASES AND WE ONLY HAVE
TREATMENT FOR 10%.
YOU CAN GET A DIAGNOSIS AND
HAVE A THERAPEUTIC DEVELOPER BUT
IF THEY DON'T HAVE A MODEL TO
TEST IT IN YOU CANNOT GET THE
DATA FOR A CLINICAL TRIAL.
WE CAN PROVIDE THOSE MODELS
THROUGH HESPROS.
THERE'S ALTERNATIVE PLATFORMS
BESIDES ANIMALS AN NOT JUST US
OUT BUT OTHER ANIMALS YOU NEED
TO LOCK AT THE NEW SYSTEMS AS AN
ALTERNATIVE TO USING ANIMAL
MODELS FOR RARE DISEASES.
THANK YOU.
QUESTIONS OR NOT?
OKAY.
>> ALL RIGHT.
WE WITH HAVE ONE LAST STORY
BEFORE WE HEAD INTO OUR LUNCH
BREAK.
I'D LIKE TO INTRODUCE DR. ANDRAY
BACHMAN AND CALEB BUPP FROM
MICHIGAN STATE STASE UNIVERSITY
AND THE HELEN DEVOS CHILDREN'S
HOSPITAL.
>> THANK YOU, WE KNOW WE'RE THE
LAST THING BETWEEN YOU AND LUNCH
IF YOU NEED SOMETHING TO
DISTRACT YOU THINK ALL THOSE
PEOPLE ONLINE EATING DELICIOUS
THINGS RIGHT NOW.
WE'RE EXCITED TO TELL YOU A
STORY OF SERENDIPITY AND SCIENCE
AND HOPEFULLY GIVE AN EXAMPLE OF
HOPE FOR THE FUTURE.
A COUPLE OF QUICK DISCLOSURES TO
LET YOU KNOW BUT SHOULDN'T
IMPACT WHAT WE ARE TALKING
ABOUT.
IT STARTS WITH PATIENT THAT CAME
INTO MY GENETICS PRACT --
PRACTICE AND HAD DELIVERY AND
WAS A LITTLE BIT BIGGER AND
SHE'S MISSING SOMETHING, SHE'S
MISSING ALL HER HAIR.
EYEBROWS, EYE LASHES INCLUDED.
THAT'S THE MOST STRIKING THING
ABOUT HER NOT BECAUSE SHE DIDN'T
HAVE HAIR BUT DID WHEN SHE WAS
BORN.
SLE -- SHE HAD A HEAD OF
SILVERY HAIR THAT CAME OUT IN
CHUNKS AND STUCK IN MY AHEAD AS
SOMETHING I HADN'T SEEN BEFORE.
THE FAMILY WASN'T READY TO JUMP
INTO GENETIC TESTING AND WE DOES
EXOME SEQUENCING.
SHE'S A CARRIER OF A RECESSIVE
GENE CALLED ODC1 WITH NO KNOWN
DISEASE ASSOCIATE.
AS A GENETIC PHYSICIAN SOMETIMES
WE FIND SOMETHING WE DON'T KNOW
IF IT'S THE ANSWER AND THIS IS
THE KIND OF CASE THAT WENT BACK
INTO THE DRAWER.
I TOLD THE FAMILY WE DON'T KNOW
WHAT TO MAKE OF IT AND MAYBE
WITH TIME WE'LL UNDERSTAND
BETTER.
A FEW MONTHS LATER AFTER WE GOT
THE RESULTS BACK I WENT TO GRAND
ROUNDS AT MY CHILDREN'S HOSPITAL
GIVEN BY THE GENTLEMAN ON THE
RIGHT AN INTENSIVE CARE UNIT
PHYSICIAN AND WORK WITH THE
GENTLEMAN BEHIND ME LOOKING AT
ORGAN DYSFUNCTION IN PEDIATRIC
ILLNESS.
I DON'T KNOW WHY I WENT TO GRAND
ROUNDS THAT MORNING BUT THEY
TALKED ABOUT POLY AMINES.
THE ONLY THING I REMEMBER IS
THAT'S A WEIRD SOUNDING WORD.
I WENT TO GROUND ROUNDS AND
HEARD THE PRESENTATION AND
NOTHING CLICKED IN THE MOMENT.
I WENT ON AND CONTINUED TO LIVE
MY LIFE UNTIL A COUPLE MONTHS
LATER I PULLED OUT MY PATIENT'S
TEST RESULTS AGAIN REVIEWING
THEM AND I SAW THAT THAT ODC1
GENE WAS INVOLVED IN THE
POLIAMINE PATHWAY AND I SAID DO
YOU THINK ANDRAY WOULD BE
INTERESTED IN THIS AND HE
GRABBED HIS PHONE AND CALLED HIM
IMMEDIATELY BECAUSE HE WAS
WORKING ON IT FOR 20 YEARS.
>> IT'S AN ENZYME IN THE
POLYAMINE PATHWAY AND CONVERTS
TO A DIAMINE AND I KNOW THE
PATHWAY NOT WELL KNOWN BUT YOU
KNOW ABOUT THE UREA CYCLE AND A
WORKED IN NEUROPATHIC BLASTOMA
AND AS THE IMPORTANT DURING
ORGANOGENESIS IN THE EMBRYONIC
DEVELOPMENT.
THE GENE IS MUTATED IN THE
PATIENT.
I COULDN'T BELIEVE IT BECAUSE I
HAD NEVER OF A PATIENT BEFORE
AND THIS IS THE SEQUENCE ON THE
LEFT AND PROTEIN SEQUENCE AND
THEY HAD A MUTATION THAT TURNED
FROM AAA TO A TAA.
THAT'S A STOP CODE WHICH MEANS
THE LAST 40 BASE PAIRS ARE NOT
BEING TRANSLATED AND THE AMINO
ACIDS GET CUT OFF FROM THE
ENZYME.
IT'S KNOWN THIS IS THE
DESTABILIZATION REGION.
WHAT HAPPENS IN LIKE MOST
PROTEINS THAT GET DEGRADED IN
THE PROTEOZOME AND IF IT'S
MISSING IT DOESN'T CLEAR FROM
THE CELLS AND THEREFORE
ACCUMULATES.
IF IT ACCUMULATES IT HAS ENZYME
ATIC ACTIVITY AND LEAD TO THE
SIN DROVE AS IT'S CALLED NOW.
WE WANTED TO LOOK AT REPORT
CELLS AND ODC IS HIGHLY PRESENT
COMPARED TO CONTROL CELLS AND IN
THE PRIMARY FIBFIBROBLASTS AND
FOUND HIGHER LEVELS IN THE
PATIENT VERSES CONTROL CELLS.
THE ENZYMATIC ACTIVITY WAS
HIGHER IN THE FIBROBLASTS ED TO
THE CONTROL CELLS.
CLEARLY SOMETHING SEEMS TO
ACCUMULATE.
IN 1996 A FRIEND OF MINE HAD
DEVELOP A MOUSE THAT DELETED THE
SAME 20 OR SO IMMUNE ACIDS AND
THE SKIN OF MICE LOST THEIR HAIR
SIMILAR TO THE ALOPECIA
DR. BACHMAN SAW IN THE CLINIC.
THAT WAS NOT DATA GENERATED FROM
US AND HELPED US UNDERSTAND.
WE PUBLISHED AND ASKED IT'S NOT
A TRUE GAIN OF FUNCTION AND NOT
BEING CLEARED AND THEREFORE HAS
HIGHER ACTIVITY AND MAYBE WE CAN
USE A DRUG.
IT'S BEEN AROUND A LONG TIME AND
SYNTHESIZED IN IN THE 78 AND
SYNTHESIZED AS AN ANTICANCER
DRUG THEN FDA APPROVED FOR THE
TREATMENT OF AFRICAN SLEEPING
SICKNESS IN 1990 AND HAZE BEEN
FAIRLY SAFE AND COULD THE
PATIENT HAVE HIGH POLYAMINE
LEVELS CAN WE BRIDGE THEM DOWN
TO PHYSIOLOGICAL LEVELS?
ALSO THEY GAVE THE MICE AN AFTER
6 DAYS THE MICE STARTED TO GROW
HAIR BACK.
OUR HOPE WAS MAYBE THAT COULD
WORK FOR THE PATIENT IN THE
FUTURE STUDY.
YOU CAN SEE THE ENZYMATIC
ACTIVITIES WERE REDUCED AND THE
PRIMARY FIBROBLASTS DID NOT
REALLY GET KILLED BY THE DRUG.
THERE'S NO APOPTOSIS GOING ON.
>> WE HAVE AN ANIMAL MODEL 25
YEARS OLD AND PATIENT SAMPLE
FROM OUR LITTLE GIRL AND OLDER
DATA.
WE WERE ABLE TO GET THREE
KILOGRAMS OF WHY'D POWDER
SHIPPED FROM OUR PHARMACY AND
PUT IT INTO HER G2 AND WHEN WE
PUBLISHED TO WHEN SHE CAME TO
CLINIC WAS 15 MONTHS.
PRETTY DARN FAST.
WHEN WE START THE TREATMENT NO
HAIR, NO EYEBROWS,
DEVELOPMENTALLY DELAYED, DID NOT
SIT UP OR WORDS ABOUT 4 YEARS
OLD.
A MONTH LATER I GOT THE MESSAGE
FROM THE FAMILY AND DON'T TELL
MY BOSSES BUT I DIDN'T WORK THE
REST OF THE DAY BECAUSE SHE
SPROUTED EYEBROWS AND EYE LASHES
AND WHAT WE THOUGHT MIGHT HAPPEN
STARTED TO SHOW ITSELF AND A
WEEK LATER MORE.
YOU SEE MORE HAIR AND THE IS
GIVING HER PUSHES TO SHOW THE
MUSCLE TONE SHE DEVELOPED AND AS
TIME GOES ON A FULL HEAD OF HAIR
AND SEE MUSCLE TONE DEVELOPING
AND IN MICHIGAN IT'S IMPORTANT
TO GO OUT AND PLAY IN THE SNOW.
HER FAMILY NEVER HAD TO BUY HER
SNOW CLOTHES BEFORE BECAUSE SHE
WOULDN'T GO OUT AND THIS IS THE
BEST PART OF THE VIDEO POPPING
UP.
LOOK AT THE CORE STRENGTH.
THIS IS A SINGLE ON A TREATMENT.
THIS IS GOOD STUFF.
AS TIME GOES ON SHE BEGINS TO BE
MORE MOBILE, ABLE TO FOLLOW
MULTIPLE STEP INSTRUCTIONS AND
USE SOME SIGN LANGUAGE AND
EVENTUALLY GET TO WHEELCHAIR AND
IS AN ABSOLUTE MENACE ON THE
WHEELCHAIR MOVING AROUND VERY
WELL.
WE TRIED TO DO THE SCIENCE OF
IT.
WE WERE WORKING OFF
COMPASSIONATE USE IND AND TRIED
TO GATHER DATA BUT IT'S HARD
WHEN YOU DO COMPASSIONATE
TREATMENTS IT'S NOT ABOUT THE
SCIENCE BUT KIND OF IS.
WE HAD AN MRI AND GOT ANOTHER
ONE AND HER BRAIN IMPROVED.
WE GATHERED GLOBAL METABOLOMIC
PROFILING AND GOT THE FIRST
SAMPLE A DAY AFTER THE
MEDICATION AND ALMOST EVERYTHING
NORMALIZED WITHIN A DAY WHICH IS
UNBELIEVABLE FROM A METABOLOMIC
PROFILE NOTHING GOT ABNORMAL.
THAT'S OUR FIRST PATIENT.
THE SECOND PATIENT YOU SEE A
UNIQUE HAIR PATTERN.
HE'S NOT IN MICHIGAN.
WE TRIED TO WORK WITH A LOCAL
MEDICAL TEAM AND TRY TO FIND A
WAY TO DO IT THAT WAY.
IT WAS IMPOSSIBLE TO DO.
THIS FAMILY ELECTED TO COME FROM
CALIFORNIA TO MICHIGAN TO BECOME
A PATIENT OF OURS TO TRY
TREATMENT FOR HIM AND ALSO THROW
OUT BECAUSE I'M IN THE RIGHT
AUDIENCE DIAGNOSED THROUGH THE
UDN SO THANK YOU.
WE EXPRESSED THE TIME LINE PORE
FROM 15 MONTHS TO 13 MONTHS FROM
WHEN HE GOT HIS DIAGNOSIS AT UDN
TO WHEN HE CAME AN GOT THE
TREATMENT.
YOU SEE MORE MUSCLE TONE AND
SOME VARIATION BUT NO HAIR, EYE
GLA
LASHES AND STARTS TO SIT UP AND
SPROUTS HAIR AND MORE ENGAGED
WITH HIS SURROUNDING.
HE HAD NOT BEEN ABLE TO SIT DOWN
AND WATCH TV AND NOW HE LIKES
MICKY MOUSE.
FROM A FAMILY PERSPECTIVE THINK
OF WHAT A HUGE DIFFERENCE THIS
MAKES.
WITH AN ASSISTIVE DEVICE HE'S
ABLE TO AMBULATE AND HE'S HAVING
THE BEST TIME.
THE TWO FAMILIES FOUND EACH
OTHER AND CONNECT AND WEARING
THEIR BACHMANN BUDDY BIBS AND
THE FAMILY SENT US A PICTURE AND
SAID IT'S THE FIRST TIME THEY'VE
DONE A PICTURE WITH EVERYBODY
STANDING.
AND FROM A LIFE STANDPOINT WHAT
A DIFFERENCE THAT MAKES.
HERE COMES PATIENT NUMBER THREE.
AN EMAIL FROM A GROUP IN ISRAEL
THAT SAYS WE HAVE A PATIENT
DIAGNOSED AT 2 YEAWEEKS OLD AND
TRIED TO DO THE MEDICATION AND
COULD NOT SORT IT OUT AND GOT
APPROVAL TO FLY TO MICHIGAN.
THIS PATIENT'S FATHER BORN IN
MICHIGAN.
THEY HAD FAMILY AND WERE ABLE TO
COME HERE AND DIRECT HOSPITAL TO
HOSPITAL TRANSFER AND THIS IS
WHAT SHOWED UP ON OUR DOOR.
A UNIQUE HAIR PATTERN AND
FEEDING TUBE AND BREATHING TUBE
AND WENT FROM DIAGNOSIS TO
TREATMENT AT NINE WEEKS AND
STARTED TREATMENT AT 11 WEEKS.
YOU FIND SOMEBODY EARLY AND
START TREATMENT AND A MONTH INTO
TREATMENT YOU SEE ALL THIS HAIR
AND THE FEEDING TUBE IS GONE.
TWO MONTHS INTO TREATMENT THE
NASAL CANNULA IS GONE.
THREE MONTHS INTO TREATMENT, I
DON'T KNOW HOW MANY THREE MONTHS
OLD YOU SEE BUT THIS IS WHAT
MOST DO, THEY DABBLE AND WAVE
AND THINGS LIKE THAT.
A LITTLE BIT OLDER GIVEN A
CUCUMBER AND HAS A NATURAL
REACTION AND FAST TRACK TO 16
MONTHS OF AGE.
SHE STILL HAS LOWER MUSCLE TONE
AND DEVELOPMENT DELAY WITH
SPEECH BUT FAR AND BEYOND WHAT
WE'VE SEEN WITH OTHER PATIENTS
AND GIVING HERSELF A HAND AS SHE
GETS THERE.
THIS TAKES YOU BACK TO THE
ORIGINAL FIRST PATIENT TO GIVE A
SENSE HOW FAR SHE'S COME.
SHE'S WEARING A LOT OF BRACING
ON HER LEG AND SHE'LL HAVE A BIG
SMILE AND YOU'LL SEE HER MOM HAS
A BIG SMILE.
THIS IS WHAT IS POSSIBLE WITH
FINDING THINGS AND APPLYING
TREATMENTS TO IT.
THINGS WE'RE TRYING TO SORT OUT
A LITTLE BIT MORE NOW IS WE
FOUND A DISEASE AND DID A
TREATMENT AND HAVE A GAP TRYING
TO UNDERSTAND WHY IT WORKS.
IT'S A NOT A BAD PROBLEM TO HAVE
BUT REAL.
THIS IS ALSO ULTRA RARE.
16 PATIENTS IN THE WORLD HAVE
THIS, FIVE IN THE UNITED STATES.
HOW DO WE MOVE THIS TOWARDS A
CLINICAL TRIAL FOR A DOUBLE
BLIND PLACEBO IT'S NOT POSSIBLE
AND WE HAVE THREE PATIENTS ON IT
AND I DON'T THINK I'D WANT TO
TAKE THEM OFF AND THE POLYAMINE
PATHWAY.
THERE'S BEEN THREE OTHER SYSTEMS
SINCE DESCRIBING THE PATHWAY AND
PROBABLY ANOTHER 15.
FROM A TREATMENT STANDPOINT WHAT
COULD BE POSSIBLE IT'S QUITE
EXCITING.
WE'VE DONE WORK TO PUT TOGETHER
A CENTER TO WORK ON THIS.
THAT'S WHERE WE'LL LAND AND
THANK THE WONDERFUL PEOPLE THAT
HAVE HELPED US.
A LOT OF THEM OUT OF THE
GOODNESS OF THEIR HEART AND HOW
ABOUT AN RO1 FOR AN ULTRA RARE
DISORDER.
THAT'S THE WORK WE WANT TO DO
AND CERTAINLY LAST BUT NOT LEAST
OUR PATIENTS AND FAMILIES WHO
HAVE BEEN THE BRAVEST FOLKS TO
SIT WITH US AND SAY, YEAH, I'LL
GIVE THAT A TRY.
THANK YOU ALL SO MUCH.
>> EXCELLENT TALK.
I JUST WANT TO THANK YOU FOR THE
ACKNOWLEDGEMENT OF THE UDN, UDP
IN THIS CASE.
DR. GOLE IS MY BOSS AND MAY NOT
BE HERE BUT WOULD BE HAPPY YOU
MENTIONED THAT AND LACY IS HERE
WHO WORKED WITH THIS DISEASE AND
MY BOSS IS ALSO THE DIRECTOR OF
THAT.
THAT'S GREAT.
I JUST WANT TO SAY IT WOULD HAVE
BEEN GREAT IF I HAD A CHANCE TO
TALK TO THE DIRECTOR OF THE NIH
TO HAVE A WORD AND SAY WE NEED
MONEY TO CONTINUE WORKING
BECAUSE THIS WORK WAS SUCCEEDED
BY THE SMALL WORK OF THE UDN,
UDPN.
I JUST WANT TO SAY THAT.
THANK YOU.
[APPLAUSE]
>> OKAY.
SO JUST A FEW REMINDER BEFORE WE
BREAK TO LUNCH, AS NOTED THIS
MORNING THE CAFETERIA IN NATCHER
IS OPEN IN THE UPPER LEVEL UNTIL
2:00 P.M.
IF YOU PREORDERED THEY'LL BE AT
THE CHECK-IN DESKS AN VISIT THE
ACTIVITIES IN THE OUTSIDE OF THE
AUDITORIUM.
ALL RIGHT, WELCOME BACK
EVERYBODY.
HOPE YOU HAD A GREAT LUNCH BREAK
AND WERE ABLE TO VISIT OUR
EXHIBITS AND ART EXHIBITIONS.
WE'RE GOING GO AHEAD AND GET
STARTED WITH OUR RARE STORY.
SO I'D LIKE TO INVITE ASHLEY
EAKIN TO THE STAGE AN ADVOCATE,
FILM DIRECTOR AND WRITER.
>> ALL RIGHT.
HELLO, EVERYONE.
THANK YOU FOR BEING HERE TODAY
AND THANK YOU TO THE NIN FOR
INVITING ME TO PEOPLE.
I'M ASHLEY EAKIN I WAS BORN WITH
A RARE DISEASE OF ASHKASHI
SYNDROME AND INCLUDES VARIOUS
MUTATION CREATES TUMORS, MOSTLY
BENIGN AND SOME CANCER ROUSE.
I'VE HAD OVER 28 SURGERIES AND
SURVIVED OVARIAN CANCER TWICE.
BUT FOR MOST MY LIFE I WAS
ASHAMED OF BEING SO DIFFERENT.
FOR THE MOST PART I HAD A GREAT
MIDWEST CHILDHOOD BUT BECAUSE MY
PARENTS WANTED TO PROTECT ME
FROM THE STIGMA OF DISABILITY I
WAS RAISED ON THE IDEA YOU'RE
NOT DISABLED YOU'RE GOOD.
IT MADE ME FEEL HAVING A
DISABILITY WAS BAD.
THE STARES AND COMMENTS STARTED
TO AFFECT ME AND A STARTED TO
HIDE MY BODY AND IN SUMMER
AVOIDING ANY AND ALL DISCUSSION
IT.
OF COURSE WHEN HAVE YOU A
DISEASE THAT AFFECTS YOUR WHOLE
BODY IT CAN START TO TO FEEL
LIKE YOU'RE LIVING A DOUBLE LIFE
AND BEFORE I GET THAT I'M GOING
TO REWIND A LITTLE BIT.
GROWING UP I ALWAYS LOVED STORY
TELLING.
I WAS THE ONE ALWAYS HOLDING THE
CAMERA AND MAKE VIDEOS AND I
NEVER THOUGHT A CAREER IN
HOLLYWOOD WAS FOR ME AND I GREW
UP IN NEBRASKA SO IT FELT FAR
AWAY AND NOT ONLY WERE WOMEN
DIRECTORS RARE BUT NEVER SEEING
SOMEONE DISABLED MADE IT SEEM
IMPOSSIBLE.
I DECIDED TO GO INTO JOURNALISM
BECAUSE I WAS ALWAYS GOOD AT
WRITING AND I HAD DESIRES TO
TELL STORIES IN VISUAL MEDIUM
AND EXPLORE THE FILM INDUSTRY.
I TOOK A CLASS ON FILM AND A
GUEST SPEAKER CAME IN AND HE HAD
A PARALYZED ARM THAT WAS VISIBLE
AND THE FIRST TIME I SAW SOMEONE
WITH A DIFFERENT BODY IN OUR
INDUSTRY AND SPARK THE IDEA
MAYBE I COULD BELONG IN THIS
WORLD.
I DOVE IN HEAD FIRST I GOT AN
INTERNSHIP AND A DID INTERN,
PRODUCTION ASSISTANT AND LANDED
AN EXECUTIVE ASSISTANT JOB FOR
THE PRODUCER WHO CREATED
AMERICA'S NEXT TOP MODEL WITH TY
RA BANKS.
IT INCREDIBLE WHERE I GOT TRAVEL
TO HONG KONG, BALI, JAMAICA.
I REALIZED I DIDN'T WANT TO WORK
IN REALITY TV AND BECAME A
WRITER'S OFFICE ASSISTANT FOR
THE NIGHT SHIFT AND THEY WENT ON
HIATUS WHILE THEY WAITED TO SEE
IF PEOPLE WOULD WATCH AND I
NEEDED A NEW JOB AND I GOT A JOB
AT AGENT X ON TNT.
BY THIS TIME I WAS SIX YEARS OF
SINKING MY TEETH IN THE
BUSINESS.
I UNDERSTAND THE WORLD BUT
WASN'T SURE I JUST WANTED TO BE
A WRITER ANYMORE.
MY PASSIONS WERE EXPANDING INTO
DIRECTING MOST THE DIRECTORS
WERE BIG TALL MEN AND WASN'T
SURE IT WAS SOMETHING I COULD
DO.
I SPOKE TO SOME FRIENDS AND THEY
TOLD ME TO TRY IT OUT AND I
SAVED UP $700 AND DIRECTED MY
SHORT FILM AND LOVED THE
PROCESS.
YES, THIS SOMETHING I WANT TO
DO.
I'D NEVER WORKED FOR A DIRECTOR
SO WASN'T SURE HOW THEY GET
HIRED TO DIRECT MOVIES AND TV
SHOWS.
I WENT ON A JOURNEY TO FIND A
DIRECT'S ASSISTANT JOB TO LEARN
EVERYTHING I CAN ABOUT THE JOB.
AFTER FIVE MONTHS I LANDED A JOB
TO THE DIRECTOR JOHN M SHU AND
WORKED ON CHRISSY RICH ASIANS.
-- CRAZY RICH ASIANS AND READ
THE BOOK AND TOLD HIM HOW TO
MAKE THE MOVIE AND A LIVED IN
MALACIA AND SING APPEAR AND IT
WAS THE BEST FILM SCHOOL I WAS
GETTING PAID TO DO AND YES, THE
CAST IS AS FUN AS ON SCREEN AND
YOU CAN SPOT ME ON THE VANITY
FAIR PHOTO.
I'M NOT HERE TO TELL YOU ABOUT
MY CAREER ADVANCES AND COOL
EXPERIENCES.
MORE IMPORTANTLY DURING THIS
PERIOD OF TIME SOMETHING WAS
HAPPENING TO MY IDENTITY.
I WAS TURNING 30 AND REALIZE THE
POWER OF REPRESENTATION AND
SEEING YOURSELF REPRESENTED IN
MEDIA AND TV HAS WEIGHT HOW YOU
FEEL ABOUT YOUR LIFE, IDENTITY
AND FUTURE.
THE ASIAN COMMUNITY WOULD WRITE
LETTERS TO JOHN SAYING HOW MUCH
IT MEANT TO THEM BECAUSE THE
CHARACTERS WERE COMPLEX LOVE
INTERESTS NOT NEGATIVE STEREO
CASTS THE PAST AND I NEVER SAW
MY EXPERIENCE REPRESENTED.
I GREW UP LOOKING AT MAGAZINES
AND TV SHOWS THAT DIDN'T INCLUDE
MANY DISABLED PEOPLE AND IF IT
DID IT USUALLY WASN'T THE
CHARACTER I CONNECTED WITH.
I BEGAN EXPLORING THE REASON
WHERE I HID MY DISABILITY AND
FELT ASHAMED AND STARTED TALKING
ABOUT IT PUBLICLY.
IN 2017 I PARTICIPATED IN A
PANCAKE VIDEO WHY I DID
SOMETHING I FEARED THE MOST.
I BECAME VULNERABLE AND TALKED
ABOUT MY SHAME.
IT WAS A PLATFORM FOR FIELD GOOD
AUTHENTIC STORIES CREATED BY
REIN WILSON.
AND I HAD COME ACROSS THE
FACEBOOK GROUP WITH PEOPLE WITH
DIFFERENT DISEASES.
IT WAS THE FIRST TIME I SAW
PEOPLE WHO LOOKED LIKE ME AND A
BLEW MY MIND ESPECIALLY WHEN I
SAW A LITTLE GIRL WITH SIMILAR
HANDS TO ME I ALL KEPT HIDDEN
AND REALIZED SHE NEEDED A ROLE
MODEL AND THERE I WAS DOING ALL
THESE AMAZING THINGS, TRAVELLING
AROUND THE WORLD WITH TV SHOWS
AND HIDING MY BODY ON SOCIAL
MEDIA AND PRETEND MY DISEASE
DOESN'T EXIST AND THE
OPPORTUNITY TO SHARE MY STORY ON
THE FACEBOOK PLATFORM CAME
ALONG.
I WAS TERRIFIED TO DO IT AND
TRIED TO BACK OUT A COUPLE TIMES
BUT THE DIRECTOR TOLD ME MY
STORY HAD SO MUCH POWER.
SO I DECIDED TO BE VULNERABLE
WITH OTHERS ABOUT MY STRUGGLES
AND IN THE VIDEO I WORE A JACKET
AND TOOK IT OFF AT THE END
SHOWING PARTS OF MY BODY I WAS
SCARED TO SHARE WITH THE
INTERNET.
WHEN THE VIDEO DROPPED IN 2017
IT WENT VIRAL AND TODAY THE
VIDEO HAS OVER 58 MILLION VIEWS
AND CONNECTED ME WITH PEOPLE I
WOULD HAVE NEVER MET INCLUDING
THE RESEARCHERS CURRENTLY WORK
ON RESEARCH FOR OUR DISEASE AT
THE NIH.
TANARA AND CAROLINA ARE
COMMUNITY IS FOREVER GRATEFUL
FOR YOU AND YOUR TEAM WHO WORKED
TIRELESSLY TO UNDERSTAND THIS
DISEASE.
ALSO INCLUDING I MET MY HUS
HUSBAND TWO TOOK THESE PHOTOS
DOCUMENTING MY EXPERIENCE.
HE SAW MY VIDEO ON FACEBOOK IS
ALSO HERE TODAY SOMEWHERE IN THE
BACK.
YOU ALSO MADE A FRIEND AND OUR
DISEASE CAUSED AN INCUR CANCER
AND SHE PASSED IN DECEMBER.
I CONTINUE TO ADVOCATE FOR HER
LEGACY.
I WANT TO SHARE THIS QUOTE FROM
BERNE BROWN VULNERABILITY IS THE
PLACE OF LOVE, COURAGE, JOY AND
CREATIVITY.
THERE'S THE SOURCE OF HOPE,
ACCOUNTABILITY, AUTHENTICITY.
IF WE WANT GREATER CLARITY IN
OUR PURPOSE OR DEEPER MORE
MEANINGFUL MORE SPIRITUAL LIVES,
VULNERABILITY IS OUR PATH.
BEING VULNERABLE SAY RISK WE
HAVE TO TAKE IF WE WANT TO
EXPERIENCE TRUE CONNECTION.
IN 2017 AFTER THE VIDEO DROPPED,
I DECIDED TO TAKE MY
VULNERABILITY LEVEL TO A WHOLE
OTHER LEVEL AND LEAP FROM FOR
WILDEST DREAMS.
WITH HIS BLESSING I QUIT WORKING
WITH JOHN CHU AND MADE A FILM
CALLED BLU WITH A REAL BUDGET
AND EXPLORED THEMES OF HIDE WHO
WILL WE ARE AND MISSING OUT ON
CONNECTIONS THAT MIGHT HEAL US.
THE FILM LANDED ME A SPOT IN THE
DIRECTING WORKSHOP FOR WOMEN.
THEY ONLY CHOOSE EIGHT WOMEN A
YEAR AND I WAS ONE OF.
I CREATED A SHORT CALLED SINGLE
WHERE I WAS ABOUT MY COMPLEX
FEELINGS ABOUT DISABILITY.
IT WAS THE ART I WAS SCARED TO
MAKE IT GOT SELECTED TO PLAY AT
THE SOUTH BY SOUTHWEST FILM
FESTIVAL AND WON AN AWARD AND
LANDED ME AGENTS AND MANAGERS AT
SOME OF THE MOST PRESTIGIOUS
COMPANIES.
FROM THERE, MY CAREER TOOK OFF
AS A WRITER DIRECTOR.
TODAY I HAVE DIRECTED TWO
EPISODES OF A SHOW CALLED BEST
FOOT FORWARD AND EPISODE OF
GROWING UP FOR DISNEY PLUS AND A
BIG BUDGET FOR NETFLIX CALLED
FORGIVE US TRESPASSES AND I
SHOWED HOLLYWOOD THAT PEOPLE
WITH DISABILITIES BELONG IN
OUR INDUSTRY I DIRECTED SIX
SHORT FILMS AND A TV SHOW IN
DEVELOPMENT WITH FX NETWORK AND
ALL THESE PROJECTS INCLUDE
AUTHENTIC DISABLED CHARACTERS
WITH NUANCED STORIES AND COMPLEX
PERSONALITY SHOWING THE RANGE OF
OUR EXPERIENCES IN HUMANITY.
NOT ONLY HAVE OUR TV AND FILM
STARTED TO GET BETTER AND SHOW
MORE REPRESENTATION BUT
COMMERCIALS, MAGAZINES, STORE
ADS, I WALKED INTO TARGET AND
THERE WAS A DISABLED DOG, I WAS
LIKE WHAT IS HAPPENING.
MOST IMPORTANTLY SOCIAL MEDIA.
I HAVE MET SO MANY AMAZING
DISABLED PEOPLE FROM ALL FACETS
OF LIFE BECAUSE EVERYONE HAS
DECIDED TO BE VULNERABLE ABOUT
THEIR JOURNEYS.
WE'RE SHOWING THE WORLD HAVING A
DISABILITY OR RARE DISEASE IS
NOT INHERENTLY NEGATIVE.
CAN HAVE A DISABILITY AND
THRIVE.
I COULD NOT BE MORE PROUD TO BE
A PART OF THIS COMMUNITY.
IN CLOSING I'M HERE TO TELL TO
YOU CHASE YOUR WILDEST DREAM.
I STOOD IN MY OWN WAY AND ALL
THE PEACE AND PURPOSE WAS ON THE
OTHER SIDE OF FEAR, GO TOWARDS
IT, CHASE IT.
IT COULD CHANGE YOUR LIFE.
>> ALL RIGHT.
UP NEXT WE HAVE DR. FUMIHIKO
URANO FOR RARE STORY 6.
>> GOOD AFTERNOON, EVERYONE.
I AM FUMIHIKO URANO FROM THE
WASHINGTON SCHOOL OF MEDICINE.
I'D LIKE TO THANK THE ORGANIZERS
OF THE MEETING FOR COORDINATING
THIS IMPORTANT MEETING.
I ALWAYS ACKNOWLEDGE AND
APPRECIATE THE SUPPORT FROM
NCATS.
THANK YOU.
SO TODAY I'M GOING TO TALK ABOUT
RARE DISEASE WOLFRAM SYNDROME
AND THE THERAPEUTIC DEVELOPMENT.
HERE ARE MY DISCLOSURES.
OUR WOLFRAM SYNDROME IS BASED ON
COLLABORATIONS INCLUDING ONE
WITH NCATS.
I HAVE SO MANY GRACIOUS
COLLABORATORS ALL OVER THE WORLD
AND OUR TEAM MEMBERS HAVE DONE A
GREAT JOB.
SO HERE IS THE STRUCTURE OF MY
TALK TODAY.
SO I WILL INTRODUCE WOLFRAM
SYNDROME TO YOU FIRST.
THEN I'M GOING TO SHARE LESSONS
AND STORIES FROM OUR PAST OUR
STUDIES AND OUR THERAPEUTIC
PROJECT FOR WOLFRAM SYNDROME AND
FINALLY I WANT TO EMPHASIZE THE
NEED FOR COOPERATION FOR PATIENT
ORGANIZATIONS AND INDUSTRY
PARTNERS.
WHAT IS WOLFRAM SYNDROME?
AS THE A RARE DISORDER
CHARACTERIZED BY JUVENILE ONSET
DIABETES AT 6.
IT'S ANTIBODY PEPTIDE POSITIVE
DIABETES.
IT'S NOT TYPE 1 DIABETES BUT THE
PATIENTS BECOME DIABETIC WHEN
THEY ARE YOUNG.
AND AROUND AGE 11 IT CAN LEAD TO
BLINDNESS AND VISION LOSS AND
DEAFNESS IS SEEN TO 80% TO 85%
OF PATIENTS WITH WOLFRAM
SYNDROME AND IT TARGETS
DIFFERENT TISSUES AND ORGANS IN
THE BODY.
NEURODEGENERATION IS A MAJOR
COMPLICATION AND APPEARS IN THE
LATER YEARS OF ADOLESCENCE AND
HAVE CEREBRAL ATROPHY AND
CEREBELLUM ATROPHY CAN LEAD TO
PROBLEMS AND CAN CAUSE BREATHING
AND SWALLOWING PROBLEMS.
MANY PATIENTS DIE TO THE
ASPIRATION OF PNEUMONIA.
THERE'S TWO CAUSATIVE GENES FOR
THE SYNDROME, WFS1 AND THE
CSID2.
THERE'S TWO TYPES OF WOLFRAM
SYNDROME.
TYPE 1 CAUSED BY PATHOGENIC
VARIANTS IN THE WFS1 GENE AND
TYPE 2 IS CALLED BY PATHOGENIC
VARIANTS IN THE CISD2 GENE.
MOST PATIENTS IN THE UNITED
STATES CARRY VARIANTS IN THE
WFS1 GENE AND IT WAS IDENTIFIED
BY WASHINGTON UNIVERSITY AND I'D
LIKE TO GO OVER HIS RESEARCH
PROGRAM.
SO PREVALENCE OF THE THESE IS 1
IN 270,000.
THIS IS AN RECESSSIVE DISORDER
WHICH MEANS WE ALL HAVE TWO
COPIES OF WFS1 GENE.
ONE FROM OUR FATHER AND ONE FROM
OUR MOTHER AND IF WE GET TWO
MUTATED COPIES WE DEVELOP
WOLFRAM SYNDROME.
AND I HAVE BEEN WORKING ON THIS
DISEASE IN THE PAST 22 YEARS AND
SO WE HAVE BOTH CLINICAL
RESEARCH PROGRAM AS WELL AS
BASIC SCIENCE RESEARCH PROGRAM.
THROUGH OUR CLINICAL PROGRAM WE
HAVE MEDICAL RECORDS OF MORE
THAN 300 PATIENTS AND WE HAVE
LONGITUDINAL STUDY DATA FROM
MORE THAN 50 PATIENTS.
WE HAVE BIOLOGICAL SAMPLES FROM
MORE THAN 100 PATIENTS AND
CREATED MORE THAN 30IPSC LINES
AND WE PROVIDE FREE GENETIC
TESTING FOR PATIENTS AND THEIR
FAMILY MEMBERS AND ACCEPT
REFERRAL FROM OTHER STATES AND
COUNTRIES.
AND THIS IS LINKED TO MY CLINIC
AT WASHINGTON UNIVERSITY MEDICAL
CENTER.
MY OF STACY HURST IS MY
COORDINATOR SO IF YOU HAVE
PATIENTS WITH WOLFRAM SYNDROME
REFER YOUR PATIENTS TO HER.
SHE'S FANTASTIC.
THROUGH STUDIES WE LEARNED
WOLFRAM SYNDROME IS A SPECTRUM
OF DISORDERS.
SO SOME PATIENTS HAVE VERY MILD
MANIFESTATIONS AND SOME PATIENTS
HAVE VERY SEVERE MANIFESTATIONS.
AND WE LEARNED THAT FEMALES HAVE
MINOR MANIFESTATIONS COMPARED TO
MALES AND IDENTIFIED TYPES OF
MUTATIONS RELATED TO MILD
MANIFESTATIONS THAT ARE
TECHNICAL AND WEFIDE VARIANTS
ASSOCIATED WITH SEVERE
MANIFESTATIONS.
THESE ARE FRAME SHIFT WARRANTS.
INTERESTINGLY WE IDENTIFIED A
WFS1 VARIANT ASSOCIATED WITH
MILD MANIFESTATIONS.
THIS VARIANT IS CALLED WFS1.
HERE YOU GO.
IT'S A VARIANT AND THE VARIANT
IS ASSOCIATED WITH VERY MILD
MANIFESTATIONS AND ALL THE
PATIENTS I HAVE OF ASHKENAZI
JEWISH POPULATIONS AND THEY MAY
NOT DEVELOP ALL THE SYMPTOMS
SEEN IN WOLFRAM BUT MAY DEVELOP
MILD DIABETES OR ATROPHY.
IF YOU HAVE A PATIENT WITH
ATYPICAL DIABETES AND OF
ASHKENAZI DESCENT REFER YOUR
PATIENTS.
THESE STUDIES ARE RUN BY OUR
MEDICAL STUDENTS.
WOLFRAM SYNDROME RELATED
DISORDERS.
WOLFRAM SYNDROME IS CAUSED BY
HAVING TWO MUTATED COPIES BUT
THERE ARE DISORDERS CAUSED BY
HAVING ONLY ONE MUTATED COPY.
AND WE CALL THEM WFS1 RELATED
DISORDERS.
SOMETIMES BY HAVING ONE MUTATED
COPY OF THE WFS1 GENE YOU MAY
DEVELOP HEARING LOSS ONLY.
THIS IS ACTUALLY OFTEN SEEN IN
PEDIATRIC PATIENTS OR DIABETES
ONLY OR OPTIC ATROPHY AND WE
IDENTIFIED THREE SPECIFIC
DOMINANT VARIANTS ASSOCIATED
WITH DEVELOPMENTAL DELAY,
INTELLECTUAL DISABILITY,
DIABETES, CATARACTS, HEARING
LOSS AND HYPOTONIA AND ATAXIA.
WE ALSO CALL THEM WOLFRAM LIKE
DISORDERS AND WE PUBLISHED
PAPERS AND ONE PROJECT WAS WITH
THE NIH.
THIS WAS AROUND EIGHT YEARS AGO.
WE IDENTIFIED A DOMINANT VARIANT
ASSOCIATED WITH DIABETES ONLY.
HERE IS OUR CURRENT INFORMATION
OF THE GENETIC SYNDROME AND WFS
RELATED DISORDERS.
TO HAVE TWO MUTATED COPIES CAN
CAUSE WOLFRAM SYNDROME
CHARACTERIZED BY DIABETES
MYELITIS AND OPTIC NERVE
ATROPHY, HEARING LOSS AND NEURO
DEGENERATION AND THERE'S OTHER
RELATED DISEASES.
ALSO RECESSSIVE WITH DOMINANT
DISEASES.
WOLFRAM IS ULTIMATELY
RECESSSIVE.
AND
THEY CANNOT SENSE THE AMOUNT OF
URINE IN THEIR BLADDER AND NOT
PUSH OUT URINE VERY EFFICIENTLY.
THIS CAN LEAD TO URINARY TRACT
INFECTION AND CAN BE PREVENT
TESTING AND MEDICATIONS AND
PROCEDURES.
RESPIRATORY FAILURE IS ONE OF
THE COMPLICATIONS AND WE CAN
PREVENT THIS IN PATIENTS.
CHOKING IS THE MOST DANGEROUS
COMPLICATION IN PATIENTS WITH
WOLFRAM.
THIS CAN BE ALSO PREVENTED BY
CONDUCTING SWALLOW TESTS AND
WORKING WITH SPEECH
PATHOLOGISTS.
IT'S IMPORTANT TO WITH THE NODE
AND RARE CAP PROGRAM WE'RE
DEVELOPING GUIDELINES.
RARE CAP IS AN INTERESTING
PROJECT BECAUSE IT'S A CLOUD
BASED SYSTEM TO CREATE CLINICAL
GUIDELINES.
MANY CAN SUBMIT IDEAS THROUGH
RARE CAP.
THIS IS WHAT WE ARE WORKING ON
RIGHT NOW.
MEARS THE SIGNIFICANCE OF
CLINICAL STUDIES.
THEY INCLUDE THE ABILITY TO
IDENTIFY PATIENT COHORTS, HELP
RESEARCHERS IDENTIFY BEST
OUTCOME MEASURES FOR CLINICAL
TRIALS AND HELP PHYSICIANS
UNDERSTAND THE IMPACT OF
COMORBID CONDITIONS.
WE NEED TREATMENT FOR WOLFRAM
SYNDROME TO ACHIEVE A CURE FOR
THE DISORDER.
HERE IS OUR THREE-STEP FORMULA
TO ACHIEVE A CURE FOR WOLFRAM
SYNDROME.
THE FIRST STEP IS TO SLOW
PROGRESSION USING ORAL
MEDICATIONS.
SECOND STEP IS TO HALT
PROGRESSION BY GENE EDITING
THERAPY OR GENE THERAPY AND STEP
THREE IS REVISED DAMAGED TISSUES
THROUGH REGENERATIVE THERAPY.
HERE IS OUR THERAPEUTIC
DEVELOPMENT PIPELINES AND THE
TIME LINE.
SO ROOT CAUSE OF THE DISEASE IS
ON THE LEFT MUTATIONS IN THE
WFS1 GENE.
THIS CAN LEAD TO ENDOPLASMIC
RETICULUM STRESS PLAYING A MAJOR
ROLE IN WOLFRAM SYNDROME AND
THIS CAN LEAD TO DEATH OF
NEURONS AND GANGLION CELLS AND
INSULIN PRODUCING CELLS AND THE
OUTCOMES ARE CLINICAL
MANIFESTATIONS LIKE DIABETES AND
VISION LOSS.
WE TRY TO TARGET THE ENDOPLASMIC
RETICULUM STRESS AND WE HAVE
COMPOUND SCREENING USING FDA
APPROVED DRUGS AND WE IDENTIFY
DANTROLENE SODIUM HAS BEEN
APPROVED FOR THE TREATMENT OF
MALIGNANT HYPERTHERMIA AND WE
TESTED THIS MOLECULE IN CELL AND
ANIMAL MODELS AND GOT POSITIVE
RESULTS AROUND 2014.
WE GOT APPROVAL AND IND IN 2013
AND STARTED TRIAL IN 2017 AND
COMPLETED PHASE 2 STUDY IN 2019.
SO 19 PATIENTS GOT THE
MEDICATION AND THE STUDY WAS
SUPPORTED BY ICTS AND NIH ALSO
PROVIDE FUNDS FOR THE CLINICAL
TRIAL AND WE GOT DONATIONS FROM
THE EDDIE WHITE AND SNOW
FOUNDATION AND OTHER PRIVATE
DONORS.
WE PUBLISHED THE DATA FOR THIS
TRIAL IN 2020 AND THIS IS WHAT
WE LEARNED.
WE IDENTIFIED THE SAFE DOSE OF
DANTROLENE SODIUM IN PATIENT
WITH WOLFRAM.
4 OF 19 PATIENTS SAW IMPROVEMENT
AND PATIENTS AND THE GREATEST
IMPROVED HAD IMPROVED VISUAL
ACUITY AND LESS DISEASE.
THE MOST COMMON SIDE EFFECTS ARE
FATIGUE AND DIARRHEA WE GOT
POSITIVE RESULTS IN ONLY FOUR OR
FIVE PATIENTS.
WE SHIFTED OUR ATTENTION TO A
NEW DRUGS.
A DRUG REPURPOSING TRIAL IS
GREAT AS WAS SHOWN IN THE
MORNING.
WE ALSO SHIFTED OUR ATTENTION TO
NOVEL DRUGS AN STARTED A
COLLABORATION WITH THE BIO TECH
COMPANY IN CAMBRIDGE,
MASSACHUSETTS.
THEIR MEDICATION AMK WAS A
COMBINATION.
BOTH MOLECULE WERE KNOWN TO
REDUCE ENDOPLASMIC RETICULUM
STRESS.
OUR COLLABORATION WAS
FACILITATED WITH A PATIENT WITH
A DOCTOR WHOSE CHILD HAD
WOLFRAM.
A
AND WE STARTED COLLABORATION IN
2017.
AND THE DRUG WAS APPROVED AND
PUBLISHED DATA USING ANIMALS AND
CELLS IN 2022 AND STARTED A
CLINICAL TRIAL UP ADULT PATIENTS
WITH WOLFRAM SYNDROME AND WE
COMPLETED THE ENROLLMENT PROCESS
AND PLAN TO REPORT THE
PRELIMINARY DATA LATER THIS
YEAR.
OUR OUTCOMES MEASURES ARE
DIABETES RELATED AND THE BRAIN
OUTCOME MEASURES.
HERE'S OUR CLINICAL TRIAL TEAM.
WE ARE ALSO TESTING A DIFFERENT
MOLECULE AS A POTENTIAL
TREATMENT FOR WOLFRAM AND THIS
PRECLINICAL STUDY IS SUPPORTED
BY THREE DIFFERENT PATIENT
ORGANIZATIONS EDDIE WHITE
FOUNDATION, SNOW FOUNDATION AND
WOLFRAM SYNDROME AND THEY
PROVIDED SOME FUNDS AND
MEDICATION.
BECAUSE WOLFRAM IS A GENETIC
DISORDER, THE BEST BEST WAY TO
TREAT THIS DISORDER COULD BE
GENE EDITING.
WE HAVE BEEN WORKING ON THE GENE
EDITING PROJECT FOR WOLFRAM
SYNDROME AND WE COLLECTED
MUTATION IN IPSCs IN PATIENTS
WITH WOLFRAM AND COULD CURE
DIABETES RELATED PHENO D CASE
HAVE BEEN TRYING TO CURE THIS
AND THIS IS A LARGE-SCALE
COLLABORATION WITH DIFFERENT
TEAMS IN THE UNITED STATES AND
EUROPE.
WE ARE ALSO TESTING TO TREAT
BRAIN ATROPHY IN THE SYNDROME
AND REGENERATE GANGLION CELLS
USING A NEUROTROPIC FACTOR
CALLED MANF ALSO A COLLABORATION
WITH A THERAPEUTIC COMPANY.
THIS IS OUR TREATMENT PIPELINE
AND AND BEFORE I END I WANT TO
EMPHASIZE THE SIGNIFICANCE OF
WORKING WITH PATIENT FOUNDATIONS
BECAUSE THEY HELP RAISE
AWARENESS OF THE DISEASE AND
FACILITATE COLLABORATION BETWEEN
ACADEMIC RESEARCHERS AND THE
INDUSTRY AND RESEARCHERS IN
DIFFERENT INSTITUTIONS.
SO PATIENT ORGANIZATIONS,
WOLFRAM SYNDROME U.K. AND SNOW
FOUNDATION AND WOLFRAM FRANCE
COORDINATE MEETINGS FOR
SCIENTISTS WORK ON THE SYNDROME
AND WE GET TOGETHER EVERY YEAR
OR TWO YEARS AND WE EXCHANGE
INFORMATION.
WE ALSO INVITE PATIENT
ORGANIZATIONS AND THE PATIENTS
TO OUR LAB SO THAT OUR LAB
MEMBERS CAN LEARN ABOUT THE
CHALLENGES OF OUR PATIENTS.
THIS IS MY LAST SLIDE SO WE
NEED TO IMPROVE CLINICAL CARE
AND NEED TO RAISE AWARENESS AND
ACHIEVE A CURE WE NEED A NEW
TREATMENT AND FOR NEW TREATMENTS
WE NEED BASICALLY MONEY TO DO
THIS SO NIH HAS PROVIDED A
SIGNIFICANT AMOUNT OF FUNDS FOR
OUR RESEARCH AND ALSO DONATIONS
PLAY AN IMPORTANT ROLE FOR US TO
DEVELOP NEW TREATMENTS SO RACHEL
HARTMAN AT WASHINGTON UNIVERSITY
HAS BEEN DOING A FANTASTIC JOB
FOR THIS ROLE.
I'D LIKE TO THANK MY TEAM
MEMBERS AND FORMER MENTORS AND
MY FAMILY AND I'D LIKE TO THANK
MY MOM.
I'D LIKE TO DEDICATE MY TALK TO
MY MOM WHO PASSED AWAY LAST
WEEK.
AND SHE WAS A FANTASTIC
PEDIATRICIAN AND FAMILY DOCTOR
AND WAS AN INCREDIBLY DEDICATED
DOCTOR AND SHE ACTUALLY WAS THE
FIRST JAPANESE DOCTOR WHO
REPORTED A CASE OF CREDOSHAW
SYNDROME IN 1965 BEFORE I WAS
BORN.
TH
THIS IS THE END OF MY TALK.
THANK YOU.
>> ALL RIGHT, NEXT UP I'D LIKE
TO INTRODUCE DR. MEREDITH
SCHULTZ THE SENIOR VICE
PRESIDENT OF CLINICAL
DEVELOPMENT AT THE MEDICAL
AFFAIRS TAYSHA GENE THERAPIES.
>> IT'S GREAT TO SEE THE STORIES
WE'RE SEEING IN RARE DISEASE AND
IT'S ONE OF MY PASSIONS.
IT'S A PLEASURE TO BE HERE
TODAY.
I WORK FOR TAYSHA GENE THERAPY
FOR RETT SYNDROME AND IT'S A
RARE DISORDER THAT PRESENTS
TYPICALLY IN YOUNG GIRLS AND
AVENL
AFFECTS THE ABILITY TO USE THEIR
HANDS, WALK, INTERACT WITH THE
WORLD.
LOTS OF UNMET NEEDS REMAINS.
WE HAVE ONE APPROVED THERAPY FOR
RETT SYNDROME BUT HAVE A LONG
TWRIE GO.
IT'S MY PLEASURE TO SPEAK TO YOU
TODAY ABOUT GENE THERAPY
DEVELOPMENT FROM THE PERSPECTIVE
OF INDUSTRY.
PAST, PRESENT AND FUTURE.
WE'LL FOCUS A LITTLE BIT TODAY
ON WHAT DECISIONS COMPANIES MAKE
INTO AND CONSIDER WHAT COMES
INTO THEIR PIPELINE AND THINK
ABOUT DEVELOPING.
HERE MY DISCLOSURES.
I HAVE A SPECIFIC PASSION FOR
GENE THERAPY AND UNIQUE
PERSPECTIVE.
I'VE SAT ON SEVERAL SIDES OF THE
TABLE.
MY FIRST EXPERIENCE WAS A
PEDIATRIC NEUROLOGIST AT THE
UNIVERSITY OF WISCONSIN WHEN I
HAD THE PRIVILEGE OF DOSING A
NUMBER OF PATIENTS WITH GENE
THERAPY AS PART OF A FOR A
DISORDER CALLED SPINAL MUSCULAR
ATROPHY OR SMA.
IT'S A RARE NEURO DEGENERATIVE
DISEASE THAT PRESENTS IN THE
FIRST SIX OF LIFE WITH WEAKNESS.
IT SUBSEQUENTLY PROGRESSES TO
WHERE PATIENTS HAVE LOST THE
ABILITY TO REALLY MOVE JUST
ABOUT AT ALL.
THEY LOSE THE ABILITY TO BREATHE
ON THEIR OWN.
THEY LOSE THE ABILITY TO EAT.
IT WAS THE EXPERIENCE OF DOSING
THEM AND SEEING THE
TRANSFORMATIVE EFFECT OF THE
GENE THERAPY THAT MADE ME LEAVE
MY PRACTICE AN JOIN INDUSTRY
WITH THE GOAL TO BRING MORE OF
THESE THERAPIES TO DISORDERS AND
PATIENTS THAT SO DESPERATELY
NEED THEM.
AND I THINK WE'RE REALLY AT THE
FOREFRONT OF WHAT GENE THERAPY
CAN POTENTIALLY DO FOR NOT ONLY
RARE DISEASE BUT FOR ALL
DISEASES.
AND SO WE'RE JUST AT THE
ICEBERG.
WE'RE CONTINUING TO WORK TOWARDS
THAT.
I'VE ALSO SMALL BIO TECH AND
LARGE PHARMA COMPANIES AS WELL
TRYING TO ADVOCATE FOR GENE
THERAPY.
I'VE ALSO BEEN A SUPPORTER OF
NEWBORN SCREENING AND WAS ABLE
TO GET SPINAL MUSCULAR ATROPHY
ADDED TO THE WISCONSIN SCREENING
BEFORE I LEFT FOR INDUSTRY SO
I'M QUITE HAPPY ABOUT THAT.
SINCE JOINING INDUSTRY I LEARNED
A LOT OF.
I THOUGHT WE HAVE DONE THIS ONCE
AND KNOW HOW TO DO IT AND KNOW
THE GENETIC TARGET.
LET'S MAKE A BUNCH OF GENE
THERAPIES AND CRANK OUT AND GET
THEM APPROVED.
WHAT WE'RE LEARNING IS DESPITE
KNOWING WHAT THE GENETIC
MUTATION IS IT'S HARD TO GET THE
PROGRAMS INTO THE CLINIC AND
IT'S EVEN HARDER TO GET THEM
INTO THE CLINIC AND SHOW
BENEFIT.
SO WE'LL TALK ABOUT WHAT
DECISIONS COMPANIES HAVE TO FACE
ABOUT WHAT PROGRAMS TO TAKE ON
IN THEIR PIPELINE.
HOW MANY PROGRAMS DO THEY WANT
TO RUN AT ONCE.
WE'LL TALK ABOUT THE CHALLENGES
OF GENE THERAPY DEVELOPMENT AN
WITH US HAVING SUCH A RAPIDLY
CHANGING LANDSCAPE AND WITH THE
RAPID GROWTH IN LEARNING IN GENE
THERAPY IT'S HARD TO KEEP UP AND
REFLECTED IN THE INDUSTRY
ENVIRONMENT AS WELL.
IT'S FAIRLY RESOURCIVE INTENSIVE
TO DEVELOP GENE THERAPY AND WE
NEED TO GET BETTER AT IT AND
MORE EFFICIENT.
I WANT TO SHARE ONE PATIENT'S
STORY WITH YOU.
THIS IS THE MEDINA FAMILY.
THIS IS AMY ANDED AN.
AND AIDAN AND THEY HAVE THREE
DIFFERENT ALL AFFECTED BY SPINAL
MUSCULAR ATROPHY.
THE OLDEST, MATO DEVELOPED WE
CANNESS AND WHEN HE WAS BORN
THERE WERE NO TREATMENTS
AVAILABLE FOR HIM.
HE SUBSEQUENTLY PROGRESSED TO
NEEDING A BREATHING TUBE BEFORE
AGE 1 AND HAS A TUBE WHERE HE'S
FED THROUGH HIS STOMACH AND NOW
CANNOT MOVE ANY ARMS AN LEGS AND
COMMUNICATES PRIMARILY WITH EYE
MOVEMENT.
HIS YOUNGER BROTHER, JAVI AT A
GRAND ROUNDS AT WISCONSIN WHEN
WE WERE TRYING TO GET UNIVERSITY
OF WISCONSIN ON BOARD TO TREAT
OUR PATIENTS WITH SINZASA AND
IT'S GIVEN VIA SPINAL TAP.
AND HE WAS LUXE ENOUGH TO BE
TREATED WITHIN THE FIRST FEW
WEEKS OF LIFE.
HE LOOKS QUITE BRIGHT AND
SITTING UPRIGHT AND DOING WELL,
ACTUALLY, MUCH BETTER THAN HIS
OLDER BROTHER.
THIS IS EME EMELIA AND WE TREAT
HER WITH A GONE THERAPY WITHIN
THE FIRST TWO WEEKS OF LIFE.
SHE WAS ASYMPTOMATIC BY THE TIME
WE STARTED TREATMENT FOR HER AND
AT THE TIME WAS THE YOUNGEST
INFANT IF THE WORLD TO RECEIVE
GENE THERAPIES AND IT WAS
NERVE-RACKING BUT SHE DID
BEAUTIFULLY AND SLEPT THROUGH
THE WHOLE INJECTION I SAT AT HER
BEDSIDE FOR FOUR HOURS WAITING
FOR SOMETHING TO HAPPEN AND
NOTHING HAPPENED AND I'LL SHARE
IN A LITTLE BIT HOW SHE'S DOING
TODAY.
TO GIVE BACKGROUND, SO WHAT IS
GENE THERAPY?
THE DEFINITION IS QUITE BROAD.
THE DEFINITION IS THE DELIVERY
OF GENETIC MATERIALS INTO CELLS
TO TREAT DISEASE.
YOU CAN INTERPRET THAT IN A
NUMBER OF WAYS BUT OFTEN WE'RE
TRYING TO REPLACE OR ALTER A
GONE THAT IS EITHER MISSING OR
ALTERED IN THE BODY.
SO ONE OF THE MOST COMMON FORMS
OF GENE IT THERAPY IS GENE
REPLACEMENT THERAPY WHERE YOU
HAVE A GENE THAT'S MISSING OR
ALTERED OR DELETED AND YOU'RE
PUTTING THAT GENE BACK IN TO TRY
TO GIVE THE BODY A HEALTHY COP
OF THE GENE TO HAVE THE PROTEINS
IT NEEDS TO DO THE FUNCTIONS IN
THE BODY.
THERE'S ALSO A NUMBER OF OTHER
METHODS OF GENE THERAPY WHERE
YOU CAN TRY AND KNOCK DOWN GENES
THAT ARE TOXIC.
WHERE YOU CAN -- YOU HEARD A LOT
ABOUT GENE EDITING AND WE'LL SEE
MORE AND MORE COME FROM THE GENE
EDITING SPACE AND THE TYPICAL
THEME IS BECAUSE DNA WE'RE NOT
ABLE TO EFFICIENTLY GET DNA INTO
CELLS.
YOU HAVE TO USE SOME SHORT OF
DELIVERY MECHANISM FOR THAT.
ONE OF THE MORE COMMON DELIVERY
MECHANISMS IS TO USE A VIRUS TO
MANUFACTURE THE PIECE OF DNA
INSIDE THE VIRUS AND THE VIRUS
GOES THROUGHOUT THE BODY AND
INSERTS THE DNA OF INTEREST IN
THE CELL AND THE CELL IS ABLE TO
USE ITS OWN MACHINERY TO
MANUFACTURE THE PROTEINS IT
NEEDS FROM THE PIECE OF DNA YOU
DELIVERED.
WITH MANY GENE THERAPIES WE'RE
INFUSING MANY COPIES OF VIRUS
INTO THE BODY WHICH CAN COME
WITH ITS OWN COMPLICATIONS.
THERE ARE I THINK GOING TO BE
MANY PERMUTATIONS YOU'LL SEE
COMING OUT IN THE FUTURE.
SO YOU'RE SEEING SOME OF THESE
ALREADY IN CLINICAL TRIALS WHERE
YOU HAVE GENE DLAPY BEING GIVEN
IN A COUPLE PLACES IN THE BODY.
IT'S BEING DELIVERED INTO THE
EYE AND DELIVERED INTO THE
SPINAL FLUID AT THE SAME TIME.
YOU HAVE SOME GENE THERAPIES
BEING DELIVERED TO THE HEART,
INTRAVENOUS IN THE BRAIN.
MANY DIFFERENT RESEARCHERS ARE
WORKING ON EVERYTHING YOU CAN
THINK OF AND I'M EXCITED TO SEE
WHAT KOMENTZ OUT IN THE NEXT
COUPLE OF YEARS.
TYPICALLY GENE THERAPIES ARE
DESIGN TO BE A SINGLE TIME
LIMITED TIME ADMINISTRATION.
ESPECIALLY IN SYSTEMS LIKE THE
BRAIN WHERE YOUR NOT HAVING A
LOT OF CELL TURNOVER, THE
THERAPIES ARE DESIGNED WHERE YOU
DELIVER IT ONCE AND THE THERAPY
STICKS AROUND.
IT'S A SINGLE TIME TO
ADMINISTRATION AND IDEALLY
PRESENT FOR LIFE.
WE'RE ABOUT SEVEN OR EIGHT YEARS
OUT FROM WHEN PATIENTS WERE
FIRST DOSED WITH GENE THERAPY
AND OVER TIME WE'LL HAVE TO SEE
HOW LONG ARE THE THERAPIES
STICKING AROUND FOR.
WE'RE STARTING TO REALLY HAVE AN
ESTABLISHED TECHNOLOGY PLATFORM
WHERE PARTICULARLY FOR SOME OF
THESE VIRUSES THAT WE'RE USING
ONE OF THE VIRUSES IN PARTICULAR
IS CALLED ADENO ASSOCIATED
VIRUS.
WE'RE LEARNING A LOT ABOUT THIS
FAMILY OF VIRUSES SO WE CAN
START TO DEVELOP MULTIPLE
THERAPIES USING THIS VIRUS AND
VIT BE AN ESTABLISHED PLATFORM
WE CAN APPLY TO A NUMBER OTHER
DISEASES.
THAT'S HELPFUL AND GOING TO
MAKE THINGS MORE EFFICIENT AND
LESS EXPENSIVE.
SOME OF THE CHALLENGES WITH GENE
THERAPY.
MANY OF OPPORTUNITIES ARE ALSO
CHALLENGES WHEN YOU FLIP THEM
AROUND.
RIGHT NOW GENE THERAPY IS QUITE
RESOURCE INTENSIVE TO DEVELOP.
SO BECAUSE THERE ARE NOT A LOT
OF STANDARDIZED PROTOCOLS FOR
HOW TO DO THIS, EVERY COMPANY IS
AND EVEN RESEARCHERS ARE DOING
THIS DIFFERENTLY.
AND THE REGULATORY ENVIRONMENT
AND EVEN WHAT WE'RE LEARNING
COMING OUT OF ACADEMIA AND WHAT
OTHER COMPANIES ARE DOING,
THINGS ARE CHANGING TO RAPIDLY,
COMPANIES ARE NEEDING TO TURN
AROUND AND PIVOT IN THE MIDDLE
OF TRIALS.
IT'S QUITE CHALLENGING TO KEEP
UP WITH EVERYTHING GOING ON.
AND THERE ARE CONSIDERATIONS TO
THINK ABOUT WHEN WE'RE DOSING
PATIENTS.
WE HAVE A THERAPY THAT'S A ONE
TIME DOSE AN POTENTIALLY PRESENT
FOR LIFE.
THIS COULD POTENTIALLY RESULT IN
SAFETY ISSUES AND SO WHEN YOU'RE
THINKING ABOUT THE BENEFIT RISK
PROFILE FOR THE PATIENTS WE'VE
TENDED TO TARGET MORE SEVERE
DISEASES BUT AS WE LEARN MORE
ABOUT GENE THERAPY WE'LL BE
MOVING TO LESS SEVERE DISEASES
AS WELL.
THE MANUFACTURING IS SOMEWHAT
CHALLENGING FOR GENE THERAPY
ALSO.
FOR CLINICAL TRIALS IN GENERAL,
TLIELZ ARE LOOKING AT SMALL
NUMBERS OF PATIENTS.
WE'RE TALKING LESS THAN 100 OR
SO.
WHEN WE SARTRE THINK OF LARGE
POPULATIONS, ALZHEIMER'S, PA
PARKINSON'S DISEASE, CONGESTIVE
HEART FAILURE WE'LL NEED TO
MANUFACTURE HUNDREDS OF THOUS
AND OF DOSES.
LOOKING AT KINETICS AND
MOLECULES DOESN'T ALWAYS APPLY
TO GENE THERAPY AND THAT CAN BE
A PROBLEM AND TRANSLATING FROM
ANIMALS TO HUMANS.
THERE'S NO STANDARD OF CARE YET
SO IT'S QUITE LABOR INTENSIVE
JUST TO GO THROUGH THAT AND
REMEMBERING IF WE HAVE A THERAPY
STICKING AROUND IN THE BODY
FOREVER.
FOR THOSE PATIENTS, IT'S
POSSIBLE THEY MAY BE EXCLUDED
FROM OTHER CLINICAL TRIALS
WHETHER IT'S GENE THERAPY NORT.
YOU DON'T KNOW WHAT THE GENE IS
WORKING EVEN IF THE TREATMENT
DIDN'T WORK YOU MAY BE -- THEY
MAY BE HAVING THE POTENTIAL TO
BE EXCLUDED.
AS FAR AS DOSING GENE THERAPY
AGAIN, THAT'S SOMETHING THAT HAS
NOT BEEN DONE IN THE CLINIC AS
OF YET EITHER.
THIS MAY SOUND OBVIOUS BUT WHAT
ARE COMPANIES IN BIO TECH AND
PHARMA THINKING ABOUT WHEN WE
THINK WHAT DISORDERS AND
DISEASES CAN WE TAKE ON?
ONE OF THE BIGGEST THINGS IS HOW
WELL DO WE UNDERSTAND THIS
DISEASE?
THIS IS TRUE WITH ANY THERAPY
YOU DEVELOP.
WE HAVE TO UNDERSTAND WHAT IS
THE UNDERLYING DISEASE
PATHOPHYSIOLOGY.
WHAT CELLS AND TISSUES ARE
AFFECTED?
WHAT ARE THE SPECIFIC MUTATIONS
DO IN THE BODY.
WHAT CELLS ARE INVOLVED AND HOW
GOOD OR THE ANIMAL MODELS.
HOW WELL DO THE ANIMAL MODELS
REPRESENT HUMAN DISEASES.
WHAT ARE THE STRENGTHS AND
LIMITATIONS OF THE ANIMAL
MODELS.
WHAT ADMINISTRATION SHOULD WE
USE?
DELIVER TO THE BRAIN OR SPINAL
CORD AND WHAT IS THE NORMAL
TRAJECTORY OF DISEASE.
THE NATURAL HISTORY STUDIES
EVERYBODY HARPS ON AND THEY'RE
NOT ALWAYS THE STUDIES THAT
PATIENTS NECESSARILY WANT AND IT
MAKES SENSE, YOU WANT THE
TREATMENT.
BUT UNTIL WE UNDERSTAND WHAT THE
DISEASE DOES WITHOUT TREATMENT
AND WHAT THE VARIABILITY IS
BETWEEN PATIENTS IT'S NEARLY
IMPOSSIBLE TO BE ABLE TO
UNDERSTAND WHAT AN IMPROVEMENT
IS GOING TO BE.
IT'S IMPORTANT WE UNDERSTAND
WHAT THE DISEASE IS DOING BEFORE
WE GO AND TRY TO MAKE
TREATMENTS.
ARE END POINTS AVAILABLE?
WHAT BIOMARKERS ARE AVAILABLE?
HOW WILL WE MEASURE CHANGE IN
THE PATIENT?
AND HOW DO WE CORRELATE THAT TO
WHAT WE ARE SEEING IN THE ANIMAL
STUDIES WE PERFORM?
I THINK YOU SPLAY HEARD EVEN IN
THE NEWS THERE'S LOTS OF TALK
ABOUT TRYING TO GET THE GENE
THERAPY PROGRAMS APPRESSED ON
SURROGATE CLINICAL END POINTS
AND I LIKE THAT.
I THINK WE'RE MOVING IN THE
RIGHT DIRECTION.
THERE'S SO MANY THERAPIES THAT
ARE PROMISING BUT WE CAN'T GET
OVER THE FINISH LINE BECAUSE OF
THE HURDLES.
ALL OF THESE THINGS ARE
IMPORTANT TO THINK ABOUT WHEN
WE'RE THINKING ABOUT DO WE TAKE
THIS PROGRAM ON TO TRY AND BRING
A GENE THERAPY TO PATIENTS.
ONE COMMENT ON THE MONOGENIC
VERSUS POLY GENIC DISEASES.
MANY GENE THERAPIES ARE
TARGETING MONOGENETIC DISORDERS
WHERE YOU HAVE A GENETIC DISEASE
AN THERE'S A SINGLE MUTATION AND
YOU CAN HAVE A GENE THERAPY THAT
ADDRESSES THAT MUTATION BUT I
THINK WE'LL START TO SEE GENE
THERAPIES MOVE INTO MORE POLY
GENETIC AND MULTI-FACTORIAL
DISEASE THAT MAY ADDRESS A
COMMON PATHWAY AS WELL.
IT'S PROBABLY GOING TO BE MORE
CHALLENGING TO SHOW BENEFIT
DEPENDING ON TE DISEASE BUT I
THINK YOU'LL SEE GENE THERAPY
HEADING IN THAT DIRECTION ALSO.
TO TELL YOU A LITTLE BIT ABOUT
OUR RETT SYNDROME GENE THERAPY
PROGRAM.
IT AFFECTS ABOUT 1 IN 10,000
FEMALE BIRTHS.
AND IT LEADS TO SEVERE
IMPAIRMENT NORMALLY BEGINNING
AROUND AGE 1 OR SO WHERE GIRLS
GO THROUGH A PERIOD OF LOSING
DEVELOPMENT MILESTONES AND 9th
AFFECTS ALL ASPECTS OF LIFE.
THE MUTATION IS MEC P2 AND IT'S
IMPORTANT FOR THE FUNCTIONING
PARTICULARLY OF THE BRAIN CELLS.
GENE THERAPY IN RETT SYNDROME IS
CHALLENGING BECAUSE THERE'S AN
OVEREXPRESSION SYNDROME.
IF YOU HAVE TOO MUCH MEC P2 CAN
CAUSE PROBLEMS AND IT'S X
LINKED.
THE MUTATION IS ON AN X
CHROMOSOME.
IN GIRLS YOU HAVE SOME CELLS
THAT HAVE NORMAL LEVELS OF MEC
P2 AND SOME HAVE THE MUTATION SO
THEY'RE DEFICIENT.
THE PROGRAM AT TAYSHA IS DESIGN
TO HAVE A REGULATORY ELEMENT
WITHIN THE PRODUCT CALLED AM I
RARE.
THE PRODUCT IS A MINI MEC 2 GENE
AND HAS THE SEMI RARE FEEDBACK
LOOP THAT OPERATES ON A CELL BY
CELL BASIS.
THE GOAL IS TO HAVE LEVELS OF
MEC P2 REGULATED IN EACH
INDIVIDUAL CELL.
WE DO HAVE TWO TRIALS ONGOING IN
CANADA AND U.S. AND DOSED TWO
PATIENTS SO IT'S EXCITING.
ONE REASON WE SELECTED RHETT
SYNDROME IS BECAUSE IT CHECKED
BOX OF US UNDERSTANDING THE
DISEASE AND HAVING THE NATURAL
HISTORY AND END POINTS AS WELL.
I THINK I TOUCHED THIS AND BIG
THINGS CONTRIBUTE TO NATURAL
HISTORY STUDIES AND WORK ON THE
END POINTS AND WE HAVE TO WORK
TOGETHER.
THINGS LIKE THE BESPOKE PROGRAM
AT NIH WHERE WE'RE LOOKING AT A
NUMBER OF DISEASES, MAKING
LEARNING PUBLIC SHARING
INFORMATION IS GOING TO BE KEY.
WHERE ARE WE GOING IN THE
FUTURE.
THE TECHNOLOGY WILL ONLY GET
BETTER AND WE'LL DELIVER NOVEL
DELIVERY SYSTEMS, MAYBE
NON-VIRAL DELIVERY SYSTEMS AND
GET BETTER AND MORE EFFICIENT
AND SEE IT MOVE TO OTHER
DISEASES MORE COMMON AND
HOPEFULLY MORE INTO ULTRA RARE.
AND I WATCHED JAVI SIT UP AND
AMELIA PROGRESS FROM SITTING TO
WALKING TO ATTENDING
KINDERGARTEN.
SHE'S LIVING A NORMAL LIFE WHICH
IS INCREDIBLE IF YOU THINK WHERE
WE STARTED WITH HER OLDEST
BROTHER.
I'M EXCITE THE TO SEE WHERE THIS
TECHNOLOGY GOES.
I THINK IT HOLDS PROMISE AND
WE'RE ONLY GOING TO CONTINUE TO
MAKE PRLGS HERE.
-- PROGRESS HERE.
SPECIAL THANK YOU TO THE MEDINA
FAMILY FOR ALLOWING KNOW SHARE
THEIR STORY.
I DON'T KNOW IF THERE'S TIME FOR
QUESTIONS.
>> THIS HAVE A VIRTUAL ATTENDEE.
WHAT IS THE MOST ETHICAL GENE
CHALLENGE ABOUT GENE THERAPY?
>> THE MOST IMPORTANT ETHICAL
CHALLENGE?
I THINK THIS HAS BEEN IN THE
NEWS.
I THINK THE COST OF GENE THERAPY
RIGHT NOW IS A BIG ONE AND I
THINK AS A SOCIETY WE HAVEN'T
QUITE FIGURED OUT HOW TO MANAGE
THAT WITH SYSTEMS NOT
NECESSARILY BEING SET UP FOR
ONE-TIME THERAPIES.
THAT'S SOMETHING WE'LL HAVE TO
FIGURE OUT TOGETHER.
>> THAT IS A GENETIC MUTATION
SEEN IN MULTIPLE KIDS IN THE
FAMILY DID YOU SEE IF THERE WAS
IMMUNITY BEING BUILT IN THE
OTHER KIDS THAT WEREN'T ELIGIBLE
FOR THE CLINICAL TRIALS AND WAS
THERE ANYTHING STUDIED ON THAT
AND WHAT WERE YOUR RESULTS?
>> THAT'S A GREAT QUESTION AND
SOMETHING WE THINK ABOUT WHEN WE
HAVE DISORDERS WHERE WE HAVE
MULTIPLE SIBLINGS IN THE SAME
FAMILY THAT MAY BE ELIGIBLE FOR
GENE THERAPY.
WITH THIS FAMILY BECAUSE THEY'RE
ON THREE DIFFERENT TREATMENTS
NOW WHICH IS AMAZING YOU DON'T
HAVE TO WORRY ABOUT THE SHEDDING
OF GENE THERAPY NOR YOUNGEST BUT
IT'S SOMETHING WE THINK ABOUT.
THIS SOMETHING THAT I THINK
HASN'T BEEN COMPLETED ANSWERED
EVEN IN THE FIELD IS IF SOMEBODY
DOES HAVE NATURAL IMMUNITY TO
THE VIRAL VECTORS CAN WE DOSE
THEM WITH GENE THERAPY AND IS IT
SOMETHING WE'RE TRYING TO FIGURE
OUT.
>> YOU'RE SEEING DIFFERENCE
BETWEEN TRIALS.
SOME ARE ALLOWING PATIENTS IN
THAT HAVE BUILT UP IMMUNITY AND
SOME AREN'T AND IT DEPENDING ON
WHERE YOU'RE DOSING IN THE
FIGURE AND SOMETHING WE'RE STILL
TRYING TO FIGURE OUT TOGETHER.
>> WHAT IS THE AAV GOING TO LOOK
LIKE FOR CROSS REACTIVITY AND
THE SHEDDING AND WILL IT BECOME
14% AND NOW 80% WITH NATURAL
IMMUNITY AND WHAT'S THAT LOOK
LIKE.
>> OR IF YOU GET ONE VARIANT CAN
YOU DOSE WITH ANOTHER VARIANT OF
AAV?
WE DON'T KNOW THE ANSWERS TO
THOSE QUESTIONS.
[OFF-MIC]
>> THAT'S A GREAT QUESTION AS
WELL.
WHEN WE DOSE AS INFANTS THEIR
SYSTEMS AREN'T FULLY DEVELOPED
WILL THEY BE ABLE TO TOLERATE
DIFFERENTLY THAN SOMEONE OLDER.
THERE'S MANY UNDERLYING
QUESTIONS IN WHAT WE SHOULD BE
DOING AS FAR AS ADMINISTERING
IMMUNOSUPPRESSIVE THERAPY AND
YOU'RE SEEING A WIDE VARIETY OF
DIFFERENCES IN TRIALS WITH
IMMUNOSUPPRESSION.
IT'S A HOT TOPIC IN THE FIELD
WE'RE NEEDING TO ADDRESS
TOGETHER AS WELL.
[OFF-MIC]
>> MANY COMPANIES DO.
WE DO IN OUR TROIL AS WELL.
>> THANK YOU FOR THE
PRESENTATION.
IT'S INFORMATIVE.
YOU ENDED ON A LOT OF EXCITEMENT
FOR THE FIELD BUT I'M ALSO
REMEMBERING THE CHILLING EFFECT
TAKING PLACE AROUND THE EARLY
2000s.
MY QUESTION TO YOU IS YOUR
PERSPECTIVE WHETHER OR NOT GENE
THERAPY IS SUSCEPTIBLE TO THE
CHILLING EFFECT OF HOLD ON
DEVELOPMENT AS THE PATIENTS MAY
OR MAY NOT HAVE THE CLINICAL
OUTCOMES WE EXPECT.
>> YOU BET.
I THINK WHAT YOU MAY BE
REFERRING TO THERE WAS EARLY ON
WHEN GENE THERAPY WAS FIRST
TAKING OFF IN THE '90s THERE WAS
A DEATH OF AN INDIVIDUAL WHO
RECEIVED A GENE THERAPY FOR A
RARE LIVER DISEASE AND SET THE
FIELD BACK.
THAT INDIVIDUAL DEVELOPED A
SEVERE IMMUNE REACTION.
EVERY PATIENT THAT'S DOSED IS
IMPORTANT AND EVERY EVENT IS
NEWS WORTHY.
WE ALWAYS SAY THIS TECHNOLOGY IS
LIKE DRIVING A LAMBORGHINI AND
WE HAVE TO BE CAREFUL AND USE IT
SAFELY AS WELL.
IT'S A GREAT POINT AND I THINK
WE'RE STILL VERY EARLY ON.
>> THANK YOU.
>> EVERYBODY, WE'RE GOING TO
TAKE A SHORT BREAK.
BE BACK BY 3:15.
THANK YOU.
>> THE NEXT SESSION, RARE STORY
NUMBER 8, IT IS MY PLEASURE TO
INTRODUCE DR. ERIC HOFFMAN AND
HE'S A PROFESSOR OF
PHARMACEUTICAL SCIENCES AT BRING
HAMPTON UNIVERSITY AND CEO OF
RARE GEN BIO PHARMA.
SHARON HETERLEE OF THE CHIEF
RESEARCH OFFICER OF THE MUSCULAR
DYSTROPHY ASSOCIATION AND
THEY'LL START BY TALKING ABOUT
THE PROGRAM AND WE'LL SIT DOWN
AND HAVE A FEW MINUTES FOR Q&A.
>> WE'RE DOING A QUICK TAG TEAM,
SHARON AND I IN PART BECAUSE
SHARON WAS AT THE MUSCULAR
DYSTROPHY ASSOCIATION.
THERE'S A HUGE REASON THE
PROGRAM WENT FORWARD WITH NCATS
THE SPONSOR SOMEONE DESCRIBED
THIS WILL BE ABOUT DUCHESNE
DISEASE AND WE HAVE A PANEL
AFTER THIS AND KWAEP.
-- Q&A.
I'M NOT GOING TO SPEAK MUCH
ABOUT DUCHESNE MUSCULAR
DYSTROPHY.
THIS IS A DRUG DEVELOPMENT
PROGRAM THAT TOOK ONE ATOM OFF
PREDNISONE.
IT'S ONE OFF THE COMMONLY PLEA
SCRIBED DRUGS.
THE YOUNG MAN LIVING WITH
DERMATO MYOSITIS TALKED ABOUT IT
THIS MORNING AND WE ENDED UP
WITH THREE DIFFERENTIATIONS FROM
THE CORTICO STEROID CLASS.
I'LL GO THROUGH HOW WE
DEVELOPED THIS BRIEFLY.
USUALLY WHEN YOU HAVE A NEW
COMPOUND SPUN A UNIVERSITY ABOUT
30% OF DRUGS ARE SPUN OFF
U.S. DIVERSITIES AND ECO SYSTEM.
THEN SPIN OFF A COMPANY, GET
VENTURE CAPITAL AND THEN THE
SMALL COMPANY GETS BOUGHT OUT BY
A BIG COMPANY.
WE WENT DOWN A DIFFERENT PATH.
I SHOULD FIRST ACKNOWLEDGE JOHN
McCALL THE CHEMIST WHO INVENTED
THE CHEMISTRY WE DID AND WELL
KNOWN TO NIH AND NCATS AND
ADVISER ON MANY NIH PANELS.
THE REASON IS WE HAD KEY
DIFFERENCES FROM THE WELL
TRODDEN PATH AND WE WERE NOT
SEXY AND V.C.s WERE NOT
INTERESTED BUT WE HAD GOOD
THINGS GOING FOR US LARGELY
BECAUSE OF NIH AND FEDERAL
FUNDING AND FOUNDATIONS AND HAD
INFRASTRUCTURE FOR MOUSE
CLINICAL TRIALS AND SET UP WITH
THEED TO -- WITH DOD AND ENDED
UP WITH THIS PHILANTHROPY CHILD
AND WE WORKED WITH THE NCATS
TREND AND WERE AN INITIAL
AWARDEE AND BROUGHT DEVELOPMENT
EXPERTS TO THE MAM.
THEY REPEATED KEY THINGS WE ADD
DONE AS ACADEMIC LABS AND FOUND
THEY WERE VALIDATED AND THAT
HELPED DERISK THE PROGRAM.
THEYED AED IN MANUFACTURING
CONTROLS, ADME AND SUPPORT IN
KIND.
THE NCATS DIDN'T GIVE US MONEY
INSTEAD THEY USED THE GREAT
MACHINE OF EXPERTS WITHIN THE
INTRAMURAL CAMPUS TO CO-DEVELOP
WITH US.
WE STARTED WORKING WITH
NONPROFITS AND SHARON HESTERLEE
WILL TALK ABOUT THIS AND HOW
THEY CONTINUE TO WORK IN
DEVELOPING COUNTRIES WITH
CONTRACTS WITH 400% ON RETURN
WITH THE NONPROFIT AND WE SAID
WITH LATER DRUG SALES WE'LL GIVE
BACK 400% ON THE INVESTMENT.
WE STARTED TO PAY BACK THOSE
FOUNDATIONS.
EN FACT OVER THE NEXT THREE
YEARS ABOUT TWO-THIRDS OF THE
INCOME TO WILL JUST BE PASSED
THROUGH TO NON-PROFIT
FOUNDATIONS.
SO HERE I'LL TURN IT OVER TO
SHARON TO TALK ABOUT THE VENTURE
PHILANTHROPY MODEL.
I'LL SAY WORDS ABOUT THIS AND
HOW THE MUSCULAR DYSTROPHY WAS
INVOLVED.
IT'S ANOTHER THING IN OUR TOOL
KIT A WAY TO DERISK AND
INCENTIVIZE RARE DEVELOPMENT FOR
RARE DISEASE BUT 20 YEARS AGO
THERE WAS LITTLE RECOGNITION
RARE DISEASE WAS A PROBLEM.
NOW THINGS HAVE CHANGED.
WE'RE NOT THERE YET BUT
CERTAINLY THERE'S A RECOGNITION
RARE DISEASES ARE COMMON IN
AGGREGATE.
20 YEARS AGO GENZYME WAS THE
ONLY COMPANY IN THE FACE.
AT THE TIME MDA WAS OVER 50
YEARS OLD AND INVESTED OVER $50
BILLION IN RESEARCH AND
NEUROMUSCULAR DISEASE AND WE
WERE IN DANGER OF SEEING A LOT
OF THINGS LANGUISH WITHOUT
MOVING ON AT THE APPROVAL
CONCEPT STAGE IN THE CLINIC.
WE STARTED IN ABOUT 2004 WITH
SEVERAL OTHER ORGANIZATIONS
JUVENILE DIABETES, CYSTIC
FIBROSIS AND FIGURING OUT HOW DO
WE FUND COMPANIES TO MOVE SOME
THINGS FORWARD AND DE RISK THEM
EVEN BEFORE ANGEL INVESTORS WERE
INTERESTED.
WE STARTED FUNDING THINGS AND IN
ABOUT 2009 WE REVAMPED THE
PROGRAM AND CALLED IT NDA
VENTURE PHILANTHROPY AND WE DID
WHAT IS CALLED A NON-DILUTIVE
INVESTMENT MEANING WE DID GET A
RETURN ON OUR INVESTMENT BUT IT
WAS BASED ON REVENUE OF AN
IMPROVED PRODUCT.
WE DID NOT TAKE AN EQUITY STAKE
IN THE COMPANY.
WE SUBSEQUENTLY DID TWO OTHER
INVESTMENTS FOR A TOTAL OF THREE
OVER THE YEARS AND OTHER
ORGANIZATIONS WERE ABLE TO USE
THE TEMPLATE AND INVEST IN
REVERA IT IS GEN AND THE GROUPS
THAT HELPED SUPPORT IT IS UNIQUE
IN THE SPACE.
SO WE MADE THAT INVESTMENT IN.
THAT'S A 14 YEAR LAG SO THAT'S
THE DIFFERENCE BETWEEN VENTURE
CAPITAL AND PHILANTHROPY.
VENTURE CAPITAL DOESN'T LOOK AT
THAT AS A STRATEGY NO THAT
THAT'S OUR GOAL EITHER BUT YOU
HAVE TO BE PATIENT AND WHEN
YOU'RE SUCCESS IN VENTURE
PHILANTHROPY IN THIS CASE OUR
RETURN ON INVESTMENT BASED ON
SALES OF A DRUG.
THAT'S DRUG SALES FOR OUR
PATIENT COMMUNITY.
SO THAT PUTS US IN THIS AWKWARD
POSITION.
WE HAVE TO THINK ABOUT CONFLICT
OF INTEREST.
HOW DO WE TALK ABOUT THE DRUG IF
WE'RE GOING BENEFIT DIRECTLY
FROM SALES.
ONE THING YOU CAN CONSIDER DOING
IS DIVESTING IN THE ROYALTY
STREAM AND HAVE AN OFFER WE'RE
THINKING
OF TAKING TO BE ABLE TO TAKE A
BIT OF A HAIRCUT ON OUR TOTAL
RETURN BUT GET THE MONEY UP
FRONT AND NO LONGER BE
AFFILIATED WITH THE SALES.
IT'S A DECISION EVERYBODY TO
THINK ABOUT AND WILL STOP THERE
AND TURN IT BACK TO ERIC.
>> ONE OTHER POINT, I WANT TO
THANK THE NCATS SBIR AND THE
EUROPEAN COMMISSION THROUGH THE
HORIZON PROGRAM WITH NEWCASTLE
UNIVERSITY.
THERE ARE SOME PROBLEMS WITH
THIS MODEL.
THERE'S NO POT OF MONEY TO DRAW
ON AND MUST KEEP THE BEAR BONES
AND REVERAGEN I'M CEO AT 10%
EFFORT BUT IT'S CRITICAL WILLING
TO FIND PEOPLE TO HELP AND KNOW
WHAT THEY'RE DOING WHICH WE'VE
BEEN FORTUNATE.
THIS IS THE PHASE 1 IN 2016 AND
I PUT THE NUMBER OF PATIENTS
INVOLVED IN EACH STUDY.
AND THE STUDIO CHAIR AND PAUL
CLEMENS FROM THE UNIVERSITY OF
PITTSBURGH AND NEWCASTLE
UNIVERSITY IN THE U.K., THE HEAD
OF MANY GRANTS TOGETHER WITH ME
AND JESSE DAMKER HERE IN THE
D.C.
ALL THIS WAS SPUN OUT OF
CHILDREN'S NATIONAL MEDICAL
CENTER A COUPLE MILES FROM
DOWNTOWN D.C.
THIS WAS DESIGN AND RUN BY
ACADEMIC MEDICINE, EXTENSIVE
DESIGN AND CONDUCT OF TRIALS.
SCIENTIFICALLY ROBUST AND
INNOVATIVE BECAUSE WE WERE NOT
RISK AVERSE.
I'LL JUST SHOW A COUPLE SLIDES
AND WE'LL TURN TO DISCUSSION.
THIS WAS A PIVOTAL TRIAL.
IT WAS A SCREENING PERIOD,
TREATMENT PERIOD.
AND THE PLACEBO AN PREDNISONE
CROSSED OVER TO THE RED IS
PLACEBO STABLE OR DECLINES AND
WI
WITH THE MEDICATION.
YOU SEE VAMOROLONE SUGGESTED THE
HIGHER DOSE IS BETTER.
THIS IS STUNTED OF GROWTH IT
SEEMS TO BRITTLE BONES AND THE
BONE MORBIDITIES.
WE DON'T SEE THAT WITH
VAMOROLONE.
THE BIOMARKERS REMAIN NORMAL AND
SEE ACCELERATED GROWTH.
THE BLUE LINE IS THE INCREASED
GROWTH ON VAMOROLONE.
THE TWO PINK ARE ON PREDNISONE
AND CROSSING OVER TO VAMOROLONE.
YOU SEE THE STUNTING OF GROWTH
FOLLOWED BY THE CROSSOVER TO
VAMOROLONE AND THE GROWTH PICK
UP.
IN CONCLUSIONS, IT'S SAFE AND
EFFECTIVE.
EQUALLY EFFECTIVE AS PREDNISONE
AND THE CO-DEVELOPMENTS AND WE
RECEIVED FDA APPROVAL AND U.K.
MRA LAST MONTH.
IT'S THE FIRST DRUG APPROVED IN
EUROPE FOR DUCHESNE MUSCULAR
DYSTROPHY.
WE WOUND UP WITH DIFFERENT
LABELS FROM DMA AND THE LABEL
SAYS WHILE THE FDA LABEL IS
WHERE PRETTY MUCH
UNDIFFERENTIATED FROM CORTICO
STEROID CLASS AND THE EMA LABEL
LOOKED AT ALL THE CLINICAL TRIAL
DATA AND THE MECHANISM OF ACTION
AND WAS WHAT I SHOWED IN THE
FIRST SLIDE.
THIS IS BONE GROWTH ON
VAMOROLONE OVER TWO AND A HALF
YEARS OR HEIGHT AND THIS IS ON
PREDNISONE AND THESE ARE
EXTERNAL COMPARATORS AND YOU SEE
THE GROWTH OVER ONE YEAR AND
STUNTING OF GROWTH AND
RECOVERING.
THE FDA LABEL SAYS THAT LONG
TERM USE OF CORTICO STEROIDS
HAVE LONG-TERM AFFECT ON GROWTH
AND DEVELOPMENT.
YOU THINK THERE'S TWO DIFFERENT
GROUPS.
IT COULD BE ANOTHER STEROID WAS
APPROVED IN THE U.S. BUT NOT
APPROVED IN EUROPE.
THERE'S ISSUES WITH BENCHMARKING
YOU HAVE TO BE CAREFUL OF.
THESE WERE THE DIFFERENT SITES
PARTICIPATING IN THE TRIALS AND
THE FOLKS INVOLVED.
TO SUMMARIZE BACK TO THE MODEL
IT CAN WORK THROUGH
INTERNATIONAL DRUG APPROVAL
THROUGH EXTENSIVE DERISKING
REDUCE THE COST OF DRUG APPROVAL
AND I HEARD 10% MENTIONED AND
DEPENDS ON HOW MUCH FILL USE ARE
BUILT IN AND IT'S A GREAT COST
REDUCTION ENGINES STAKEHOLDERS
AND PATIENTS AND FAMILIES AND
INNOVATIVE RISK TOLERANT AND NOW
WE'LL TALK AND HAVE A DISCUSSION
AND ONE QUESTION IS THIS A
GENERALIZABLE MODEL GOING
FORWARD.
>> IF THERE'S QUESTIONS FROM THE
AUDIENCE, COME UP TO THE
MICROPHONE.
LOSE, GO AHEAD.
>> I THINK THE VENTURE
PHILANTHROPY MODEL IS INSPIRED
AND THE CYSTIC FIBROSIS MODEL IS
A SUCCESS.
THE PATIENT GROUP PHILANTHROPY
THE GOAL IS TO BRING BETTER AND
NEWER.
IT'S ALWAYS AN INCREMENTAL
PROCESS AND SAY YOU INVESTED AND
HAVE SOME THERAPY BRINGING IN
$40 MILLION A YEAR AND THEN YOU
ARE TRYING TO FUND NEW PROMISING
THERAPIES AND THERE'S ONE THAT
MAY DIRECTLY COMPETITOR ONE
MAKING MONEY FOR YOU NOW.
WOULD YOU BE JUST AS WILLING TO
FUND THIS COMPETING THERAPY.
AND IS THERE SOME SORT OF
CONFLICT OF INTEREST THAT MAY BE
THERE AND SOME MECHANISM TO TRY
TO ELIMINATE THAT?
>> I'M HAPPY TO HANDLE THAT.
I THINK THAT'S WHY IT'S
IMPORTANT TO CONSIDER DIVESTING
YOUR INTEREST IF YOU CAN.
USUALLY THEY WANT BIG ROYALTY
STREAMS.
THAT'S WHAT THEY DID.
WE HAD CHALLENGES WITH A SMALLER
ROYALTY STREAM.
WE GOT AN OFFER.
YOU LOSE MONEY AND CLEARLY
THEY'RE NOT GOING TO GIVE YOU
WHAT YOU WOULD HAVE GOTTEN.
THEY'LL GET MONEY UP FRONT.
AT THAT POINT YOU'RE OUT OF THE
GAME AND YOU'RE FREE TO FUND
SOMETHING THAT COMPETES.
YOU HAVE GOTTEN YOUR MONEY AND
OUT AND FOR SURE IT'S A CONCERN.
ONE CONFLICT THAT CAN COME UP
YOU MAY HAVE TWO INTERESTING
OPPORTUNITIES.
ONE A HIGH UNMET NEED.
THE OTHER ONE MUCH MORE LIKELY
TO BE FINANCIALLY LUCRATIVE AND
YOU HAVE TO MAKE TOUGH DECISIONS
LIKE THAT.
>> I'LL ASK A SIMILAR QUESTION.
I'M STEPPING BACK.
WHAT WERE THE DECISIONS.
WHAT WERE THE PROS AND CONS YOU
THOUGHT ABOUT BEFORE THIS WAS A
MODEL YOU DECIDED THAT THE
FOUNDATION THE ASSOCIATION
DECIDED TO PURSUE.
YOU TALKED NOW WHAT ARE SOME OF
THE THOUGHTS AFTER YOU ARE
SUCCESSFUL.
WHAT WERE THE PROS AND CONS
GOING INTO IT AND THEN ALSO IF
YOU CAN JUST FOR THOSE THAT
AREN'T FAMILIAR WITH THIS DEFINE
WHAT SOME OF THE TERMS ARE.
WHAT ARE ROYALTIES.
WHAT DOES IT MEAN TO DIVEST
THEM.
THAT'S A TWO-PART QUESTION FOR
YOU.
>> SURE.
WHEN WE FIRST LAUNCHED THE
PROGRAM YOU HAVE TO UNDERSTAND
MDA IS A LEGACY ORGANIZATION AND
BEEN AROUND A LONG TIME AND
TENDS TO BE CONSERVATIVE.
TO BE ABLE TO TALK THROUGH THIS
NOVEL IDEA WAS A LITTLE BIT
CHALLENGING.
THERE WAS LEGITIMATE CONCERNS.
ONE IS WHAT IS OUR LIABILITY IF
WE'RE FUNDING THE SPONSOR OF A
CLINICAL TRIAL AND WE TOOK OUT A
POLICY TO PROTECT THE
ORGANIZATION.
THE OTHER THING TOO IS WE WERE
CONCERNED ABOUT WHAT WOULD
HAPPEN WITH WE TOOK AN EQUITY
STAKE.
AS A NONPROFIT IF YOU TAKE AN
EQUITY STAKE YOU HAVE TO VALUE
EVERY YEAR WHICH CAN BE
COMPLICATED AND HARD TO DO AND
YOU THINK OF RESEARCH.
IT COUNTS ON YOUR BOOKS IF
YOU'RE FUNDING RESEARCH AS A
PROGRAM EXPENSE AN IT'S A GOOD
THING TO PUT MONEY INTO A
PROGRAM EXPENSE.
THIS IS AN ASSET THAT MAY OR MAY
NOT PAY OFF AND MAY GO SOUTH AND
MAY HAVE TO WRITE DOWN AND THAT
DOES NOT LOOK GOOD ON YOUR BOOKS
ESPECIALLY THROUGH A LARGER
PERCENTAGE OF YOUR MISSION
INVESTMENT.
SO EARLY ON WE DECIDED WE WERE
WILLING TO DO THESE NON-DILUTIVE
INVESTMENTS BUT NOT TO TAKE AN
EQUITY STAKE.
WE MOVED OUR POSITION SINCE THEN
AND WITH THE UNDERSTANDING OF
OTHER CHALLENGES.
YOU STRUGGLE WITH A LOT.
OUR ACADEMIC INVESTIGATORS
MULTIMEDIALY SAID WAIT A MINUTE
YOU'RE GOING TO START GIVING
MONEY TO COMPANIES WHAT ABOUT
US?
IS THAT COMING STRAIGHT OUT OF
THERE?
IS A ZERO SUM GAME OR ARE YOU
MAKING THE PIE BIGGER.
YOU MAY HAVE CHALLENGES THAT WAY
TOO.
THE SECOND HALF WAS DEFINITIONS.
>> FOR PEOPLE UNFAMILIAR.
>> I USED THE TERM DILUTIVE AND
NON-DILUTIVE.
>> WE DIDN'T HAVE DILUTIVE.
>> WHAT THAT MEANS IS WHEN YOU
TAKE AN EQUITY STAKE YOU HAVE A
PARTIAL OWNERSHIP POSITION IN
THE COMPANY.
THAT'S DILUTIVE THE COMPANY GAVE
UM UP SOME VALUE TO YOU AND
EVERYONE GETS MORE DILUTIVE IF
THERE'S MORE PEOPLE IN THE
SPACE.
NON-DILUTIVE WE ONLY GET A
PAYBACK BASED ON ROYALTIES.
ROYALTIES ARE THE REVENUE YOU
RECEIVE FROM AN APPROVED DRUG.
IT REQUIRED THAT IF IT HADN'T
BEEN APPROVED WE WOULDN'T HAVE
GOTTEN ANYTHING.
FOR US WE WERE MAKING GRANTS
ALREADY AND THIS WAS THE
POTENTIAL TO MAKE A GRANT WITH A
PAYOFF ATTACHED.
>> YOU MENTIONED I THINK YOU
SAID 15 NONPROFITS INVOLVED.
THERE WERE CERTAINLY LOTS OF
FUNDING SOURCES.
AND ONE QUESTION I HAVE FOR YOU
IS WHAT DIFFERENT ROLES DO THE
NONPROFITS PLAY.
IS IT THAT THEY ALL INVESTED
EARLY IN BASIC SCIENCE THAT
RESULT IN THIS DID TAY PLAY
DIFFERENT ROLES IN HELPING
CLINICAL TRIAL RECRUITMENT
VERSUS FUNDING EARLY RESEARCH?
>> I CAN PROBABLY SAY THEY HAD
ALL ROLES, ALL OF THOSE.
THE MOST RECENT VENTURE CONTRACT
WAS EMA TO THE PEDIATRIC
INVESTIGATION PLAN FOR
EXPANSION.
ALL THE TRIALS WERE 4 TO
7-YEAR-OLDS AND DID UP TO
17-YEAR-OLDS AND THOSE CROSSING
FROM PREDNISONE TO FEMORLONE AND
IT WASN'T JUST THE ECONOMIC
RELATIONSHIP.
THERE WERE PARENTS THAT WERE ON
THE LEADERSHIP TEAM THROUGH THE
ENTIRE PROCESS INCLUDING PICKING
THE PRIMARY OUTCOME AND
SELECTING SITES.
WITH COVID WE WERE SLOWING DOWN
AND ONE PARENT SAID LET'S DO
GREASE.
THEY WEREN'T EXPERIENCED IN
TRIALS BUT UNDER OUR MODEL WE
WERE WILLING TO TAKE THAT RISK
TO TRAIN THE SITE AND THEY ENDED
UP ATOP RECRUITER AND AUDIT AND
INSPECTED AND DID GREAT.
>> THERE'S DIFFERENT ROLES TO
PLAY.
DIFFERENT GROUPS CAN BRING
DIFFERENT THINGS TO THE TABLE
WHICH IS IMPORTANT TO WALK AWAY
WITH.
NOT EVERY GROUP IS COMFORTABLE
WITH MAKING THAT TYPE OF AN
INVESTMENT FINANCIALLY OR LONG
TERM.
THEY MAY SAY WE HAVE PATIENTS AN
CAN OPEN THE SITE.
WE'RE CLOSING ON THE LAST
MINUTE.
COULD I GET EACH OF YOU TO GIVE
US YOUR CLOSING THOUGHTS ON IS
THIS A MODEL YOU THINK SHOULD
MOVE FORWARD AND SHOULD BE USED
MORE FREQUENTLY?
>> I THINK THE MODEL WAS USED
FOR RIVERAGEN WORKED WELL AND IT
MADE SENSE TO DO IN THIS CASE
BECAUSE STEROIDS WEREN'T SEXY
DRUGS AND AN UNDERSTAND YOU
WEREN'T GETTING A LOT OF
INTEREST FROM YOUR TYPICAL V.C.s
AND INVESTORS BUT STEROIDS WERE
EFFECTIVE BUT LIMITED BY THE
SIDE EFFECT AND THE COMMUNITY
RECOGNIZED IT WAS A NEED AND
WORTH DOING.
FROM THAT SENSE IT WORKED WELL
TO HAVE THE NONPROFIT
INVESTMENT.
>> I'LL ECHO WHAT SHARON SAID.
AS WE HEARD VENTURE PHILANTHROPY
NOT A NEW CONCEPT BUT TAKING IT
TO THE EXTENT WE DID IS PROBABLY
NOVEL TO DRUG APPROVAL AND
KEEPING IT IN THE ACADEMIC
PUBLIC-PRIVATE SPACE WITH NO
DILUTIVE FUNDING OR INVESTMENT.
IF YOU HAVE THE INFRASTRUCTURE
FOR THAT YOU NEED THE EXISTING
INFRASTRUCTURE, WHICH NCATS AND
MUSCULAR DYSTROPHY ARE
SUPPORTING.
>> AND YOU NEED TO PARTNER IN
THE DRUG TO GET IT TO THE
APPROVAL COMMERCIALIZATION
PHASE.
IT GOT REALLY FOR BEFORE YOU DO
THAT.
>> WONDERFUL.
I KNOW THIS WAS SHORT AND SWEET.
THANK YOU FOR SHARING THE
SUCCESS STORY AND WE WILL MOVE
ON.
THANK YOU.
>> ALL RIGHT, NOW WE'RE GOING TO
GET STARTED WITH SESSION 2.
I'D LIKE TO INTRODUCE OUR
MODERATOR PJ BROOKS OUR DEPUTY
DIRECTOR AT THE DIVISION OF RAFR
DISEASE INNOVATION AT NCATS AND
WORKS ON PROJECTS INCLUDING ACT
THAEGZ WORKING GROUP COORDINATOR
NOR NIH COMMON FUND PROGRAM AND
SOMATIC CELL EDITING AND THE
VECTOR GENE PILOT PROGRAM.
ALSO THE CO-CHAIR OF THE BESPOKE
GENE THERAPY CONSORTIUM.
>>
>> I'LL GIVE A BRIEF
INTRODUCTION AND THEN INTRODUCE
SPEAKERS.
AT THE BASIC LEVEL WHAT I'VE
DRAWN IS A SIMPLIFIED CELL AND
NUCLEUS AND CHROMOSOME AND A
GENE IS A STRETCH OF THAT THAT
CONTAINS INSTRUCTIONS TO MAKE A
PROTEIN THAT DOES SOME FUNCTION
IN THE CELL.
SO PROTEINS ARE THINGS LIKE
HEMOGLOBIN, COLLAGEN THAT KEEPS
SKIN AND CELLS TOGETHER, ENZYMES
THAT DEGRADE CELLULAR
BYPRODUCTS, ETCETERA.
THAT'S ESSENTIALLY WHAT AGAINST
ARE AND HOW THEY WORK.
THERE'S A MUTATION IN THE GENE.
I'M SHOWING ONE GONE HERE BUT AS
WE HEARD EARLIER WE HAVE TWO
COPIES BUT WE'LL GO WITH ONE.
THERE'S A MUTATION IN THE GEN BY
THIS RED DELTA AND END UP WITH
NO PROTEIN AND IT LEADS TO
DISEASE.
SOME PROTEINS HAVE SPECIFIC
ROLES IN SPECIFIC CELL TYPES AND
HOW YOU GET THE CELL TYPE
SPECIFIC ABNORMALITIES.
THE FUNDAMENTAL PROBLEM IS THE
SAME THE GENE MUTATION THAT
RESULTS IN THIS FUNCTION NOT
GETTING DONE.
THE GENE MAY BE DIFFERENT, THE
PROTEIN MAY BE DIFFERENT BUT THE
FUNDAMENT PROBLEM IS THE SAME.
THE GOOD NEWS IS THE SOLUTIONS
ARE THE STATEMENT.
WE PUT A COPY IN THE VIRUS AND
IT DOESN'T HAVE TO REPLACE THE
MUTANT GENE OR GO IN THE SAME
PLACE BUT HAS TO BE ABLE TO
ENCODE AND MAKE THE PROTEIN AND
CARRY OUT THE FUNCTION AND TREAT
THE DISEASE AT THE RIGHT TIME
AND DISEASE DEVELOPMENT AN
THERE'S DOMINANT DISEASES WHERE
THE PROTEINS BECOMES TOXIC AND
GENE THERAPY IS NOT SO GOOD FOR
THAT BUT FROM THE STANDPOINT OF
THE CONFERENCE THAT'S WHAT
ESSENTIALLY WHAT IT IS AN GENE
EDITING, WHAT WE DO IS DELIVER
ENZYMES THAT GO INTO THE CELL
AND ACTUALLY CORRECT THE
MUTATION, CUTS AND PASTE AND
FIXES THE MUTATION.
NOW YOU HAVE A NORMAL MESSENGER
RA
RNA AND CARRY IT OUT IN DISEASE
DEVELOPMENT IT SHOULD HAVE AN
EFFECT AND IT'S GOOD FOR
RECESSIVE AND DOMINANT DISEASES.
BOTH GENE THERAPY AND GENE
EDITING HAVE THE SAME EFFECT.
THEY FIX THE PROBLEM.
THEY DO IT IN DIFFERENT WAYS.
ONE INVOLVING PASTING AND
EDITING HAS IMPLICATIONS FOR THE
REGULATORY PATHWAY WE'LL HEAR
ABOUT LATER.
THERE'S TWO FLAVORS.
YOU CAN DELIVER THEM DIRECTLY
INTO THE BODY AND THAT'S CALLED
IN VIVO.
ONE CHALLENGE IS TO FIND
DELIVERY REAGENT GOES TO THE
TISSUES AND CELLS WE NEED TO
TREAT.
THAT'S THE GOAL OF THAT TARGET
PRIZE COMPETITION DOMINIQUE
MENTIONED EARLIER AND EX VIVO
GENE THERAPY.
YOU TAKE CELLS FROM THE PERSON,
TYPICALLY STEM CELLS AND DO THE
GONE CORRECTION AND PUT THEM
BACK.
THIS LOOKS ALMOST SIMPLE.
IN REALITY IT'S VERY DIFFICULT
AND A BIG PROBLEM OF IT IS HOW
DO YOU DELIVER ENOUGH CELLS,
ENOUGH GENOME EDITORS TO CELLS
AND TISSUES AT THE RIGHT TIME
AND DEVELOPMENT.
AND THE REG H REGULATORY PATH IS
REMARK
REMARKABLE.
WE'LL BE TALKING ABOUT THROW
APPROVED THERAPIES AND EDITINGS
APPROVED IN THE LAST YEAR.
SO WE'LL BE HEARING FROM FDA
REPRESENTATIVE WHO IS A SUPER
OFFICE DIRECTOR OF THE OFFICE OF
THERAPEUTIC PRODUCTS AND SHE'LL
TALK ABOUT AN FDA RARE DISEASE
GENE THERAPY INITIATIVE AN HEAR
ABOUT THE APPROVALS FIRST IS
GENE THERAPY FOR PATIENTS WITH
ADRENOLEUKODYSTROPHY BY FLORYN
EICHLER AND HERE FROM PATIENT
WITH SICKLE CELL DISEASE BY
ALEXIS LEONARD FIRST IS NICOLE
VERDUN ON HER FIRST TALK.
>> THANK YOU.
WHILE THEY'RE PULLING THAT UP I
WANT TO SAY HOW EXCITED I AM TO
BE HERE.
IT'S BEEN GREAT TO HEAR SOME OF
THE CONVERSATION TODAY AND LOOK
TO DO OUR PART AT FDA TO TRY TO
MOVE THE FIELD FORWARD IN A
MEANINGFUL WAY.
I'M NICOLE VERDUNOFF OF
THERAPEUTIC TRACTS.
I'M HERE TO TALK ABOUT SOME OF
THE GENE THERAPY INITIATIVES WE
HAVE AT FDA AND FOR AWARENESS,
SOME OF THE THINGS WE'RE TRYING
TO DO TO ADVANCE THE FIELD.
THE IMPORTANCE OF THERAPIES FOR
DISORDERS RARE IN NATURE IS
EXTREMELY IMPORTANT TO BE ABLE
TO OFFER PATIENTS THERAPIES
WHERE THERE'S SIGNIFICANT IN MET
NEED.
REALLY OUT OF THOUSANDS OF
ACQUIRED AND RARE DISEASES
THERE'S HUNDREDS OF DISORDERS
AFFECTING 1 TO THOUSANDS PER
YEAR THAT COULD BE ADDRESSED BY
THERAPIES.
ADDRESSING MOLECULAR DEFECTS MAY
REDUCE MORE COMMON DISEASES TO
RARE DISEASES AND THAT'S THE
OVER ALL GOAL.
SO THE OFFICE OF THERAPEUTIC
PRODUCTS IS A FAIRLY NEW OFFICE.
THE SUPER OFFICE WAS CREATED
ABOUT A YEAR AGO NOW AND IT WAS
TO TRY TO ADDRESS THE
SIGNIFICANT INCREASE IN THIS
AREA WHICH IS QUITE EXCITING.
INSTEAD OF ONE OFFICE WE NOW
HAVE SIX OFFICES.
AND THIS IS AN ORGANIZATIONAL
CHART THAT OUTLINES THE OFFICES
THAT WE CURRENTLY HAVE.
AND SO WE NOW HAVE THEM
SPECIALTY DRIVEN.
WE HAVE AN OFFICE FOR GENE
THERAPY FOR THE CHEMISTRY
MANUFACTURING AND CONTROL.
WE HAVE OFFICE OF CELLULAR
THERAPY AND OFFICE PLASMA
THERAPEUTICS, CMS AND OFFICE OF
CLINICAL EVALUATION WHICH IS THE
PHYSICIAN STAFF AND THEN WE HAVE
AN OFFICE OF PHARMACOLOGY AND
TOXICOLOGY AND OFFICE OF REVIEW
AND I WAS TO INCREASE THE
WORKFORCE AND THE SPECIALTIES
NEEDED TO CONTINUE TO SUPPORT
THIS WORK THAT AS MANY OF YOU
KNOW IS CHANGING ON A DAY TO DAY
BASIS IN TERMS OF KEEPING UP
WITH THE SCIENCE.
WE ARE EXCITE ABOUT THE NEW
ORGANIZATION AND THINK IT WILL
MEET THE NEEDS.
AS MANY OF YOU KNOW, I WISH THE
U.S. APPROVED THERAPIES COULD
NOT FIT ON ONE SLIDE, THAT'S THE
GOAL.
WE HAVE HAD FIVE GENE THERAPIES
APPROVED IN 2023, FIVE IN 2022
AND WE HOPE TO EXPONENTIALLY
INCREASE THE NUMBER OF GENE
THERAPIES APPROVED.
THERE'S DEVELOPMENT ISSUES WE'RE
FACED WITH AND DISCUSS
INTERNALLY.
IN RARE DISEASE THE NATURAL
HISTORY OF DISEASE MAY BE
LIMITED.
THAT PROVIDES CHALLENGES IN
SMALL POPULATIONS ESTABLISH
EFFICACY.
THE OTHER PIECE OF THIS IS
THERE'S A LOT OF HETEROGENEITY
IN DISEASE MANIFESTATIONS.
AND SO WITHIN EVEN A CERTAIN AGE
GROUP THERE MAY BE DIFFERENCES
IN TERMS OF HOW A DISEASE
MANIFESTS.
THE TIME COURSE OF ILLNESS CAN
BE PROLONGED AND PROTECTIVE IN
SOME DISEASES.
AND DISEASE MANIFESTATIONS CAN
BE IRREVERSIBLE.
HOW DO YOU FIT THEM INTO A
REGULATORY PARADIGM?
SO AT FDA, THINGS WE'RE WORKING
TO DO IS TO MORE CLEARLY DEFINE
THE USE OF ACCELERATED APPROVAL
FOR GENE THERAPY.
I'LL TALK A LITTLE BIT MORE
ABOUT THAT.
IN ADDITION WE'VE BEEN EXPLORING
CONCURRENT SUBMISSION AND
PRODUCT REVIEW TO HAVE MORE
COLLABORATION AND COMMUNICATION
IN THE AREA.
AND SPECIFICALLY COMMUNICATION
PILOTS WHICH ALLOW US TO
INTERACT AND INTERFACE WITH
PEOPLE THAT ARE DEVELOPING GENE
THERAPIES WITH A RARE DISEASES
AT VARIOUS TIME POINTS AND
SOONER RATHER THAN LATER IS
REALLY OUR PARADIGM THERE.
THE SCIENCE INHERENT FACILITATES
THE USE OF BIOMARKERS AS END
POINTS.
THIS IS REASONABLY UNLIKELY TO
PREDICT CLINICAL OUTCOMES END
POINT.
I THINK IN THE AREA WE HAVE TO
USE THE ACCELERATED APPROVAL
MORE.
WE HAVE TO DEVELOP BIOMARKERS WE
FEEL ARE PREDICTIVE AND USE
THOSE MORE WITH A COMMITMENT THE
OTHER SIDE TO CONTINUE TO FOLLOW
PEOPLE AND MAKE SURE WE ARE
CONFIRMING CLINICAL BENEFIT.
I THINK THIS IS AN AREA YOU'LL
SEE GROWTH IN OUR ABILITY TO DO
THIS.
WE'RE TRYING TO LEAN IN AND
PARTNER TO MAKE THIS HAPPEN.
AS MUCH AS WE CAN ENZYME
ACTIVITY LEVELS STRUCTURAL
PROTEIN LEVELS THAT CAN BE
MEASURED AND CORRELATE WITH
CLINICAL END POINTS AND MODEL
SYSTEMS AND WE'RE TRYING TO
LEVERAGE THIS MORE TO GET
THERAPIES TO PATIENTS SOONER
THAT IS THE GOAL.
THIS IS THE START PILOT.
I WON'T GO INTO A LOT OF DETAILS
BUT SOME OF THE WAYS AT FDA
WE'RE TRYING TO FOSTER AN
INCREASE IN COMMUNICATION.
THIS IS A PILOT OPEN NOW FOR
SUBMISSIONS BUT COMPANIES ARE
ABLE TO COME TO US AND ASK FOR
PARTICIPATION IN THE PILOT AN
IT'S TO ACCELERATE THE PACE OF
DEVELOPMENT FOR PRODUCTS WITH A
SIGNIFICANT UNMET MEDICAL NEED
AND TREAT A RARE DISEASE.
IT'S FOR CELLULAR AND GENE
THERAPIES.
YOU HAVE TO WORK TOWARD A
MARKETING APPLICATION AND FOR
THE PILOT PHASE IT'S A DISEASE
THAT WILL LIKELY LEAD TO
SIGNIFICANT DISABILITY OR DEATH
WITHIN THE FIRST DECADE OF LIFE.
SO WE ARE TRYING TO FIND
THERAPIES THAT WE CAN HELP TO
GET TO THE FINISH LINE FOR
PATIENTS THAT HAVE THE MOST
SEVERE DISEASE THAT'S IMPACTING
LIFE.
I WILL SAY THIS IS A PILOT BUT
THIS IS REALLY A PARADIGM WE'RE
EMBRACING IN FDA FOST ERIC
COLLABORATION.
-- FOSTERING COLLABORATION.
WE HAVE ANOTHER PROGRAM TO
ADVANCE RARE DISEASE PROGRAMS
AND PROVIDES A MECHANISM TO
COLLABORATE THROUGH EFFICACY END
POINT DEVELOPMENT.
THE SPONSORS GET INCREASED
COMMUNICATION WITH FDA AND
THERE'S A NOVEL END POINT THAT
IN GENERAL HAS NOT BEEN USED.
AND THEN YOU STILL HAVE ALL THE
ADDITIONAL MEETINGS YOU CAN
REQUEST.
THERE'S FOUR MEETINGS AROUND AND
POINT AND DESIGN.
AND HOW CAN WE USE DATA BEFORE
IT GETS LEVERAGED FOR ANOTHER
PRODUCT AND THERE'S A WAY TO
MOVE THE APPLICATIONS FASTER.
THE GOAL IS ACCELERATION OF GENE
THERAPY PRODUCT DEVELOPMENT AND
AN EXAMPLE WOULD BE WHERE YOU
HAVE THE SAME AAV BACKBONE BUT
FOR A DIFFERENT RARE DISEASE.
THERE'S AN DESIGNATION THAT IS
THE QUOTE PLATFORM DESIGNATION
WHERE THE SAME SPONSOR IS NEEDED
IN ORDER TO HAVE THE SPECIFIC
DESIGNATION.
AGAIN, THIS IS SOMETHING WE'RE
EMBRACING AT FDA AND EVEN IN THE
ABSENCE OF THAT WE'RE STARTING
TO HAVE CONVERSATIONS WITH HOW
CAN WE LEVERAGE NON-CLINICAL
DATA OR DATA IN ANIMALS IN
PRODUCTS AND TALK TO US IF THIS
GOES IT TO YOU AND THE GOAL IS
TO REDUCE REDUNDANCY AND EXP
EXPEDITE DEVELOPMENT.
THIS IS A PILOT PROGRAM WHERE WE
LOOK FOR GENE THERAPIES AN
THERE'S DEVELOPMENT GOING ON AT
FDA AND EMA.
THE INITIAL PARTICIPATION IS
ANYONE THAT'S A MEMBER OF THE
HCH AND HEALTH CANADA IS A
PARTNER AND THE GOAL IS TO AND
WE CAN DISCUSS REVIEWS AND ALL
MEETINGS ARE UNDER
CONFIDENTIALITY AGREEMENTS BUT
IT'S TO INCREASE THE EFFICIENCY
OF THE REGULATORY PROCESS.
REDUCE TIME AND COSTS FOR
AGENCIES AND FOR SPONSORS.
QUICKLY, ANOTHER KEY PIECE TO
THIS IS COMMUNICATION AND
COLLABORATION.
THIS IS AN EXAMPLE OF A WORKSHOP
WE JUST HELD LAST WEEK AND IT
WAS WITH LOOKING AT QUALIFYING
BIOMARKERS FOR RARE DISEASE
REGULATORY PATHWAYS.
SPECIFICALLY THERE WAS A LOT OF
THE CONVERSATION AND DISCUSSION
AROUND MUCOPOLYSACCHARIDOSIS AND
THEY HELPED WITH THE PLANNING OF
THE WORKSHOP AND IT'S AN EXAMPLE
OF HOW WE CAN ENGAGE MORE AT FDA
AND WE'RE LOOKING TO DO SEVERAL
OF THESE THINGS TO INCREASE THE
COMMUNICATION AND TO HOPEFULLY
GET THINGS APPROVED QUICKER.
IN SUMMARY, FDA IS COMMITTED TO
WORKING TO SUPPORT THE
DEVELOPMENT OF NOVEL CELL AND
GENE THERAPIES AND WE LOOK
FORWARD TO FORGING
COLLABORATIONS AND PARTNERSHIPS
AND ADDRESSING RARE CHALLENGES
AND THERAPEUTICS ARE THE
FOREFRONT OF OUR GOALS AND
ADVANCING THERAPY PRODUCTS FOR
PATIENT WITH UNMET NEED.
THANK YOU FOR HAVING ME AND AN
APPRECIATE ALL THE WORK BEING
DONE IN THIS AREA.
THANK YOU.
>> THANK YOU.
OUR NEXT SPEAKER WILL BE PETER
MARINKOVICH TALKING ABOUT
DISTROPHIC EPIDERMOLYSIS
BULLOSA.
>> THANK YOU, EVERYBODY.
I'LL BE TALKING ABOUT THIS
EPIDERMOLYSIS BULLOSA INHERENT
DISEASE.
IT CAN BE A SEVERE DISEASE WHERE
PATIENTS GET WIDESPREAD
BLISTERING AS WELL AS AN
EXAGGERATED TYPE OF SCARRING
OVER LARGE PARTS OF THEIR BODY
WHERE THE SKIN IS TRAUMATIZED
THEY CAN DEVELOP SEVERE
BLISTERING AND SCARRING.
WHAT HAPPENS OVER TIME IS
THERE'S SO MUCH SCARRING THAT
OCCURS THE HANDS AND FEET CAN
GET ENCLOSED IN A MITTEN OF SKIN
AND LOSE THE USE OF HANDS CAN BE
DISABLING.
WE LOOK AT THE EPIDERMIS AND IT
HOLDS THE SKIN TOGETHER AND IT'S
EXPOSED TO DISRUPTIVE EXTERNAL
FORCES.
THE SKIN, EYE MUE COSA AND
RECTAL MUCOSA CAN GET SCARRING.
COLLAGEN 7 ASSEMBLES IN THE
STRUCTURES WHICH GIVE THE SKIN
THE EXTRA STRENGTH.
AT STANFORD WE HAD AN EX VIVO
THERAPY AND I WAS APPROACHED
WITH THIS NEW IN VIVO GENE
THERAPY BASED ON THE HSV1
EPISOMAL VECTOR.
IT'S GOT A HIGH CAPACITY AND NOT
IMMUNOSUPPRESSIVE.
YOU CAP -- CAN GET A COLD SORE
AND LAY DORMANT TO RE-EMERGE
LATER.
AND WE ALSO KNOW NOT BY LACK OF
TRYING THAT NO ONE'S BEEN ABLE
TO DEVELOP AN HSV1 VACCINE.
BOTH ARE REFLECTIVE OF THE IDEA
THAT HSV1 AND THE SYMBIOSIS WITH
HUMANS HAS BEEN ABLE TO EVOLVE
THE ABILITY TO EVADE THE HUMAN
IMMUNE SYSTEM.
PEOPLE HAVE WORKED OUT
MECHANISMS AS TO HOW IT'S DONE
THIS.
ONE WELL WORKED OUT IS IT'S
KNOWN TO BIND TO THE TRANSPORTER
FOR ANTIGEN PROCESSING TO STOP
THE IMMUNE PROCESS AT THE VERY
EARLY STAGE.
THERE'S PROBABLY OTHER
MECHANISMS AS WELL AT PLAY.
UP TO NOW THE FIELD OF IN VIVO
GENE THERAPY AS WE HEARD FROM
PREVIOUS TALKS HAS BEEN LIMITED
BY THE I'D -- IDEA YOU CAN HAVE
EXTREME IMMUNE REACTIONS BUT
THIS IS ONE ADVANTAGE OF THE
VECTOR.
WE PUT THE TWO COPIES OF THE
COLLAGEN 7 GENE IN THE VECTOR
AND IT GETS PUT ON THE SKIN AND
THEN THE SKIN PRODUCE THE
COLLAGEN 7.
IT HAS A FAIRLY LONG HALF LIFE
OF TWO TO THREE MONTHS IN THE
SKIN.
IT FORMS THE ANCHORING FIBRILS
AND THE SKIN HEALS.
WE DRIP IT AT INTERVALS ACROSS
THE WOUND AND COVERED IN SARAN
WRAP AND THEY HEAL IN ABOUT A
WEEK.
YOU CAN SEE THE WOUNDS THAT
RECEIVE THE DRUG.
ALL BUT ONE OF THE WOUNDS
RECEIVED THE DRUG WE ENROLLED
THE PATIENT AT A LATER STAGE OF
THE TRIAL AND IT DID HEAL.
ALL THE WOUNDS DID HEAL AND WHAT
YOU SEE ON THE PLACEBO TREATED
WOUNDS IN THE NATURAL HISTORY OF
THE DISEASE THE WOUNDS START TO
HEAL AND GET REBUMPED AND THIS
OPENING AN CLOSING THAT OCCURS.
YOU CAN SEE THAT WITH THE BLUE
LINE GOING UP AND DOWN WHEREAS
THE TREATED WOUNDS TREATED WITH
THE DRUG THEY HEAL AND STAY
HEALED AND REFLECTIVE OF THE
COLLAGEN 7 MAKE IT STRONGER AND
RESISTANT TO THE BLISTERING AND
BASICALLY CORRECTS THE DISEASE.
YOU CAN SEE WHEN YOU SEE PANELS
LIKE THIS YOU MAY THINK THE
GREEN LINE IS THE BEST THEY
HAVE.
THEY'RE PROBABLY SHOWING US THE
BEST OF THE ONES THEY DID.
TO ADDRESS THAT WE PUT TOGETHER
MULTIPLE LOW POWER IMAGES ACROSS
THE SKIN SPECIMEN.
YOU SEE THE EXPRESSION OF
COLLAGEN 7 ACROSS THE SKIN.
VERY NICE ROBUST EXPRESSION OF
COLLAGEN 7.
WE CAN SEE THE FIBRILS BEING
FORMED.
THEY'RE NOT PRESENT AT THE
BASELINE BUT AFTER TREATMENT YOU
CAN SEE NICE BANDED STRUCTURES
COMING OUT FROM THE CENTRAL
MEMBRANE AND WRAPPING AROUND
INTERSTITIAL COLLAGEN FIBRILS
LOOKING LIKE WILD TYPE ANCHORING
FIBRILS.
THIS SUCCESSFUL PHASE 1 TRIAL
LED TO A TRIAL WITH STANFORD AS
A LEAD SITE.
AND I'LL SHOW YOU THE RESULTS OF
THAT.
IT WAS SET UP AS A PLACEBO AND
WE TREATED SOME PATIENTS OPEN
LABEL WITH ADDITIONAL WOUNDS SO
THE PATIENTS CAN GET BENEFIT AND
IT WILL HELP IN RECRUITMENT.
WE HAVE SEVERAL YEARS OF
EXPERIENCE OF PATIENTS USING THE
DRUG.
IF IT'S 95% HEALED IT DOESN'T
COUNT.
IT HAS TO BE 100% HEALED.
THE SECOND END POINT WAS WOUND
HEALING AT THREE MONTHS.
WE SAW A DIFFERENCE IN THE WOUND
HEALING COMPARED TO THE PLACEBO
CONTROL WITH HIGH STATISTICAL
SIGNIFICANCE.
ONE THING THAT EXCITES ME IS THE
SAFETY GOING BACK TO COMPARISON
WITH WHERE WE'VE BEEN WITH IN
VIVO GENE THERAPY.
THESE PATIENTS GOT THE DRUG
WEEKLY FOR 26 WEEKS.
THEY GOT MULTIPLE PREETED DOSAGE
AND DID NOT SEE SIGNIFICANT
ADVERSE EVENTS.
THIS COULD BE APPLICABLE TO
OTHER GENES AND INDICATIONS.
I THINK THIS HAS POTENTIAL FOR
OTHER FOLKS IN THE AUDIENCE TO
BE ABLE TO UTILIZE THE DRUG WITH
DIFFERENT GENES.
HERE'S ONE PATIENT WHO CAME TO
ME FROM ITALY AND HAD CHRONIC
WOUNDS ON MOST HIS BACK.
BY THEN OF THE PHASE 3 TRIAL HE
MOSTLY HEALED THE WOUNDS EXCEPT
FOR THE TWO SMALL AREAS HE
HEALED THE TWO SMALL AREAS AND
THEN WENT BACK TO ITALY AND
CALLED ME BACK LAST YEAR AND WAS
SAYING I WANTED TO GET BACK ON
THE THERAPY.
I THOUGHT HE WANTED KNOW TREAT
HIS BACK BUT 17 MONTHS OF THE
HIS THERAPY THIS BACK WAS GOOD
AND WANTED ME TO TREAT HIS LEGS.
THIS IS AN EXAMPLE OF LONG-TERM
RESULTS.
THIS IS ANOTHER PATIENT WHO WAS
ABLE TO HE'S HAD ABOUT FOUR
YEARS OF THERAPY AND ABLE TO SEE
SUBSTANTIAL HEALING HERE.
ALSO HIS WEIGHT AND HEIGHT HAVE
GONE UP DUE TO THE LESS
METABOLIC STRAIN ON THE WOUND
HEALING HE'S NOT HAVING TO DO
AND HIS NUTRITIONAL MARKERS HAVE
GONE UP TOO.
I'M HOPING THE VIDEO WORKS HERE.
YES.
>> I'M HERE TO TALK ABOUT MY
EXPERIENCE AS A GENE THERAPY
PATIENT.
I WAS BORN WITH A RARE SKIN
CONDITION CALLED DYSTROPHIC
EPIDERMOLYSIS BULLOSA AND MY
BODY DOESN'T PRODUCE COLLAGEN 7
WHICH HOLD THE TOP LAYER OF SKIN
TO MY BODY.
ANY AMOUNT OF FRICTION APPLIED
TO MY SKIN CAN TEAR IT RIGHT
OFF.
I HAVE TO BE EXTREMELY CAREFUL
WITH EVERYTHING I DO IN DAILY
LIFE.
MY FIRST EXPERIENCE IN GENE
THERAPY DATES BACK TO 2019 WHEN
I DECIDED TO PARTICIPATE IN A
TRIAL FOR EPIDERMOLYSIS BULLOSA.
BEFORE I START THE TRIAL, 70% OF
MY BACK WAS AN OPEN WOUND THAT
WOULD NOT HEAL.
THE MAJORITY OF BOTH MY UPPER
ARMS WOULD BE WOUND THAT WOULD
NOT HEAL.
I WAS ANEMIC AND LOSING SO MUCH
BLOOD AND IN PAIN AND DOING
EVERY DAY ACTIVITIES WOULD BE A
GREAT CHALLENGE AND SIMPLE
THINGS SUCH AS SLEEPING ON MY
BACK WAS DIFFICULT.
AFTER CONSISTENT REAPPLICATION
TO PARTS OF MY UPPER BACK AND
ARMS, THEY STARTED TO HEAL UP
AND STAY HEALED.
THAT WAS SURPRISING BECAUSE I
DIDN'T THINK IT WAS GOING TO
WORK AFTER YEAR HALF OF
REAPPLYING THE GENE THERAPY TO
MY BACK AND UPPER ARMS, 70% OF
MY BACK HEALED UP AND THE
MAJORITY OF MY UPPER ARMS HEALED
AND THIS IMPROVED MY LIFE
BECAUSE I WASN'T IN SO MUCH PAIN
AND WASN'T LOSING SO MUCH BLOOD
AND ABLE TO DO THINGS LIKE
SLEEPING ON MY BACK.
FAST FORWARDING TO TODAY, 90% OF
MY BACK IS COMPLETELY HEALED.
ALL MY ARMS ARE ALSO HEALED.
OTHER PARTS OF MY BODY ARE
STARTING TO HEAL.
I HOPE IN THE NEAR FUTURE
THERE'LL BE MORE ADVANCEMENTS
FOR THOSE WITH MY CONDITION AND
OTHERS WHO CAN BENEFIT FROM IT.
THAT'S A SHORT SUMMARY OF MY
EXPERIENCE IN GENE THERAPY AND
HOPE HAVE YOU A GOOD REST YOUR
DAY.
THANK YOU FOR YOUR TIME.
>> HE'S REALLY ARTICULATE AN
GREAT TO WORK WITH.
WE HAVE THE FIRST APPROVED GENE
THERAPY APPROVED LAST YEAR.
WE'RE FROM SILICON VALLEY SO
WITH HAVE TO DO THE ONE MORE
THING AND WE CAN USE THE THERAPY
IN THE EYE.
IN THE NEW ENGLAND JOURNAL ABOUT
TWO WEEKS AGO THE CASE REPORT
WAS PUBLISHED AND THERE WAS A
STUDY A PATIENT WITH CLINICAL
TRIAL HAS EYE SCARRING AND WAS
BLIND AND RECEIVED THE GENE
THERAPY MULTIPLE TIMES OVER
SEVERAL MONTHS AND WAS ABLE TO
GET IMPROVEMENT IN HIS VISUAL
ACUITY TO APPRECIATE HAND MOTION
UP TO 20, 40 VISION.
IT MADE A HUGE DIFFERENCE IN HIS
QUALITY OF LIFE.
HE'S HAPPY TO HAVE PARTICIPATED
IN THAT.
WE'LL BE GOING AFTER MUCOSAL
SERVICE AND MORE EYE PATIENTS
AND ORAL PHARYNX AND OTHER
MUCOSAL AREAS.
I WANT TO THANK ALL THE SMART,
TALENTED PEOPLE WHO WORKED ON
THIS AND ESPECIALLY THE PATIENTS
WHO DONATED THEIR TIME IN AN
ALTRUISTIC WAY TO PARTICIPATE IN
THE TRIALS AND HELP OTHERS.
THANK YOU VERY MUCH.
NEXT SPEAKER WILL BE FROM MASS
GENERAL TALKING ABOUT GENE
THERAPY FOR CEREBRAL DYSTROPHY.
>> THANKS NOR ABILITY TO PRESENT
ON PATIENTS WITH CEREBRAL
ADRENOLEUKODYSTROPHY.
I'D THOUGHT I'D GIVE A
DEFINITION OF THE DISORDERS.
IT'S A SINGLE GENE DISORDERS
THAT IMPAIR NORMAL BRAIN.
THAT MEANS THE CHILDREN ARE
USUALLY BORN WITHOUT STRUCTURAL
MALFORMATIONS.
THEY'RE BRAIN IS WELL IN FACT
AND WELL FORMED THEY LOSE MYELIN
AND IT'S COMMONLY FAILED
DISORDERS.
CHILDREN OFTEN HAVE EARLY
COGNITIVE PROGRAMS AND SUBSTANCE
ABUSE IS NOT UNCOMMON AND
ABNORMALITIES AND DEMENTIA AND
DEATH SETS IN WITHIN MONTHS IN
CHILDREN AND IN THE ADULT ONSET
CASES.
THE DISORDER I'LL FOCUS ON IS
ADRENOLEUKODYSTROPHY DUE TO
MUTATIONS IN THE GENE CALLED
ABCD1 WHICH ENCODE THE ADL
PROTEIN WHICH SITS PEROXISOMAL
TRANSPORTER AND CAN AFFECT ACUTE
BRAIN DEE -- DEMYELINATION AND
AMN.
SO YOUR BORN WITH THE GENE
DEFECT AND HAVE LONG CHAIN FATTY
ACID DEFECTS.
IT'S LED TO A NEW SCREEN PROGRAM
AND THEN IN THE AND YOU CAN
DEVELOP THE SPINAL CORD FORM OF
DISEASE.
IN ADULTHOOD YOU STILL HAVE A
RISK OF ADULT ONSET CEREBRAL
ALD.
THE SPINAL CORD DISEASE AND
BRAIN DISEASE ARE REALLY QUITE
DIFFERENT.
YOU HAVE INFLAMMATORY
DEMYELINATION AND IT AFFECTS
GAIT AND BALANCE.
VERY IMPORTANT FOR OUR
DEVELOPMENT PROCESS WAS THE FACT
THAT WE WERE ABLE TO INSTITUTE
NEWBORN SCREENING FOR THIS
DISORDER CONCURRENTLY WITH THE
TRIAL WE STARTED THIS WAS DUE TO
TECHNOLOGY AND TIRELESS EFFORTS
OF PATIENT ADVOCATES WHO HELPED
LAUNCH THIS NEWBORN SCREENING
PROGRAM THIS THAT IS NOW
RECOMMENDED IN 2016 AND IS
HAPPENING ACROSS ALL STATES IN
THE COUNTRY.
TO DESCRIBE HOW
ADRENOLEUKODYSTROPHY PROGRESSES
YOU GET AN MRI THAT'S NORMAL AND
START SEEK A LESION IN THE WHITE
MATTER THAT SPREAD OUTWARD AND
LIKE WILDFIRE STARTS TAKING OVER
THE ENTIRE BRAIN.
IMPORTANTLY, THE FIRST SYMPTOMS
CAN BE QUITE SUBTLE AND LOOK
ATTENTION DEFICIT AND IN SHORT
ORDER THESE BOYS START TO LOSE
THE ABILITY TO WALK AND TALK
WITHIN YEARS BECOME UNABLE TO
AMBULATE.
TO GIVE AN EXAMPLE, ONE OF MY
PATIENTS WHO CAME TO ME JUST
MONTHS AFTER THIS VIDEO WAS
TAKEN PRECOCIOUS YOUNG BOY IN
KARATE CLASS VERY ARTICULATE AND
COULD TELL ME PLENTY OF STORIES
WHEN HE ARRIVED AND CAN SEE A
FEW MONTHS AFTER HE HAD BRAIN
DISEASE DEVELOPING AND WAS NO
LONGER ABLE TO AMBULATE
INDEPENDENTLY AND NEEDS
ASSISTANCE TO WALK AROUND AND
MARK ATAXIA.
HOW DO YOU MEASURE SUCH A
DEVASTATING DISORDER THAT
AFFECTS DOMAINS.
WE HAVE A NEUROLOGIC FUNCTION
SCORE THAT ENCOMPASSES 25 POINTS
AND SINGLE OUT FUNCTIONAL
DISABILITIES SHOWN HERE IN BOLD.
THREES INTEREST THE THINGS YOU
CAN RECOGNIZE THE ROOM, LOSS OF
CORTICAL BLINDNESS AND BEING
WHEELCHAIR BOUND, ETCETERA.
WE HAVE THE MRI AND MRI SEVERITY
SCORE WHERE YOU CAN REALLY USE
THE EXTENT AND SPREAD OF THE
LESION TO INFORM A SCORING
SYSTEM WE CALL THE LESS MRI
SEVERITY SCORE AND IMPORTANTLY
THERE'S AN ER OF ACTIVE CEREBRAL
ALD IN THE GARLAND OF
ENHANCEMENT WHERE TE BLOOD BRAIN
BARRIER IS BREAKING DOWN.
WHAT DOES THE PATHOLOGY OF THE
BRAIN MRI LOOKS LIKE?
MRI SAY GOOD SURROGATE FOR THE
PATHOLOGY
IT'S A ZONAL PATHOLOGY WHERE
THERE'S COMPLETE LOSS OF MYELIN
AND THE INFLAMMATORY
INFILTRATION AROUND THE VESSELS
AND IMPORTANTLY THERE'S A ZONE
OF MICROGLIAL CELL LOSS AROUND
THE PROGRESSIVE SPREADING
DISEASE.
AND THERE'S IMPORTANT INSIGHT
BONE MARROW TRANSPLANTATION
COULD BE HELPING HERE.
THIS HAD BEENI GOING ON TWO
DECADES BEFORE I STEPPED IN THE
FIELD AND IT WAS WELL KNOWN
TRANSPLANTATION COULD IMPROVE
WITH VIEFRL IF DONE EARLY IN THE
DISEASE COURSE WITH A WELL
MATCHED DORNE AND SEE THE
DIFFERENCES IN SURVIVAL BUT AT A
COST.
THERE WAS GRAFT VERSUS HOST
DISEASE AND THINGS AILING THE
FAMILIES.
THIS WAS PERTINENT TO THOSE WHO
DIDN'T FIND A GOOD WELL MATCHED
DONOR AND THIS WAS MORE
PROMINENT AMONG HISPANIC
FAMILIES AND BLACK AND AFRICAN
AMERICAN FAMILIES LEADING TO A
LOT OF INEQUITY IN THE FIELD.
AT BOSTON CHILDREN'S WE LAUNCHED
A TRIAL USING HEMATOPOIETIC
CELLS AND WE TRANSDUCE THE HIM
WITH A VECTOR DELIVERING A
HEALTHY COPY AND RETURNED THE
CELLS BACK TO THE BOYS AFTER A
BRIEF ABLATION AND FOLLOWED THE
BOYS FOR A TWO-YEAR PERIOD.
IT'S IMPORTANT NOTE THIS IS WHAT
HAPPENS IN AN ALGENEIC
TRANSPLANTATION WITH THE CELLS
FROM THE BOYS THEMSELVES.
WE FIRST PUBLISHED THIS IN 2017
WHERE WE REPORTED ON THE FIRST
17 BOYS WHO DIDN'T HAVE A WELL
MATCHED DONOR.
WE FOUND 88% WERE ALIVE WITHOUT
MAJOR FUNCTIONAL DISABILITY.
TWO PATIENTS DECIDE AND ONE WAS
RAPIDLY PROGRESSING AND OTHER
PATIENT HAD UNDER GONE A
SEPARATE BONE MARROW
TRANSPLANTATION.
THEY HAD SUCCUMB.
WE TREATED PATIENTS WORLDWIDE
AND WIN TRIAL USING A REGIMENT
AND TO SHOW THE LONG-TERM
EFFICACY.
THE LESS SCORE AND MRI LESION
SCORE IS THAT USUALLY PROGRESSES
AND YOU SEE HOW QUICKLY THE
SCORE WENT UP.
MOST PATIENTS STABILIZE
IMMEDIATELY AFTER TREATMENT OR
WITHIN 12 TO 24 MONTHS AFTER
ADMINISTRATION OF DRUG.
HIGHER SCORES BEING MORE
PATIENTS.
94% ACHIEVE STABLE NEUROLOGIC
FUNCTION WITHOUT MAJOR
FUNCTIONAL DISABILITIES.
TO GIVE A PICTURE OF HOW GENE
THERAPY CAME ABOUT FOR THIS WE
WERE FORTUNATE TO BUILD ON THE
EXPERIENCE OF BONE MARROW
TRANSPLANTATION AND THAT WAS
SOMETHING THAT COULD WORK AND
THIS WAS WORK DONE IN PARIS AND
WE LAUNCHED A FIRST TRIAL IN
BOSTON AND WERE ABLE TO EXTEND
THAT WORLDWIDE WITH THE HELP OF
THE EUROPEAN GROUPS.
UNFORTUNATELY, WHILE THAT THERE
WAS RECOMMENDED APPROVAL THE
SPONSOR EXITED EUROPE AND WE HAD
SETBACKS WITH TWO FACES OF A
SYNDROME AND THE THIRD
FOLLOWING.
NEVERTHELESS THE FDA COMMITTEEA
RECOMMENDED UNANIMOUS APPROVAL
AND LET TO THE FIRST FDA
APPROVAL FOR THE THERAPY OF
ADRENOLEUKODYSTROPHY.
I MENTIONED THE SYNDROME THAT
HAS BECOME OF CONCERN.
WE GAVE RISE TO THE BLAST FORM
ATION S.
THEY UNDERWENT SEPARATE BONE
MARROW TRANSPLANTATIONS.
FOUR OF THESE FIVE BOYS ALL HAD
A CONDITIONING REGIMENT AND ONE
HAD PSYCH JOE FOSS MIGHT.
THIS IS GIVING US HOPE FIRSTING
WHAT THE CONDITIONING REGIMENT
OPTIMAL COULD HELP REDUCE RISK
HERE.
SO SUMMARIZE THE TRANSPLANTATION
THAT LED TO APPROVAL, YOU CAN
SEE IN THE ORANGE LINE THE
MATCHED SURVIVAL AT BONE MARROW
TRANSPLANT GROUP COMPARED TO OUR
GROUP AND 91% OF PATIENTS WITH
GENE THERAPY REACHED THE PRIMARY
EFFICACY END POINT OF MAJOR
FUNCTIONAL DISABILITY FREE
SURVIVAL.
TO CONCLUDE, I HOPE I'VE SHOWN
HOW THE STAGE WAS SET BY PATIENT
ADVOCACY STARTING NEWBORN
SCREENING AND BUILDING COMMUNITY
THAT WAS CRITICAL FOR OUR
RECRUITMENT EFFORTS.
THERE WAS CHILDREN IDENTIFIED IN
EARLY PRE SYSTEM AT INNING
STAGES HELPED TREMENDOUSLY.
MORE THAN 70%S WITH ALD HAVE
BEEN TREATED WITH GENE THERAPY
AND IN MOST TRIALS 94% ACHIEVED
STABLE NEUROLOGIC FUNCTION AND
THE EX VIVO THERAPY HAS
SIMILARITIES AND AFFECT FROM
CHEMOTHERAPY WITH IMMUNE
SUPPRESSION AND WITH WE HAVE
GRAPH VERSUS HOST AND THERE'S
THE EMERGENCE OF THE SYNDROME WE
HAVE TO KEEP A CLOSE EYE ON.
I WANT TO ACKNOWLEDGE THE
COLLABORATORS AROUND THE WORLD.
IT TOOK A VILLAGE AND A WANT TO
ACKNOWLEDGE THE FAMILIES THAT
PARTICIPATED HERE AND I WANT TO
DRAW ATTENTION TO SOME STORIES
HERE.
THERE ARE THREE BOYS FROM SOUTH
AMERICA WHOSE FIRST NAMES HAVE
THE INITIALS OF A, D AND L.
YOU CAN SEE THEY WERE
CELEBRATING A BIRTHDAY AND
CROSSED OUT ALD AND WROTE ADL.
IN MY MIND REAFFIRMING THEIR OWN
IDENTITY AND PINTING TO THE FACT
THEY THERE WERE FAR MORE THAN
THE DISEASE AND GENE THERAPY
HELPED THEM OVERCOME THAT.
HERE'S THE FIRST BOY TREATED IN
OUR TRIAL WHO IS PARENTS SENT ME
PICTURE OF HIM PLAYING SOCCER
LAST YEAR AND SOMEONE NOW
THRIVING IN THE MIDDLE OF THEIR
LIFE SHOWING ALL THE QUALITY WE
WISH FOR THEM.
HERE'S THE FIRST BOY WHO IS NOW
TREATED WITH COMMERCIAL PRODUCT
EARLY IN STAGE OF DISEASE DOING
WELL.
I WANT TO SHOW THE CONSORTIA
REFORMED TO BRING TOGETHER THE
PATIENT VOICE AND HIGHLIGHT
THERE'S STILL A LOT OF UNMET
NEED IN THE COMMUNITY.
WE DON'T HAVE TREATMENT FOFRZ
ADULTS RIGHT NOW.
WE DON'T KNOW HOW TO BRING THIS
TO ADULTS WITH CEREBRAL ALD OR
TREAT THE SPINAL CORD FORM OF
THE DISEASE.
I THINK WE MADE A START AND HOPE
THERE'S MORE PROGRESS TO BE MADE
IN THE FIELD.
THANK YOU.
>> THANK YOU, FLORIAN.
I'LL INTRODUCE OUR LAST SPEAKER
PRESENTING VIRTUALLY, DR. ALEXIS
LEONARD FROM ST. JUDE CHILDREN'S
HOSPITAL.
WHY IT'S A SINGLE MISSPELLING IN
THE MUTATION AND THE JOB OF H
HEMOGLOBIN IS TO DELIVER AND
WHEN IT'S HAMPERED IT FORMS THE
SICKLE SHAPE OF THE RED CELL AND
IT'S DENSE AN HARD AND CAUSES
THE COMPLICATIONS OF THE DISEASE
WHICH INCLUDES HAVING LOW BLOOD
COUNTS OR OCCLUSION OF BLOOD
VESSELS.
IN THE UNITED STATES SICKLE CELL
DISEASE IS A CHRONIC HEALTH
DISORDER AND AFFECTS PATIENTS
FROM HEAD TO TOE IN EVERY ORGAN
FROM THE ABNORMAL BLOOD CELL AND
AS A PATIENT AGES THE LIST OF
COMPLICATIONS GROWS AND IN RED
YOU SEE THE COMPLICATION ARE
IRREVERSIBLE AT ANY AGE.
THIS IS A GROWING GLOBAL HEALTH
DISEASE WITH HIGH MORBIDITY,
LOTS OF COMPLICATIONS, EARLY
MORTALITY.
YOU STE THE INCREASE GLOBALLY
FROM 5 MILLION IN 2000 TO NEARLY
8 MILLION IN 2021 AND SEE WHERE
THE VAST MAJORITY OF THE BURDEN
OF THE DISEASE AND MORTALITY
OCCURS.
IN THE U.S. THE AVERAGE LIFE
EXPECTANCY IS 20 YEARS YOUNGER
THAN PATIENTS OF 52 YEARS WHICH
TRANSLATES TO REDUCED LIFE TIME
INCOME OF NEARLY A MILLION
DOLLARS.
VERY EXPENSIVE.
INDIVIDUALLY YOU CAN SEE WHAT
SOME COSTS ARE INCLUDING HIGH
OUT OF POCKET COSTS FOR
PATIENTS.
SO WE DO NEED TO FOCUS ON THESE
TREATMENT OPTIONS THAT HELP TO
REDUCE THE DISEASE BURDEN
PARTICULARLY FOR THOSE SEVERE
FORMS OF THE DISEASE.
HOW DO WE TREAT THIS DISEASE.
WE HAVE A TOTAL OF FOUR FDA
APPROVED DRUGS.
THREE OF WHICH WERE JUST
APPROVED IN THE RECENT YEARS.
THESE HAVE THEIR LIMITATIONS.
YOU HAVE TO TAKE THEM EVERY DAY
AND HAVE TO CHRONICALLY MONITOR
THEM AND ALWAYS ISSUE WITH
ADHERENCE AND THEY'RE NOT ALL
EFFECTIVE AND ARE EXPENSIVE.
WE CAN POTENTIALLY CURE SOMEBODY
WITH SICKLE CELL DISEASE DOING A
BONE MARROW TRANSPLANT.
IT'S CURATIVE BUT COMES WITH
MORBIDITY AND MORTALITY.
WE'RE TALKING ABOUT REPLACING OR
REPLACING THE STEM CELLS YOU
HEARD ABOUT.
WE HAD A LOT OF EXPERIENCE
DEFERRAL DECADES OF DOING THE
TRANSPLANT USING DONOR STEM
CELLS.
WE KNOW THE BEST OUTCOMES IS IF
YOU HAVE A MATCHED BROTHER OR
SISTER OR YOUNGER BECAUSE OF
LESS ORGAN DAMAGE FROM THE
SICKLE CELL DISEASE.
THERE'S SIGNIFICANT LIMITATION
TO THIS.
ONLY A SMALL FRACTION OF PATIENT
HAVE A MATCHED SIBLING.
THERE'S DISEASE CAN LEAD TO
DEATH.
PATIENTS CAN REJECT THEIR GRAFT
AND POTENTIAL MORBIDITY AND
MORTALITY.
IN GENE THERAPY WE TAKE THE
PATIENT'S OWN CELLS AND MODIFIED
THEM CAN LIMIT THIS.
HOW'S IT DIFFERENT FROM A DONOR
TRANSPLANT.
IN SICKLE CELL IT TAKES A LITTLE
BIT LONGER FOR PATIENT TO GOOD
THROUGH THIS PROCESS.
WE PUT THEM ON CHRONIC TRAN
FUSIONS, COLLECT THE STEM CELLS
AND PUT THEM BACK AND THE
PATIENT NEEDS TO RECEIVE SOME
FORM OF CONDITIONS AND THE CELLS
GET IN FUSED AND IN THE DONOR
PLANS TRANSPLANT YOU INFUSE THE
DONOR CELLS.
THERE'S DIFFERENCES.
IN 2024 WE USED HIGH DOSES OF
CHE
CHEMOTHERAPY AND IT CAN INCLUDE
A DONOR TRANSPLANT AND NO IMMUNE
, NO GDHB OR REJECTION.
IN DECEMBER OF LAST YEAR THE FAA
APPROVED TWO GENE THERAPIES TO
TREAT PATIENTS WITH SICKLE CELL
DISEASE AND ONE IS THE FIRST
CRISPR APPROVED GENE THERAPY FOR
ANY DISORDER.
IT'S A MILESTONE.
IT'S BEEN DECADES IN THE MAKING
THAT WE STILL HAVE A LOT OF WORK
TO DO TO MAKE IT SAFER, TO MAKE
IT MORE ACCESSIBLE, MORE
AFFORDABLE.
THE FIRST TRIAL OPENED IN 2014
AND THE FIRST TRIAL FOR CRISPR
CAS 9 WITHIN 2018.
WE'RE TALKING ABOUT SMALL
NUMBERS OF PATIENTS WITH LIMITED
FOLLOW UP.
HOW'S THIS EVOLVED OVER TIME.
THE FIRST ITERATION OF GENE
THERAPY USED VIRUSES, HIV-BASED
VIRUS WHERE WE TOOK OUT ALL THE
BAD PARTS OF HIV INCLUDED A COPY
OF NORMAL HEMOGLOBIN AND
INSERTED THAT INTO THE PATIENT'S
STEM CELLS AND THES CRISPR CAS 9
IS FOCUSSED ON INCREASING LEVEL
OF FETAL HEMOGLOBIN WHICH IS
PROTECTIVE IN PATIENTS WITH
SICKLE CELL DISEASE.
WE'VE LEARNED QUITE A GREAT
AMOUNT FROM THE CLINICAL TRIALS.
WE LEARNED WE HAD TO DO THIS
PERIOD OF TRANSFUSIONS.
WE HAD TO STOP AND THE MAIN TYPE
OF THERAPY AND IT MATTERED HOW
MUCH WE GAVE AND HOW WE
MANUFACTURED.
WE SAW CHANGES AND IN THE FIRST
PATIENTS THEY DID NOT HAVE
CLINICAL BENEFITS AND IT
ULTIMATELY LED TO WHAT IS
AVAILABLE TO ALL PATIENTS WHO
WOULD OTHERWISE QUALIFY FOR
TRANSPLANTATION AND WE RESERVED
THIS FOR PATIENTS THAT WITH
SEVERE DISEASE COMPLICATIONS.
SO THE CLINICAL STUDIES THAT
WE'RE DESCRIBING HAVE STRICT
INCLUSIONARY, EXCLUSIONARY
CRITERIA.
IN GENERAL INCLUDING PATIENTS
THAT HAD REOCCURRENCE OF VASO
OCCLUSIVE EVENTS IN THE YEARS
LEADING UP TO TRANSPLANT AND HAD
AN HLA MATCHED SIBLING BECAUSE
OF THE HISTORY AND TIME WE'VE
KNOWN WITH GOOD OUTCOMES WITH
DONOR TRANSPLANT FROM A SLING
THEY EXCLUDED PATIENTS WITH
NEUROVASCULAR COMPLICATIONS AN
OTHERS IT'S IMPORTANT THE
PATIENTS WERE ABLE TO TOLERATE
THE CONDITIONS NOT ALL ARE ABLE
TO TOLERATE GIVEN THE TOXICITY
THAT CAN OCCUR TO ORGAN
FUNCTIONS.
PATIENTS NEED TO KNOW WITH THE
SHORT TERM TOXICITY OF USING
THIS AND HAIR LOSS AND INFECTION
AND LONG-TERM THE PATIENTS HAVE
A RISK OF SECONDARY MALIGNANCIES
AND BEING INFERTILE.
ABOUT 30 PATIENTS WERE IN EACH
STUDY THAT WERE EVALUATED BY THE
FDA PRIMARILY THE GENOTYPE AND
AVERAGE AGE WAS ABOUT 20 AND A
QUARTER IN EACH STUDY IN THE
ADOLESCENT POPULATION AND
OUTCOMES SHOWED IN BOTH STUDIES
94% OF PATIENTS HAD COMPLETE
RESOLUTION OF THOSE VASO
OCCLUSIVE EVENTS LEADING UP TO
TRANSPLANT.
THE HEMOGLOBIN WAS NORMALIZED
AND FOLLOW UP WAS 5 YEARS AND
THIS IS SHOWING EACH HORIZONTAL
LINE SAY PATIENT AND EACH OF
THOSE DOTS REPRESENTS AN EVENT
SUCH AS PAIN CRISIS AND YOU SEE
MANY LEADING UP TO TRANSPLANT
AND SIGNIFICANT REDUCTION AFTER
GENE THERAPY.
THESE PATIENTS REPORTED
CLINICALLY MEANINGFUL
IMPROVEMENTS AN THEIR PAIN
INTENSITY AND INTERFERENCE OF
FATIGUE SUSTAINED OVER TIME.
HALF THEIR HEMOGLOBIN WAS COMING
FROM THIS INSERTED NORMAL
HEMOGLOBIN GIVEN NORMAL
HEMOGLOBIN AND THE ANEMIA
IMPROVED.
SUE MANY LEADING UP TO TRANS
PLANT AND EITHER COMPLETE
ELIMINATION OR SIGNIFICANT
REDUCTION AFTER GENE THERAPY
WITH TOTAL HEMOGLOBIN
NORMALIZING AND SUSTAINING OVER
TIME HALF COMING FROM NORMAL
FETAL HEMOGLOBIN INDUCTION GOING
FROM 15% TO 40% SUSTAINED OVER
TIME.
NOW, OF COURSE WE HAVE TO TALK
ABOUT SAFETY SO THE MAJOR EVENTS
OCCURRED SECONDARY TO
CHEMOTHERAPY AND SICKLE CELL
DISEASE AND MOST EVENTS WERE
OCCURRING DURING THE TRANSPLANT
MONTH RECEIVING CHEMO.
THERE WERE NO CASES OF PATIENTS
REJECTING THE GRAPH OR GETTING
DISEASE THAT USE THE HIV-BASED
VECTOR.
THE PATIENTS DON'T HAVE HIV AS
WE TAKE OUT ALL THOSE BAD PARTS
AND INSERT WHAT WE WANT THE
NORMAL HEMOGLOBIN AND THERE'S
PATIENTS WHO ARE TWO GENE
DELETIONS WHO SHOULD NOT RECEIVE
IT.
WE HAVE REPORTED PARTNER
PREGNANCIES AFTER THIS AND A
WORD ON SECONDARY CANCER AFTER
GENE THERAPY IN SICKLE CELL
DISEASE.
THIS OCCURRED IN TWO PATIENTS
FROM THE GROUP A OF THE STUDY
THAT OCCURRED EARLY ON WHEN GENE
THERAPY WAS INEFFECTIVE.
THE WHOLE FIELD PAUSED TO
REFLECT ON WHAT WAS UNIQUE ABOUT
THIS DISEASE AND REALIZED
PATIENTS WITH SICKLE CELL
DISEASE ARE AT SLIGHTLY HIGHER
RISK OF AML AT BASELINE AND THE
TRANSPLANT IS TOXIC AND PATIENTS
MAY HAVE PREEXISTING CANCER
MUTATIONS.
PATIENTS WHO REJECT THEIR GRAFT
MAY GO ON TO DELIVER LEUKEMIA AS
WELL.
IF PATIENTS REJECT THEIR GRAPH
OR THERAPY HAS BEEN INEFFECTIVE
THE STEM CELLS REVERTING MAY
DRIVE CANCER CELLS.
WE BELIEVE THE PATIENTS WITH
EFFECTIVE GENE THERAPY WOULD BE
AT LOWER RISK FOR DEVELOP
SECONDARY CANCER.
BECAUSE OF LYFGENIA THE RISK OF
ALL SICKLE CELL DISEASES WHO
UNDER GO THESE THERAPIES IS WHY
THEY HAVE TO BE FOLLOWED FOR A
LONG TIME AND THESE ARE OPEN
CLINICAL TRIALS FOR SICKLE CELL
DISEASE.
WE STILL HAVE UNANSWERED
QUESTIONS AND AGE GROUPS THAT
HAVEN'T BEEN TESTED.
THIS IS ALSO SHOWING THE MANY
QUESTIONS PATIENTS WITH US SEE
IF THERE IS AN UNDERLYING
MALIGNANCY MUTATION AND CAN WE
AFFORD IT AND CAN PATIENTS
AFFORD THE FERTILITY AND CRYO
PRESERVATION AND WE FEEL WE
SHOULD BE TRANSFORMATIVE INSTEAD
OF CURATIVE UNTIL WE HAVE
LONG-TERM DATA ON ORGAN FUNCTION
AND DURE ABILITY DURABILITY AND
WHAT MAY BE BEST FOR PATIENTS.
TRANSFORMATIVE THERAPY IS HERE
AND EXCITING AND FEEL PATIENTS
SHOULD STILL HAVE ACCESS TO
CLINICAL TRIALS AND APPROVALS
WITH DECADES OF , FA FIVE TO 10
YEARS OF CLINICAL TRIAL AND
THOSE WHO RISK THEIR LIVES,
HEALTH, FERTILITY AND TIME TO
ADVANCE THIS.
I'LL CLOSE WITH A MOVING MESSAGE
FROM A PATIENT.
>> HELLO, EVERYBODY.
MY NASN MASON AND I'M 20 YEARS
OLD AND BORN WITH AN S TYPE OF
SICKLE CELL DISEASE AND HAVE
UNDER GONE THERAPY ON JANUARY 9
OF 2023.
I WANT TO START WITH A LITTLE
BIT ABOUT HOW I GOT INVOLVED
WITH THIS CLINICAL TRIAL.
MY JOURNEY STARTS AS A
3-MONTH-OLD BABY HAVING MY FIRST
PAIN CRISIS.
THIS IS WHERE I WOULD BE
DIAGNOSED WITH SICKLE CELL
DISEASE AND SHOWING NARROWING IN
SOME OF THE BLOOD VESSELS IN MY
BRAIN PUTTING ME AT RISK OF A
STROKE.
I WOULD START ONCE A MONTH BLOOD
TRANSFUSIONS AT THE AGE OF 8 AND
STAY ON THESE UNTIL I TURNED
ABOUT 17.
AND WITH THE TRANSFUSIONS MY
SICKLE CELL WAS PRETTY WELL
MANAGED AND I WOULD ONLY HAVE A
PAIN CRISIS ONCE OR TWICE A YEAR
TO THE EMERGENCY ROOM BUT
EVERYTHING CHANGED ONCE I CAME
AFTER THE TRANSFUSIONS AND
STARTED MY FRESHMAN YEAR OF
COLLEGE.
MY CONDITIONS HEALED PRETTY
FAST.
I WOULD GO FROM BEING IN THE
EMERGENCY ROOM ONCE OR TWICE A
YEAR TO FOUR TO FIVE TIMES A
MONTH AND THIS IS DIFFERENT AND
BECAUSE MY CONDITION GOT SO BAD
SO QUICKLY I COULDN'T GO TO
SCHOOL ANYMORE AND GO TO CLASSES
THOUGH IT'S 10 MINUTES AWAY AND
COULDN'T LIFT ANYTHING HEAVY
EVERYTHING I DID WAS A TRIGGER
FOR MY SICKLE CELL.
LY WAS WALKING OR BEING OUTSIDE
TOO LONG IN THE IN THE COLD OR
BEING TOO HOT MY BODY EVERYTHING
WAS A TRIGGER.
I COULDN'T DO ANYTHING.
AROUND THE SAME TIME I HAD A
FRIEND IN TRINIDAD WHO ALSO HAD
SICKLE CELL DISEASE BUT
UNFORTUNATELY PASSED TO HER
DISEASE AND THE MOMENT MY
DOCTORS HEARD THIS NEWS THEY
WOULD IMMEDIATELY GO AND CONTACT
THE DOCTORS AT CHILDREN'S
NATIONAL ABOUT GETTING ME ON TO
THE GENE THERAPY TRIAL.
I SPENT MOST MY 2022 GETTING
READY FOR A TRANSPLANT WHETHER
THAT WAS GOING BACK AND FORTH TO
D.C. APPOINTMENTS OR TESTING.
JUST MAKING SURE EVERYTHING WAS
IN LINE AND CORRECT BEFORE I
STARTED TRANSPLANT BUT ONCE I
GOT PASSED ALL THAT I WAS
FINALLY ADMITTED JANUARY 2 OF
2023.
THE FOLLOWING DAY I'D START MY
CHEMOTHERAPY WHICH INTENDED TO
GET ME READY FOR MY NEW CELLS.
AFTER MY FIVE DAYS OF
CHEMOTHERAPY I WOULD HAVE ONE
REST DAY AND GIVEN MY NEW CELLS
ON THAT NIGHT COLLECTED FROM A
PRIOR APPOINTMENT.
IT WAS AN EXCITING DAY AND I
STILL THINK ABOUT IT PRETTY
OFTEN HONESTLY.
I'LL GO ON AND WAIT FOR MY CELLS
TO ENGRAPH FOR THE NEXT THREE
WEEKS AND THEN AFTER THEY
INGRAFT I WAS SENT TO ANOTHER
HOSPITAL FOR THREE WEEKS AND
FINALLY SENT BACK HOME.
NOW, I WANT TO TALK ABOUT HOW I
FEEL AFTER RECEIVING THE GENE
THERAPY.
NOW, MY BASELINE HEMOGLOBIN
WITHOUT TAKING ANYTHING WAS
ABOUT 7.0.
AND WITH HIGH DROXERIA I COULD
GET UP TO 8.5, 9.
NOW, POST TRANSPLANT MY
HEMOGLOBIN IS AT 14.0 WHICH
IS -- I MEAN, I'M EFFECTIVELY
DOUBLED MY HEMOGLOBIN SINCE
RECEIVING GLEAN THERAPY.
I WANT TO REMIND YOU GUYS THAT
BEFORE TRANSPLANT I COULDN'T DO
ANYTHING.
I FELT LIKE JUST BEING ALIVE WAS
A TRIGGER FOR MY SICKLE CELL.
I COULDN'T LIFT ANYTHING, I
COULD NOT BE TOO HOT OR TOO
COLD.
I COULDN'T WALK ANYWHERE.
I COULDN'T GO ANYWHERE WITHOUT
HAVING MY MEDICATION ON ME JUST
TO FEEL SECURE.
NOW ALL THAT DISAPPEARED AND HAS
GONE AWAY.
AND I'M STILL NOT USED TO IT
REALLY BECAUSE I'VE LIVED MY
ENTIRE LIFE IN PAIN WITH
MEDICATION AND WITH THIS THOUGHT
OF SICKLE CELL UP MY HEAD IN
EVERY DECISION I MADE WAS WITH
ME EVERYWHERE.
NOW THAT I HAVE GONE THROUGH
GENE THERAPY AND TRANSPLANT THE
THOUGHT IS GONE.
I CAN DO PRETTY MUCH ANYTHING
NOW HONESTLY.
I STARTED GOING TO THE GYM.
I'VE BEEN HANGING OUT WITH
FRIENDS MORE.
IT'S BEEN A YEAR AND ALMOST TWO
MONTHS NOW AND I'VE STILL HAD
ZERO PAIN SINCE TRANSPLANT.
ZERO PAIN.
IT'S AMAZING.
HONESTLY IT'S BEEN AMAZING.
I'M JUST NOT SITTING AROUND FOR
MY NEXT PAIN CRISIS ANYMORE AND
IT'S KIND OF UNBELIEVABLE FOR
ME.
THIS IS WHAT I'VE KNOWN MY WHOLE
LIFE BUT SECOND HALF IS --
SICKLE CELL IS GONE AND PAIN IS
GONE AND NEXT WEEK I'LL BE DONE
WITH MEDICATION AND MY LIFE IS
COMPLETELY DIFFERENT.
IT'S IN EVERY WAY POSSIBLE.
QUALITY OF MY LIFE HAS GONE UP
SO MUCH.
I'M SO GRATEFUL.
IT'S AMAZING.
IT REALLY IS.
I WISH MORE PEOPLE WERE IN MY
SHOES AND IN MY OPPORTUNITY.
A TAKEAWAY FOR THE AUDIENCE IS
NUMBER ONE, TO BE AS PROACTIVE
AS POSSIBLE WITH YOUR HELP.
AND INSTEAD OF TRYING TO REACT
BECAUSE SICKLE CELL I FEEL LIKE
IF I WAS REACTING IT WAS ALREADY
TOO LATE FOR ME.
AND WHAT I MEAN BY THIS IS
SHOWING UP TO YOUR APPOINTMENTS
ON TIME.
TAKING MEDICATION BECAUSE I
DON'T WANT TO MISS APPOINTMENTS,
I TRIED NOT TO MISS MY
MEDICATION BECAUSE EVERY DAY I
MISSED A DOSE FELT LIKE ONE LESS
DAY I WAS HERE ON THIS EARTH.
AND HONESTLY MY MEDICATION KEPT
ME HEALTHY ENOUGH TO GO THROUGH
TRANSPLANT.
THAT'S IT.
IT WAS HONESTLY SUPER IMPORTANT.
THOUGH IT DOESN'T SEEM LIKE IT
OR IT'S HARD TAKING SOME OF
THESE PILLS AND MEDICINE, TRUST
ME, I KNOW.
IT'S SUPER, SUPER IMPORTANT.
IT REALLY IS.
MY LAST TAKEAWAY FOR THE
AUDIENCE IS TO KEEP YOUR FAITH.
AND TO KNOW THAT NO MATTER YOUR
SITUATION THAT THINGS WILL GET
BETTER.
THERE'S BEEN MANY TIMES IN MY
LIFE THAT I THOUGHT THINGS WOULD
NOT TURN OUT SO WELL OR THIS
WOULD BE THE END OF MY WORLD.
I'VE HAD SOME PRETTY SEVERE
PAIN.
I JUST SIT BACK NOW AND LOOK AT
EVERYTHING I'VE BEEN THROUGH AND
REALIZE I'VE COME THIS FAR JUST
BELIEVING AND PRAYING AND HAVING
MY SUPPORT SYSTEMS AROUND ME AND
HERE I AM NOW SICKLE CELL FREE
WHICH IS PRETTY AMAZING.
I THOUGHT I'D NEVER SEE THE DAY.
I'M HERE NOW SICKLE CELL FREE
AND IT FEELS AMAZING.
THERE'S BEEN TIMES I THINK I'D
GET THROUGH IT BUT I DID.
I JUST WANT YOU GUYS TO KNOW
THAT TOO.
THANK YOU FOR GIVING ME THE TIME
TO SPEAK.
>> THANK YOU, DR. LEONARD.
WE HAVE TIME FOR A FEW
QUESTIONS.
IF I CAN ASK ALL THE SPEAKERS TO
COME UP ON THE STAGE.
WHILE PEOPLE ARE THINKING I HAVE
ONE QUESTION FOR DR. IKELER THAT
FOLLOWS ON THE COMMENTS MADE
ABOUT SICKLE CELL.
YOU TALKED ABOUT THE MYELOID
DYSPLASTIC SYNDROME IS THAT
RESULT OF THE CHEMOTHERAPY
NECESSARY OR THE TRANS PLANT
ITS
ITSELF OR NOT KNOWN YET?
>> WE DO NOT KNOW THERE'S TOO
MANY FACTORS AN IN EVERY FOR
LYING DISEASE STATE THERE'S THE
DIFFERENCES IN WHAT'S
CONTRIBUTING HERE.
>> THANK YOU.
>> QUESTION OVER HERE.
>> WAS IT DR. MARINKOVICH AND I
DON'T KNOW IF YOU HEAR THE
WHEEZING WHEN HE'S SPEAKING.
IF SO, HAVE YOU CONSIDERED USING
GENE THERAPY FOR THIS EFFECT OF
COLLAGEN 7 LACKING IN THE LUNG.
E.B. ONLY AFFECT THE STRATIFIED
EPITHELIUM THE ORAL PHARYNX AND
THE ESOPHAGUS BUT THE
INTERSTITIAL LUNG.
I THINK HE JUST HAD A SENSITIVE
MICROPHONE BUT YOU BRING UP A
GOOD POINT.
AND WHO I PARTNERED WITH HAVE
ANOTHER PIPELINE FOR CYSTIC
FIBROSIS AND DELIVERING THE SAME
VECTOR WITH THE CYSTIC FIBROSIS
GENE WITH INHALATION THERAPY NOR
LUNGS SO IT'S NOW BEING USED IN
EARLY CLINICAL TRIALS AS AN
INHALENT THERAPY.
>> THANK YOU.
>> I'M WITH PPB AND JUST
WONDERING IF YOU HAVE ADVICE ON
PLACEBO CONTROL OR IF THAT'S
PART OF THE INITIATIVES ONGOING
RIGHT NOW.
>> IT'S A GREAT QUESTION.
THANK YOU FOR THAT QUESTION.
THE QUESTION WAS AROUND ADVICE
ABOUT PLACEBO CONTROL TRIALS.
I THINK WE NEED TO SHIFT THAT
PARADIGM SOME.
I DON'T THINK IT'S ALWAYS
NECESSARY.
AND SO I WOULD SAY THAT THAT'S A
BIT OF INDIVIDUAL CONVERSATION
BIFFED ON THE DISEASE AND THE
PROGRAM BUT WE HAVE BEEN LOOKING
AT WHERE IT'S APPROPRIATE SAGE
ARM TRIALS AND NOVEL END POINTS,
INTERMEDIATE END POINTS AND
FOLLOWING THOSE PATIENTS LONGER
TERM AFTER AN ACCELERATED
APPROVAL.
WE'RE LOOKING AT DIFFERENT WAYS
TO DESIGN PROGRAMS NOT
NECESSARILY INVOLVING PLACEBO.
>> THANK YOU.
>> LOOKS LIKE THERE'S NO MORE
QUESTIONS.
I'M GOING TO FIRST THANK THE
SPEAKER FOR THEIR WONDERFUL
PRESENTATIONS AND INSPIRING
RESEARCH WE HEARD ABOUT.
NOW I'D LIKE TO INVITE DR. JONI
RUTTER FOR CLOSING REMARKS.
>> LOOK, IT'S THE END OF THE
DAY.
IT WAS AN INCREDIBLY EMPOWERING,
ENGINEER, THOUGHT-PROVOKING DAY.
I DON'T KNOW I CAN SAY ANYTHING
MORE SO I'M NOT GOING TO.
WHAT I WANT TO DO IS I'VE NOW
BEEN IMPRINTED FROM WHAT
HAPPENED LAST YEAR AT THIS TIME
AND IF ANY OF YOU WERE HERE LAST
YEAR, RON BARTEK CAME RUNNING
DOWN THE AISLE WAVING HIS HANDS
AND HAD THIS WONDERFUL
ANNOUNCEMENT FOR A NEW TREATMENT
FOR THE DISEASE HE'S BEEN
WORKING ON AND SO PASSIONATE
ABOUT FOR MANY YEARS.
I'M GOING TO PAUSE A MOMENT IN
CASE ANYBODY'S GOING TO RUN DOWN
THE AISLE.
I DON'T WANT TO MISS THAT.
I WANT TO TAKE A MOMENT TO SAY
THANK YOU TO ALL THE SPEAKERS TO
ALL OF OUR POSTER PRESENTERS AND
THERE'S MEETINGS AND BECAUSE
BUSINESS TAKING PLACE AND
CONVERSATIONS HAPPENING WHICH IS
FANTASTIC TO SEE AND I WANT TO
THANK THE ARTISTS WHO SHARED
WITH US TODAY AS WELL.
IF YOU HAVEN'T HAD A CHANCE TO
SEE THAT TAKE A LOOK AT THAT AND
WE'RE ON THE STREAMING EVENT AS
WELL.
AND THEN LASTLY I WOULD JUST
LIKE TO SAY THANK YOU TO THE
YOUNG ADULT ADVOCATES COUNCIL
WHO PRESENTED US WITH A NOTE OF
THANKS FOR THE WORK WE'RE DOING.
I WANT TO THANK YOU FOR ALL THE
WORK YOU'RE DOING.
WE'RE MAKING A TON OF PROGRESS.
THERE'S MORE NEED AND MORE TO
COME.
KEEP UP THE FANTASTIC WORK AND
WE'LL SEE YOU NEXT YEAR. 7775 06:11:53,257 THANK YOU.