SO I'M GLEN NUCKOLLS.
I'M THE DESIGNATED FEDERAL
OFFICIAL FOR THE MUSCULAR
DYSTROPHY COORDINATING
COMMITTEE.
AND I'D LIKE TO WELCOME YOU TO
THE 29TH MEETING OF THE MDCC.
SO FIRST WHAT WE'D LIKE TO DO IS
GO AROUND AND DO KIND OF A ROLL
CALL OF MEMBERS, MAKE SURE WHO'S
HERE AND GIVE EVERYBODY AN
OPPORTUNITY TO IDENTIFY
THEMSELVES AND THEIR
AFFILIATION, AND LET US START
WITH OUR CHAIR, DR. BIANCHI.
>> GOOD MORNING, EVERYONE, AND
THANK YOU, DR. NUCKOLLS.
I'D JUST LIKE TO WELCOME
EVERYONE.
I'M THE DIRECTOR OF THE EUNICE
KENNED SHRIVER NATIONAL
INSTITUTE OF CHILD HEALTH AND
HUMAN DEVELOPMENT, AND I'M A
MEDICAL GENETICIST AS WELL, AND
IT'S BEEN MY PRIVILEGE TO SERVE
AS CHAIR OF THIS COMMITTEE FOR
THE LAST FOUR YEARS.
I'LL HAND IT OVER BACK TO YOU,
GLEN.
>> THANK YOU.
DR. CRISWELL.
>> GOOD MORNING, EVERYBODY.
I'M LINDSEY CRISWELL.
I'M THE DIRECTOR OF THE NATIONAL
INSTITUTE OF ARTHRITIS AND
MUSCULOSKELETAL AND SKIN
DISEASES, OR NIAMS, AND IT'S
BEEN A PRIVILEGE BEING ON THIS
COMMITTEE FOR THE LAST COUPLE OF
YEARS SINCE I JOINED THE NIH IN
FEBRUARY OF 2021.
>> GUSTAVO.
>> GOOD MORNING, EVERYONE.
I'M GUSTAVO DZIEWCZAPOLSKI.
I'M THE SCIENTIFIC DIRECTOR AT
THE PATIENT AD ADVOCACY ASSOCIAN
CALLED QC & G, IT'S A PLEASURE
TO BE HERE.
I THINK IT'S MY FIFTH YEAR ON
THE COMMITTEE.
THANK YOU.
>> THANKS.
EMILY FRELLICH.
>> GOOD MORNING.
I'M DR. EMILY FREILICH, DIRECTOR
OF THE DIVISION OF NEUROLOGY ONE
IN CEDAR AT FDA.
>> THANK YOU.
MICHAEL GOLDSTEIN.
>> I'M HERE.
JUST TAKING ME A MOMENT TO GET
OFF MUTE.
GOOD MORNING, EVERYONE.
MY NAME IS MICHAEL GOLDSTEIN.
I'M EXCITED TO BE HERE.
I AM THE DIRECTOR OF THE OFFICE
OF MEDICAL POLICY AT THE SOCIAL
SECURITY ADMINISTRATION.
WE ADMINISTER OUR DISABILITY
PROGRAM OR PORTIONS OF IT
THROUGH MY OFFICE, INCLUDING
NEUROLOGICAL MEDICAL LISTINGS,
WHICH CONTAIN A NUMBER OF
DYSTROPHIES AND MUSCULAR
DYSTROPHIES ARE ALSO WRINKLES
AND PARTS AND ELEMENTS OF OUR
DISABILITY PROGRAM IN A BROADER
SENSE.
SO VERY EXCITED TO HEAR FROM
EVERYONE TODAY.
THANK YOU.
>> THANK YOU, MICHAEL.
ALISHA KEEHN.
>> GOOD MORNING, EVERYONE.
I'M ALISHA KEEHN, I'M THE BRANCH
CHIEF OF THE GENETICS SERVICES
BRANCH IN THE DIVISION OF
CHILDREN WITH SPECIAL HEALTH
NEEDS AT THE HEALTH RESOURCES
AND SERVICES ADMINISTRATION.
I'VE BEEN FORTUNATE TO BE ON
THIS COMMITTEE FOR THE LAST FEW
YEARS.
IN OUR BRANCH, ONE OF THE KEY
THINGS THAT WE DO IS WE SUPPORT
THE ADVISORY COMMITTEE ON
HERITABLE DISORDERS IN NEWBORNS
AND CHILDREN, WHICH MAKES
RECOMMENDATIONS TO THE SECRETARY
OF HHS FOR RECOMMENDING
CONDITIONS TO THE UNIFORM
NEWBORN SCREENING PANEL.
SO I'M ALWAYS VERY INTERESTED IN
THE DISCUSSIONS WE HAVE IN THIS
COMMITTEE AND LOOK FORWARD TO
OUR CONVERSATION TODAY.
>> THANK YOU.
SO OUR MEMBER FROM NHLBI, JIM
KILEY, IS NOT ABLE TO JOIN
TODAY, BUT IN HIS PLACE, WE HAVE
SAMITA KATRI.
>> I'M ACTUALLY FILLING IN FOR
DR. NATARAJAN WHO WAS FILLING IN
FOR JIM KILEY.
I AM THE CMRO, NEW POSITION IN
THE DIVISION OF LUNG DISEASE.
I'M A PULMONOLOGIST AND I'M
VERY, VERY HAPPY TO BE HERE
BECAUSE I'M INTERESTED IN THIS
TOPIC AND WANT TO MOVE IT
FORWARD.
>> THANK YOU.
WALTER?
>> WALTER KOROSHETZ.
I'M THE DIRECTOR FOR THE
NEUROLOGIC INSTITUTE WHERE I'M
HAPPY TO WORK WITH GLEN AND A
NUMBER OF OTHER PEOPLE HERE.
>> SO I KNOW THAT OUR MEMBER
FROM THE DEPARTMENT OF DEFENSE,
CDMRP, MARIA McGUIRE, IS NOT
ABLE TO JOIN US TODAY.
DENISE MYLAR?
>> HI.
I'M DENISE MYLER FROM IDAHO.
>> THANK YOU.
IS DAN PEREZ -- HAS DAN JOINED
US TODAY?
DAN LET ME KNOW THAT THERE WAS A
MEDICAL EMERGENCY IN HIS FAMILY,
AND HE MAY BE TIED UP WITH THAT
TODAY.
WE WISH THEM THE BEST.
NATALIE STREET?
>> HI.
MY NAME IS NATALIE STREET.
I'M A HEALTH SCIENTIST ON THE
RARE DISORDERS AND HEALTH
OUTCOMES TEAM THAT HOUSES ALL
THE MUSCULAR DYSTROPHY
ACTIVITIES AT THE CENTERS FOR
DISEASE CONTROL AND PREVENTION.
>> AND ERIC WANG.
>> HI.
MY NAME IS ERIC WANG.
I'M ASSOCIATE PROFESSOR,
UNIVERSITY OF FLORIDA.
MY LAB STUDIES MYOTONIC
DYSTROPHY, AND I'M VERY ACTIVE
WITH THE MYOTONIC DYSTROPHY
FOUNDATION AS WELL.
>> AND WE HAVE A NUMBER OF OTHER
PEOPLE HERE IN THE ROOM WITH US.
I'D LIKE TO JUST KIND OF GO
AROUND AND ASK YOU TO INTRODUCE
YOURSELF QUICKLY.
WE'LL KIND OF START AT THIS
CORNER.
PAUL?
>> GOOD MORNING, EVERYBODY.
I'M PAUL MILMEIR, VICE PRESIDENT
OF PUBLIC POLICY AND ADVOCACY AT
THE MUSCULAR DYSTROPHY
ASSOCIATION.
>> I'M EMILY, PROGRAM DIRECTOR
FOR MUSCLE DISEASES AND
THERAPEUTICS AT THE NIAMS.
>> GOOD MORNING, EVERYONE.
THIS IS RAMONA, EXECUTIVE
DIRECTOR OF THE DUCHENNE
REGULATORY SCIENCE CONSORTIUM
AND CRITICAL PATH INSTITUTE.
>> GOOD MORNING.
I'M FROM THE NATIONAL INSTITUTE
ON INDEPENDENT LIVING DISABILITY
AND REHABILITATION RESEARCH
WITHIN ADMINISTRATION FOR
COMMUNITY LIVING.
>> GOOD MORNING, CAROL
TAYLOR-BURDS.
I'M AT THE NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND
STROKE AND DIVISION OF
TRANSLATIONAL RESEARCH.
>> GREAT.
I THINK WE HAVE A NUMBER OF
OTHER PEOPLE ON SOO ZOOM.
ALL OF OUR PRESENTERS FOR TODAY
WILL HAVE AN OPPORTUNITY TO
INTRODUCE YOU LATER ON.
IN THE INTEREST OF TIME, I THINK
WE'LL GO AHEAD AND GET STARTED.
SO THIS MEETING IS BEING
CONDUCTED IN COMPLIANCE WITH THE
FEDERAL ADVISORY COMMITTEE ACT
TO ENSURE THAT THE COMMITTEE
PROVIDES EXPERT ADVICE AND
DIVERSE OPINIONS TO INFORM
DECISION-MAKING BY OFFICIALS AND
AGENCIES IN THE EXECUTIVE BRANCH
OF THE FEDERAL GOVERNMENT IN A
MANNER THAT'S TRANSPARENT AND
FREE OF CONFLICTS.
THERE WILL BE NO CLOSED SESSION
PLANNED FOR TODAY'S MEETING.
WE DON'T ANTICIPATE DISCUSSIONS
OR ACTIONS SPECIFIC TO
ORGANIZATIONS OR FINANCIAL
INTERESTS OF OUR MEMBERS, SO
THERE'S NO NEED FOR ANY RECUSALS
TODAY.
SO WE POSTED A NOTICE IN THE
FEDERAL REGISTER ABOUT THIS
MEETING, INVITING PUBLIC
COMMENT.
WE DID NOT RECEIVE ANY REQUEST
FROM THE PUBLIC TO MAKE A
COMMENT TO THE COMMITTEE, SO
WE'VE NOT SCHEDULED THAT FOR
THIS MEETING.
THIS MEETING IS BEING STREAMED
LIVE FOR PUBLIC VIEWING, AND
IT'S ALSO BEING RECORDED.
THE STREAM AND THE RECORDING ARE
AVAILABLE AT VIDEOCAST.NIH.GOV,
AND WE ALSO PROVIDE A LINK ON
OUR WEBSITE, WHICH IS
MDCC.NIH.GOV.
SO FOR THOSE COMMITTEE MEMBERS
AND OTHER DESIGNATED PANELISTS
THAT ARE CONNECTING THROUGH
ZOOM, YOU CAN EITHER RAISE YOUR
DIGITAL HAPPENED HAND OR UNMUTEE
QUESTIONS AND ADD COMMENTS TO
OUR MEETING.
IF YOU'RE NOT A COMMITTEE MEMBER
AND YOU'RE DESIGNATED AS A --
YOU'RE NOT DESIGNATED AS A
PANELIST, YOU WILL BE ABLE TO
SUBMIT QUESTIONS VIA THE CHAT
FEATURE THROUGHOUT TODAY'S
MEETING AND WE'LL READ THOSE OUT
FOR YOU.
SO I'D LIKE TO THANK SOME OF THE
NIH AND CONTRACTOR STAFF WHO
HAVE REALLY HELPED PREPARE FOR
THIS MEETING, INCLUDING MARIE
PIERRE, DERRICK SMITH, SOSHA
MORRIS, TOY YA RODGERS, EMILY,
WAI CHEN LEE, KATHLEEN
HUNTZINGER, AND ALSO GINA
WILLIAMS.
AND I'D LIKE TO TAKE THIS
OPPORTUNITY TO ESPECIALLY THANK
DR. BIANCHI FOR HER LEADERSHIP
AND CHAIR, AS CHAIR OF THE MDCC.
SO THIS IS THE LAST MEETING
DURING HER CURRENT TERM AS
CHAIR, AND I'D REALLY LIKE TO
EXPRESS MY APPRECIATION FOR THE
HONOR OF WORKING WITH YOU ON
THIS COMMITTEE.
SO WE'VE COVERED, I THINK, SOME
REALLY IMPORTANT TOPICS DURING
DR. BIANCHI'S TERM AS CHAIR
SINCE 2020, INCLUDING
PATIENT-REPORTED OUT COME
MEASURES, NEWBORN SCREENING,
RESPIRATORY AND SLEEP
COMPLICATIONS, STRATEGIES TO
INCREASE DIVERSITY IN RESEARCH
STUDIES, DRUG R REPURPOSING,
STRATEGIC PLANNING.
FOR TODAY'S MEETING, WE'LL BE
TALKING ABOUT REGULATORY
APPROVALS.
SO WE REALLY APPRECIATE YOUR
DEDICATION TO THIS COMMITTEE AND
NICHD'S SUPPORT FOR THE MUSCULAR
DYSTROPHIES.
AND I'M EXCITED TO ANNOUNCE THAT
DR. LINDSEY CRISWELL, THE
DIRECTOR OF THE NATIONAL
ARTHRITIS -- SKIN DISEASES WILL
BE THE NEXT CHAIR FOR THE MDCC,
AND I REALLY LOOK FORWARD TO
WORKING WITH HER DURING THE MDCC
ACTION PLAN AND OTHER TOPICS FOR
THIS COMMITTEE.
UNLESS THERE ARE OTHER QUESTIONS
OR COMMENTS, I'LL TURN IT OVER
TO DR. BIANCHI FOR YOUR CHAIR
PRESENTATION.
>> THANK YOU SO MUCH,
DR. NUCKOLLS, AND ESPECIALLY
THANK YOU FOR YOUR KIND COMMENTS
AND YOUR IMMENSE SUPPORT OF THIS
COMMITTEE.
I'VE LEARNED SO MUCH FROM YOU,
AND IT'S BEEN A TRUE PLEASURE
WORKING WITH YOU.
I WILL STILL SERVE ON THE
COMMITTEE AND I LOOK FORWARD TO
HANDING THE BATON OVER TO MY
GOOD COLLEAGUE DR. CRISWELL.
SO WITH THAT, THANK YOU FOR
BRINGING UP THE SLIDES.
MAY I HAVE THE NEXT ONE, PLEASE?
SO TODAY BRIEFLY I'M GOING TO BE
TALKING -- JUST GIVE YOU A
LITTLE INTRODUCTION.
WE HAVE A NEW NIH DIRECTOR IN
TOWN.
I'LL SAY VERY BRIEFLY WHAT WE
KNOW ABOUT FISCAL YEAR 24
APPROPRIATIONS.
AND THEN I THOUGHT IT WOULD BE
IMPORTANT TO JUST GIVE AN UPDATE
ON THE ADVISORY COMMITTEE TO THE
NIH DIRECTOR'S WORKING GROUP ON
DIVERSITY SUBGROUP ON
INDIVIDUALS WITH DISABILITIES,
AND THEN SOME SELECTED ADVANCES
IN MUSCULAR DYSTROPHY RESEARCH.
NEXT SLIDE, PLEASE.
SO AS OF NOVEMBER 9TH, WE HAVE A
NEW PERMANENT NIH DIRECTOR.
THIS IS DR. MONICA BERTAGNOLLI,
WHO'S THE 17TH DIRECTOR OF NIH,
AND ONLY THE SECOND FEMALE
DIRECTOR.
SHE'S BEEN AT THE NIH FOR A
YEAR.
SHE CAME IN OCTOBER OF 2022 TO
BECOME THE DIRECTOR OF THE
NATIONAL CANCER INSTITUTE, AND
AS OF NOVEMBER 9TH, SHE'S NOW
THE OVERALL DIRECTOR OF NIH.
SHE COMES WITH A LONG ACADEMIC
HISTORY AS A SURGEON ONCOLOGIST
AT THE DANA FARBER CANCER
INSTITUTE IN BOSTON.
AND SHE IS HIGHLY ENERGETIC AND
HAS A FOCUS ON CLINICAL TRIAL
RESEARCH, AND I'M SURE WE'RE
GOING TO BE HEARING MORE ABOUT
HER PRIORITIES AS THE WEEKS PASS
BY.
I WISH I COULD TELL YOU MORE
ABOUT FISCAL YEAR 24 NIH
APPROPRIATIONS.
WE ARE ON A CONTINUING
RESOLUTION UNTIL GROUNDHOG DAY.
AND WHAT THAT MEANS IS, WE ARE
OPERATING ON A BUDGET THAT IS
THE SAME AS FISCAL YEAR 2023'S
BUDGET, BUT IT'S NOT REALLY A
PERMANENT BUDGET.
CONGRESS HAS TO COME UP WITH A
PERMANENT APPROPRIATION.
THEY COULD KEEP US ON A
CONTINUING RESOLUTION FOR THE
REST OF THE FISCAL YEAR, BUT IT
MAKES IT VERY DIFFICULT FOR US
TO SET PAY LINES TO PAY GRANTS,
TO PLAN TO DECIDE, YOU KNOW,
WHAT ARE OUR PRIORITIES FOR THE
REST OF THE FISCAL YEAR, AND
BEST CASE SCENARIO, WE WILL BE
HALFWAY THROUGH THE FISCAL YEAR
IF WE GET A PERMANENT BUDGET IN,
SAY, FEBRUARY OR MARCH.
SO I WANT TO GIVE A SHOUT OUT TO
ALL OF THE PROGRAM STAFF WHO
HAVE TO DEAL WITH THIS,
ESPECIALLY THE BUDGET PEOPLE.
I DON'T KNOW ABOUT NIAMS AND
NINDS, BUT I KNOW IN NICHD, OUR
FINANCIAL OFFICE MAKES MULTIPLE
CONTINGENCY BUDGETS, AND RIGHT
NOW WE ARE OPERATING UNDER A
VERY CONSERVATIVE PAYLINE
BECAUSE WE CAN'T SPEND MONEY
THAT WE DON'T REALLY KNOW THAT
WE HAVE.
SO HOPEFULLY THINGS WILL RESOLVE
IN THE EARLY SPRING, BUT THAT'S
WHERE WE ARE.
AND IF YOU READ THE NEWSPAPERS,
YOU PROBABLY KNOW JUST AS MUCH
AS WE DO.
SO THE ADVISORY COMMITTEE TO THE
DIRECTOR MEETS LIKE A COUNCIL
FOR THE DIRECTOR OF THE NIH, AND
OFTENTIMES THERE ARE WORKING
GROUPS THAT ARE ESTABLISHED TO
DEAL MORE DEEPLY WITH IMPORTANT
ISSUES.
AND SO THERE WAS A WORKING GROUP
THAT WAS ESTABLISHED AS PART OF
THE DIVERSITY SUBGROUP TO TALK
ABOUT INDIVIDUALS WITH
DISABILITIES.
AND HERE THEY'RE TALKING ABOUT
BOTH PHYSICAL AND INTELLECTUAL
DISABILITIES.
BUT THE REPORT, WHICH HAS BEEN
PUBLISHED AND IS PUBLICLY
AVAILABLE, RECOMMENDED ONE
IMMEDIATE ACTION TO SUPPORT
DISABILITY INCLUSION.
AND THAT WAS TO REMOVE THE
LANGUAGE OF REDUCING DISABILITY
FROM THE NIH MISSION STATEMENT.
EUM GOING TOI'M GOING TO SHOW YE
CURRENT MISSION STATEMENT IN A
MOMENT BUT THE COUNCIL FELT THIS
COULD BE INTERPRETED AS
PERPETUATING ABLEIST BELIEFS
THAT DISABLED PEOPLE ARE FLAWED
AND NEED TO BE FIXED.
SO THE CURRENT MISSION STATEMENT
AS OF THIS MINUTE, THIS IS FOR
THE OVERALL NIH, IS TO SEEK
FUNDAMENTAL KNOWLEDGE ABOUT THE
NATURE AND BEHAVIOR OF LIVING
SYSTEMS, AND THE APPLICATION OF
THAT KNOWLEDGE TO ENHANCE
HEALTH, LENGTHEN LIFE, AND
REDUCE ILLNESS AND DISABILITY.
AND IT'S THE PART IN ITALICS
THAT WAS OF CONCERN.
SO AFTER MUCH DISCUSSION, THE
PROPOSED MISSION STATEMENT, THE
REVISED ONE, IS AS FOLLOWS: TO
SEEK FUNDAMENTAL KNOWLEDGE ABOUT
THE NATURE AND BEHAVIOR OF
LIVING SYSTEMS AND TO APPLY THAT
KNOWLEDGE TO OPTIMIZE HEALTH AND
PREVENT OR REDUCE ILLNESS FOR
ALL PEOPLE.
NOW, THERE WAS A PUBLIC REQUEST
FOR INFORMATION AND FEEDBACK ON
THIS NEW PROPOSED MISSION
STATEMENT.
THE RESPONSES WERE DUE JUST
AFTER THANKSGIVING, AND WE HAVE
NOT HEARD YET WHAT THOSE
RESPONSES ARE GOING TO BE.
BUT I WOULD MENTION THAT WHEN
NICHD CHANGED THEIR MISSION
STATEMENT, BECAUSE WE DO HAVE
THE NATIONAL CENTER FOR MEDICAL
REHABILITATION RESEARCH IN OUR
INSTITUTE, WE CHANGED OUR
MISSION STATEMENT TO OPTIMIZING
ABILITIES FOR ALL.
SO THERE IS A CONNECTION BETWEEN
OURS AND WHAT THE PROPOSED
MISSION STATEMENT WILL BE FOR
OVERALL NIH, AND I'M HAPPY TO
DISCUSS THIS WHEN WE TAKE
QUESTIONS.
VERY, VERY IMPORTANTLY, AS OF
OCTOBER 2023, THE NIH DESIGNATED
PEOPLE WITH DISABILITIES AS A
HEALTH DISPARITY POPULATION.
SO THIS IS SOMETHING THAT WILL
ALLOW FOR NEW FUNDING
OPPORTUNITIES FOR INNOVATIVE
APPROACHES AND INTERVENTIONS
THAT ADDRESS THE INTERSECTION OF
PHYSICAL DISABILITY, RACE AND
ETHNICITY AND SOCIOECONOMIC
STATUS ON HEALTHCARE ACCESS AND
HEALTH OUTCOMES.
NICHD HAS A SPECIFIC MISSION
AREA OF INCLUDING PEOPLE WITH
DISABILITIES IN RESEARCH, BUT
THIS IS GOING TO BROADEN THE
AREA OF RESEARCH ACROSS ALL OF
THE INSTITUTES AND CENTERS.
SO WE'RE VERY EXCITED ABOUT IT.
AND THAT BRINGS ME TO SOME OF
THE ADVANCES IN MUSCULAR
DYSTROPHY RESEARCH.
SO THE FIRST ONE IS A STUDY THAT
WAS SUPPORTED BY NICHD, NIAMS,
NHLBI, NINDS, AND THE ROBERT A.
WELCH FOUNDATION, PUBLISHED IN
NATURE COMMUNICATIONS AND IT
INVOLVES UNDERSTANDING MYOFIBER
DEVELOPMENT AND NEUROMUSCULAR
DISEASE PATHWAYS.
SO THE PROBLEM THAT THEY WERE
TRYING TO SOLVE IS THAT GENE
REGULATORY NETWORKS THAT
ACTIVATE SUCCESSIVE PHASES OF
MYOGENESIS IN VIVO HAVE NOT BEEN
FULL FULLY DESCRIBED TO DATE.
SO THESE RESEARCHERS CONSTRUCTED
AN ATLAS OF MOUSE SKELETAL
MUSCLE DEVELOPMENT AND
MATURATION ACROSS DIFFERENT TIME
PERIODS, SUCH AS EMBRYONIC,
FETAL, AND POSTNATAL.
THEY USE SINGLE-NUCLEUS RNA AND
ATAC SEQUENCING TO IDENTIFY
THREE TRANSCRIPTION FACTORS THAT
FORM A COMPLEX AND TRIGGERS
ACTIVATION OF MUSCLE GENE
EXPRESSION IN NEW MUSCLE FIBERS.
THEY ALSO IDENTIFIED A
TRANSCRIPTION FACTOR THAT
ACTIVATES THE MATURATION PHASE
IN FAST MUSCLES.
AND ALTHOUGH THIS IS BASIC
RESEARCH, THE FINDINGS COULD
INFORM FUTURE THERAPEUTIC AND
RESEARCH TARGETS.
THE NEXT STUDY PUBLISHED IN CELL
WAS SUPPORTED BY NIAMS AND THE
NATIONAL INSTITUTE ON AGING.
THIS WAS ALSO BASIC RESEARCH,
AND WAS ON DEVELOPING A
SPECIALIZED CLASS OF DELIVERY
VEHICLES THAT ARE SPECIFIC FOR
SKELETAL MUSCLE.
SO OBVIOUSLY SOME PRE-CLINICAL
WORK THAT MIGHT HAVE THERAPEUTIC
IMPLICATIONS.
SKELETAL MUSCLE DEVELOPMENT
REQUIRES MEMBRANE FUSION EVENTS
TO FORM MYOFIBERS.
MYOMAKER AND MYOMERGER ARE
MUSCLE-SPECIFIC CELL FUSOGENS.
AND THIS PARTICULAR STUDY SHOWED
THAT INCLUDING MYOGENIC SPECIFIC
FUSOGENS ON THE SURFACE OF
ENVELOPED VIRUSES, SUCH AS
LENTIVIRUSES, IMPROVES THE
SPECIFICITY AND DELIVERY OF
REPORTER AND THERAPEUTIC
TARGETS.
THIS STUDY SHOWED THAT
PREVENTING OFF TARGET EXPRESSION
OF VIRAL CARGO DURING GENE
TRANSFER OR GENE EDITING
THERAPEUTICS MAY REDUCE THE
TOXICITY GENERALLY SEEN WITH
THESE THERAPEUTICS.
OF COURSE THE CAVEAT IS THAT
MORE PRE-CLINICAL AND
TRANSLATIONAL RESEARCH ARE
NEEDED TO FURTHER DEVELOP THIS
METHOD.
THIRD STUDY IS SUPPORTED BY --
WAS SUPPORTED BY NIAMS, NICHD,
NINDS.
THE FSHD SOCIETY, THE CHRIS KREE
KNOW FOUNDATION, FRIENDS OF FSH
RESEARCH AND OTHER CAREER
DEVELOPMENT PROGRAMS, AND I KNOW
THAT IN THE PAST, WE'VE TALKED
ABOUT DUX4.
THIS WAS A STUDY OF DUX4 POST
TRANSLATIONAL MODIFICATIONS, AND
IT REVEALED POTENTIAL NOVEL
TARGETS FOR SMALL MOLECULE
TREATMENTS.
SO FSHD IS CAUSED BY NORMAL
DE-REPRESSION OF THE
TRANSCRIPTION FACTOR DUX4.
TRANSCRIPTIONAL REGULATION OF
THE DUX4 PROTEIN IS UNCLEAR, SO
THESE RESEARCHERS CHARACTERIZED
DUX4 POST TRANSLATIONAL
MODIFICATIONS, AND THEIR IMPACT
ON THE TOXIC FUNCTION OF DUX4 IN
VITRO.
THESE RESEARCHERS IDENTIFIED
DUX4 AMINO ACIDS WITH POST
TRANSLATIONAL MODIFICATIONS AND
GENERATED MUTANTS TO PREVENT OR
MIMIC THEM.
FIVE MUTANTING PROTECTED THE
CELLS AGAINST TOXICITY AND
REDUCED THE ABILITY OF DUX4 TO
ACTIVATE FSHD BIOMARKERS.
I'M SPEAKING TOO FAST.
THE POTENTIAL FOR KINASES WITH
HIGH DUX4 PHOSPHORYLATION
ACTIVITY, THERE'S A POTENTIAL
THAT THE PHOSPHORYLATION
ACTIVITY WILL BE TARGETS FOR
SMALL MOLECULE TREATMENT.
SO WE HAVE THREE STUDIES SO FAR
THAT ARE BASIC STUDIES THAT
POTENTIALLY WILL HAVE RELEVANCE
IN TERMS OF FUTURE TREATMENT.
OKAY, THE FOURTH STUDY WAS
SUPPORTED BY NINDS, THE MDA
CLINICAL RESEARCH NETWORK, THE
FSHD SOCIETY, AND FRIENDS OF FSH
RESEARCH.
PUBLISHED IN NEUROMUSCULAR
DISORDERS.
AND IT VALIDATED -- IT WAS ON
VALIDATING BIOMARKERS AND
OUTCOME MEASURES FOR FSHD.
SO AS WE ANTICIPATE UPCOMING
THERAPEUTIC TRIALS IN FSHD,
THERE'S A NEED FOR
COST-EFFECTIVE, READILY
AVAILABLE OBJECTIVE MEASURES TO
TEST THE EFFECTS OF THERAPY.
SO THERE WAS A STUDY CALLED THE
RESOLVE STUDY, CLINICAL TRIAL
READINESS TO SOLVE BARRIERS TO
DRUG DEVELOPMENT IN FSHD.
IT'S A PROSPECTIVE LONGITUDAL
OBSERVATIONAL MULTISITE STUDY.
THESE RESEARCHERS USED DEXA
MEASUREMENTS, SO DUAL ENERGY
X-RAY AB SORP TOM TREE
MEASUREMENT OF ASSOCIATIONS WITH
STRENGTH AND FUNCTIONAL OUTCOMES
TO MEASURE LEAN TISSUE MASS.
AND THEIR DATA DEMONSTRATED A
CORRELATION BETWEEN ARM AND LEG
STRENGTH AND LEAN TISSUE MASS
FOR BOTH THE RIGHT AND LEFT
EXTREMITIES.
SO BOTTOM LINE IS THAT THESE
DEXA SCANS COULD SERVE AS AN
EASY AND ECONOMICAL MEASURE IN
EARLY-PHASE STUDIES AND AS A
SECONDARY END POINT IN EFFICACY
TRIALS.
I THINK IT'S THE FIFTH STUDY NOW
THAT WAS SUPPORTED BY NHLBI IN
CIRCULATION HEART FAILURE, AND
THIS IS LOOKING AT ONE OF THE
IMPORTANT CAUSES OF MORTALITY IN
DUCHENNE MUSCULAR DYSTROPHY, AND
THEY WERE LOOKING SPECIFICALLY
AT CARDIAC END POINTS IN DMD
THERAPEUTIC TRIALS.
AS I SAID, CARDIOPULMONARY
FAILURE IS THE LEADING CAUSE OF
DEATH IN DUCHENNE MUSCULAR
DYSTROPHY.
THERE ARE NO FDA-APPROVED
CARDIAC END POINTS.
SO THEORY SEARCHERS EVALUATED
THE RATE OF CHANGE FOR CARDIAC
MAGNETIC RESONANCE AND BLOOD
BIOMARKERS TO DETERMINE WHICH
MEASURES ASSOCIATE WITH
CARDIOVASCULAR DEATH.
THERE'S SOMETHING MISSING THERE.
THEY IDENTIFIED SURROGATE
OUTCOME MEASURES FOR CLINICAL
TRIALS FOR DMD.
SO THESE KINDS OF END POINTS ARE
EXTREMELY IMPORTANT TO BE ABLE
TO DOCUMENT EITHER THERAPEUTIC
EFFECTS OR UNFORTUNATE SIDE
EFFECTS.
SO THE NEXT STUDY WAS SUPPORTED
BY NINDS, AND IT WAS PUBLISHED
IN MUSCLE AND NERVE AND WAS
LOOKING AT THE ASSOCIATION
BETWEEN CANCER AND MYOTONIC
DYSTROPHY.
SO PEOPLE WHO HAVE BOTH FORMS OF
MYOTONIC DYSTROPHY, THE DM1 AND
DM2 VARIETIES, HAVE AN INCREASED
RISK OF DEVELOPING CANCER SO AS
A CLINICAL RESEARCH STUDY, THEY
ASKED WHETHER FREQUENCY AND
CANCER TYPE DIFFERED BETWEEN
MYOTONIC DYSTROPHY SUBTYPES AND
A NON-MYOTONIC DYSTROPHY
MUSCULAR DYSTROPHY COHORT.
AND THEY FOUND THAT THERE WAS AN
INCREASED RISK OF
NON-SEX-RELATED CANCERS IN
DM1 COMPARED TO DM2.
AND THERE WAS ALSO AN INCREASED
RISK OF SEX-RELATED CANCERS
INCLUDING OVARIAN CANCER IN
DM1 RELATIVE TO NON-MUSCULAR
DYSTROPHY -- THE NON-MYOTONIC
DYSTROPHY MUSCULAR DYSTROPHY
COHORT.
THERE WAS NO SIGNIFICANT
ASSOCIATION BETWEEN CTG REPEAT
LENGTH AND CANCER IN THE
MYOTONIC DYSTROPHY PATIENTS.
THESE RESEARCHERS RECOMMENDED
ANNUAL SKIN CHECKS TO RULE OUT
SKIN CANCER, THYROID GLAND
PALPATION AT ANNUAL VISITS TO
RULE OUT THYROID CANCER, AND TO
HAVE A LOW THRESHOLD TO
INVESTIGATE POSSIBLE UROLOGICAL
AND HEMATOLOGICAL CANCERS IN DMR
IN DM2 PATIENTS.
SO THOSE ARE THE HIGHLIGHTS.
I'M HAPPY TO ANSWER QUESTIONS.
PLEASE RAISE YOUR HAND AND
DR. NUCKOLLS WILL CALL ON YOU.
>> ANY QUESTIONS OR COMMENTS FOR
DR. BIANCHI?
AND IF YOU'RE IN THE ROOM,
PLEASE BRING YOUR MIC UP CLOSE
SO WE CAN HEAR YOU.
>> I'M GOING TO GUESS IT WAS
CRYSTAL CLEAR.
OH, SORRY.
LINDSEY.
>> THANKS, DR. BIANCHI, FOR A
CLEAR PRESENTATION AND EXPRESS
MY EXCITEMENT ABOUT ALL OF THE
PROGRESS.
SO THIS IS REALLY IMPRESSIVE.
AND REALLY EXCITING TO THINK
ABOUT WHERE THIS MAY LEAD.
SO THANKS SO MUCH.
THAT WAS A GREAT OVERVIEW.
>> THANK YOU.
>> I HAVE A SHORT QUESTION ABOUT
THE BUDGET FOR THE YEAR.
IS THERE ANY POSSIBILITY THAT
THEY CAN APPROVE A REDUCTION IN
THE BUDGET OR WE KNOW THAT THE
BUDGET IS AS IS NOW AND IT COULD
BE AN INCREASE BUT NOT A
REDUCTION?
>> WHAT A WONDERFUL QUESTION.
I THINK THIS --
>> I UNDERSTOOD THE --
>> I THINK THE SHORTEST WAY TO
ANSWER THAT IS ALL BETZ ARE OFF,
REALLY.
YOU HEAR ONE FACTION IN CONGRESS
SAYING THEY'RE GOING TO SLASH
THE FEDERAL BUDGET BY 30%.
YOU HEAR OTHER PEOPLE TALKING
ABOUT INCREASES IN SPECIFIC
AREAS.
WE DO OUR BEST JOB WITH THE
CONGRESSIONAL JUSTIFICATION.
I KNOW THAT THE STAFF ARE STILL
MEETING AND ASKING QUESTIONS.
FOR EXAMPLE, I HAVE A BRIEFING
ON MONDAY WITH SOME OF THE
CONGRESSIONAL STAFF ABOUT A
COUPLE OF TOPICS IN OUR
INSTITUTE.
SO THEY ARE WORKING ON IT.
THE QUESTION IS, YOU KNOW, RIGHT
NOW, IT'S SO POLITICAL THAT IT'S
HARD TO TELL WHAT'S GOING TO
HAPPEN.
WE KNOW THAT WE HAVE BIPARTISAN
SUPPORT.
I SHOULD HAVE MENTIONED THAT DRY
STRONG BIPARTISAN SUPPORT IN HER
CONFIRMATION HEARING.
WE KNOW THAT THERE ARE SOME VERY
PROMINENT MEMO MEMBERS OF BOTH
PARTIES WHO SUPPORT THE NIH.
SO WE HOPE FOR THE BEST, AND WE
ARE PREPARED FOR ALL KINDS OF
CONTINGENCIES, BUT WE REALLY --
WE DON'T KNOW WHAT'S GOING TO
HAPPEN.
WE CAN DO OUR BEST WITH GIVING
EVERY MEMBER WHO ASKS
INFORMATION BACK ABOUT WHY THIS
MAKES A DIFFERENCE FOR PEOPLE IN
THE UNITED STATES AND AROUND THE
WORLD.
WE CAN -- I KNOW THAT ADVOCACY
GROUPS ARE WORKING VERY HARD,
BUT AT THE END OF THE DAY, IT
WILL RELATE TO THE
APPROPRIATIONS COMMITTEES AND
THEN THE FULL SENATE AND HOUSE
VOTING ON THE BUDGETS.
I WISH I COULD BE MORE
DEFINITIVE.
>> I SEE DAN PEREZ HAS JOINED.
SO DAN, WOULD YOU LIKE TO
INTRODUCE YOURSELF?
>> HI.
I'M DAN.
NICE TO BE HERE.
I'M SORRY FOR MY DELAY.
MY NAME IS DANIEL PR PEREZ.
I AM THE CO-FOUNDER AND DIRECTOR
EMERITUS OF THE SSHD SOCIETY,
AND ONE OF THE LONGEST STANDING
MEMBERS OF THE MDCC.
I WOULD LIKE TO SAY HI TO JUNE
KINOSHITA WHO IS WITH US FROM
THE FSHD SOCIETY.
THANK YOU, JUNE, FOR JOINING US.
AND I WANT TO SAY HI TO ALL MY
COLLEAGUES ON THE MDCC, AND GOOD
TO SEE YOU ALL, AND THANK YOU
FOR YOUR GOOD WORK.
I'VE SPENT 30 YEARS WORKING
ON -- GAPS IN MUSCULAR
DYSTROPHY.
MY ORGANIZATION, ALONG WITH NIH
HAVE LED TO THE UNRAVELING OF
THE MECHANISM OF FSHD, AND NOW
WE ARE LARGELY ON TO TRYING TO
TREAT THE DISEASE AND CURE IT.
SO WITH THAT, I'LL SAY THANK
YOU, AND GOOD TO SEE YOU.
>> THANK YOU SO MUCH, DAN AND
JUNE FOR JOINING US.
DAN, I HOPE WHATEVER WAS GOING
ON WITH YOUR FAMILY HAS RESOLVED
AND THAT EVERYTHING IS OKAY.
WE DID PRESENT SOME HIGHLIGHTS
OF RECENT RESEARCH ON FSHD.
SO YOU CAN LOOK AT THE RECORDING
TO HEAR WHAT WE SELECTED.
>> I DID JUST WANT TO SAY,
HAVING BEEN IN THE ER TWICE THIS
WEEK WITH MY WIFE, IT'S REALLY
UNPRECEDENTED TO SEE HOW -- IT'S
QUITE EYE OPENING JUST TO SEE
THE DISTRESS UNDER WHICH THE
HOSPITALS ARE, AND QUITE
SOBERING AND QUITE FRIGHTENING.
I HOPE THINGS DO CHANGE.
THANK YOU.
>> WE'RE GLAD THAT YOU COULD BE
WITH US.
OKAY.
>> I HAD A QUESTION AND I'M
SORRY I HAD TO STEP AWAY WHEN
YOU WERE DOING INTRODUCTIONS, SO
DAN, I THINK, HAS SEMI
INTRODUCED ME AND IT HAS BEEN MY
INCREDIBLE HONOR TO WORK
ALONGSIDE DAN FOR THESE PAST 12
YEARS.
I'M CURRENTLY SERVING AS THE
SENIOR DIRECTOR OF RESEARCH AND
EDUCATION FOR THE FSHD SOCIETY,
AND YOU'LL HEAR MORE ABOUT THAT.
BUT I DID ACTUALLY HAVE A
QUESTION REGARDING THE REVISION
OF THE MISSION STATEMENT.
SO ONE OF THE CONUNDRUMS WE ARE
WORKING WITH RIGHT NOW IN FSHD
IS, AS WE ENTER INTO CLINICAL
TRIALS, THEY EXCLUDE
NON-AMBULATORY INDIVIDUALS.
LIKE DAN WOULD NOT BE ABLE TO
PARTICIPATE IN ANY CURRENT
CLINICAL TRIALS.
AND WE CERTAINLY UNDERSTAND
THAT, YOU KNOW, ONE HAS TO
TEMPERATURE GU --HAS TO STRATIFN
TO TRY TO REMOVE A LOT OF NOISE
AND TRY TO GET AS CLEAN DATA AS
YOU CAN FROM THE TRIAL, BUT MANY
OF THE INDIVIDUALS WHO HAVE
PROGRESSED OR HAVE LOST
AMBULATION ARE ALSO THE MOST
MOTIVATED TO PARTICIPATE IN
TRIALS.
THEY HAVE CONTINUING PROGRESSION
OF MUSCLE WEAKNESS IN THEIR
UPPER BODY, AND WE ARE WORKING
ON OUTCOME MEASURES THAT LOOK AT
UPPER BODY STRENGTH, IN FACT,
THAT'S ONE OF THE PRIMARY
OUTCOMES, YET DESPITE THAT BEING
A PRIMARY OUT COME,
NON-AMBULATORY INDIVIDUALS ARE
STILL EXCLUDED, AND WE HAVE A
FAMILY WITH -- AND ALSO
PEDIATRIC PATIENTS RIGHT NOW ARE
NOT -- YOU KNOW, THAT'S A WHOLE
'NOTHER STORY, BUT WE'RE ALL
CONSTANTLY HEARING FROM FAMILIES
THAT, YOU KNOW, LIKE, I HAVE A
CHILD WHO HE COULDN'T
PARTICIPATE IN THE TRIAL BECAUSE
HE WAS UNDER 18, BUT NOW HE'S
18, HE'S STILL EXCLUDED BECAUSE
HE'S NON-AMBULATORY.
SO WHAT I WAS WONDERING IS IF
THERE WILL BE FUNDING TO DEVELOP
TRIAL OUTCOME MEASURES THAT
ARE -- THAT WILL CREATE GREATER
ACCESSIBILITY FOR TRIALS TO
ALLOW PEOPLE WITH DISABILITIES
TO PARTICIPATE.
>> THAT'S CERTAINLY OUR HOPE.
WHETHER THERE'S SPECIFIC FUNDING
OR NOT, I CAN'T SAY, BECAUSE IN
MY ANSWER TO THE PREVIOUS
QUESTION, WE DON'T KNOW WHAT THE
BUDGET IS GOING TO BE, BUT
CERTAINLY I CAN SPEAK FOR
MYSELF, AND I THINK FOR THE
OTHER DIRECTORS, THAT
INCLUSIVITY OF AS MANY PEOPLE AS
POSSIBLE IS SO IMPORTANT.
AND DON'T GET ME STARTED ON
EXCLUDING CHILDREN.
YOU'RE SUPPOSED TO BE ABLE TO
INCLUDE CHILDREN IN ALL CLINICAL
TRIALS.
SO YOU KNOW, I CAN'T SPEAK FOR
THE PEOPLE WHO ARE DESIGNING
THOSE CLINICAL TRIALS, BUT I CAN
SAY THAT IT'S IMPORTANT TO
COMMUNICATE WITH THEM THE
IMPORTANCE OF INCLUSIVITY.
AND I ASSUME THEY HAD THEIR
REASONS FOR SELECTING CERTAIN
POPULATIONS.
BUT I TOTALLY AGREE WITH YOU,
PEOPLE WHO HAVE THE MOST INTENSE
LIVED EXPERIENCES ARE OFTEN THE
BEST PARTICIPANTS OR THE MOST
MOTIVATED PARTICIPANTS.
THEY WILL FOLLOW UP, ET CETERA.
ISO THIS IS REALLY AN
ASPIRATIONAL GOAL, AND THE
ARTICULATION OF IT IN WRITING IS
THE FIRST STEP.
BUT IT'S SOMETHING THAT WE ALL
NEED TO WORK TOWARDS
COMMUNICATING WITH PEOPLE WHO
ARE DESIGNING CLINICAL STUDIES.
>> THANK YOU.
>> AND I SAW THAT DR. CRISWELL
PUT A NOTE IN THE CHAT, WHO ALSO
REAFFIRMED THAT INCLUSIVITY IS A
SHARED GOAL FOR HER INSTITUTE AS
WELL.
OKAY.
THANK YOU, JUNE, FOR YOUR
COMMENTS.
I THINK THAT IN THE INTEREST OF
TIME, WE ARE GOING TO MOVE
AHEAD, UNLESS -- I'LL GIVE ONE
MORE CHANCE.
OKAY.
SO, SHE'S ALREADY INTRODUCED
HERSELF, BUT WE'RE VERY EXCITED
TO INVITE A NEW MEMBER TO OUR
COMMITTEE.
THAT IS DR. RADHA HOLAVANAHALLI,
WHO'S A PROJECT OFFICER WITH THE
NATIONAL INSTITUTE ON
DISABILITY, INDEPENDENT LIVING
AND REHABILITATION RESEARCH OF
THE ADMINISTRATION FOR COMMUNITY
LIVING.
SHE'S A FORMER PROFESSOR OF
PHYSICAL MEDICINE AND
REHABILITATION AT THE UT
SOUTHWESTERN MEDICAL SCHOOL AND
CENTER, WHERE SHE WAS ALSO THE
DIRECTOR OF THE PHYSICAL
MEDICINE AND REHABILITATION
RESIDENCY PROGRAM.
DR. HOLAVANAHALLI IS A CURRENT
MEMBER OF THE COUNCIL ON AGING.
SHE'S GOING TO SERVE AS AN AD
HOC MEMBER ON OUR COMMITTEE
PENDING FINAL APPROVAL FROM
SECRETARY BECERRA'S OFFICE.
WELCOME, DR. HOLAVANAHALLI.
I'VE PRACTICED THAT MANY TIMES,
BUT NOW I CAN SAY IT!
>> THANK YOU SO MUCH FOR THAT
INTRODUCTION.
AND YES, YOU SAID MY NAME
PERFECT.
SO I HAVE SOME SLIDES HERE.
CAN I DO IT HERE OR -- I'M SO
SORRY.
CAN EVERYBODY HEAR ME?
ALL RIGHT.
SO THIS IS MY FIRST MEETING
TODAY, AND I DID PUT TOGETHER
SOME SLIDES ABOUT MY BACKGROUND,
BUT DR. BIANCHI ALREADY
MENTIONED THAT.
MY BACKGROUND IS IN MEDICAL
SOCIOLOGY AND GERONTOLOGY, AND
AS WAS MENTIONED A FEW MINUTES
AGO, I WAS PROFESSOR IN THE
PHYSICAL MEDICINE AND
REHABILITATION DEPARTMENT AT UT
SOUTHWESTERN MEDICAL CENTER IN
DALLAS.
DURING THAT TIME, I WAS
PRIMARILY ENGAGED IN BURN
REHABILITATION RESEARCH, AND DID
SOME SIGNIFICANT WORK WITH THE
AMERICAN BURN ASSOCIATION, AND I
WAS THE CO-CHAIR FOR AFTER CARE
AND REINTEGRATION COMMITTEE OF
THE AMERICAN BURN ASSOCIATION
AND ALSO SERVED ON THE ELDERLY
CARE COMMITTEE AND THE
REHABILITATION COMMITTEES OF THE
ABA.
ALSO, FROM -- SINCE 2021, I
TRANSITIONED TO NIDILRR, WHICH
IS NATIONAL INSTITUTE ON
DISABILITY, INDEPENDENT LIVING,
AND REHABILITATION RESEARCH.
I CURRENTLY SERVE AS THEIR
PROJECT OFFICER, AND I'M ALSO
THE COMPETITION MANAGER FOR THE
FIELD INITIATED PROJECTS
PROGRAM.
I'M THE CO-CHAIR FOR THE
DISABILITY STATISTICS
SUBCOMMITTEE.
SORRY ABOUT THAT.
I CURRENTLY SERVE ALSO AS THE
CO-CHAIR FOR THE DISABILITY
STATISTICS SUBCOMMITTEE, WHICH
IS UNDER THE INTERAGENCY
COMMITTEE ON DISABILITY
RESEARCH.
AND AS MENTIONED EARLIER, I ALSO
SERVE ON THE NATIONAL ADVISORY
COUNCIL ON AGING WITH THE
NATIONAL INSTITUTE ON AGING.
AND OF COURSE MY PRESENCE HERE
IS PENDING APPROVAL.
AND SO, I'M HERE TODAY
REPRESENTING NIDILRR, WHICH IS A
PART OF ACL ADMINISTRATION FOR
COMMUNITY LIVING.
AND ACL, ADMINISTRATION FOR
COMMUNITY LIVING, IS ONE OF 11
OPERATING DIVISIONS WITHIN
HEALTH AND HUMAN SERVICES.
IT IS THE PRINCIPAL AGENCY IN
HHS ON AGING AND DISABILITY
PROGRAMS.
NIDILRR IS AN ORGANIZATIONAL
UNIT WITHIN ACL, AND IT IS THE
GOVERNMENT'S PRIMARY RESEARCH
AGENCY ON DISABILITY ACROSS THE
LIFESPAN.
SO THE ADMINISTRATION FOR
COMMUNITY LIVING WORKS ON ITS
PRINCIPLES -- IT WAS ACTUALLY
CREATED AROUND THE FUNDAMENTAL
PRINCIPLE THAT OLDER ADULTS AND
PEOPLE OF ALL AGES WITH
DISABILITIES SHOULD BE ABLE TO
LIVE WHERE THEY CHOOSE, WITH THE
PEOPLE THEY CHOOSE, AND WITH THE
ABILITY TO PARTICIPATE FULLY IN
THEIR COMMUNITIES.
AND BY FUNDING SERVICES AND
SUPPORTS PROVIDED BY NETWORKS OF
COMMUNITY-BASED ORGANIZATIONS
AND WITH INVESTMENTS IN
RESEARCH, EDUCATION, AND
INNOVATION, ACL HELPS MAKE THIS
PRINCIPLE A REALITY FOR MILLIONS
OF PEOPLE WITH DISABILITIES.
SO NIDILRR'S MISSION IS TO
SUPPORT THE GENERATION OF NEW
KNOWLEDGE AND PROMOTE ITS
EFFECTIVE USE TO IMPROVE THE
ABILITIES OF INDIVIDUALS WITH
DISABILITIES, TO PARTICIPATE IN
COMMUNITY ACTIVITIES OF THEIR
CHOICE, AND ALSO TO ENHANCE
SOCIETY'S CAPACITY TO PROVIDE
OPPORTUNITIES AND ACCOMMODATIONS
FOR INDIVIDUALS WITH
DISABILITIES.
AS MANDATED BY THE
REHABILITATION ACT, NIDILRR IS
FOCUSED ON THE LONG TERM
OUTCOMES AND EXPERIENCES AND
NEEDS OF INDIVIDUALS WITH THE
MOST SIGNIFICANT DISABILITIES.
AND NIDILRR'S RESEARCH PROGRAMS
ARE INCLUSIVE OF ALL PEOPLE WITH
DISABILITIES ACROSS THE
LIFESPAN.
CHILDREN AND YOUTH, ADULTS, AND
OLDER ADULTS.
AND THIS MEANS IT'S ALL AGE
GROUPS AND ALL DISABILITY
POPULATIONS.
NIDILRR'S SPONSORED ACTIVITIES,
WE HAVE A VERY SMALL BUDGET
COMPARED TO SEVERAL NIH BUDGETS.
WE OPERATE WITH AN ANNUAL BUDGET
OF $119 MILLION.
AND OUR SPONSORED ACTIVITIES,
THERE ARE THREE FOCUS AREAS.
THE RESEARCH AND DEVELOPMENT,
CAPACITY BUILDING, AND KNOWLEDGE
TRANSLATION.
KNOWLEDGE TRANSLATION ACTIVITIES
CAN INCLUDE DISSEMINATION,
TRAINING, AND TECHNICAL
ASSISTANCE.
NIDILRR ALSO HAS THREE MAIN
OUTCOME DOMAINS, AND THEY
INCLUDE: COMMUNITY LIVING AND
PARTICIPATION, EMPLOYMENT, AND
HEALTH AND FUNCTION.
WHILE MOST FEDERAL RESEARCH
ENTITIES FOCUS ON THE PREVENTION
OR CURE OF CHRONIC CONDITIONS
AND DISABILITY, NIDILRR INVESTS
IN RESEARCH THAT IS TIED TO
IMPROVING LONG TERM OUTCOMES FOR
PEOPLE WITH DISABILITIES,
SPECIFICALLY IN THESE DOMAINS.
THE COMMUNITY LIVING AND
PARTICIPATION, EMPLOYMENT, AND
HEALTH AND FUNCTION.
NIDILRR ALSO EVERY FIVE YEARS
DRAFTS A LONG-RANGE PLAN WHICH
IS APPROVED BY THE
ADMINISTRATION, AND I THINK THE
RECENT ONE THAT'S GOING TO BE
PUBLISHED IS INITY FI IN ITS FIS
FOR BEING MADE PUBLICLY
ACCESSIBLE, BUT UNTIL THEN, THE
2018-2023 LONG RANGE PLAN TALKS
ABOUT THE TOLEDO M THREE DOMAINT
NIDILRR FOCUSES ON AND WHAT
ACTUALLY CONSTITUTES THOSE
TOLEDO MAINS.
FOR EXAMPLE, ON THE SLIDE I'VE
INCLUDED MEASUREMENT,
TRANSPORTATION ACCESS,
ACCESSIBLE HOMES, FAMILY
CAREGIVING, ALL FALL UNDER
COMMUNITY LIVING AND
PARTICIPATION.
THESE ARE EXAMPLES.
AND UNDER EMPLOYMENT, WE FOCUS
ON EMPLOYMENT STATISTICS, PEOPLE
WITH PSYCHIATRIC DISABILITY,
EMPLOYMENT DISINCENTIVES AND
EMPLOYER PRACTICES.
HEALTH AND FUNCTION INCLUDES
ADAPTATIONS OF EVIDENCE-BASED
PRACTICE/PROGRAMS, POLICY
IMPACTS ON HEALTHCARE SERVICES,
AND AGING INTO AND WITH
DISABILITY.
AND CROSS-CUTTING DOMAINS
INCLUDE TECHNOLOGY FOR ACCESS
AND FUNCTION AND CAN INCLUDE ANY
OF THE ABOVE TOLEDO MAINS THAT
I'VE JUST MENTIONED.
SORRY FOR THIS MESSY SLIDE.
I DON'T KNOW HOW THE FONT BECAME
SO LARGE, BUT JUST TO GIVE YOU
AN EXAMPLE OF RESEARCH GRANT
PROJECTS BY DOMAIN, WE HAVE
MOSTLY HEALTH AND FUNCTION, 34%
OF THE GRANT PROJECTS ARE IN THE
HEALTH AND FUNCTION DOMAIN, AND
THEN 35% -- I'M SORRY YOU'RE NOT
ABLE TO SEE THAT IN THAT GRAPH,
BUT 35% IS ABOUT CROSS-CUTTING,
WHICH MEANS THAT THESE PROJECTS
FOCUS ON TWO OR MORE DOMAINS.
THEY COULD BE COMMUNITY LIVING
AND PARTICIPATION OR EMPLOYMENT,
OR HEALTH AND FUNCTION.
AND ALSO TECHNOLOGY FOR ACCESS.
PARTICIPATION AND COMMUNITY
LIVING AND EMPLOYMENT ARE 17%
AND 14% RESPECTIVELY.
SO TO SUMMARIZE ACTUALLY, 69%,
ABOUT 69% OF OUR GRANT PROJECTS
FOCUS ON HEALTH AND FUNCTION AND
CROSS-CUTTING DOMAINS.
AND THESE ARE, AGAIN, THE
RESEARCH PROJECTS ARE DIFFERENT
FROM THE DEVELOPMENT PROJECTS
THAT NIDILRR FUNDS, AND HERE
AGAIN WITH THE DEVELOPMENT
PROJECTS, WE AGAIN HAVE HEALTH
AND FUNCTION IS 20%, BUT IF YOU
LOOK AT CROSS-CUTTING TWO OR
MORE DOMAINS, IT'S 49%.
AGAIN, WE HAVE THE SAME TREND OF
ABOUT 69% OF OUR DEVELOPMENT
PROJECTS FUNDED BY NIDILRR ARE
WITHIN THE DOU DOMAINS OF HEALTD
FUNCTION AND CROSS-CUTTING
DOMAINS WHICH INCLUDE HEALTH AND
FUNCTION, EMPLOYMENT, AND
PARTICIPATION IN COMMUNITY
LIVING.
SO NIDILRR HAS 11 GRANT
MECHANISMS AND I'VE LISTED THEM
HERE.
THEY VARY FROM THE 11TH ONE, THE
SWITZER RESEARCH FELLOWSHIP
PROJECTS, THAT'S FUNDING
PROVIDED TO AN INDIVIDUAL TO
REHABILITATION RESEARCH AND
TRAINING CENTERS.
THOSE ARE OUR HIGHLY FUNDED
RESEARCH INITIATIVES, RESEARCH
AND TRAINING INITIATIVES.
WE ALSO HAVE REHABILITATION
ENGINEERING RESEARCH CENTERS.
WE HAVE WHAT'S CALLED THE
DRRPs, THE DISABILITY AND
REHABILITATION RESEARCH
PROJECTS.
NIDILRR ALSO FUNDS MODEL SYSTEMS
OF CARE AND REHABILITATION FOR
TRAUMATIC INJURIES, SPINAL CORD
INJURY, TRAUMATIC BRAIN INJURY,
AND ALSO MAJOR BURN INJURIES.
WE FUND THE ADA NATIONAL
NETWORK.
WE HAVE FIELD-INITIATED
PROJECTS, WHICH ARE SLIGHTLY
SMALLER IN FUNDING AND ALSO THE
ACTUAL STRENGTH OF THE PROJECTS.
AND WE HAVE KNOWLEDGE
TRANSLATION CENTERS, AS
INDEPENDENT CENTERS, ALSO AS
CENTERS SERVING THE MODEL
SYSTEMS, WHICH ARE SPECIFIC TO
THE MODEL SYSTEM ACTIVITIES.
WE HAVE THE SBIRs, PHASE ONE
AND PHASE TWO.
SBIR IS THE SMALL BUSINESS
INNOVATION RESEARCH PROJECTS.
AND WE HAVE ADVANCED
REHABILITATION RESEARCH TRAINING
PROGRAMS, WHICH ARE FOCUSED ON
POSTDOCTORAL TRAINING FOR
PROFESSIONALS IN THE FIELD OF
REHABILITATION.
SO THESE ARE SEVERAL GRANT
MECHANISMS THAT NIDILRR FUNDS,
AND THERE ARE SOME THAT ARE
ANNOUNCED EVERY YEAR AND SOME
ARE -- SOME GO THROUGH THE THREE
AND THE FIVE-YEAR CYCLES.
THE FIELD-INITIATED PROJECTS ARE
ANNOUNCED EVERY YEAR AND, IN
FACT, THE APPLICATIONS ARE DUE
THIS COMING MONDAY.
JUST TO GIVE YOU A COMPARATIVE
UNDERSTANDING OF NIDILRR'S
PROGRAM TYPES WITH NIH, WE HAVE
THE DRRP, THE DISABILITY
RESEARCH REHABILITATION
PROJECTS, THE RE-ENGINEERING
RESEARCH TRAINING AND THE FIELD
INITIATED PROJECTS, AND THE
RETABL TAIREHABILITATION RESEARH
TRAINING, THEY ARE COMPARABLE TO
THE NIH R SERIES.
WE HAVE THE ARRT COMPARABLE TO
THE K SERIES, AND RRTC, THAT'S
THE RESEARCH TRAINING CENTERS,
THAT'S COMPARABLE TO THE T
SERIES.
SWITZER FELLOWSHIPS ARE, AGAIN,
THE F SERIES, VERY SIMILAR TO
THAT.
SO I CAN GO THROUGH THE PROGRAMS
IN BRIEF BUT IN THE INTEREST OF
TIME -- I'D LIKE TO SAVE SOME
TIME FOR QUESTIONS IF YOU ALL
HAVE ANY.
THE SWITZER FELLOWSHIP, LIKE I
MENTIONED, WE HAVE TWO
CATEGORIES THERE WITH THE MERIT
AND THE DISTINGUISHED
FELLOWSHIP, AND ALL THE
INFORMATION CAN BE -- I'LL SHARE
THE WEBSITE WHERE YOU CAN FIND
ADDITIONAL INFORMATION ON SOME
OF THESE PROGRAMS.
AGAIN, THIS IS THE
FIELD-INITIATED PROJECTS.
I SERVE AS THE COMPETITION
MANAGER FOR THEM, AND HERE
AGAIN, IT'S
INVESTIGATOR-INITIATED RESEARCH.
WE HAVE BOTH OUR RESEARCH AND
DEVELOPMENT CATEGORIES, AND IT'S
ABOUT 200,000 PER YEAR FOR THREE
YEARS.
WE HAVE THE DRRPs.
THESE ARE ANNOUNCED SOMETIMES
BASED ON THE DIRECTOR'S
DISCRETION.
SOME OF THE TOPICS ARE
PREDETERMINED.
SOMETIMES IT'S OPEN TO ANY TOPIC
IN THE FIELD OF REHABILITATION.
AND THIS IS $500,000 PER YEAR
FOR THREE TO FIVE YEARS.
AND SINCE THESE VARY, WHEN THE
NOTICE OF FUNDING OPPORTUNITIES
ARE ANNOUNCED, FURTHER
INFORMATION WILL BE SHARED AND
MADE PUBLIC.
AND THE ARRT, ADVANCED
REHABILITATION RESEARCH TRAINING
PROJECTS, THESE AGAIN, AS I
MENTIONED, ARE AT THE
POSTDOCTORAL LEVEL, AND THEY ARE
ANNOUNCED SPECIFICALLY WITH ALL
THE THREE DOMAINS THAT NIDILRR
FOCUSES ON: COMMUNITY,
PARTICIPATION AND LIVING, HEALTH
AND FUNCTION AND EMPLOYMENT.
SO WE HAVE SEPARATE AWARDS FOR
THESE PROJECTS.
AND THESE ARE, AGAIN, $200,000
PER YEAR.
IT'S A FIVE-YEAR AWARD AND,
AGAIN, IT'S COMPETED EVERY YEAR.
THE RESEARCH AND TRAINING
CENTERS, THESE ARE SOME OF OUR
BIGGER GRANTS.
THEY CONDUCT MULTIPLE RESEARCH
PROJECTS AT VARIOUS STAGES, AND
THEY'RE ALSO REQUIRED TO ENGAGE
IN RESEARCH AS WELL AS TRAINING,
DISSEMINATION, AND TECHNICAL
ASSISTANCE.
THEY ARE ALSO COMPETED EVERY
YEAR, AND IT'S $850,000 PER YEAR
ON AVERAGE, AND THEY'RE
FIVE-YEAR AWARDS.
I THINK WE NOW CURRENTLY HAVE
ABOUT 29 ACTIVE RRTCs.
AND WE HAVE THE ENGINEERING
RESEARCH CENTERS AS WELL.
THESE FOCUS ON ADVANCED RESEARCH
AND DEVELOPMENT OF AN
ENGINEERING OR TECHNICAL NATURE
PROJECTS.
THESE ARE, AGAIN, HAVING
MULTIPLE PROJECTS PROPOSED
WITHIN ONE APPLICATION.
AND SOME ARE AGENCY-INITIATED,
SOME ARE FIELD-INITIATED IN
BROAD AREAS OF REHABILITATION
ENGINEERING.
AGAIN, IT'S $925,000 PER YEAR
FOR FIVE YEARS.
WE AWARD TWO TO FIVE PER YEAR,
AND WE HAVE ABOUT 24 ACTIVE RERC
GRANTS NOW.
AND THE MODEL SYSTEMS PROGRAMS,
AGAIN, THEY'RE VERY SPECIFIC TO
THE THREE TRAUMATIC INJURIES I
MENTIONED EARLIER.
WE ALSO HAVE THE SBIRs, PHASE
ONE AND PHASE TWO.
THESE ARE ALSO COMPETED EACH
YEAR, AND THEY HAVE ABOUT -- FOR
THE PHASE ONE, WE FUND ABOUT
$100,000 FOR SIX MONTHS, AND FOR
PHASE TWO, IT'S ABOUT 200 TO
$300,000 PER YEAR, AND IT'S AN
AWARD FOR TWO YEARS.
SO THIS IS THE WEBSITE.
IT'S VERY SIMILAR TO THE NIH
REPORTER.
IT'S AN INTERACTIVE DATABASE.
IT'S A SEARCHABLE DATABASE.
YOU COULD SIGN IN TO NARIC,
WHICH STANDS FOR NATIONAL
REHABILITATION INFORMATION
CENTER.
NARIC.COM.
AND YOU CAN TYPE IN YOUR
KEYWORDS AND GET THE INFORMATION
THAT YOU'RE SEEKING, WHETHER IT
IS FOR FUNDING MECHANISMS OR
PUBLICATIONS OR CURRENTLY
ONGOING RESEARCH PROJECTS,
DISSEMINATION OR TRAINING
PROJECTS, AND EVEN COMPLETED
PROJECTS.
SO YOU CAN FIND STUDIES THAT
WERE FUNDED -- PROJECTS THAT
WERE FUNDED EVEN IN THE 1980s,
WHEN NIDILRR WAS NIDIR AND
BEFORE IT WAS HHS, IT WAS PART
OF DEPARTMENT OF ED.
YOU STILL HAVE HISTORICAL --
IT'S A LOG OF ALL THE STUDIES
THAT WERE FUNDED BY NIDILRR.
SO THIS BRINGS ME TO THE END OF
MY PRESENTATION.
JUST BEFORE I END, IF YOU DO A
SEARCH ON NARIC, AND IF YOU
SEARCH BY THE KEYWORD "MUSCULAR
DYSTROPHY," WE HAVE NOT FOCUSED
SPECIFICALLY ON MUSCULAR
DYSTROPHY PROJECT, BUT THERE
HAVE BEEN SEVERAL PROJECTS THAT
HAVE LOOKED AT THE POPULATION,
LOOKED AT THE CLINICAL
POPULATION IN SOME OF THEIR
BIGGER STUDIES LIKE COMPARING IT
WITH OTHER SIMILAR OR OTHER
ISSUES IN TERMS OF COMMUNITY
LIVING AND PARTICIPATION, AND IN
TERMS OF TECHNOLOGY FOR ACCESS,
AND, IN FACT, WE HAVE ONE
CURRENTLY FUNDED RERC, IT'S A
REHAB ENGINEERING RESEARCH
CENTER, AND THEY ARE HAVING --
YOU WILL FIND -- THEY'RE WORKING
ON SOME VARIABLE TECHNOLOGY, THE
ROBOTICS AND EXOSKELETONS, AND
THERE'S A LOT OF WORK BEING DONE
ON THAT.
AND THEY HAVE INCLUDED SOME
TRIALS, AND THERE IS SOME DATA
AVAILABLE ON THE SUBPOPULATION
THAT THEY ARE LOOKING AT.
SO WE WOULD LIKE TO INCREASE
THIS AWARENESS MORE, SO I'M
HOPING THAT EVEN FOR THE EARLIER
SPEAKER I THINK WAS JUNE WHO WAS
TALKING ABOUT CLINICAL TRIALS
THAT WERE -- YOU'RE NOT ABLE TO
INCLUDE SOME OF THE PEOPLE THAT
YOU WOULD LIKE TO, I THINK THIS
MIGHT BE A GOOD CHANNEL FOR
PROPOSING OR TO EVEN SHARE THIS
INFORMATION WITHIN YOUR NETWORKS
TO MAKE SURE THAT THESE FUNDING
OPPORTUNITIES ARE UTILIZED AND
APPLICATIONS COME IN AND IT
FALLS WELL WITHIN THE PURVIEW OF
COMMUNITY LIVING AND
PARTICIPATION AND EVEN
TECHNOLOGY FOR ACCESS, WITH SO
MUCH OF WORK THAT'S BEING DONE
TO MAKE THE LIVES OF PEOPLE WITH
DISABILITIES TO BE A LITTLE MORE
EASIER AND TO BE ABLE TO LIVE IN
THE COMMUNITY, LIVE
INDEPENDENTLY AND TO ALSO
PARTICIPATE IN THE COMMUNITY.
SO THERE ARE SEVERAL PROJECT
OFFICERS WHO WOULD BE MORE THAN
HAPPY TO TALK WITH YOU ALL.
WE SHARE OUR INFORMATION.
PLEASE REACH OUT TO ME AND I CAN
FORWARD YOUR INFORMATION TO THE
RIGHT SOURCE, AND I CAN ALSO
ENGAGE IN ANY CONVERSATION YOU
ARE WANTING TO GET INFORMATION
ON.
THANK YOU SO MUCH FOR YOUR TIE.
>> THANK YOU SO MUCH,
DR. HOLAVANAHALLI.
AND I REALLY APPRECIATED YOUR
OVERVIEW OF NIDILRR.
THAT WAS REALLY VERY
INFORMATIVE, AND WE'RE TRULY
APPRECIATIVE OF THE PERSPECTIVE
AND THE EXPERTISE THAT YOU ARE
GOING TO BRING TO OUR COMMITTEE.
I THINK WE HAVE TIME FOR ONE OR
TWO QUESTIONS.
DR. NUCKOLLS.
>> THANKS FOR YOUR PRESENTATION.
SO I'M CURIOUS, ARE THERE
FEATURES OF A REHABILITATION
RESEARCH GRANT APPLICATION THAT
WOULD CAUSE TO BE A BETTER FIT
FOR NIDILRR RELATIVE TO THE
NICHD REHABILITATION CENTER?
>> SO WE DO HAVE THE PRIORITIES
WHEN WE ANNOUNCE OUR FINAL
PRIORITY, WE DO MAKE SURE THAT
THERE ARE CERTAIN BASIC THINGS
THAT WE ARE LOOKING FOR IN ANY
APPLICATION.
FOR EXAMPLE, EQUITY,
INTERSECTIONALITY, AND HOW IT
APPLIES TO THE DISABILITY
POPULATION, AND WE ALSO HAVE A
LIST OF SELECTION CRITERIA WHICH
I CAN SHARE WITH YOU.
OF COURSE THESE ARE ALL REVIEWED
AND SCORED BY PEERS WHO ARE
EXPERTS IN THE FIELD.
AND SO WE DO HAVE -- IF IT IS
SPECIFICALLY ANNOUNCED WITH A
TOPIC AREA, THEN WE WILL PROVIDE
MORE DETAILS.
IF NOT, IT JUST GETS COMBINED
INTO THE GENERAL DISABILITY
APPLICATION.
BUT THE FIELD INITIATED
PROJECTS, THAT MECHANISM HAS
DRAWN APPLICATIONS FROM MANY
DIFFERENT AREAS OF DISABILITY
AND MANY DIFFERENT CLINICAL
SUBPOPULATIONS.
SO THAT WOULD BE A GREAT
RESOURCE.
THAT WOULD BE A GREAT VENUE FOR
PROJECTS THAT START OFF AS, SAY,
EXPLORATORY IN NATURE, AND THEN
TO BUILD UPON THAT AND TO TAKE
TO THE NEXT LEVEL OF, SAY,
CLINICAL TRIALS AND, YOU KNOW,
COMPARATIVE STUDIES ACROSS
CENTERS AND ACROSS DIFFERENT
POPULATIONS.
AND SO IT JUST -- IT CAN
TRANSITION, THAT MECHANISM IS
THERE, AND THE SWITZER
FELLOWSHIP IS ANOTHER WAY TO
BUILD CAPACITY IN THE FIELD BY
ENCOURAGING INDIVIDUAL
RESEARCHERS TO APPLY FOR THE
FELLOWSHIP AND TO WORK IN THE
AREA.
SO DIFFERENT MECHANISMS WORK
DIFFERENTLY AS YOU ALREADY KNOW.
WITHIN NIDILRR ITSELF, I THINK
THE BEST MECHANISM TO START
FOCUS IN THIS AREA WOULD BE THE
FIELD INITIATED AND ALSO THE
SWITZERS.
I HOPE I ANSWERED YOUR QUESTION.
SORRY ABOUT THE LONG WINDED
ANSWER.
>> THANK YOU.
DR. KOROSHETZ.
>> I JUST HAVE A KIND OF IN THE
WEEDS QUESTION.
THE APPLICATION DATES FOR THESE
GRANTS, HOW FREQUENT DO THEY
OCCUR?
>> SO THEY ALL HAVE DIFFERENT
CYCLES.
SOME OF THEM, WE COMPETE
ANNUALLY, AND THOSE ARE ALL
TYPICALLY COMING OUT NOW,
THEY'VE STARTED, WE JUST HAD
ANNOUNCED THE SBIRs AND THE
SWITZERS, I THINK THE SWITZERS
ARE DUE COMING UP IN JANUARY,
BUT THE FIELD-INITIATED PROJECTS
ARE DUE ON MONDAY, AND SO THESE
ARE ALL TYPICALLY ANNOUNCED IN
THE MONTH OF OCTOBER OF EACH
YEAR.
WHETHER IT'S THE ANNUAL ONES OR
EVEN THE THREE OR THE FIVE-YEAR
COMPETITIVE CYCLES, COMPETITION
CYCLES ARE ALL ANNOUNCED DURING
OCTOBER.
>> SO I GUESS I WAS THINKING
WHETHER OR NOT WE COULD HELP --
WHETHER IT WOULD BE OF VALUE FOR
US TO HELP PUT THIS OUT IN OUR
SOCIAL MEDIA TO OUR GRANTEES TO
KNOW ABOUT THESE PROGRAMS.
>> DEFINITELY.
THAT WOULD BE REALLY HELPFUL,
AND I THINK NIDILRR WOULD LOVE
THAT, AND WE DO ENGAGE IN
CAPACITY BUILDING AT ALL LEVELS,
SO I THINK THAT COULD BE A GREAT
WAY TO PROMOTE THIS AND MAKE
THIS INFORMATION ACCESSIBLE AND
KNOWN TO A LOT OF FOLKS.
>> SO NEXT OCTOBER.
>> YES.
AND THERE ARE SOME THAT HAVE NOT
YET BEEN ANNOUNCED, AND I CAN
SEND YOU AN EMAIL AND GIVE YOU
AN UPDATE OF THAT.
>> THANK YOU.
OKAY.
LAST QUESTION FROM DAN PEREZ.
>> YES.
EXCELLENT PRESENTATION.
I WAS CURIOUS TO GET YOUR
THOUGHT ON WHETHER -- WHAT TYPES
OF RESEARCH IN ADULT AND
PEDIATRIC MUSCULAR DYSTROPHY
YOUR INSTITUTE WOULD BE BEST
SUITED TO FUND.
SO WHAT KIND OF PROJECTS DO YOU
THINK WOULD BE AN EXCELLENT FIT
FOR YOUR INSTITUTE?
JUST A FEW KIND OF SUGGESTIONS,
MOVING AWAY FROM THE MECHANICS
OF GRANTS AND FUNDING CHANNELS,
JUST CURIOUS TO KNOW WHAT TYPES
OF THINGS YOU FEEL THAT YOUR
INSTITUTE COULD REALLY ADVANCE
KNOWLEDGE IN MUSCULAR DYSTROPHY?
>> SO NIDILRR IS HUGE INVOLVING
STAKEHOLDERS AT ALL LEVELS,
RIGHT FROM THE DECISION OF A
TOPIC FOR A RESEARCH STUDY TO
HOW THAT CAN BE CARRIED OUT, AND
HOW IT IS GOING TO SERVE THE
NEEDS OF PEOPLE WITH
DISABILITIES, AND WE ARE LOOKING
FOR ALL PROJECTS TO MAKE IT
CLEAR THAT THEY ARE WORKING WITH
PEOPLE WITH DISABILITY IN TERMS
OF -- AT ALL STAGES OF THEIR
RESEARCH OR DEVELOPMENT.
AND I'M NOT SURE IF I'M
ANSWERING YOUR QUESTION RIGHT.
IS THAT WHAT YOU MEANT?
DAN?
>> YES.
I WAS GOING TO SAY, JUST -- IT
DOESN'T QUITE ANSWER MY QUEST
QUESTION.
I'M NOT SAYING -- SPECIFICALLY,
WHICH I KNOW IS GENERALLY -- THE
ANSWER, I WAS JUST WONDERING,
YES I TAKE SUCH AND SUCH AND
SUCH WOULD BE A GREAT THING FOR
OUR INSTITUTE TO UNDERTAKE.
SO -- AN OFFLINE DISCUSSION.
SO THANK YOU.
>> THANK YOU.
>> OKAY.
THANK YOU, EVERYONE, FOR YOUR
QUESTIONS.
NEXT WE'RE GOING TO HAVE A
SERIES OF SHORT PRESENTATIONS
SUMMARIZING RECENT CONFERENCES
AND WORKSHOPS OF INTEREST TO THE
MUSCULAR DYSTROPHY COMMUNITIES.
THE FIRST PRESENTATION IS FROM
DR. CAROL TAYLOR-BURDS, WHO IS A
PROGRAM DIRECTOR AT NINDS.
SHE'S GOING TO TELL US ABOUT A
RECENT WORKSHOP ORGANIZED BY
SEVERAL NIH INSTITUTES ON
DIGITAL HEALTH OUTCOMES.
CAROL, ARE YOU WITH US?
>> I AM HERE.
CAN YOU HEAR ME?
>> YES.
THANK YOU.
>> I WILL JUST SHARE MY SLIDE
REALLY QUICKLY.
>> MAYBE A LITTLE CLOSER TO THE
MICROPHONE.
THANK YOU.
THANKS TO THE COMMITTEE AND TO
GLEN FOR THE INVITATION TO
PRESENT.
SO I'M TALKING TODAY ABOUT THE
RECENT WORKSHOP SERIES THAT WE
HAD ON ADVANCING DIGITAL -- END
POINT IN DIGITAL HEALTH
TECHNOLOGIES FOR NEUROLOGICAL
AND NEUROMUSCULAR DISORDERS.
>> SORRY, CAROL, MAYBE A LITTLE
CLOSER TO THE MICROPHONE.
>> IS THAT BETTER?
USUALLY I'M TOO SHORT FOR
MICROPHONES.
THIS ONE, I MIGHT NOT BE.
ALL RIGHT.
SO THIS WAS A COLLABORATIVE
EFFORT BETWEEN NINDS, NICHD, AND
NCMRR IN COLLABORATION WITH
NIAMS AND NATIONAL INSTITUTE ON
AGING AND MENTAL HEALTH AS WELL.
AND WE DID THIS THREE DAY
VIRTUAL WORKSHOP SERIES TO
REALLY BRING TOGETHER GROUPS
ACROSS DISEASES, ACROSS INDUSTRY
PUBLIC PRIVATE PARTNERSHIPS,
INDIVIDUALS WITH LIVED
EXPERIENCE, AND DIFFERENT
STAKEHOLDERS ON THE FUNDING SIDE
TO GET LESSONS LEARNED AND SEE
SOME OF THE BREADTH OF WORK
THAT'S HAPPENING IN DIGITAL END
POINT DEVELOPMENT AND DIGITAL
HEALTH TECHNOLOGIES.
I DON'T THINK I NEED TO
HIGHLIGHT THE IMPORTANCE OF
HAVING GOOD OBJECTIVE OUT COME
ASSESSMENTS FOR THIS COMMITTEE,
AND WE KNOW THE RISE IN DIGITAL
HEALTH TECHNOLOGIES AND END
POINT DEVELOPMENT IS REALLY
EXPONENTIALLY GROWN, ESPECIALLY
WITH THE COVID PANDEMIC.
SO I WANT TO THANK AND RECOGNIZE
ALL OF THE PROGRAM STAFF THAT
WERE INVOLVED IN ORGANIZING THIS
WORKSHOP SERIES, INCLUDING GLEN
AND EMILY WHO ARE HERE.
JUGS TO GIVE YOU AN OVERVIEW OF
HOW THE WORKSHOP SERIES WAS
STRUCTURED, WE HAD A SERIES OF
SPECIAL WORKSHOP TOPICS AND EACH
DAY HAD THREE PARALLEL SESSIONS,
ONE LOOKING AT EXISTING
VALIDATION EFFORTS, ANOTHER ON
THE TECHNOLOGY SIDE, AND A THIRD
ON GAPS AND OPPORTUNITIES,
MULTIPLE CLINICIANS ACROSS
DISEASE AREAS.
THEN WE HAD A COUPLE OF SESSIONS
ON REGULATORY PANEL AND THEN
BREAKOUT SESSIONS ON DAY TWO.
THE THIRD DAY, WE HAD A PUBLIC
PRIVATE PARTNERSHIP DISCUSSION.
SO I'M GOING TO VERY, VERY
QUICKLY HIGHLIGHT A FEW THINGS
FROM THAT WORKSHOP.
AND GO THROUGH ANY QUESTIONS AT
THE END.
SO JUST WANT TO HIGHLIGHT THE
THREE SPECIAL TOPIC TALKS THAT
WE HAD.
AND IN PARTICULAR, MENTION
JENNIFER GOLDSACK, WHO'S FOUNDER
AND CEO OF DIGITAL MEDICINE
SOCIETY WHO KICKED US OFF.
AND IF YOU'RE NOT FAMILIAR WITH
THIS ORGANIZATION, IT'S A
NON-PROFIT WORKING HEAVILY WITH
INDUSTRY AND ACADEMICS, TRYING
TO ADVANCE DIGITAL END POINT
DEVELOPMENT AND DIGITAL MEDICINE
IN GENERAL ACROSS THE GLOBE.
AND THEY'VE DONE A LOT OF WORK,
SHE DID A NICE JOB OF
HIGHLIGHTING SOME OF THE
ACTIVITY THEY'VE BEEN DOING,
REALLY TRYING TO MAKE RESOURCES
AVAILABLE TO UNDERSTAND HOW TO
GET DIGITAL HEALTH MORE
EFFECTIVELY USED, HOW TO GET END
POINTS VALIDATED, AND
HIGHLIGHTING SOME OF THE
CHALLENGES WHERE THEY WORK WITH
A LOT OF INDUSTRY PARTNERS AND
SEE THE VARIETY OF WAYS THAT
INDUSTRY ARE USING EXPLORATORY
DIGITAL ASSESSMENTS AS
EXPLORATORY OR SECONDARY END
POINTS IN TRIALS, EVERYONE IS
USING AN ACCELEROMETER IN A
DIFFERENT WAY, EVERYONE IS
MEASURING SLEEP BUT IN A
DIFFERENT WAY, SO HIGHLIGHTING
SOME OF THE CHALLENGES IN TRYING
TO STANDARDIZE ACROSS HOW
ASSESSMENTS ARE BEING DONE.
AND JUST WANT TO POINT OUT THIS
PLAYBOOK IS A GREAT RESOURCE FOR
ANYONE WHO'S INTERESTED IN
DEVELOPING DIGITAL END POINTS,
ESPECIALLY NOVEL ONES, LOOKING
AT START TO FINISH, WHAT ARE
SOME OF THE EXAMPLES AND WHAT
ARE SOME OF THE THOUGHTS THAT
NEED TO GO INTO HOW YOU DEVELOP
THESE FOR REGULATORY APPROVAL.
SO I'M NOT GOING TO TALK ABOUT
ALL OF THESE, JUST WANT TO
HIGHLIGHT THE SPEAKERS THAT WE
HAD ACROSS ALL THREE DAYS FOR
OUR SESSION ONE.
EACH DAY, WE HAD THE FIRST ONE
ON MOTOR FUNCTION, SECOND WAS ON
SLEEP AND FATIGUE, AUTONOMIC
FUNCTION, AND THEN COGNITION ON
DAY THREE.
SO I'M GOING TO MAKE A COUPLE
POINTS ON JUST A FEW OF THESE
EXAMPLES, BUT A LOT OF SHARED
LESSONS AND COMMON THEMES THAT
CAME OUT FROM ASSESSMENTS ACROSS
ALL THREE LARGE FUNCTIONAL
DOMAINS.
THE FIRST I'M SURE THE GROUP
HERE IS FAMILIAR WITH, THE
STRIDE VELOCITY AT THE 95TH
CENTILE, SV95C, THE FIRST AND SO
FAR ONLY QUALIFIED DIGITAL END
POINT FOR DUCHENNE'S MUSCULAR
DYSTROPHY.
WHAT THE WORK WAS TO GET THIS
QUALIFIED AT EMA, THEY'RE
WORKING ON FDA QUALIFICATION AS
WELL, AND A LOT OF OVERLAP IN
COORDINATION BETWEEN EMA AND FDA
ON REGULATORY EFFORTS HERE.
AND SOME OF THE KEY POINTS ON
HOW THIS IS DONE, IN THIS CASE,
THIS IS A DIGITAL ASSESSMENT
REALLY GOING OFF THE SIX-MINUTE
WALK TEST, BUT A NICE EXAMPLE OF
WHERE YOU CAN SEE REALLY
EFFECTIVE USE OF DIGITAL HEALTH
TECHNOLOGIES, ENABLING MORE REAL
WORLD DATA CHECK SHUP COLLECTIOD
IMPROVING CLINICAL EFFICIENCY
AND CLINICAL TRIALS BY REDUCING
THE VARIABILITY AND SEEING MUCH
SMALLER SAMPLE SIZES NEEDED IN
CLINICAL TRIALS.
THE SECOND TWO I WANT TO
HIGHLIGHT ARE TWO LARGE EUROPEAN
CONSORTIUM.
THESE ARE MULTI-STAKEHOLDER
EFFORTS ACROSS DISEASE AREAS,
AND THAT'S WHAT'S PARTICULARLY
UNIQUE ABOUT THESE.
THEY HAVE QUITE A FEW
INTERNATIONAL PARTNERS, AND
THEY'RE REALLY LOOKING AT TRYING
TO GENERALIZE AND GET SOME OF
THE BASELINE DATA AND UNDERSTAND
WHAT TECHNOLOGIES AND HOW TO
MAKE THESE MEASUREMENTS FOR
MULTIPLE DISEASE AREAS AND
TRYING TO DO IT MORE EFFICIENTLY
BY TAKING A LARGER COHORT AND
LOOKING AT IT ACROSS DISEASES
WHICH CERTAINLY ADDS TO THE
COMPLEXITY OF THE ANALYSIS, BUT
ALALSO MAY BE MORE EFFICIENT IN
THE LONG RUN.
SO JUST QUICKLY SOME KEY THEMES.
OBVIOUSLY PATIENTS AND
PARTICIPANTS NEED TO BE ENGAGED
EARLY TO ENSURE WHAT'S MEASURED
IS MEANINGFUL.
EARLY AND FREQUENT ENGAGEMENT
WITH REGULATORS WAS CERTAINLY
HIGHLIGHTED AS WELL.
WITH REAL WORLD DATA COLLECTION,
OF COURSE THE CONTEXT OF WHAT
DATA IS BEING MEASURED IS
ESSENTIAL TO REALLY UNDERSTAND
AND INTERPRET WHAT THOSE NUMBERS
MEAN.
CERTAINLY SOME CHALLENGES IN
DEVICE SELECTION AND
GENERALIZABILITY.
IN PARTICULAR, A NUMBER OF
GROUPS BROUGHT UP THE FACT THAT
TECHNOLOGY IS ADVANCING SO
QUICKLY THAT WE REALLY NEED
DEVICE AGNOSTIC END POINTS SO
THAT THERE'S SOME STANDARD AND
YOU CAN APLAY THE SAME CLINICAL
OUTCOME ASSESSMENT ACROSS
MULTIPLE DEVICES.
AS THEY ADVANCE.
SO FOR THE TECHNOLOGY SESSION,
AGAIN, I'M JUST GOING TO
HIGHLIGHT THE SPEAKERS THAT WE
HAD FOR ALL THREE DAYS.
AND THEN TWO QUICK EXAMPLES.
SO WHEN WE'RE MOVING INTO
MULTICOMPONENT DIGITAL
ASSESSMENTS, AND NOVEL END POINT
DEVELOPMENT, LOOKING AT NOT JUST
A PARTICULAR CLINICAL CONCEPT
THAT'S BEING MEASURED LIKE
STRIDE VELOCITY, BUT LOOKING AT
A MORE GLOBAL PERSPECTIVE OF
MULTIPLE SYMPTOMS, FUNCTIONS
THAT ARE HAPPENING, THE AMOUNT
OF DATA THAT CAN BE COLLECTED
AND THE NUMBER OF MEASUREMENTS
THAT CAN BE COLLECTED FOR SOME
OF THESE WEARABLES AND
ASSESSMENTS IS ENORMOUS, RIGHT?
HUGE POTENTIAL HERE.
BUT THAT ALSO ADDS TO THE
CHALLENGE OF WHAT'S MOST
IMPORTANT, WHAT'S MOST
MEANINGFUL, AND WHAT'S MOST
PREDICTIVE FOR THE OUTCOME OF
INTEREST.
AND SIMILARLY, AN EXAMPLE
LOOKING AT VOICE AND SPEECH AS A
DIGITAL BIOMARKER CLINICAL
OUTCOME ASSESSMENT, THERE'S A
HIGHLIGHT FROM FRANCESCA CO
CORMACK, THEY'VE LOOKED AT ABOUT
700 DIFFERENT SPEECH VARIABLES
THAT ARE EXTRACTED, SO HUGE
POTENTIAL TO CAPTURE A LOT OF
DIFFERENT ELEMENTS OF COGNITION
AND MOTOR FUNCTION, BUT DEFINING
WHAT'S MOST IMPORTANT FOR
DIFFERENT POPULATIONS IS
CRITICAL.
SO JUST A COUPLE OF THEMES FROM
THE DEVICE USERS.
OBVIOUSLY, AGAIN, THERE'S ALWAYS
THE NEED TO HAVE THE CONSUMERS,
BOTH PATIENTS AND CLINICIANS,
INVOLVED IN THESE DEVICES.
DEVELOPMENT FROM THE EARLY STAGE
SO THAT THEY ARE MOST
EFFICIENTLY DESIGNED FOR THE
USERS IN MIND.
GETTING SUFFICIENT SAMPLE SIZES
CAN BE CHALLENGING FOR THOSE
SMALL DEVICE COMPANIES AS
THEY'RE GETTING STARTED.
OF COURSE THE NUMBER OF FEATURES
AS I JUST HIGHLIGHTED IS
COMPUTATIONALLY CHALLENGING AND
I THINK WE HEARD FROM A FEW
PEOPLE WHERE THEY MIGHT NOT HAVE
THE DATA AVAILABILITY OR THE
STATISTICAL EXPERTISE IN SOME OF
THESE SMALLER COMPANIES THAT ARE
GETTING GOING.
THEN SOFTWARE OUTPUT AND
DISPLAYS REALLY NEED TO BE
SIMPLE AND INTERPRETABLE IF
THERE'S GOING TO BE WIDESPREAD
UPTAKE IN USE.
GOING TO THE THIRD SESSIONS OF
THE THREE PANELS, REALLY
APPRECIATED THE DISCUSSIONS,
THOUGHTFUL DISCUSSIONS FROM ALL
OF OUR CLINICIANS AND REHAB
SPECIALISTS WHO JOINED.
A LOT OF SIMILAR THEMES HERE AS
WELL.
WE'VE TALKED ABOUT
OPPORTUNITIES.
AGAIN, THERE'S I THINK PRETTY
UNIVERSAL RECOGNITION OF THE
POTENTIAL FOR USING DIGITAL OUT
COME ASSESSMENTS FOR REMOTE
MONITORING, RECOGNIZING WE CAN
REALLY REACH INDIVIDUALS WHO
MIGHT NOT BIBLE A -- MIGHT NOT E
TO PARTICIPATE IN TRIALS.
MUCH RICHER AND MORE NUANCED
INFORMATION.
THE INCREASED FREQUENCY THAT
HELPS REDUCE THE INHERENT
STATE-DEPENDENT VARIABILITY FROM
CLINIC ASSESSMENTS.
OF COURSE THE CHALLENGE WE KEEP
TALKING ABOUT ARE THE FEATURES,
WHAT'S MOST MEANINGFUL.
THE COMFORT WITH TECHNOLOGY FOR
SOME POPULATIONS THAT MIGHT NOT
BE AS DIGITALLY LITERAL OR NOT
AS WILLING TO HAVE WEARABLES OR
OTHER DEVICES IN THEIR HOME.
AND THEN CHALLENGES WITH DEVICE
SELECTION.
YOU KNOW, A NUMBER OF CLINICIANS
WE'RE TALKING ABOUT, THERE'S SO
MANY OUT THERE, WHICH IS THE
RIGHT ONE.
AND A FEW GAPS, THERE WASN'T
REALLY A LOT OF CONVERSATION
ABOUT THE GAPS FOR TECHNOLOGIES
THEMSELVES.
OTHER THAN PEDIATRIC, WHICH THIS
GROUP MIGHT BE OF SHARED
INTEREST IS THAT ESPECIALLY ON
THE WEARABLE SIDE, THERE'S MORE
VIDEO ASSESSMENTS BECAUSE THERE
AREN'T MANY WEARABLES DESIGNED
FOR PEDIATRIC OP LAITI POPULATID
PEDIATRIC OUTCOMES.
INCREASING THE ACCESSIBILITY OF
THE TECHNOLOGIES TO BE
DEPLOYABLE IN LOW BANDWIDTH
AREAS IS CERTAINLY HIGHLIGHTED,
AND RE REGULATORY APPROVAL END
POINTS AND LACK OF
STANDARDIZATION.
SO JUST ABOUT DONE HERE.
WITH SESSION FOUR, WE HAD A
REALLY NICE PANEL OF REGULATORS
FROM SEVERAL GROUPS IN THE FDA,
AS WELL AS SUSAN MILLER FROM
CMS.
THEY GAVE SOME OVERVIEWS OF
WHAT'S HAPPENING IN THEIR SPACE
AND SOME OF THE REGULATORY
CONSIDERATIONS AND GUIDANCE
DOCUMENTS THAT ARE OUT THERE.
AND A NUMBER OF COMMON REVIEW
POINTS THAT WERE BROUGHT UP,
PATIENT-CENTERED EVIDENCE OF
CLINICAL MEANINGFULNESS.
EVIDENCE OF FIT-FOR-PURPOSE
VALIDATION, WHAT THE PURPOSE IS
AT EACH STAGE OR EACH CENTER IS
A LITTLE BIT DIFFERENT, BUT
ALWAYS ESSENTIAL TO HIGHLIGHT
AND SHOW.
AND THEN REITERATING THAT THERE
IS A LOT OF GUIDANCE BEING
DEVELOPED CURRENTLY BY THE FDA
FOR THE DIGITAL ASSESSMENTS.
THIS AREA IS REALLY BLOWING UP.
AND THEN GETTING ADVICE FROM THE
FDA OR FROM CMS EARLY AND
FREQUENTLY.
AND THEN FINALLY, OUR LAST DAY
AND LAST SESSION, WITH HE CLOSED
OUT WITH PERSPECTIVES ON
ADVANCING DIGITAL END POINT
DEVELOPMENT ON PUBLIC PRIVATE
PARTNERSHIPS, AND REALLY
APPRECIATED HAVING DIANE
STEPHENSON THERE FROM CRITICAL
PATH INSTITUTE TALKING ABOUT THE
PARKINSON'S DIGITAL EFFORT, AS
WELL AS THE INDUSTRY
REPRESENTATIVES, STEVE HOFFMANN.
AND PENNY DACS HIGHLIGHTED SOME
EFFORTS THAT THEY'VE ALREADY
BEEN WORKING ON COLLABORATING
FOR RESOURCE SHARING BETWEEN FTD
AND ONE OF THE ALS ASSOCIATIONS
TRYING TO SHARE AND POOL
RESOURCES TO GET GROUPS TO COME
TOGETHER TO IDENTIFY END POINTS
THAT ARE OF INTEREST TO BOTH
COMMUNITIES.
SO AGAIN, HIGH ON THAT NEED FOR
REGULATORY APPROVED END POINTS.
OBVIOUSLY THE VALUE OF PUBLIC
PRIVATE PARTNERSHIPS TO ENGAGE
MULTIPLE STAKEHOLDERS.
AND NEED FOR FASTER DEVELOPMENT
AND VALIDATION.
AND OF COURSE NEED FOR DATA
SHARING.
I THINK THE TAKE-HOME AND THE
THOUGHTS, WE WANT TO INCREASE
THE RATE OF TRANSLATION, WE WANT
TO INCREASE THESE DIGITAL
ASSESSMENTS TO BE USEFUL IN
CLINICAL TRIALS, IN CLINICAL
PRACTICE AS QUICKLY AS POSSIBLE.
AND HOW DO WE ACCELERATE THAT.
AND HOW DO ALL OF THE
STAKEHOLDERS COME TOGETHER TO
ACCELERATE THAT.
ESPECIALLY IN THESE LATER STAGE
CLINICAL VALIDATION AREAS, WHERE
THE AMOUNT OF RESOURCES BECOME
MUCH MORE EXTENSIVE, AND IT'S
HARDER TO DO IF YOU'RE DOING IT
ALONE.
AGAIN, AS PEOPLE ARE DEVELOPING
END POINTS, THERE ARE A LOT OF
CRITICAL QUESTIONS THAT NEED TO
BE ANSWERED TO BE SUCCESSFUL.
AND THE MORE THAT GROUPS CAN
COORDINATE AND IDENTIFY SHARED
NEEDS, AND DEFINE THESE UP
FRONT, AND CAN COME TOGETHER TO
DECIDE WHAT THEY ARE, THE BETTER
CHANCE OF SUCCESS THERE IS,
RATHER THAN EACH GROUP DOING IT
ALONE.
FINALLY, YOU KNOW, JUST THE KEY
TAKEAWAYS, YOU KNOW, IMPLEMENT
THE LESSONS FROM EXISTING
EFFORTS.
THIS WAS PART OF THE GOAL OF THE
WORKSHOP, REALLY TO LEARN FROM
EACH OTHER AND LEARN WHAT ELSE
IS HAPPENING ACROSS DIFFERENT
AREAS.
GET MULTIPLE STAKEHOLDERS
INVOLVED.
IDENTIFY SHARED NEEDS.
WE KNOW THAT THESE SMALL END
STUDIES ARE MUCH LESS LIKELY TO
TRANSLATE THAN THE LARGER
EFFORTS THAT ARE GOING TO BE
VALIDATED WITH MORE ROBUST
DESIGN.
AND OF COURSE COLLABORATE,
STANDARDIZE AND SHARE RESOURCES.
SO WITH THAT, I WILL THANK YOU
ALL AGAIN.
ANY QUESTIONS?
>> THANKS, CAROL, FOR LEADING
THE EFFORTS TO ORGANIZE THAT
CONFERENCE AND FOR PROVIDING A
SUMMARY.
WE HAVE TIME FOR JUST ONE
QUESTION.
DR. CRISWELL?
>> I WAS JUST GOING TO MAKE A
COMMENT.
I REALLY APPRECIATE THE SUMMARY
OF THAT MEETING.
SO IMPORTANT FOR THIS COMMUNITY
AND MANY OTHERS.
AND I WOULD HOPE THAT THE
EXPERIENCES OF THE PANDEMIC HAS
REALLY INCREASED INTEREST AND
MOMENTUM AND A SENSE OF URGENCY
ABOUT DEVELOPMENT ALONG THESE
LINES.
SO ANYWAY, WHAT AN IMPORTANT
EFFORT.
THANK YOU SO MUCH FOR THAT
SUMMARY, AND TO THOSE OF YOU
AROUND THE TABLE AND ELSEWHERE
WHO PARTICIPATED.
>> THANK YOU.
>> DAN?
I THINK WE HAVE TIME FOR ONE
MORE QUICK QUESTION.
>> THANK YOU FOR THAT EXCELLENT
PRESENTATION.
I WAS JUST CURIOUS, SITTING HERE
WITH MUSCULAR DYSTROPHY AS A
PATIENT, I WAS JUST CURIOUS OR
TRYING TO UNDERSTAND HOW YOU
INTEGRATE THE PATIENT EXPERIENCE
INTO THE DISCUSSION OF WHERE THE
PATIENT IS IN THIS DISCUSSION.
SO A LOT OF TIMES, I WORRY IT'S
NOT JUST WELL TRAINED, HIGHLY
TRAINED EXPERTS SITTING AROUND
DISCUSSING WHAT IT IS THE
PATIENT SHOULD HAVE OR WHAT IT
IS THAT'S IMPORTANT FOR THE
CLINICAL TRIAL PROCESS WITHOUT
HAVING THE CONSUMER IN THE ROOM.
-- IN THE THEATER.
I WAS JUST CURIOUS TO KNOW HOW
YOU CHECK AND BALANCE THAT WHAT
YOU'RE DRIVING TO ASCERTAIN
DIGITALLY HAS RELEVANCE TO THE
PATIENT EXPERIENCE.
>> THANK YOU FOR THE QUESTION.
ACTUALLY, I THINK IF THERE WAS
ONE -- IF I HAD TO PICK ONE
THEME FROM ALL THREE DAYS, IT
WAS, WE ABSOLUTELY NEED THE
CONSUMERS -- THE INDIVIDUALS
WITH LIVED EXPERIENCE IN THE
ROOM FROM THE BEGINNING, WHETHER
IT'S THE DEVICE DEVELOPMENT OR
IT'S THE END POINT DEVELOPMENT,
AND THAT WAS REITERATED BY THE
REGULATORS, BY THE PRIVATE
PARTNERS, AND BY THE RESEARCHERS
AND CLINICIANS, JUST RECOGNIZING
THAT, YOU KNOW, WE CAN'T --
MEANINGFUL NEEDS TO HAVE THE
CONSUMER VOICE.
>> THANKS, CAROL.
SO THE NEXT PRESENTATION WILL BE
FROM JUNE KINOSHITA FROM THE FSH
SEW SIDE AND SHE'LL TELL US
ABOUT THE INTERNATIONAL RESEARCH
CONFERENCE AND SOME OTHER
EVENTS.
JUNE?
>> YES, THANK YOU SO MUCH FOR
INVITING US TODAY.
WE'VE BEEN ASKED TO REPORT ON
THE INTERNATIONAL RESEARCH
CONGRESS.
UNFORTUNATELY I DID NOT HAVE
ACCESS TO DATA SLIDES SO I'M
GOING TO TALK THROUGH THE
SESSIONS, GIVE YOU A 10,000-FOOT
VIEW, THAT I HOPE WILL GIVE YOU
KIND OF A GENERAL SENSE OF THE
LEVEL OF ACTIVITY AND THE TYPES
OF AREAS THAT ARE -- WERE DEEMED
REALLY INTERESTING BY OUR
PROGRAM COMMITTEE.
FIRST I WANTED TO HIGHLIGHT AS
PART OF THE GREATER CONTEXT IN
WHICH ALL THIS WORK IS HAPPEN
HAPPENING, WHERE WE ARE IN
THERAPY DEVELOPMENT.
THIS HAS CHANGED DRAMATICALLY
OVER THE LAST FEW YEARS.
YOU CAN SEE FROM OUR PIPELINE
DIAGRAM THAT WE HAVE THREE
COMPOUNDS NOW IN CLINICAL
TRIALS.
A PHASE THREE, TWO PHASE 1/2 AND
THERE'S THREE ADDITIONAL
COMPANIES THAT ARE PLANNING TO
LAUNCH PHASE 1/2 TRIALS NEXT
YEAR.
SO THAT INFORMS A LOT OF THE
DIRECTION THAT WE NEED TO GO AS
A SOCIETY.
SO OUR INTERNATIONAL RESEARCH
CONGRESS TOOK PLACE THIS PAST
JUNE IN MILAN, ITALY.
YOU CAN SEE THAT WE HAVE A
GROWING NUMBER OF
BIOPHARMACEUTICAL COMPANIES
INVOLVED IN ATTENDING AND
SPONSORING THE MEETING.
AND WE HAD 240 PARTICIPANTS.
160 IN PERSON AND ABOUT 80
VIRTUAL.
THERE WERE 15 COMPANIES WHO
ATTENDED.
WE HAD 26 ORAL PRESENTATIONS, A
PANEL DISCUSSION, AND
73 POSTERS.
AND PRIOR TO THE MEETING, THE
DAY BEFORE, WE HAD AN INDUSTRY
COLLABORATIVE MEETING WITH I
THINK MAYBE 40 KEY OPINION
LEADERS AND INDUSTRY
REPRESENTATIVES, PATIENT
ADVOCACY REPRESENTATIVES.
AND THE DAY AFTER THE MEETING,
WE HAD A WORLD ALLIANCE MEETING
OF FSHD PATIENT ADVOCACY
ORGANIZATIONS FROM MORE THAN TWO
DOZEN COUNTRIES.
SO OUR 2023 IRC ORGANIZING
COMMITTEE WAS CHAIRED BY DAVIDE
AND NICOL.
WE ALWAYS HAVE A BASIC
RESEARCHER AND CLINICAL
RESEARCHER CHAIR THESE
COMMITTEES.
IT WAS ONE OF OUR MOST DIVERSE
TO DATE.
WE HAD COMMITTEE MEMBERS FROM
ARGENTINA, BELGIUM, TURKEY,
NETHERLANDS, ITALY, AND U.S.
I THINK THAT THE GROWING
INTERNATIONAL PARTICIPATION IS
VERY IMPORTANT, ESPECIALLY IN A
RARE DISEASE.
OUR UNOFFICIAL THEME THIS YEAR
WAS PEDIATRIC FSHD.
FOR THE FIRST TIME WE HAD A
SESSION DEVOTED TO THIS TOPIC.
AND OUR OPENING KEYNOTE WAS
GIVEN BY JAYA MOTTA, AN ITALIAN
COLLEGE STUDENT STUDYING
BIOMECHANICS.
HE WAS ADOPTED AS AN INFANT FROM
NEPAL AND DIAGNOSED WITH EARLY
ONSET FSHD.
HE HAS USED A WHEELCHAIR SINCE I
THINK AROUND THE AGE OF 14, AND
HE CREDITS PHYSICAL THERAPY FOR
HIS CURRENT HEALTH AND POSITIVE
ATTITUDE.
HE'S WORKING ON A DEGREE IN
ENGINEERING AND HE HOPES TO BE
INVOLVED IN INVENTING
TECHNOLOGIES TO HELP PEOPLE WITH
DISABILITIES.
SO HE HAS A PURPOSE, HE HAS A
VERY SUPPORTIVE ITALIAN FAMILY.
AND I THINK HIS STORY
ILLUSTRATES THE IMPORTANCE OF
LOOKING AT MULTIPLE FACTORS THAT
GO INTO WELL-BEING.
AND THAT'S ALSO A POINT THAT WAS
UNDERSCORED BY OUR FIRST KEYNOTE
SPEAKER, BAZIEL VAN ENGELEN.
BAZIEL PROVIDED A BEAUTIFUL
REVIEW OF THE WORK BY THE DUTCH
OVER THE PAST DECADE.
THEY HAVE BEEN AT THE FOREFRONT
OF FSHD RESEARCH, LEADING THE
WAY IN GENETICS, MRI AND
ULTRASOUND IMAGING, AND TRIAL
READINESS WITH ADULT AND
PEDIATRIC NATURAL HISTORY
STUDIES NOW WITH 10 YEARS OF
DATA.
HE ALSO PRESENTED A BROADER VIEW
OF FSHD AS NOT JUST AN ORGANIC
DISEASE OF MUSCLE BUT AN
EXPERIENCE OF ILLNESS.
PAIN, FATIGUE, ANXIETY AND SLEEP
DISTURBANCE BY INDIVIDUALS ALONG
WITH THE ADDED BURDEN PLACED ON
THEM BY SOCIETY.
THE DUTCH RESEARCHERS HAVE LED
THE WAY IN STUDYING
INTERVENTIONS SUCH AS EXERCISE
AND COGNITIVE BEHAVIORAL THERAPY
TO REDUCE FATIGUE, TARGETED
PHYSICAL THERAPY TO ADDRESS
ISSUES LIKE SHOULDER DYSKINESIA
AND MENTAL HEALTH INTERVENTIONS
FOR BOTH ADULTS AND CHILDREN TO
REDUCE THE BURDEN OF DISEASE.
ANOTHER IMPORTANT POINT MADE BY
DR. VAN ENGELEN SHOWN IN THIS
DIAGRAM HERE IS THAT TO BE
EFFECTIVE IN DEVELOPING BETTER
TREATMENTS, IT'S IMPORTANT TO
CONSIDER FSHD FROM THE
PERSPECTIVE OF MANY
STAKEHOLDERS.
OUR SECOND PRESENTATION WAS
GIVEN BY BENEDICTE CHASZAUD IN
LEON, FRANCE.
SHE PRESENTED HER EXTENSIVE
RESEARCH ON THE ROLE OF THE
IMMUNE SYSTEM IN NORMAL MUSCLE
REGENERATION, AND IN DUCHENNE
MUSCULAR DYSTROPHY.
HER STUDIES FOCUSED ON
MACROPHAGES, WHICH INITIALLY
EXHIBIT PRO-INFLAMMATORY
PROPERTIES TO CLEAN OUT DAMAGED
MUSCLE TISSUE, AND THEN LATER
SWITCHED TO REGENERATION
FAVORING TYPE THROUGH CYTOKINE
AND GROWTH FACTORS.
AND A GROWING BODY OF EVIDENCE
SUGGESTS THESE MECHANISMS MAY
ALSO BE ALTERED IN FSHD.
OUR FIRST SESSION ON DISEASE
MECHANISM -- DISCOVERY RESEARCH
AND GENETICS WAS CHAIRED BY
DAVIDE AND DARKO.
IDUX HSA EXPRESSES MOUSE DUX IN
MYOFIBERS.
COMPARED TO CURRENT FSHD MOUSE
MODELS BASED ON HUMAN DUX4 GENE
EXPRESSION.
THESE DATA INDICATE THE MOUSE
AND HUMAN PROTEINS DRIVE SIMILAR
PATHOLOGICAL PATHWAYS IN VIVO.
INTERPLAY BETWEEN DUX4 AND
HERPES VIRUS IN VITRO AND IN
VIVO.
THAT WAS INTRIGUING BECAUSE IT'S
THOUGHT THAT FSHD INVOLVES AN
INTERPLAY OF THE GENETIC -- WITH
SOME SORT OF ENVIRONMENTAL HIT
OR OTHER GENETIC HITS.
AMELIA FOX FROM ST. LOUIS
UNIVERSITY DISCUSSED THE SIX
PROTEIN AS KEY REGULATORS OF
DUX4 GENE EXPRESSION.
MACWDR5 CHROMATIN REMODELING
PROTEIN AS A POTENTIAL DRUGGABLE
TARGET FOR FSHD.
652 PREVIOUSLY UNKNOWN
INTERGENIC LOCI ACTIVATED BY
DUX4, OF WHICH HALF CONTAIN
POTENTIAL DUX4 BINDING SITES.
THESE FINDINGS CAN BE UTILIZED
TO IDENTIFY POTENTIAL NOVEL
BIOMARKERS FOR DISEASE
DIAGNOSIS, PROGRESSION AND
THERAPEUTIC INTERVENTION.
JOEL CHAMBERLAIN FROM THE
UNIVERSITY OF WASHINGTON
DISCUSSED A NOVEL FSHD BIOMARKER
INITIATED BY GENE EXPRESSION
PROFILING OF A MOUSE MODEL
EXPRESSING DUX4.
NEUTROPHIL ACTIVATION WAS
IDENTIFIED AS AN ALTERED
PATHWAY, AND SIMILAR PATTERNS
WERE SEEN IN FSHD PATIENTS AS
COMPARED TO CONTROLS.
FINALLY, IN THE SESSION, RICHARD
PRESENTED RESULTS ON FSHD
MOLECULAR TESTING CONDUCTED IN
INDIA.
THE RESULTS SUGGEST THAT PEOPLE
OF INDIAN DESCENT HAVE LOWER
CLINICAL SUSCEPTIBILITY THAN
EUROPEAN-BASED PATIENTS.
BASED ON THE SIZE OF THEIR FSHD
1 ALLELE REPEAT.
AND LARGER EPIDEMIOLOGICAL STU
STUDIES IN MORE DIVERSE
POPULATIONS COULD INFORM ABOUT
POTENTIAL FACTORS AFFECTING FSHD
SUSCEPTIBILITY.
IN OUR SECOND SESSION THAT WAS
MODERATED BY KATE EICHINGER AND
MAW ROW MONFORTE, TALKS PROVIDED
AN OVERVIEW OF DIFFERENT
TECHNIQUES THAT ARE BEING
DEVELOPED TO ASSESS THE SEVERITY
OF PROGRESSION OF FSHD.
COMPARING ULTRASOUND AND MRI IN
A LONGITUDINAL STUDY.
RESULTS SUGGEST THAT ULTRASOUND
IS BETTER IN DETECTING EARLY
MUSCLE CHANGES, WHILE MRI
APPEARS MORE SENSITIVE AT
TRACKING CHANGES MORE
INTERMEDIATELY AN IN SEVERELY
AFFECTED MUSCLES.
FINDINGS OF A 24 MONTH
LONGITUDAL MRI STUDY THAT FOUND
PROMISING CORRELATIONS BETWEEN
CLINICAL AND MRI ASSESSMENTS.
IN ADDITION, THE PRESENCE OF --
CONFIRMED PREVIOUS FINDINGS THAT
CORRELATE EDEMA AND SUBSEQUENT
TEASE PROGRESSION.
DISEASE PROGRESSION.
CHEN OF THE CHILDREN'S NATIONAL
MEDICAL CENTER IN WASHINGTON
FOCUSED ON CIRCULATING
BIOMARKERS DESCRIBING
DIFFERENTIALLY EXPRESSED
PROTEINS AND MICRORNAs BETWEEN
PATIENTS AND CONTROLS IN A
COHORT OF EARLY ONSET FSHD
SUBJECTS.
AND A NUMBER OF PROMISING
CANDIDATES WERE IDENTIFIED AND
THEIR VALIDATION IS PENDING.
IN OUR THIRD SESSION, ON DISEASE
MECHANISM AND INTERVENTIONAL
STRATEGIES, THAT'S SESSION WAS
CHAIRED BY ALEXANDRA AND ALBERTO
ROSA.
STUDIES HIGHLIGHTED THE
POTENTIAL ROLE OF THE IMMUNE
SYSTEM IN FSHD.
TRANSCRIPTOMIC AND HISTOLOGICAL
ANALYSES OF FSHD PATIENT
BIOPSIES.
THE CLINICAL SEVERITY CORRELATED
WITH MARKERS OF QUIESCENT
SATELLITE CELLS AND EARLY BUT
NOT LATE MYOGENESIS.
WHICH SUGGESTS INCOMPLETE MUSCLE
REGENERATION IN FSHD PATIENTS.
PROTEIN PARTNERS THAT COPURIFY
WITH DUX4 OR ITS HOMOLOGUE, DUX4
C, AND PROPOSED A DUX4
COMPETITION FOR PROTEIN PARTNERS
MIGHT BE A NEW TOXICITY
MECHANISM IN FSHD.
E3 UBIQUITIN LIGASE AS A PROTEIN
PARTNER OF DUX4, AND PRESENTED
DATA SUGGESTING THAT DUX4 COULD
BE EU BIC NATEED AND DEGRADED BY
THE PROTEASOME.
SCOTT HARPER OF NATIONWIDE
CHILDREN'S HOSPITAL CONCLUDED
THE SESSION WITH A TALK ON THE
DEVELOPMENT OF A CRISPR COMPLEX
COMPRISING OF DEAD CAS13 THAT
TARGETS RNA INSTEAD OF DNA.
AND WHEN INFUSED TO ADAR, A BASE
MODIFYING ENZYME, THE AUTHORS
AIM TO INTRODUCE STOP CODONS
INTO THE DUX4 MRNA.
THEREBY PREVENTING THE SYNTHESIS
OF THE TOXIC DUX4 PROTEIN.
IN OUR FOURTH SESSION, MODERATED
BY NICOL AND PIRAYE, THEY
PRESENTED SOME ONGOING AND
PLANNED TRIAL DESIGNS IN FSHD.
LEO WANG AND MARIE HELEN
PRESENTED THE RESULTS OF THE
REDUCTDUX4 WITH A P38 KINASE
INHIBITOR.
THEY PROVIDED DETAILS ON A 48
WEEK PLACEBO CONTROLLED AND
FOLLOW ON 48 WEEK OPEN LABEL
EXTENSION OF THE PHASE TWO
TRIAL.
A TOTAL OF 76 PATIENTS AND
CONTROLS WERE FOLLOWED FOR
96 WEEKS.
CHANGES IN A FUNCTIONAL OUT COME
CALLED REACHABLE WORK SPACE OR
RWS INDICATED SLOWING OF DISEASE
PROGRESSION.
AND RWS FOR THOSE OF YOU WHO
AREN'T FAMILIAR WITH IT,
QUANTIFIES THE CHANGE OF MOTION
OF THE ARMS IN THREE-DIMENSIONAL
SPACE.
PHASE 3 PLACEBO CONTROLLED 48
WEEK TRIAL CALLED REACH HAS
SINCE BEEN LAUNCHED, AND WITH A
PRIMARY END POINT OF REACHABLE
WORK SPACE AND SECONDARY END
POINTS OF MUSCLE FAT FACTION AND
MUSCLE FAT INFILTRATION.
AND THAT STUDY COMPLETED
ENROLLMENT THIS PAST SEPTEMBER.
IT'S A 48-WEEK TRIAL AND WITH
DATA COLLECTION THEN EXPECTED TO
BE COMPLETED BY AUGUST OF 2024.
AMY OF AVIDITY BIOSCIENCES
PRESENTED THE TRIAL DESIGN FOR
FORTITUDE, A STUDY OF AOC1020,
AN ANTIBODY OLIGONUKE CLEE TIED
CONGREGATE THAT CONSISTS OF DUX4
TARGETING SI RNA LINKED TO A
HUMANIZED ANS TRANSFERRIN
RECEPTOR ANTIBODY.
FORTITUDE IS A DOUBLE BLIND
PHASE 1/2 TRIAL IN 72
GENETICALLY CONFIRMED FSHD 1 AND
FSHD 2 ADULT PATIENTS.
THE PRIMARY END POINTS OF THE
STUDY ARE SAFETY AND
TOLERABILITY.
AND EXPLORATORY BIOMARKER
READOUTS INCLUDE MRI AND DUX4
REGULATED GENE PANELS, AS WELL
AS CLINICAL END POINTS
CONSISTING OF REACHABLE WORK
SPACE AND VARIOUS FUNCTIONAL
MOBILITY AND STRENGTH
MEASUREMENTS.
THE THIRD TRIAL DESCRIBED WAS BN
BEHALF OF ROCHE PHARMACEUTICALS.
THIS WAS A TRIAL OF GYM329, A
LONG LASTING MONOCLONAL
ANTIMYOSTATIN ANTIBODY.
THE TRIAL WAS CALLED MANEUVER,
AND IT'S IN A PHASE 3 -- I'M
SORRY -- PHASE 2 PLACEBO
CONTROLLED DOUBLE BLIND STUDY IN
AMBULATORY ADULTS WITH
GENETICALLY CONFIRMED FSHD 1 AND
FSHD 2.
PARTICIPANTS WILL BE
ADMINISTERED THE DRUG
SUBCUTANEOUSLY EVERY FOUR WEEKS
FOR A TOTAL OF 52 WEEKS.
AND THE ASSESSMENTS INCLUDE
PHARMACOKINETIC MEASURES FOR
SAFETY AND TOLERABILITY WITH A
PRIMARY END POINT OF CHANGES IN
CONTRACTILE MUSCLE TISSUES A
MEASURED BY MRI AS WELL AS
EXPLORATORY FUNCTIONAL END
POINTS SUCH AS REACHABLE WORK
SPACE.
RECRUITMENT FOR THAT TRIAL IS
ONGOING.
THE FINAL PRESENTATION IN THE
SESSION WAS BY DELILAH IN
FRANCE.
SHE PRESENTED RESULTS FROM A
PERSONALIZED NEUTROCEUTICAL
STUDY AIMED AT MITIGATING THE
OXIDATIVE STRESS RESPONSE SEEN
IN FSHD.
IN THEIR PILOT TRIAL IN 54
PATIENTS, THESE PERSONALIZED
COMBINATIONS OF ANTIOX TANT
DREETMENTS REDUCED MARKERS OF
OXIDATIVE STRESS, INCREASED
ENDOGENOUS ANTIOXIDANT DEFENSES,
AND IMPROVED FUNCTIONAL
OUTCOMES, SUCH AS A 2-MINUTE
WALK TEST AND MAXIMUM ISOMETRIC
VOLUNTARY CONTRACTION, AND
ENDURNSENDURANCE OF QUADRICEPS .
IN A THREE-YEAR LONGITUDAL STUDY
CALLED PERSPECTIVE, HAFT OF THE
74 PARTICIPANTS WHO MAINTAINED
THE REGIMENT OF SUPPLEMENTS
SHOWED STABILIZATION ACROSS SOME
OF THESE FUNCTIONS.
AND CURRENTLY HER GROUP IS
DEVELOPING SOFTWARE TO CUSTOMIZE
SUPPLEMENT REGIMENS FOR
INDIVIDUAL PATIENTS.
THE 2023 CONGRESS CONCLUDED WITH
A SPECIAL SESSION ON PEDIATRIC
FSHD, A NEGLECTED AREA OF
RESEARCH WITH SIGNIFICANT
POTENTIAL IMPACT FOR FUTURE DRUG
DEVELOPMENT.
CORY HIGHLIGHTED A
MULTI-YEARLONG TEUDAL PEDIATRIC
FSHD STUDY IN THE NETHERLANDS.
IN THE TWO-YEAR PERIOD, 95% OF
PEDIATRIC PATIENTS MANIFESTED
FACIAL WEAKNESS AND 40% SHOWED
SCAPULAR WEAKNESS ALONG WITH
ADDITIONAL MUSCULAR
MANIFESTATIONS SUCH AS IMPAIRED
HEARING AND IRREGULAR EKGs.
RESULTS FROM FIVE YEAR FOLLOW-UP
ARE BEING PREPARED FOR
PUBLICATION.
IN ADDITION, AN EIGHT-YEAR STUDY
IS NOW BEING PLANNED.
ROYAL CHILDREN'S HOSPITAL
MELBOURNE PRESENTED WORK ON
ADAPTING FOR PEDIATRIC PATIENTS
THE FSHD COM, A COMPOSITE
MEASUREMENT OF MOTOR COMPONENTS
IN ADULTS.
THEIR STUDIES SHOWED HIGH
TEST/RE-TEST RELIABILITY ALONG
WITH SIGNIFICANT CORRELATIONS
WITH OTHER FUNCTIONAL IMAGING
AND QUALITY OF LIFE MEASURES.
LONGITUDAL VALIDATION AND
CLINICAL INTERPRETATION OF THESE
MEASURES ARE ONGOING.
AND THE SESSION CONCLUDED WITH A
PANEL DISCUSSION ON THE STATUS
AND PRIORITIES FOR ADVANCING THE
UNDERSTANDING OF PEDIATRIC FSHD,
AND FEEDBACK FROM THE AUDIENCE
STRONGLY SUPPORTED THE NEED FOR
MORE EXTENSIVE WORK IN THIS AR
AREA.
NOW AS A DIRECT OUTCOME OF THE
SESSION, THE CANADIAN COMPANY
SOLVE FSHD REACHED OUT TO A
GROUP OF PARENTS WITH FSHD TO
ORGANIZE A WORKSHOP.
THE MEETING WAS HELD AT THE END
OF SEPTEMBER THIS YEAR AND
BROUGHT TOGETHER PEDIATRIC
RESEARCH LEADERS, COMPANIES AND
REGULATORY EXPERTS TO DISCUSS
HOW TO ENSURE THAT CHILDREN WITH
FSHD WILL HAVE ACCESS TO NEW
THERAPIES.
SOME KEY TAKEAWAYS FROM THAT
WORKSHOP INCLUDED THE IDEA THAT
EARLY INTERVENTION IS DESIRABLE,
THAT COMPANIES DO WANT TO TREAT
CHILDREN AND ARE SEEKING A PATH
FORWARD, THAT MORE ROBUST
NATURAL HISTORY DATA AND THE
DEVELOPMENT OF PEDIATRIC TRIAL
OUT KOUTCOMES WOULD BE IMMENSELY
HELPFUL IN THIS, AND THAT
INNOVATIVE TRIAL DESIGNS SHOULD
BE CONSIDERED.
I ALSO WANTED TO MENTION THAT
BECAUSE OF THE RAPID GROWTH IN
THE NUMBER OF CLINICAL TRIALS
AND THE FILLING UP OF OUR
PIPELINE, THE FSHD CLINICAL
TRIAL RESEARCH NETWORK HAS
EXPANDED SIGNIFICANTLY OVER THE
PAST YEAR.
IT CURRENTLY INCLUDES 15 SITE IN
THE UNITED STATES, INCLUDING
THIS YEAR FOR THE FIRST TIME A
PEDIATRIC CENTER THAT WOULD BE
NATIONWIDE CHILDREN'S HOSPITAL
IN COLUMBUS.
THERE ARE THREE SITES IN CANADA
NOW, SEVEN IN THE U.K. AND E.U.,
ONE IN YOU A STRAIL JA, ONE IN
BRAZIL AND THERE ARE NINE
POTENTIAL NEW SITES UNDER
CONSIDERATION.
IN ADDITION, WE HAVE BEEN
WORKING VERY CLOSELY TO SUPPORT
PATIENT ADVOCACY IN COUNTRIES
AROUND THE WORLD.
I THINK WE NOW HAVE 29 MEMBERS
IN THE WORLD FSHD ALLIANCE, AND
WE WORK WITH THEM TO SUPPORT
THEIR EFFORTS IN PATIENT
EDUCATION AND ENGAGEMENT,
CLINICIAN ENGAGEMENT, REGISTRIES
IN RESEARCH, AND NOW AS WE
APPROACH THE POSSIBILITY OF
DRUGS COMING ON THE MARKET IN
THE U.S. AND SOON IN EUROPE, WE
NEED TO WORK WITH THEM ON
ADVOCACY TO MAKE SURE THAT THEY
CAN SPEED UP REGULATORY APPROVAL
AND ACCESS TO THERAPIES IN OTHER
COUNTRIES AS WELL.
SO, WE HAVE SCHEDULED OUR 2024
INTERNATIONAL RESEARCH CONGRESS
AND OUR BIANNUAL FSHD CONNECT
PATIENT CONFERENCE THAT WILL
TAKE PLACE DECEMBER.
I'M SORRY, IN DENVER, COLORADO
JUNE 13TH AND 14TH AND CONNECT
IS ON THE 15TH AND 16TH.
SO SAVE THE DATE.
AND THE MORE DETAILS ABOUT THE
CONGRESS THAT I JUST ZIPPED
THROUGH SO FAST ARE AVAILABLE IN
A RECENTLY PUBLISHED ARTICLE IN
NEUROMUSCULAR DISORDERS, WHICH
YOU CAN DOWNLOAD FOR FREE USING
THIS QR CODE UNTIL JANUARY 6TH.
THANK YOU SO MUCH.
>> THANK YOU, DR. KINOSHITA.
I DID WANT TO MENTION THAT YOUR
COMMENT ABOUT PEDIATRIC CLINICAL
TRIALS, ACE MENTIONED REALLY
RESONATED WITH ME, AND I FORGOT
TO MENTION THAT WE HAVE BEEN
EXPLORING THERAPY IN YOUNG
CHILDREN AT THE CLINICAL CENTER
AT THE NIH.
SO THERE'S BEEN A GROUP OF
REPRESENTATIVES FROM MULTIPLE
DIFFERENT INSTITUTES AND CENTERS
AT THE NIH, REALLY EXPLORING
WHAT THE NEEDS ARE IN TERMS OF
INFRASTRUCTURE AND SAFETY
CONSIDERATIONS, BUT IT SOMETHING
WE HOPE WE'LL BE ABLE TO PUT
ANOTHER PIN ON YOUR MAP TO SAY
THAT THERE WOULD BE
OPPORTUNITIES FOR CLINICAL
TRIALS IN CHILDREN FOR THE
MUSCULAR DYSTROPHIES.
>> THAT WOULD BE GREAT.
WE'D LOVE TO KEEP IN TOUCH WITH
THAT ABOUT THAT.
I DO ALSO WANT TO MENTION THE
PREVIOUS SPEAKER ABOUT --
SPEAKING ABOUT DIGITAL HEALTH,
YOU KNOW, AND REMOTE ASSESSMENTS
AND SO ON, AND THAT WAS --
THAT'S AN AREA OF GREAT INTEREST
FOR THIS PEDIATRIC GROUP
OBVIOUSLY BECAUSE IN A RARE
DISEASE, A RARE SUBSET AMONG
RARE DISEASE, THE FAMILIES ARE
FAR BETWEEN, IT'S NOT EASY FOR
THEM TO TRAVEL TO STUDY SITE,
AND KIDS EVEN MORE THAN ADULTS
MAY HAVE THEIR UPS AND DOWNS,
AND TO BE ABLE TO HAVE
ASSESSMENTS THAT THEY CAN USE,
MAYBE THAT'S EVEN FUN FOR THEM
TO USE, THEY MIGHT THINK OF IT
AS A GAME, COULD BE A GAME
CHANGER.
>> GREAT.
WELL, THANK YOU VERY MUCH FOR
THAT.
THAT VERY INFORMATIVE
PRESENTATION.
I THINK BECAUSE WE'RE ACTUALLY
SUPPOSED TO BE AT A BREAK NOW
AND WE STILL HAVE ONE MORE
SPEAKER, WE'RE GOING TO HOLD
QUESTIONS AND IF YOU'RE IN THE
ROOM, MAYBE WE CAN MAKE A LIST
OF QUESTIONS THAT WE COULD
HANDLE IF WE HAVE A GAP LATER ON
IN THE MEETING.
SO THE NEXT SPEAKER IS DR. ANDY
ROHRWASSER, WHO IS GOING TO
PROVIDE A SUMMARY OF THE
MYOTONIC DYSTROPHY FOUNDATION'S
ANNUAL COMBINED RESEARCH AND
FAMILY CONFERENCE THAT WAS HELD
IN WASHINGTON, D.C.
DR. ROHRWASSER?
>> THANK YOU VERY MUCH, AND
THANK YOU FOR THE INVITATION,
AND I'M NEW TO THIS GROUP.
I'M A HUMAN GENETICIST, MY
BACKGROUND IS HUMAN GENETICS,
AND I JUST TRANSITIONED TO A
CHIEF SCIENTIFIC OFFICER
POSITION WITH THE MYOTONIC
FOUNDATION.
THE LEADING GLOBAL ADVOCACY
GROUP HELPING PATIENTS AND
FAMILY NAVIGATE THE COMPLEX
ENVIRONMENT OF THE DISEASE, AND
WE ARE ALSO OFTEN THE FIRST
RESOURCE THAT IS CONTACTED BY
NEWLY DIAGNOSED PATIENTS.
IN LIGHT WITH THE MISSION,
RIGHT, TO SUPPORT AND CONNECT
THE COMMUNITY AND TO ACCELERATE
RESEARCH AND TREATMENT, WE HOLD
AN ANNUAL CONFERENCE AND AS
DR. BIANCHI SAID, THIS YEAR'S
CONFERENCE WAS HELD IN
WASHINGTON, D.C. IN SEPTEMBER.
RATHER THAN GOING INTO RATTLING
OFF SCIENTIFIC DEAL TAILS, THE E
LINKS ARE ON MY SLIDES, I WANT
TO HIGHLIGHT ON A COUPLE OF
THEEMTTHEMES THAT ARE REALLY, RY
IMPORTANT.
SO OUR CONFERENCE WAS THE 15TH
ANNUAL EVENT.
WE HAD RECORD PARTICIPATION.
MORE THAN 500 PEOPLE ATTENDED.
IT WAS HELD FOR THE SECOND TIME
IN A HYBRID FORMAT.
AND MOST EXCITINGLY, THERE WERE
OVER 200 PROFESSIONALS.
THE THEME HERE IS REALLY THAT
THE CONFERENCE BROUGHT TOGETHER
THE ENTIRE DM COMMUNITY.
SO WE HAD AFFECTED INDIVIDUALS,
FAMILIES, CAREGIVERS, WE HAD
CLINICIANS AND RESEARCHERS, WE
HAD PHARMA/BIOTECH, WE HAD
REGULATORS, AND MOST
IMPORTANTLY, WE HAD FUNDERS AND
DONORS.
IT WAS A THREE-DAY EVENT.
IT STARTED WITH AN ADVOCACY DAY,
AND THEN THERE WERE FULL DAYS OF
CONFERENCE PROGRAMS.
SO IN TOTAL, 51 SESSIONS.
THERE WERE OPPORTUNITIES FOR
FAMILY REGISTRY ENROLLMENT,
THERE WERE MOVEMENT ACTIVITY AND
EXTENSIVE NETWORKING SESSIONS.
BUT REALLY, ONE OF THE MOST
IMPORTANT THINGS WAS THE
INTENTIONAL DESIGN TO INTEGRATE
AND CONNECT SCIENTISTS AND
CLINICIANS WITH FAMILIES AND
CAREGIVERS DEALING WITH THE
DISEASE ON A DAILY BASIS.
DAY ONE, ADVOCACY DAY ON CAPITOL
HILL.
THE GOAL OF THE SESSION WAS TO
INCREASE CONGRESSIONAL
UNDERSTANDING OF MYOTONIC
DYSTROPHY.
THERE WERE OVER 130 DISEASE
ADVOCATES FROM THE U.S. AND FIVE
OTHER COUNTRIES.
THERE WERE OVER 100 MEETINGS
WITH POLICY MAKERS AND STAFF.
AND THE HIGHLIGHT WAS A
CONGRESSIONAL BRIEFING AND A
LUNCH IN THE SENATE BUILDING.
THIS MEETING WAS ATTENDED BY DRH
GOLDMAN, DEPARTMENT OF DEFENSE,
CHUCK HUNT, FROM THE ADVOCACY
COMMITTEE, SENATOR KLOBUCHAR,
AND DR. GALLAGHER REPRESENTED
INDUSTRY.
THERE WAS EVEN MORE ADVOCACY AT
THE CONFERENCE ITSELF.
DURING ONE OF THE GENERAL
SESSIONS, IT WAS A PANEL
DISCUSSION BETWEEN FDA AND THEN
PATIENTS DISCUSSING THEIR
PERSPECTIVE ON DRUG DEVELOPMENT
AND THE APPROVAL PROCESS.
FDA PARTICIPANTS WERE
DR. CAMPBELL AND DR. MANKODI.
THE SESSION WAS CHAIRED BY NICK
JOHNSON, A NEUROLOGIST, DISEASE
EXPERT.
AND THEN WE HEARD FROM MARK,
HALEY AND JEANINE.
FROM THE CONFERENCE
PARTICIPANTS, THEY LEARNED ABOUT
THE HISTORY AND MISSION OF THE
FDA, AND THEN THE FDA PRESENTER
REALLY GAINED KNOWLEDGE FROM THE
DISEASE AND PATIENT WILLINGNESS
TO ACCEPT RISK, RIGHT, IN THE
DRUG DEVELOPMENT PROCESS,
BRINGING NEW DRUGS TO MARKET.
THE EDUCATIONAL PART OF THE
CONFERENCE, THERE WERE GENERAL
SESSIONS, THERE WERE COMMUNITY
TRACKS, PROFESSIONAL TRACKS,
THERE WERE POSTER PRESENTATIONS,
THERE WERE INDUSTRY UPDATES, AND
THEN WELLNESS SESSIONS AND SMALL
GROUP DISCUSSIONS OR FIRESIDE
CHATS.
AND THEY RANGED FROM MANAGING
DAILY ACTIVITIES TO ADVOCACY AND
CLINICAL TRIALS.
THE COMMUNITY TRACKS, THERE WERE
34 SESSIONS.
THEY WERE STRATIFIED BY -- FIRST
BY DISEASE SUBCATEGORIES, SO WE
HAD SOME FOR DM1, FOR DM2, WE
HAD SESSIONS FOR CAREGIVERS AND
SELF-CARE.
WE HAD SESSIONS FOR PATIENTS
WITH A CONGENITAL FORM OF THE
DISEASE, AND THEN JUVENILE-ON
JUVENILE-ONSET.
THE PROFESSIONAL TRACK, THERE
WERE 11 SESSIONS, AND NE WERE TE
CAREFULLY DEVELOPED AND
CO-DESIGNED WITH OUR SCIENTIFIC
ADVISORY COMMITTEES.
AND TOPICS RANGED HERE FROM
BASIC SCIENCE TO EMERGING DRUG
TARGETS.
SO THERE WERE TALKS ON DISEASE
MECHANISMS IN DM1 AND 2, ANIMAL,
CELL AND TISSUE MODELS, DRUG
TARGETS AND GENETIC MODIFIERS,
AND VERY SPECIFIC PRESENTATIONS
WITH REGARDS TO THE
PATHOPHYSIOLOGY MECHANISMS IN
TISSUE AND ORGAN SYSTEMS.
AND THEN ONE OF THE COOLEST
THINGS WERE LIGHTNING ROUND
PRESENTATIONS WHERE THE TOP
POSTERS WERE ACTUALLY SELECTED
FOR VERY SHORT AND CONCISE
PRESENTATION, AND THAT GAVE THE
EARLY CAREER FELLOWS A CHANCE TO
SHOWCASE THEIR WORK, RIGHT, AND
MAKE CONNECTIONS WITH THE
ESTABLISHED RESEARCH
COMMUNITIES.
THE POSTER SESSION WAS -- I'VE
ATTENDED MANY MEETINGS, BUT THIS
POSTER SESSION WAS REALLY
INTERESTING AND COOL.
IT WAS A GINORMOUS NETWORKING
AND CONNECTION EVENT WHERE THE
PRESENTERS COULD CONNECT WITH
INDUSTRY PARTNERS AND OTHERS
WALKING INWORKING IN THE SPACE.
IT WAS HELD ACTUALLY IN THE SAME
ROOM WHERE EVERYONE WAS THERE,
SO IT WAS KIND OF A FORCED
MINGLING AND EXCHANGE OF IDEAS.
REALLY, REALLY NICE SYSTEM.
THERE WERE 45 POSTER
PRESENTATIONS, 13 FROM CURRENT
MDF FELLOWS, AND THEN THREE FROM
EARLY CAREER RESEARCH GRANTEES.
WE HAD INDUSTRY UPDATES, SO NINE
INDUSTRY PARTNERS PRESENTED
THEIR DRUG DEVELOPMENT PROGRESS
AT THEIR VARIOUS STAGES IN TWO
BLOCKS.
WE HEARD FROM -- ON DAY ONE FROM
AVIDITY, JUVENA -- THE MEETING
ITSELF ALSO PROVIDED THE FIRST
OPPORTUNITY FOR A FIRST-EVER
IN-PERSON MEETING OF THE GLOBAL
ALLIANCE FOR MYOTONIC DYSTROPHY.
THE GOAL OF THIS NEW
ORGANIZATION THAT, BY THE WAY,
GREW FROM JUST OVER 20 PARTNERS
TO CLOSE TO 60 PARTNERS IN LESS
THAN -- IN ABOUT TWO YEARS, TO
RAISE INTERNATIONAL AWARENESS
ABOUT THE DISEASE.
I SAID -- WHEN I INTRODUCED THE
PRESENTATION, THAT A GOAL WAS
REALLY TO CONNECT RESEARCH AND
DEVELOPMENT IN PATIENTS AND THAT
WAS ACCOMPLISHED IN SEVERAL
MECHANISMS, SO THERE WAS SEVERAL
STUMP THE DOCTOR PRESENTATIONS
WHERE PRESENTERS COULD SEE WHAT
REALLY BUGS THE PATIENT, WHAT DO
THEY NEED TO KNOW IN TERMS OF
THE SPEED OF DRUG DEVELOPMENT
AND THE SPEED OF EMERGING
TREATMENTS.
THERE WAS A LUNCH WITH A
DEDICATED NETWORKING BUDDY
SYSTEM, SO WHERE RESEARCHERS
WERE FORCED TO SIT ON
PRE-ASSIGNED SEATS AND MEET
PATIENTS AND FAMILY AND LEARN
ABOUT THE DISEASE, AND THEN
THERE WERE NUMEROUS
OPPORTUNITIES TO MEET PATIENTS
DURING DINNERS OR SOCIAL EVENTS.
THIS MEETING ALSO SHAPED MY OWN
PERSONAL JOURNEY, BECAUSE I
NEEDED TO EVALUATE WHETHER I
WANTED TO TAKE THE JOB AS
SCIENTIFIC OFFICER.
I ASKED IF I COULD ATTEND THE
MEETING, AND OBVIOUSLY I'M HERE,
AND FOR ME, THE MEETING WAS
SIMPLY VERY POWERFUL AND VERY
SUCCESSFUL CONNECTING PATIENTS
AND SCIENCE.
SO IN SUMMARY, THE MEETING
PROVIDED A PLATFORM FOR ADVOCACY
AND MEETING WITH REGULATORS.
SCIENCE BLEW ME AWAY.
I COMPARED IT MORE LIKE TO THE
QUALITY OF A GORDON CONFERENCE.
IT WAS VERY POWERFUL TO SEE HOW
COMMUNITY DONATIONS DIRECTLY
INFLUENCE SCIENCE, SO FOR
EXAMPLE, FOR THE EARLY CAREER
MECHANISMS.
THE MEETING ALLOWED FOR
SCIENTIFIC -- FOR MEETINGS WITH
SCIENTIFIC AND CLINICAL OPINION
LEADERS.
CURRENT AND PREVIOUS FELLOWS
COULD MEET, THEY COULD MEET WITH
THEIR MENTORS.
THE GLOBAL ALLIANCE MET IN
PERSON.
OUR SCIENTIFIC ADVISORY
COMMITTEE MET IN PERSON.
AND THEN IT WAS REALLY
SUCCESSFUL IN MAKING THE PAINS
AND URGENCIES OF THE DISEASE
COMMUNITY TANGIBLE FOR THE
RESEARCHERS AND THE RESEARCH
COMMUNITY.
AND THEN FROM A FOUNDATION
PERSPECTIVE, OF COURSE IT
ALLOWED IN-PERSON SHARING OF
RESOURCES AND CARE
RECOMMENDATIONS.
AND FROM THE PATIENT SIDE, IT
EVEN ENDED WITH A MARRIAGE
PROPOSAL.
SO WHAT WE WANT TO DO -- SO NEXT
YEAR, AS WE TRANSITION FROM A
FALL CONFERENCE TO A SPRING
CONFERENCE, WE WANT TO ACTUALLY
TRY SOMETHING A LITTLE BIT
DIFFERENT.
WHAT WE WANT TO TRY OUT, WE WANT
TO TRY OUT A CONCEPT OF REGIONAL
DM CONFERENCES.
SO WE WANT TO ORGANIZE SIX
REGIONAL CONFERENCES IN THE EAST
COAST MIDWEST CENTRAL AND WEST
COAST REGION, AND TRY TO SEE
WHETHER WE CAN REPLICATE AND
CONNECT WITH MORE PEOPLE IN
THESE LOCALIZED -- IN THESE
SMALLER AND MORE LOCALIZED
SETTINGS.
OF COURSE AS WE LEARN, WE WILL
NOT HESITATE TO SHARE OUR
EXPERIENCE.
AND WITH THIS, I WANT TO END AND
TAKE ANY QUESTIONS.
THANK YOU VERY MUCH.
>> THANK YOU, ANDY.
OF COURSE I'M VERY INTRIGUED
ABOUT THE MARRIAGE PROPOSAL.
IS THAT A FIRST FOR ANY
PARTICULAR --
>> YEAH, IT WAS A FIRST.
THERE WERE TWO PATIENTS.
THEY MET ACTUALLY IN -- I THINK
IN PREVIOUS MDF CONFERENCE AND
THEY STAYED IN TOUCH, STARTED
DATING, AND HERE WE GO.
>> FANTASTIC.
SO WE'RE RUNNING A LITTLE
BEHIND, BUT MAYBE ONE QUESTION.
ANYBODY HAVE A QUESTION?
IF NOT, GLEN HAS SOME
ANNOUNCEMENTS.
>> ANY QUESTIONS FOR ANDY?
OKAY.
SO WE'RE RUNNING A LITTLE BIT
BEHIND.
WE'RE SUPPOSED TO TAKE A
10-MINUTE BREAK.
LET'S SHORTEN TO LIKE FIVE
MINUTES.
FOR THOSE OF YOU WHO ARE HERE IN
THE ROOM, THERE'S FRESH FRUIT
FOR YOU TO ENJOY OVER THERE, AND
IF YOU'D LIKE TO PLACE AN ORDER
FOR LUNCH DELIVERY, WE'RE
GETTING DELIVERY FROM CAVA, SEE
GINA, AND SHE'S AT THE TABLE AT
THE END OF THE HALL JUST AS YOU
WERE COMING IN.
ALSO THE RESTROOMS GO BACK TO THE LOO BEETHE LOBBY, GO BACK AD
IT'S JUST TO THE RIGHT. SO FIVE MINUTES, TRY TO BE BACK AT 11:10, 11:08, 11:10.
>> WELL, FOR THOSE OF YOU WHO
ARE BACK FROM BREAK, WE WELCOME
YOU BACK.
OUR NEXT PRESENTER IS
DR. CARSTEN BONNEMANN, WHO IS
FROM THE NINDS INTRAMURAL
RESEARCH PROGRAM.
HE IS GOING TO TELL US ABOUT A
WORKSHOP, AAV-RELATED
TOXICITIES, THAT WAS HELD AT THE
NIH IN JUNE OF THIS YEAR.
CARSTEN, OVER TO YOU.
>> WELL, THANKS VERY MUCH FOR
HAVING ME TO REPORT ON THIS.
I WOULD LIKE TO GIVE A LITTLE
BACKGROUND, THOUGH.
ON AAV JUST AS IT RELATES TO
WHAT I'M GOING TO TALK ABOUT.
AAV IS A VERY SMALL VIRUS, THIS
LITTLE GUY HERE, THAT IS REALLY
NOT ABLE TO REPLICATE ON ITS
OWN.
IT NEEDS HELPER VIRUSES LIKE THE
BIG GUYS OVER HERE.
THE ADVANTAGE OF THIS SMALL
VIRUS IS THAT IT IS LARGELY
NON-PATHOGENIC, AT LEAST AT THE
DOSES THAT HAPPEN IN NATURAL
INFECTION.
BUT A DISADVANTAGE, ITS
PACKAGING CAPACITY IS RATHER
LOW, ONLY 4.6 KB, BUT IT COMPANY
INDUSTRIALIZED AND THE VIRAL
GENES CAN BE REPLACED BY TRANS
GENES THAT NEED TO BE DELIVERED.
CURRENTLY, MOSTLY IN CLINICAL
USE ARE NATURALLY OCCURRING ZERO
TYPES, BUT THE FUTURE IS IN
SPECIFICALLY ENGINEERED
PHENOTYPES WITH BETTER ORGAN
TARGETING AND, THEREFORE,
ALLOWING FOR LOWER DOSES, WHICH
IS REALLY KEY TO LOWER THE
TOXICITY OF THIS OTHERWISE VERY
USEFUL TOOL.
SO WHO ARE TWO PAPERS THAT
DESCRIBE TWO FORMS OF MYOS&P AAV
IN CLINICAL DEVELOPMENT TO HELP
WITH GENE THERAPY AND DECREASING
TOXICITY BY DECREASING DOSES
WHILE WHILE INCREASING EFFICACY.
NOW MANY CLINICAL TRIALS ARE
UNDERWAY, YOU CAN SEE A LIST OF
THOSE.
IT'S IMPORTANT TO HAVE A LITTLE
PREVIEW OF WHAT HAPPENS WHEN AAV
ENTERS THE BODY.
SO THERE IS BINDING TO THE CELL
SURFACE, TAKEUP INTO THE CELL,
UNCODING IN THE KNEE C NUCLEUS D
LIBERATION OF THE DNA THAT THE
VIRUS DELIVERS AS A SINGLE
STRAND, WHICH NEEDS TO BE DOUBLE
STRANDED OR IF ITS COMPLEMENTARY
ALREADY AS A DOUBLE STRAND.
MOSTLY THIS LIVES AS AN EPISOMAL
DNA ELEMENT SO IT DOESN'T
INTEGRATE INTO THE GENOME FOR
THE MOST PART, BUT THERE IS SOME
INTEGRATION INTO THE HOST GENE.
THE CLINICAL CONSEQUENCES OF ANY
OF THAT IN HUMAN HAVE NOT BEEN
ADDRESSED AT THIS POINT IN TIME.
THIS IS, OF COURSE, A VIRUS AND
THE IMMUNE SYSTEM KNOWS HOW TO
DEAL WITH VIRUSES AND THERE ARE
DIFFERENT WAVES OF IMMUNITY THAT
CAN ENCOUNTER A GENE THERAPY.
THERE'S PRE-EXISTING IMMUNITY,
IF A PERSON IS ALREADY EXPOSED
TO THE VIRUS, THERE MAY BE
NEUTRALIZING ANTIBODIES
PREVENTING -- ADAPTIVE IMMUNITY
WHEN THE IMMUNE SYSTEM DEVELOPS
ANTIGEN-SPECIFIC IMMUNITY
AGAINST EITHER THE CAPSID OR THE
TRANS GENE.
ALL OF THESE HAVE CLINICAL
CONSEQUENCES AT THE PREDOSING,
PRE-EXISTING NEUTRALIZING
ANTIBODIES CAN -- DOSING, BUT
IMMUNE ACTIVATION EVEN AT THE
INNATE NONSPECIFIC LEVEL CAN
CAUSE PROBLEMS.
THE MOST IMPORTANT PROBLEM THAT
WE HAVE ENCOUNTERED IN THE FIELD
IS THAT OF THROMBOTIC MICRO
ANGIOPATHY.
IT LIKES TO BE ACTIVATED BY
VIRUSES.
THIS DIAGRAM HERE IS FROM A
COVID-19 EXAMPLE, BUT THESE
PATHWAYS CAN BE -- COMPLEX
MEDIATED AND THEN ACTIVATE A
COMPLEMENT CASCADE THAT CAN LEAD
TO INJURY OF THE ENDOTHELIAL
COMPARTMENT LEADING TO TMA.
TMA IS A SERIOUS CLINICAL
CONSEQUENCE THAT HAS OCCURRED IN
A NUMBER OF THE GENE THERAPY
TRIALS.
THIS IS A SLIDE PUT TOGETHER BY
DR. LAFORET.
THERE'S ALSO A TENDENCY, OF
COURSE, TO HIGH TOTAL DOSES THAT
ARE REQUIRED IN MUSCLE DISEASE
TREATMENT AT THE MOMENT.
ALL THE PATIENTS AT VERY HIGH
DOSES ARE AT PARTICULAR RISK OF
THIS.
THERE'S ALSO NOW OCCURRING IN
SMALL PATIENTS WITH SMA TRIALS
WHERE THERE HAVE BEEN SEVERAL
FATAL CASES OF TMA.
SOME OF THAT PROBABLY MEDIATED
BY SUSCEPTIBILITY IN THE
COMPLEMENT PATHWAY.
THIS IS IMPORTANT TO FIGURE OUT
BECAUSE THERE ARE WAYS TO
INTERVENE WITH THE COMPLEMENT
PATHWAY IN PARTICULAR, CLINICAL
TRIALS.
A SECOND PROBABLY INNATE DRIVEN
ADVERSE EVENT THAT CAN HAPPEN IN
AAV MEDIATED GENE THERAPY,
YOU'RE AWARE OF THIS PAPER HERE,
WHERE IT LOOKS LIKE AN AAV
TRIGGERED HYPERINFLAMMATORY
STATE/CYTOKINE RELEASE STATE
THAT ALSO IS ON THE LEVEL OF
INNATE IMMUNITY.
BUT IN CAN ALSO BE LIVER
INVOLVEMENT, LIVER TOXICITY AS
PART OF PROBABLY AN ADAPTIVE
IMMUNE RESPONSE AGAINST THE
CAPSID ITSELF.
THIS HAS BEEN KNOWN SINCE THE
DAYS OF HEMOPHILIA GENE THERAPY
AND IS STILL HAPPENING.
IT'S LARGE LEHMANAGEABLE WI LARH
IMMUNE MODULATION.
THERE ARE ALSO DISEASE SPECIFIC
FACTORS WE CAN SEE, WE HAD A
NUMBER OF PATIENT DEATHS -- NOT
FULLY RECOGNIZED DISEASE
SUSCEPTIBILITY IF NA CHOLE --
STASIS IS EXACERBATED BY THE
HIGH LOAD OF VIRUS TO THE LIVER.
THEN LASTLY THERE'S THE TRANS
GENE DEVELOPED WITH THE GENE
THERAPY, THIS IS WHAT REALLY
TRIGGERED THE WORKSHOP THAT I
WOULD BE BRIEFLY REPORTING
ABOUT.
THIS HAPPENED IN THE DUCHENNE
MUSCULAR DYSTROPHY TRIALS.
YOU CAN SEE THESE ARE THE FOUR
CONSTRUCTS CURRENTLY IN THE
CLINIC.
THEY'RE ALL MINIATURIZED
BECAUSE -- IS TOO BIG FOR AAV TO
BE LOADED INTO IT.
THEY ALL HAVE COMMON ELEMENTS,
IN PARTICULAR THE P -- REPEAT
DOMAINS IN THEM.
YOU SEE THE VARIOUS SPONSORS
THAT ARE IN CLINICAL TRIALS.
WHAT HAPPENED IS THAT IN FIVE
DUCHENNE SUBJECTS, RIGHT ABOUT
THE SAME TIME OF THIS AGE THEY
DEVELOPED A SEVERE MYOSITIS AND
MYOCARDITIS ABOUT THREE TO FOUR
WEEKS AFTER GENE TRANSFER,
LEADING TO ICU STAYS, LOSS OF
AMBULATION, SOME RESPIRATORY
REQUIREMENTS, AND IMMUNE
MODULATION REQUIREMENT.
ALL OF THEM IMPROVED IN THE END,
BUT THESE WERE CRITICAL EVENTS
THAT WERE ASSOCIATED WITH THE
MYOSITIS.
WHAT HAPPENED REALLY AROUND THIS
WAS QUITE REMARKABLE.
IT WAS FRANCESCA MUNTONI WHO HAD
OVERSIGHT ON A LOT OF THESE
TRIALS AND RECOGNIZED
SIMILARITIES IN THEM.
HE CONTACTED ME AND WE TOGETHER
CONTACTED ALL THE SPONSORS
INVOLVED IN THESE CLINICAL
TRIALS AND THERE WAS NO
RESISTANCE TO GET TOGETHER AND
REALLY REALTIME TO COME TOGETHER
IN A CLOSED DOOR MEETING TO
DISCUSS THESE EVENTS AND SEE
WHAT WAS COMMON TO THEM.
WE HAD AN EXPERT PANEL PRO BONO
THAT HELPED US ANALYZE THESE
EVENTS, AND THIS IS NOW
PUBLISHED AS A LETTER.
WHAT WAS IMMEDIATELY CLEAR
COMPARING THESE EVENTS IS THAT
THE PATIENT HAD -- THESE
PATIENTS HAD GENOMIC DELETIONS
THAT OVERLAPPED WITH COMMON PART
OF THE TRANS GENES DELIVERED.
IN OTHER WORDS, THESE PATIENTS
WERE IMMUNONAIVE FOOR THIS NEW
ANTIGEN, THIS NEW TRANS GENE
THAT WAS DELIVERED WITH THE GENE
THERAPY.
THEY RECOGNIZE IT AS FOREIGN AND
MOUNTED A REJECTION AGAINST THE
T-CELL REACTION AGAINST IT THAT
CAUSED THESE CRITICAL EVENTS.
THAT HAS LED TO IMMEDIATE
ADJUSTMENT TO THE
INCLUSION/EXCLUSION CRITERIA IN
ALL OF THESE TRIALS TO EXCLUDE
THESE HIEMP CRITICAL REGIONS
THAT ARE THE MOST IMMUNOGENIC AS
FAR AS WE UNDERSTAND AT THIS
POINT IN TIME.
IT ALSO LED THEM TO THE
REALIZATION THAT THIS IS A
REALLY CONSTRUCTIVE WAY TO GO
AFTER THIS REALLY COMPARING
DATA, PUTTING THINGS ON THE
TABLE THAT ARE REALLY CLASS
EFFECTS TO TRY TO DE-RISK GENE
THERAPY GOING FORWA FORWARD.
THERE ARE A NUMBER OF MEETINGS
PREVEPRECEDING THIS, ANOTHER EDN
COMING UP SOON, AND THEN ALSO A
MEETING BY THE ENMC.
THESE ARE OPEN MEETINGS, A
MEETING THAT WE THEN DID AT THE
NIH WAS MEANT TO RE-CREATE THAT
CLOSED DOOR -- THIS OPEN
DISCUSSION, THIS DATA SHARING
WITHOUT RESTRICTION IN A
SITUATION WHERE THERE WAS
ABSOLUTE CONFIDENTIALITY.
AGAIN, FRANCESCA MUNTONI AND
MYSELF INITIATED THIS AND WE HAD
SUPERB SUPPORT FROM NINDS AS
WELL AS NCATS TO PUT THIS
TOGETHER AT THE NIH IN THE
NATCHER CENTER IN JUNE OF THIS
YEAR.
AND THESE ARE THE ATTENDEES.
IT'S A LARGER GROUP BECAUSE WE
HAD MORE GROUND TO COVER.
WE WANTED TO COVER THE EMERGENT
ADVERSE EVENTS WITH THE TMAs,
THE LIVER, THE HEART EVENTS THAT
WE'VE SEEN ACROSS THE CLINICAL
TRIALS, AND YOU CAN SEE THE
ATTENDEES AT THIS MEETING, THE
PARTICIPANTS WERE BOTH FROM
ACADEMIA, BUT ALSO FROM ALL THE
COMPANIES INVOLVED IN THESE
TRIALS, AND THEY WERE RIGHT
THERE AT THE TABLE, READY TO
SHARE AND DISCUSS DATA.
WE HAD SOLID CONTRIBUTION, OF
COURSE, ALSO FROM THE NIH ITS
ITSELF.
A NUMBER OF PROGRAM OFFICERS
WERE ALSO IN THE ROOM, INCLUDING
GLEN, OF COURSE, TO REALLY TAKE
MEASURE OF WHAT IS HAPPENING IN
THE FIELD.
THIS WAS A VERY, VERY PRODUCTIVE
DISCUSSION THAT LED TO THE
FORMATION -- BEFORE I MOVE
FORWARD, MY SINCERE THANKS TO
OUR ADMINISTRATIVE ORGANIZERS,
IN PARTICULAR DEANNA AND
CHRISTOPHER AT NINDS THAT MADE
THIS HAPPEN.
HERE IS A RUNDOWN OF THE MEETING
AGENDA.
YOU CAN SEE WE ORGANIZED IT
AROUND THESE EMERGING
TOXICITIES, THE ANTI-TRANS GENE
IMMUNITY, THE TMA AND ORGAN
TOXICITY, INCLUDING THE HEART
AND THE HEPATOP ATHIES.
THE FORMATION OF WORKING GROUPS
AROUND THESE AREAS OF TO TOXICI.
COMING OUT OF THIS, THESE
MEETING GROUPS ARE GOING TO MEET
TWO TIMES ON LINE TO REALLY
DRILL DEEPER INTO THESE EVENTS,
SEE WHAT DATA NEEDS TO BE
REPORTED, WHAT DATA NEEDS TO BE
RECORDED, WHAT ARE THE OPTIONS
FOR INTERVENTION, AND HOW DO WE
SHARE THIS DATA SO THAT WE CAN
DE-RISK AND DEVELOP PROTOCOLS
AROUND THESE EVENTS THAT MAKE
GENE THERAPY SAFER, WITH THE
HOPE TO BE ABLE TO DISSEMINATE
AND COMMUNICATE AND FIND DATA
SHARING PLATFORMS THAT HELP THE
FIELD TO UNDERSTAND THESE
TOXICITIES, WHICH IF THEY'RE
UNDERSTOOD, CAN BE MANAGED AND
CONTROLLED.
BUT THEY CAN ONLY BE UNDERSTOOD
IF THE DATA IS RECORDED AND
SHARED AMONGST THE FIELD.
SO THAT WAS THE TA TANGIBLE OUTE
OF THIS MEETING, AND HOPEFULLY
NEXT YEAR WE CAN REPORT ON WHAT
THESE WORKING GROUPS CAME UP
WITH AND HOW WE DISSEMINATE THAT
INFORMATION.
THANK YOU.
>> THANK YOU SO MUCH, CARSTEN.
WE LOOK FORWARD TO FUTURE
RECOMMENDATIONS FROM THIS GROUP
ON STRATEGIES TO ENHANCE THE
SAFETY AND EFFICACY OF THE AAV
GENE THERAPIES.
AND WE'RE HOPING THAT SOME OF
THE THERAPIES CAN BE PERFORMED
IN THE CLINICAL CENTER.
I DON'T KNOW IF YOU HEARD MY
PREVIOUS COMMENT, BUT -- NEXT,
WE'RE GOING TO HEAR FROM
DR. ANDY BERGLUND FROM THE
UNIVERSITY OF ALBANY.
I'M ASSUMING THAT'S SUNI ALBANY,
BUT YOU CAN CORRECT ME -- YES.
THERE IT IS.
I DIDN'T KNOW ABOUT A UNIVERSITY
OF ALBANY.
DR. BURG LAND WILL TELL US ABOUT
A CONFERENCE ON MYOTONIC
DYSTROPHY, THE NEXT GENERATION.
>> THANK YOU VERY MUCH FOR THIS
TIME TO SHARE A FEW UPDATES.
SUNI ALBANY, UNIVERSITY OF
ALBANY, AND I'M DIRECTOR OF THE
RNA INSTITUTE HERE.
I'M GOING TO TELL YOU ABOUT A
RECENT MEETING IN OCTOBER THAT
REALLY FOCUSED ON YOUNG
INVESTIGATORS.
I'LL BRIEFLY TOUCH ON AN EFFORT
WE'RE DOING WITH UNIVERSITY OF
ROCHESTER AND CHARLES THORTON IN
PARTICULAR ON A NEW YORK STATE
MYOTONIC DYSTROPHY CENTER.
SO IT SOMETHING WE'VE DECIDED TO
BUILD BECAUSE WE HAVE EXPERTISE
HERE IN ALBANY AND AT ROCHESTER
AROUND MYOTONIC DYSTROPHY, AND
IT'S ALSO BOLSTERED BY THE
RECENT PUBLICATION BY NIC
JOHNSON AND COLLEAGUES SHOWING
THAT THE PREVALENCE IN NEW YORK
STATE OF THE DM1 MUTATION IS
1 IN 2100, WHICH IS RELATIVELY
HIGH.
SO WE'VE DECIDED THAT THIS IS AN
OPPORTUNITY TO HOPEFULLY MAKE
THE STATE AWARE OF THIS AND
FOCUS RESOURCES ON IT.
SO WE ARE WORKING WITH THE STATE
TO GET A CENTER OF EXCELLENCE IN
RNA RESEARCH AND THERAPEUTICS
FUNDED WHICH WOULD PROVIDE SOME
STATE STABLE FUNDING FOR
MYOTONIC DYSTROPHY AND WE'RE
BUILDING THIS OFF OF A NEW YORK
AUTISM CENTER MODEL.
ONE OF THE OPPORTUNITIES IS TO
DRAW MORE RESEARCHERS,
CLINICIANS AND PATIENTS INTO
NEW YORK STATE.
SO WE'RE ALSO RAISING AWARENESS
WITHIN THE STATE BECAUSE AS
MAYBE MANY OF YOU ARE AWARE,
MYOTONIC DYSTROPHY IS
UNDERAPPRECIATED IN TERMS OF
PREVALENCE AND SORT OF
RECOGNITION SO WE'RE WORKING
WITH MDF AND THE ALLIANCE TO
RAISE AWARENESS.
SO WE'VE HAD SOME SUCCESS
WORKING WITH OUR NEW YORK STATE
COLLEAGUES TO LIGHT UP NEW YORK
GREEN ON SEPTEMBER 15TH, AND I
JUST WANTED TO SHOW A FEW
PICTURES.
THIS PAST YEAR WE WERE ABLE TO
GET NIAGARA FALLS LIT UP GREEN
AND THEN THE STATE CAPITAL AND
THE SUNY CENTRAL BUILDINGS AND
THE MOYNIHAN TRAIN HALL IN NRKZ.
SO WE ARE CONTINUING TO PUSH ON
THIS EFFORT TO RAISE AWARENESS
AND WE PLAN TO RAISE A
FUNDRAISER AROUND THESE EFFORTS
AROUND SEPTEMBER 15TH, 2024,
WHICH IS INTERNATIONAL MYOTONIC
DYSTROPHY DAY.
SO THE MEETING WE DID WAS REALLY
A COLLABORATION WITH THE
MARIGOLD FOUNDATION, THE
MYOTONIC DYSTROPHY FOUNDATION,
OURSELVES AND THE UNIVERSITY OF
ROCHESTER.
WHAT WE WANTED TO DO WAS PROVIDE
AN OPPORTUNITY TO SUPPORT THE
YOUNG INVESTIGATORS IN THE FIELD
AND CONTINUE TO BUILD THEIR
CONNECTIONS AND HELP THEM BE
SUCCESSFUL IN THE FIELD.
SO WE BROUGHT THEM ALL TOGETHER
AT THE MOHONK MOUNTAIN HOUSE
BETWEEN THE THIRD AND THE SIXTH.
SENIOR PH.D. STUDENTS, POST TOK
TO RECALL FELLOWS AND FACULTY.
WE BROUGHT FOLKS FROM
GOVERNMENT, INDUSTRY, AND THEN
WE HAD A NICE GROUP OF PATIENT
ADVOCACIES -- ADVOCATES AND
ACTUALLY OUR DM AMBASSADORS WERE
CRITICAL TO REALLY PROVIDE THAT
INTERACTION WITH THE
RESEARCHERS, THE BASIC AND
CLINICAL RESEARCHERS, TO CONNECT
WITH THE FAMILIES, SO MANY OF
THEM HAVE CONNECTED WITH
FAMILIES BEFORE BUT WE REALLY
WANTED THEM TO FEEL A PERSONAL
CONNECTION AND MAYBE EVEN MAKE A
LONG-TERM CONNECTION.
SO WE HAD TALKS BY EXPERTS IN
THE FIELD WITH BREAKOUT SESSIONS
TO DISCUSS AND COLLECT IDEAS
WHERE WE COULD MOVE FORWARD AS A
FIELD TOGETHER.
TALKS FOCUSED ON ANSWERING
QUESTIONS IN THE FIELD AND WHAT
NEEDS TO BE DONE TO MOVE THE
FIELD FORWARD.
AND ONE OF THE THINGS THAT I
ACTUALLY HAD NEVER SEEN BEFORE
WAS A CLINICAL DEMONSTRATION.
ONE OF OUR CLINICIANS WITH ONE
OF THE INDIVIDUALS AFFECTED BY
MYOTONIC DYSTROPHY DID A WHOLE
HOUR-LONG SORT OF OBSERVATION
AND DEMONSTRATION OF HOW
CLINICIANS INTERACT WITH
PATIENTS, SORT OF THAT FIRST
TIME, UNDERSTANDING WHAT'S
HAPPENING AND THE NEEDS AND
THINGS LIKE THAT, SO THAT WAS
REALLY A POWERFUL THING I THINK
FOR ALL OF US TO WITNESS, AND IT
WAS GREAT THAT ONE OF THE
PATIENT WAS WILLING TO DO THAT
WITH US.
SO THE WAY WE WENT ABOUT THIS IS
WE CONTACTED AS MANY SENIOR DM
RESEARCHERS AS WE COULD FIND.
WE ASKED THEM TO NOMINATE WHO
THEY THOUGHT WOULD BE A GREAT
JUNIOR INVESTIGATOR WHO WOULD
REALLY BENEFIT FROM THIS
MEETING, SO WE RECEIVED 51
RESPONSES FROM THE DM COMMUNITY.
WE MADE 44 INVITATIONS, AND
ALMOST EVERY ONE OF THEM JOINED
US.
TWO HAD TO JOIN US REMOTE.
FOR VARIOUS REASONS.
AND THE CRITERIA AND
INSTRUCTIONS FOR THE NOMINEES,
WE HAD ONE PER LAB.
THEY MUST SPEND A SIGNIFICANT
PORTION OF THEIR RESEARCH OR
CLINICAL WORK ON MYOTONIC
DYSTROPHY, THEY HAVE TO BE EARLY
YEAR AND HAVE POTENTIAL TO MAKE
A LASTING IMPACT ON THE FIELD.
AS I TOLD YOU, THEY WERE, IN
GENERAL, JUNIOR.
THERE'S THE -- THE WAY WE DEFINE
THAT.
THEN WE THOUGHT THEY WOULD
BENEFIT FROM LEARNING ABOUT THE
CURRENT LANDSCAPE IN DM
THERAPEUTIC APPROACHES AND DRUG
DEVELOPMENT, AND SORT OF THE
OPPORTUNITIES AND GAPS THAT THEY
COULD TAKE ADVANTAGE.
AND SO THEY COULD APPLY THIS
KNOWLEDGE TO THEIR FUTURE CAREER
EFFORTS.
IT WAS A RELATIVELY SMALL
MEETING.
WE FELT LIKE THAT WOULD BE A
REAL STRENGTH FOR THE JUNIOR
INVESTIGATORS, SO AS I SAID, 41
NOMINEES JOINED US.
THERE WERE TWO VIRTUAL AND ONE
UNFORTUNATELY DIDN'T JOIN US.
WE BROUGHT IN ADRIENNE CRANER
WHO'S DONE SOME GREAT WORK IN
SPINAL MUSCULAR ATROPHY AS A
PLACE WE WANT TO GET TO, SO HE
WAS SOMEONE WHO STAYED THE WHOLE
MEETING AND REALLY ENGAGED WITH
US, WHICH WAS GREAT.
WE HAD THE INDIVIDUALS AFFECTED
WITH MYOTONIC DYSTROPHY AND SOME
OF THEIR FAMILY MEMBERS JOIN US.
WE HAD 10 INDUSTRY LEADERS, AND
THEN ONE OF THE THINGS WE REALLY
WANTED TO DO IS WE HAD GROUP
LEADERS WHO HAD JUST, FOR
EXAMPLE, RECEIVED TENURE OR HAD
BEEN REALLY SUCCESS FELL SUCCESY
AND GOT SOME GRANTS.
WE SET UP GROUP LEADERS WHERE
THEY HAD SEVEN TO EIGHT OF THE
JUNIOR TRAINEES, THEY BUILT
THESE COHORTS SO HOPEFULLY THEY
WOULD HAVE THESE CONNECTIONS TO
GO FORWARD WITH.
THOSE SMALL GROUPS ALLOWED THEM
TO HAVE LOTS OF PERSONAL
CONNECTIONS AND TO BUILD OUT
OPPORTUNITIES.
WE HAD FUNDING AGENCIES JOIN US,
WE HAD TALKS ACTUALLY FROM GLEN
AND OTHERS TO TELL US ABOUT THE
OPPORTUNITIES FOR OUR JUNIOR
INVESTIGATORS.
SOME OF THE STAFF MEMBERS AND
FOUNDATIONS.
A GOOD MIX OF FEMALES AND MALES
AND THEN 11 DIFFERENT COUNTRIES
WERE REPRESENTED.
HERE'S JUST ONE OF THE SMALL
BREAKOUTS WHERE ONE OF OUR
INDUSTRY SCIENTISTS FROM AVIDITY
ARE TELLING THE PATIENTS AND THE
FAMILIES ABOUT THEIR CLINICAL
TRIAL.
SO REALLY OUR GOALS WERE TO
BUILD THE PROFESSIONAL AND
PERSONAL NETWORK, THE DM NETWORK
FOR THESE INDIVIDUALS, IDENTIFY
POTENTIAL NEW COLLABORATIONS,
RESOURCES, TALKING ABOUT
BIOBANKS, WHERE THEY CAN GET THE
CELL LINES, BUILDING ALLIES, AND
AS I TALKED, IT WAS REALLY AN
OPPORTUNITY FOR THE YOUNG
INVESTIGATORS TO IDENTIFY THE
GAPS AND OPPORTUNITIES IN THE DM
FIELD SO THEY COULD MOVE THEIR
RESEARCH FORWARD.
WE REALLY ALSO WERE STRATEGIC
ABOUT PAIRING CLINICAL AND BASIC
RESEARCHERS TOGETHER AND THE
POSSIBILITY THAT THEY MIGHT WANT
TO FORM COLLABORATIONS.
WE ALSO HAD COMMUNITY MEMBERS
BUILT IN TO THOSE GROUPS WITH
GROUP LEADERS.
AND THEN WE TALKED ABOUT NEW
IDEAS AND OPPORTUNITIES FOR THE
FIELD TO THINK ABOUT HOW WE
COULD ALL MOVE FORWARD AND A LOT
OF THIS WAS DONE, OF COURSE,
WITH MYOTONIC DYSTROPHY
FOUNDATION AND OTHERS.
WE DISCUSSED CAREER
OPPORTUNITIES ON HOW TO
INCORPORATE MYOTONIC DYSTROPHY,
EVEN IN CURRICULUM AS
PROFESSORS.
WE TALKED ABOUT PICKING
OPPORTUNITIES TO TARGET AND
GETTING FEEDBACK FROM YOUR GROUP
LEADERS AND SENIOR SCIENTISTS.
AND THEN, OF COURSE, IT'S ALWAYS
FUN TO HAVE FUN AS A GROUP AND
BUILD THOSE PERSONAL
CONNECTIONS.
SO JUST A FEW THINGS WE DID A
LITTLE DIFFERENTLY TOO.
AGAIN, ALL THE ATTENDEES WERE
NOMINATED BY SOMEONE IN THE
FIELD, THEN WE ACTUALLY ASKED
THEM TO BASICALLY PUT TOGETHER A
ONE-PAGE DESCRIPTION OF THEIR
CURRENT RESEARCH, THEIR FUTURE
CAREER GOALS SO THAT WE COULD
USE THAT INFORMATION TO BUILD
THE GROUPS AND HELP THEM BUILD
CONNECTIONS.
THE OTHER THING WE DID WITH OUR
POSTER SESSION IS WE DIDN'T
ACTUALLY HAVE THEM DO A POSTER
JUST ON THEIR RESEARCH.
WE ASKED THEM TO DO A POSTER ON
THE KEY COMPETENCIES OF THEIR
LAB OR CLINICAL RESEARCH SO WE
COULD HAVE THAT PERSON BE A
REPRESENTATIVE FOR THAT WHOLE
GROUP AND THEN HOPEFULLY SEE THE
OPPORTUNITIES SO THAT IT WAS,
AGAIN, SORT OF BUILDING OUT THE
INTERACTIONS ACROSS THE FIELD.
SO THE GOAL WAS TO SIMULATE --
STIMULATE DISCUSSION AND PROMOTE
COLLABORATIONS, AND I KNOW OF
SEVERAL THAT HAVE STARTED MOVING
FORWARD IN THIS SPACE, EVEN
THOUGH THE MEETING JUST HAPPENED
A FEW MONTHS AGO.
WE HAD LOTS OF GREAT KEY
SPEAKERS BUT WE HAD TWO SPECIFIC
WORKSHOP FACILITATORS, AND ONE
OF THEM IS ON YOUR COMMITTEE,
ERIC WANG, WHO TALKED ABOUT DRUG
DEVELOPMENT FROM CONCEPT TO
STARTUP.
SO THOSE ARE THINGS THAT WE
DON'T ALWAYS -- OUR JUNIOR
INVESTIGATORS DON'T ALWAYS GET
TO HEAR ABOUT, IS HOW AS A NEW
PROFESSOR OR EVEN AS A
POSTDOCTORAL FELLOW, HOW TO
THINK ABOUT THAT TRANSITION FROM
AN IDEA OR REALLY EXCITING DATA
TO GO TO A STARTUP, SO ERIC DID
A GREAT JOB SHARING HIS PATH AND
WAYS TO DO THAT.
MARIO FROM FRANCE ACTUALLY
TALKED ABOUT OPPORTUNITIES IN
THE EUROPEAN UNION AND WAYS TO
COLLABORATE BETWEEN THE U.S. AND
EUROPE, AND LOTS OF OTHER
COLLABORATIONS AND SORT OF
TALKED ABOUT OPPORTUNITIES AND
GAPS.
SO AGAIN ERIC AND MARIO ARE BOTH
REALLY SUCCESSFUL BUT HAVE
RECENTLY MADE THE JUMP TO MORE
SENIOR POSITIONS.
AND SO SOME OF OUR MORE SENIOR
FOLKS, MAURY SWANSON WHO'S DONE
SOME OF THE KEY WORK IN MYOTONIC
DYSTROPHY, SO HE GAVE US A WHOLE
HIHISTORY OF THE EARLY WORK IN
MYOTONIC DYSTROPHY AND REALLY
FRAMED AND TALKED ABOUT THE
OPPORTUNITIES.
ADRIENNE KRAINER TALKED ABOUT
LESSONS LEARNED FROM OTHER
THERAPEUTIC PROGRAMS, TOLD US
ABOUT SPINAL MUSCULAR ATROPHY
AND SORT OF THE PATH AND SORT OF
OPPORTUNITIES AND CHALLENGES
THEY'VE FACED IN THAT FIELD AND
THINGS WE COULD LEARN.
AS I SAID, IT WAS GREAT THAT
ADRIENNE STAYED WITH US FOR THE
WHOLE MEETING AND REALLY ENGAGED
IN THE GROUP DISCUSSIONS AND
THINGS LIKE THAT.
THEN CHARLES, WHO, YOU KNOW, HAS
BEEN A LEADER IN THE MYOTONIC
DYSTROPHY FIELD SINCE THE
BEGINNING, SHARED HIS WISDOM AND
TALKED ABOUT ACTUALLY SORT OF
THINKING ABOUT WHEN THINGS ARE
APPROVED IN OUR SPACE, SORT OF
HOW WE NEED TO THINK ABOUT
INTERACTING CAN THE PEAMS AND
THE PATIENTS AND SORT OF
OPPORTUNITIES FOR WHEN HOPEFULLY
THINGS ARE APPROVED IN THE
MYOTONIC DYSTROPHY SPACE AND
PREPARING FOR THOSE
OPPORTUNITIES AS WELL.
SO WE HAD LOTS OF BREAKOUT
SESSIONS BECAUSE WE WANTED TO BE
A VERY INTERACTIVE -- AS I
TALKED ABOUT, THE CLINICAL
DEMONSTRATION I THOUGHT WAS
GREAT, WE TALKED ABOUT
MECHANISMS AND MODELS, WE TALKED
ABOUT CLINICAL DEVELOPMENT, WE
HAD A LOT OF INDUSTRY ENGAGEMENT
AND SOME OF THE INDUSTRY
ENGAGEMENT WAS AROUND
PROFESSIONAL DEVELOPMENT, HAVING
THE INDUSTRY FOLKS TALK ABOUT
THE INDUSTRIES IN INDUSTRY AND
HOW TO BE SUCCESSFUL COLLABING
WITH INDUSTRY.
AGAIN WE DO A LOT OF TRAINING
WITH GRANT-WRITING BUT WHAT WE
DON'T ALWAYS DO IS TRAIN OUR
JUNIOR SCIENTISTS HOW TO
EFFECTIVELY COLLABORATE WITH
INDUSTRY, SO WE HAD
CONVERSATIONS ABOUT THAT.
AND THEN ALSO THE FUNDERS WERE
GREAT WITH ENGAGING WITH OUR
JUNIOR INVESTIGATORS AND HOW TO
BE SUCCESSFUL.
I TOLD YOU A LITTLE ABOUT THE
POSTER SESSION.
WE BROUGHT IN DM AMBASSADORS WHO
WOULD ENGAGE WITH ALL OF OUR
JUNIOR INVESTIGATORS AND TELL
THEM ABOUT IT.
THEN LASTLY, I THINK IT'S GREAT
FOR EVERYONE TO DO ADVOCACY, SO
WE TALKED ABOUT OPPORTUNITIES IN
ADVOCACY AND WAYS TO DO THAT AND
BRAINSTORMED HOW WE CAN DO IT
TOGETHER.
SO AS I SAID, WE HAD THE DM
AMBASSADORS, THEY SHARED THEIR
STORIES, THEY WERE GREAT ABOUT
TELLING THE YOUNG INVESTIGATORS
SORT OF HOW THEY'VE DEALT WITH
MYOTONIC DYSTROPHY, SORT OF
THEIR HOPES AND DREAMS.
WE AGAIN ASKED THE DM
AMBASSADORS TO WRITE UP ONE OR
EVEN MULTIPAGE STORIES, SO THIS
IS ALL MATERIAL THAT WAS SHARED
WITH EACH OTHER SO THAT WE COULD
ALL LEARN FROM EACH OTHER.
IN THE HANDBOOK.
AS I SAID THAT CLINICAL
ASSESSMENT WAS GREAT BY MARK
PLONCO AND -- SAMPSON FROM
STANFORD.
SO LOOKING FORWARD WHAT WE'RE
HOPING TO SEE AND WE EXPECT TO
SEE IS AN INCREASE IN THE NUMBER
OF PROPOSALS TO NIH, DOD, NSF
SORT OF OPPORTUNITIES OUT THERE,
WE WANT TO MAINTAIN/RETAIN OUR
GRADUATE STUDENTS AND
POSTDOCTORAL FELLOWS IN THE DM
FIELD AND HELP THEM BE
SUCCESSFUL.
AND THEN BUILDING AWARENESS WITH
THE PHYSICIANS AND EXPERIENCE IN
THE DM CARE AND TREATMENT, AND
THEN MORE BUILDOUT WITH EARLY
STAGE CLINICAL TRIALS AND
STARTUPS FOCUSED ON MYOTONIC
DYSTROPHY.
WE'RE EXCITED TO SEE MORE
COLLABORATIONS AMONGST THE
JUNIOR INVESTIGATORS AND WITH
THE GROUP LEADERS AND EXPERTS TO
REVIEW THEIR PROPOSALS.
WE'RE ENCOURAGING THEM TO SEND
THEIR PROPOSALS TO THE GROUP
LEADERS, TO THE EXPERTS, TO GET
ADVICE BEFORE THEY SUBMIT THEIR
PROPOSALS SO THEY CAN BE MORE
COMPETITIVE.
WE TALKED ABOUT THE INTERACTION
BETWEEN THE AMBASSADORS, THE
FAMILIES WITH THE COMMUNITY, AND
THEN THINKING ABOUT THE
DIVERSITY IN RESEARCH
APPROACHES, DIVERSITY IN
TRAINEES, THAT'S AN AREA WE CAN
CONTINUE TO IMPROVE IN, AND
DIVERSITY IN CLINICAL TRIAL
PARTICIPANTS AS WELL, THAT CAME
UP.
SO WE'RE GOING TO BE WRITING UP
A PUBLICATION ON THIS MEETING,
TALKING ABOUT THE OUTCOMES AND
LESSONS.
AND THEN THINKING ABOUT SORT OF
HOW TO BUILD ON THIS AT MDF
MEETINGS, IDMC MEETINGS AND
THINGS LIKE THAT.
AND WITH THAT, I'LL TAKE
QUESTIONS.
THANK YOU.
>> CAN WE TAKE THE SLIDES DOWN,
PLEASE, SO WE CAN SEE?
THANK YOU.
>> SORRY ABOUT THAT.
>> ALL RIGHT.
DR. CRISWELL HAS A QUESTION.
>> IT'S ANOTHER COMMENT.
I REALLY APPLAUD ALL OF THE
CREATIVITY YOU APPLIED TO
MEETING WITH THESE YOUNG
INVESTIGATORS.
I'M ALREADY TAKING NOTES FOR
SOME IDEAS TO BRING BACK TO OUR
INSTITUTE.
THANK YOU VERY MUCH FOR SHARING
THAT.
SOUNDS LIKE A FANTASTIC
OPPORTUNITY.
>> THANKS, DR. CRISWELL.
>> YES, I WOULD AGREE.
I THINK THESE KINDS OF MEETINGS
ARE TRANSFORMATIVE.
I MEAN, BRINGING IN THE PATIENTS
WITH LIVED EXPERIENCE AND THEN
ALSO THE YOUNG INVESTIGATORS,
THEY FORM A NETWORK AS WELL.
IT'S ALSO IN A BEAUTIFUL
SURROUNDING.
IT'S QUITE MEMORABLE, LEAVES A
LASTING IMPRESSION AND REALLY
INSPIRES THE YOUNG
INVESTIGATORS.
SO CONGRATULATIONS.
ANY OTHER QUESTIONS?
>> WE'RE LUCKY, THE FOUNDATION
WE WORKED WITH REALLY WANTS TO
WOULD YOU AND DAZZLE THE YOUNG
INVESTIGATORS AS A WAY TO REALLY
KEEP THEM IN THE FIELD.
>> I PARTICIPATED REMOTELY.
IT WAS A VERY NICE CONFERENCE
SITE, BUT I DIDN'T GET A CHANCE
TO VISIT.
>> NEXT TIME, GLEN.
>> AND THERE'S A COMMENT IN THE
CHAT BOX.
ERIC, DO YOU WANT TO JUST COME
OFF MUTE BRIEFLY AND SHARE THAT?
>> YEAH, I THINK I JUST SORT OF
APPLAUD ANDY FOR -- I MEAN, I
THINK ANDY REALLY SPEARHEADED A
LOT OF THIS AND IT JUST EMBODIES
HOW MUCH THE LEADERS IN THE
FIELD CARE ABOUT SUPPORTING THE
NEXT GENERATION OF RESEARCHERS.
VERY IMPORTANT TO ENSURE
LONGEVITY OF THESE COMMUNITIES,
AND THAT THERE'S GOING TO BE A
LOT MORE WORK TO DO EVEN AFTER
THERE ARE APPROVED THERAPIES, SO
THE JOURNEY DOESN'T END.
>> GREAT.
OKAY, MOVING ALONG.
NEXT WE'RE GOING TO HAVE A
MEETING REPORT FROM MS. KATHRYN
BRYANT OF THE SPEAK FOUNDATION
AND DR. BRAD WILLIAMS OF THE
JAIN FOUNDATION ON THE
LIMB-GIRDLE MUSCULAR DYSTROPHY
INTERNATIONAL CONFERENCE.
WHICH WAS HELD IN
WASHINGTON, D.C.
>> YES.
THANK YOU.
THANKS FOR INVITING US.
IT'S A PLEASURE TO BE HERE, AND
BRAD AND I ARE BOTH LIVING WITH
LIMB-GIRDLE MUSCULAR DYSTROPHY.
I HAVE LGMD 2I AND BRAD HAS --
BOTH OF US ARE INDIVIDUALS THAT
ARE AFFECTED, AND THIS
CONFERENCE WAS ORGANIZED BY
PATIENTS, AND THINK THAT'S WHAT
MAKES IT VERY UNIQUE, IS WE
BASICALLY ORGANIZED THIS
OURSELVES, AND THIS IS OUR THIRD
EVENT THAT WE'VE ORGANIZED.
SO I'M EXCITED TO SHARE TODAY
MORE ABOUT IT.
AT THE INTERNATIONAL LGMD
CONFERENCE, WE BROUGHT TOGETHER
EVERYONE WITH THE PURPOSE OF
EDUCATING.
WE WANT TO EDUCATE OUR PATIENTS,
OUR CAREGIVERS, BUT ALSO BRING
ALL OF THE SCIENTISTS TOGETHER
IN ONE AREA WITH INDUSTRY
REGULATORS AND HAVE EVERYONE
TOGETHER TO HEAR FROM EACH,
THEIR EXPERTISE.
WE WANT OUR TARGET AUDIENCE TO
ALWAYS BE OUR PATIENTS AND
FAMILY MEMBERS AND CAREGIVERS,
BECAUSE IN OUR AREA, LIMB-GIRDLE
IS SOMETHING THAT IS SO DIVERSE,
AND WE HAVE OVER 30 SUBTYPES
PLUS, SO THERE'S A LOT OF
DIFFERENT SUBTYPES AND PATIENTS
HAVE A LOT OF QUESTIONS, SO IT'S
IMPORTANT FOR OUR PATIENTS TO BE
ABLE TO COME.
WE REPRESENTED A LOT OF
DIFFERENT COUNTRIES, SO IT WAS
AN INTERNATIONAL EVENT, SO WE
HAD PATIENTS COMING FROM
COUNTRIES WHERE THEY REALLY
DON'T HAVE A LOT OF MEDICAL
CARE, AND THIS WAS AN EXCITING
TIME FOR THEM BECAUSE THEY GOT
TO MEET A LOT OF THE DOCTORS
THAT THEY HEAR ABOUT.
WE HAD CLINICIANS, ADVOCACY
ORGANIZATIONS, PHARMA,
RESEARCHERS, AND OUR MAJOR
THEMES WERE LGMD DIAGNOSIS AND
DISEASE MANAGEMENT.
WE HAD DRUG DEVELOPMENT,
CLINICAL STUDIES AND CLINICAL
TRIAL SESSIONS.
LIFE HACKS FOR LIVING WITH LGMD,
AND MAKING CONNECTIONS WITH
FELLOW COMMUNITY MEMBERS.
I WOULD SAY THAT THIS CONFERENCE
WOULDN'T NECESSARILY BE A
SCIENTIFIC CONFERENCE, BUT IT'S
PROBABLY AN INTERSECTION BETWEEN
A SCIENTIFIC CONFERENCE AND A
PATIENT CONFERENCE.
AND WE KIND OF DO BOTH OF THOSE
THINGS.
SO THAT EVERYONE'S NEEDS ARE
MET.
YOU'LL SEE PHOTOS THROUGHOUT
THIS PRESENTATION AS WELL.
SO THIS WAS OUR THIRD CONFERENCE
LAKE I MENTIONED.
LIKE I MENTIONED.
IN 2019, WE HAD OUR FIRST ONE IN
CHICAGO AND WE HAD 400 IN
ATTENDANCE.
AGAIN, THIS WAS ACTUALLY
ORGANIZED BY THREE PATIENTS WITH
LGMD.
MYSELF, I'M THE CONFERENCE ADD
STRAY, TO BRAD WILLIAMS, AND
CAROL ABRAHAM.
AND WE BASICALLY DID ALL THIS
HARD WORK IN 2019, AND IT REALLY
WENT OVER JUST SO WELL.
THEN IN 2021, WE HAD A VIRTUAL
EVENT, AND WE HAD ABOUT 1700
ATTEND.
AND THEN THIS YEAR, WE DID OUR
2023 CONFERENCE THAT I'M TALKING
ABOUT RIGHT NOW, AND IT WAS
HYBRID WITH A VIRTUAL AND AN
IN-PERSON.
WE HAD 700 REGISTRANTS, ABOUT
HALF IN PERSON AND HALF
VIRTUALLY, AND WE HAD 16
COUNTRIES REPRESENTED.
WHAT'S VERY UNIQUE AS WELL AS I
MENTIONED, WE HAD THIS MANY
PARTICIPATING ADVOCACY
ORGANIZATIONS IN THE LIMB-GIRDLE
SPACE.
I THINK WHAT MAKES LIMB-GIRDLE
VERY UNIQUE IS THE DIFFERENT
SUBTYPES, BUT THE RA CAMARADERIE
AND THE UNITY THAT WE HAVE
AMONGST ALL THE ORGANIZATIONS.
AND SO WE ALL WORKED TOGETHER ON
THIS CONFERENCE, AND ALL OF
THESE FOUNDATIONS HELPED, THEY
VOLUNTEERED, THEY SPONSORED, AND
WE COULDN'T HAVE DONE THIS
WITHOUT ALL OF THESE
PARTICIPANTS.
AND WHEN YOU LOOK AT ALL OF
THESE ORGANIZATIONS THAT FUND
RESEARCH FOR LGMD, IT'S IN THE
MULTI-, MULTI-, MULTIMILLIONS OF
DOLLARS WHEN YOU LOOK AT THE
CUMULATIVE EFFECT.
AND THEN WE ALSO HAD A BANQUET
AND KEYNOTE AWARD AND SOME
WONDERFUL STORIES.
OUR CLINICIAN OF THE YEAR WENT
TO DR. JERRY MENDELL OF
NATIONWIDE CHILDREN'S CHILDREN'.
WE ALSO WERE ABLE TO SHARE TWO
VIDEOS WHERE PARENTS OF
PEDIATRIC LGMD PATIENTS SHARED
ABOUT WHAT IT'S LIKE TO HAVE
CHILDREN WITH LGMD AND THE
SYMPTOMS THAT THEIR CHILDREN
EXPERIENCED EARLY ON.
AND THEN WE HAD FIVE PATIENT
WITH VARIOUS LGMD SUBTYPES SHARE
WHAT IT'S LIKE FOR THEM AS
ADULTS.
AND THAT WAS A VERY UNIQUE
EXPERIENCE FOR PEOPLE TO HEAR
WHAT THAT'S LIKE.
AND THEN DR. PETER MARKS,
DIRECTOR OF CBER, SPOKE WITH OUR
ENTIRE GROUP, AND THERE WAS A
FIRE SIDE CHAT AND THAT WAS VERY
FASCINATING, WHERE WE WERE ABLE
TO ASK QUESTIONS ABOUT DRUG
DEVELOPMENT.
WE JUST REALLY HAD A GREAT TIME
AS THIS CONFERENCE AND PATIENTS
WERE REALLY GRATEFUL AND SAID
THAT IT WAS SO HELPFUL TO THEM.
OUR COMMUNITY, TO BE ABLE TO
MEET ONE ANOTHER IN PERSON AND
BUILD THOSE CONNECTIONS.
IT'S VERY LIFE-CHANGING FOR SO
MANY.
I'M GOING TO BRING BRAD ON RIGHT
NOW, AND HE'S GOING TO BE
SHARING ABOUT WHAT OUR CLINICAL
SESSIONS WERE LIKE.
>> THANK YOU, KATHRYN.
IF YOU COULD ADVANCE THE SLADE.
SO WE TOOK ADVANTAGE OF BEING IN
D.C. TO HAVE NOT ONLY DR. MARKS
OF FDA BUT ALSO THREE PRESENTERS
FROM NIH.
ONE OF WHOM IS GLEN NUCKOLLS.
THANK YOU VERY MUCH FOR
PARTICIPATING, GLEN.
AND HE TALKED ABOUT THE MDCC,
WHAT IT DOES AND ALSO ABOUT
NIH'S RESEARCH SUPPORT FOR
RESEARCH THAT'S RELEVANT FOR
DEVELOPING BETTER DISEASE
UNDERSTANDING AND TREATMENTS FOR
LGMDs.
WE ALSO HAD P.J. BROOKS, WHO
SPOKE ABOUT THE BESPOKE GENE
THERAPY INITIATIVE.
SINCE LGMD HAS MANY SUBTYPES,
MANY OF WHICH HAVE VERY SMALL
PATIENT POPULATIONS, THIS
INITIATIVE IS POTENTIALLY VERY
IMPORTANT FOR THE LGMD SPACE TO
MAKE THOSE SUBTYPES WHICH HAVE
FEWER PATIENTS ABLE TO BENEFIT
FROM THE GENE THERAPY AS IT'S
DEVELOPED.
AND WE ALSO HAD SANDRA
DONKERVOORH WHO WORKS WITH
CARSTEN BONNEMANN TALK ABOUT
THAT PROGRAM AND SOME OF THE
RECENT DISCOVERIES BOTH IN NEW
LGMD SUBTYPES AS WELL AS
DIFFERENTIAL DIAGNOSES THAT CAN
MIMIC LGMDs.
SO SINCE A LOT OF THE CONFERENCE
WAS EDUCATING PATIENTS ABOUT
RESEARCH AND CLINICAL TRIALS,
CLINICAL STUDIES, A LOT OF THE
PRESENTERS WERE CLINICIANS
REPRESENTING A LARMI LARGE NUMBF
MEDICAL SPECIALTIES, NOT ONLY
NEUROLOGY AND PHYSICAL THERAPY,
BUT ALSO CARDIOLOGY,
PULMONOLOGY, AND RESPIRATORY
THERAPY.
WE HAD SEVERAL DRUG DEVELOPERS
PRESENT ON THEIR CURRENT DRUG
DEVELOPMENT PATHWAYS AND
CLINICAL TRIALS.
WE ALSO TOOK ADVANTAGE, AGAIN,
OF BEING IN D.C. TO TALK ABOUT
ADVOCACY.
WE WERE THANKFUL TO HAVE PAUL
MELMEYER OF MDA SPEAK ABOUT SOME
OF THEIR ADVOCACY PROGRAMS, AS
WELL AS THE EVERYLIFE
FOUNDATION.
AND IN ADDITION, WE TALKED ABOUT
SOME OF THE ADVOCACY THAT THE
LGMD SPACE HAS BEEN PURSUING
REACHING OUT TO FDA.
I ALSO WANT TO MENTION THAT 14
OF THE -- EITHER THE PRESENTERS
OR THE SESSION HOSTS ARE PEOPLE
LIVING WITH LGMD, AND THAT'S IN
A VARIETY OF ROLES AS
RESEARCHERS, AS CLINICIANS, AS
MEMBERS OF ADVOCACY
ORGANIZATIONS OR ALSO SHARING
THEIR EXPERIENCES WITH FELLOW
MEMBERS OF THE COMMUNITY.
SO FOR -- WE HAD SIX PLENARY
SESSIONS, AND THE TOPICS FOR
THAT WERE, FIRST TO GIVE AN
OVERVIEW OF LGMDs FOR PEOPLE
WHO MAY BE NEW TO THIS SPACE,
AND WHO WERE LOOKING FOR SOME
MORE BACKGROUND INFORMATION, AS
WELL AS NATURAL HISTORY STUDIES.
IT WAS RECOGNIZED A FEW YEARS
AGO THAT KNOWLEDGE OF THE
NATURAL HISTORY OF LGMDs
ACROSS ALL SUBTYPES WASN'T
REALLY WHERE IT NEEDED TO BE FOR
ENABLING CLINICAL TRIALS.
SO THERE ARE CURRENTLY SEVERAL
NATURAL HISTORY STUDIES GOING ON
ON A VARIETY OF DIFFERENT
SUBTYPES, SO WE HEARD ABOUT AN
OVERVIEW OF THAT.
ALSO THE GENETICS IS VERY
COMPLICATED FOR LGMDs.
THERE WAS ABOUT 30 DIFFERENT
GENETIC SUBTYPES, EACH OF THEM
HAS MANY MUTATIONS ASSOCIATED
WITH DEVELOPING THE DISEASE, SO
UNRAVELING ALL OF THAT TO GIVE
PEOPLE A CLEAR DIAGNOSIS AS WELL
AS MANAGING THEIR CLINICAL CARE
IS AN IMPORTANT TOPIC.
WE HAD A SESSION ON THAT.
AS I MENTIONED BEFORE, WE HAD A
SESSION ON ADVOCACY INITIATIVES
THAT ARE RELEVANT TO LGMD, AND
THEN FINALLY, WE HEARD UPDATES
ON THE CLINICAL TRIALS THAT ARE
HAPPENING IN LGMDs.
THERE'S SEVERAL CLINICAL, ACTIVE
CLINICAL TRIALS ON DIFFERENT
THERAPEUTIC MODALITIES FOR
DIFFERENT SUBTYPES AS WELL AS
LOOKING FORWARD, HEARING ABOUT
SOME NEW TREATMENTS UNDER
DEVELOPMENT THAT AREN'T YET TO
CLINICAL TRIALS BUT WHICH ARE
SHOWING A LOT OF PROMISE.
AND IN ADDITION TO THE PLENARY
SESSION, WE HAD BREAKOUT
SESSIONS WHICH COVERED A WIDER
VARIETY OF TOPICS.
WE HAD SOME ON CLINICAL CARE
FOCUSING ESPECIALLY ON MANAGING
CARDIAC AND RESPIRATORY
INVOLVEMENT WHICH ARE VERY
SIGNIFICANT IN SOME ALTHOUGH NOT
ALL SUBTYPES OF LGMD, AS WELL AS
WE HAD A PRESENTATION BY
DR. RAVANTE JONES WHO IS HERSELF
LIVING WITH LGMD 2B, WHO'S ALSO
A CLINICIAN AND SEES MD PATIENT,
SO SHE KIND OF GAVE HER VIEW
FROM BOTH PERSPECTIVES ABOUT HOW
PATIENTS CAN BEST INTERACT WITH
CLINICIANS AND GET THE MOST OUT
OF THEIR CLINIC VISITS.
THERE WERE ALSO TOPICS ON LIVING
WITH LGMD, PARENTING, MANY
PEOPLE WITH LGMD BECOME PARENTS,
AND SO FOR PEOPLE WHO ARE
PATIENTS AND ARE PARENTS, SHARED
THEIR EXPERIENCES WITH OTHERS,
AS WELL AS LIVING A FULFILLING
LIFE IN TERMS OF MENTAL HEALTH
AND WELL-BEING.
THAT WAS ALSO DONE BY A PATIENT
WHO'S ALSO A THERAPIST.
IN RESEARCH, WE HAD A SESSION,
AND THIS, NOT ONLY DR. BROOKS OF
NIH BUT ALSO SHARON HESTERLEE OF
MDA PRESENTED ABOUT MAKING GENE
THERAPY MORE VERSATILE.
HOW CAN IT APPLY TO MORE
DISEASES, HOW CAN -- MIGHT WE BE
ABLE TO DO RETREATMENT, HOW
MIGHT WE BE ABLE TO GET AROUND
SOME OF THE PROBLEMS THAT WE'RE
NOW RUNNING INTO.
AND ALSO THERE WAS AN ASK THE
EXPERT QUESTION AND ANSWER
SESSION.
FINALLY, SINCE A LOT OF THE
PEOPLE -- PATIENTS WERE FAMILY
MEMBERS, WE HAD FOUR BREAKOUT
SESSIONS, ONE FOR PARENTS, AND
THREE OTHERS FOR DIFFERENT AGES
OF PATIENTS JUST TO MEET AND
TALK AND SHARE EXPERIENCES TO
EACH OTHER.
AND IN THIS PICTURE, YOU'LL SEE
THE HOSTS OF ONE OF THE BREAKOUT
SESSIONS FOR YOUNGER PEOPLE.
SO IN ADDITION TO THE FORMAL
PROGRAM ON THE SCHEDULE, WE HAD
A FEW OTHER THINGS GOING ON.
WE ACTUALLY HAD TWO CLINICAL
STUDIES WHICH WERE CONDUCTED AT
THE CONFERENCE.
ONE WAS BY PEOPLE FROM
NATIONWIDE CHILDREN'S HOSPITAL,
AND THE UNIVERSITY OF NEW
CASTLE, WHICH WAS PROVIDING --
WHICH WAS CONDUCTING PHYSICAL
ASSESSMENTS GIVEN THE WIDE
VARIETY OF LGMD PATIENTS
REPRESENTING DIFFERENT SUBTYPES
AT THE MEETING.
ALSO THERE WAS A STUDY WHICH
COLLECTED SAMPLES.
THIS WAS CONDUCTED BY THE
UNIVERSITY OF MINNESOTA LED BY
DR. PETER KENG, AND TAKEN
SAMPLES TO LOOK INTO GENETICS,
PEOPLE WITH LGMD AND TO HELP
ENABLE GENOMIC STUDIES TO SOLVE
AND DIAGNOSE CASES.
DRUG DEVELOPERS HAVE NOT ONLY
BOOTHS WHERE THEY COULD MEET
PATIENTS, TALK TO THEM, SHARE
MORE DETAILS ABOUT THEIR DRUG
DEVELOPMENT PROGRAMS, BUT THEY
ALSO CONVENED PATIENT FOCUS
GROUPS, YOU KNOW, FOR PARTICULAR
TYPES, SHARING ABOUT PATIENTS'
ATTITUDES TOWARDS ORGANIZATION
OF CLINICAL TRIALS, AS WELL AS
THE PERCEPTIONS OF RISKS OF
POTENTIAL FUTURE TREATMENTS AND
BENEFITS OF FUTURE TREATMENTS.
SO IT WAS -- THERE WAS A LOT OF
THINGS GOING ON, AND IN MANY
CASES AT THESE MEETINGS, THIS
WILL BE THE FIRST TIME THAT
PEOPLE WILL HAVE EVEN MET A
FELLOW PATIENT OR LET ALONE A
LARGE NUMBER OF FELLOW PATIENTS,
LET ALONE GET TO KNOW THEM IN
SOME DETAIL.
NEXT SLIDE.
SO ALL OF THE SESSIONS THAT WERE
IN SORT OF THE MAIN ROOM, WHICH
WERE ALL OF THE PLENARY SESSIONS
AS WELL AS THE BREAKOUT SESSION
ON SORT OF THE NEXT GENERATION
OF GENE THERAPIES AND MANAGEMENT
OF CARDIAC AND RESPIRATORY
SYSTEMS WERE STREAMED AND
RECORDED, AND THOSE ARE ALL
AVAILABLE ON SPEAK FOUNDATION'S
YOUTUBE CHANNEL.
THE EASIEST WAY IS JUST GO TO
YOUTUBE, LOOK FOR 2023
LIMB-GIRDLE MUSCULAR DYSTROPHY
CONFERENCE, AND WE SHOULD BE
HAVING THE NEXT ONE IN TWO YEARS
AND THANK YOU FOR ALL OF YOUR
ATTENTION.
GLL THANK YO
>> THANK YOU SO MUCH, KATHRYN
AND BRAD.
IT'S SO GREAT TO SEE THE
COLLABORATION BETWEEN YOUR TWO
ORGANIZATIONS.
DO WE HAVE ANY QUESTIONS?
I DON'T SEE ANY.
SO IN THE INTEREST OF TIME,
WE'RE GOING TO MOVE ALONG.
WE THANK BOTH OF YOU FOR YOUR
PRESENTATION.
AND OUR LAST MEETING REPORT IS
FROM DR. ERIC CAMINO OF THE
PARENT PROJECT MUSCULAR
DYSTROPHY.
HE IS GOING TO TELL US ABOUT THE
PPMD ANNUAL CONFERENCES AND
OTHER SPECIALTY MEETINGS.
ERIC, YOU ARE ON.
>> THANK YOU.
SO I'M ERIC CAMINO, VICE
PRESIDENT OF RESEARCH AND
CLINICAL INNOVATION AT PPMD.
SO OUR FOCUS IS ON DUCHENNE AND
BECKER MUSCULAR DYSTROPHY, AND
SO I'M GOING TO DO KIND OF A
HIGH LEVEL OVERVIEW OF A FEW OF
THESE CONFERENCES THAT WE'VE
HELD IN THE PAST KIND OF YEAR
AND YEARS.
SO TO START, I WANTED TO TALK
ABOUT OUR ANNUAL CONFERENCE.
YOU CAN PROBABLY TELL BY THE
PICTURE ON THE RIGHT FROM THE
DANCE FLOOR AT THE END, WE HELD
THIS IN DALLAS, TEXAS THIS PAST
YEAR.
AND SO OUR ANNUAL CONFERENCE IS
A FAMILY-FOCUSED EVENT TO BRING
TOGETHER MEMBERS OF OUR
COMMUNITY, HELP CONNECT
FAMILIES, CREATE SOME OF THOSE
BONDS, AND THEN PROVIDE
EDUCATION ON KIND OF THIS
CONSTANTLY EVOLVING CLINICAL
CARE LANDSCAPE AND TRIAL
LANDSCAPE, AND THEN AGAIN
FACILITATE KIND OF CONNECTIONS
BETWEEN FAMILY MEMBERS.
SO SOME OF THE HIGHLIGHTS FROM
OUR 2023 CONFERENCE, WE HAD SOME
TALKS THAT WERE ON THE
IMPORTANCE OF SOCIAL CONNECTION.
THIS IS REALLY A THEME THAT I
THINK PROBABLY MANY GROUPS HAVE
FELT ACUTELY SINCE THE PANDEMIC,
IS THIS NEED FOR CONNECTION.
SO DR. BRANDON KOZAR GAVE A
REALLY GOOD TALK ON KIND OF
FINDING YOUR TRIBE AND WHAT THAT
MEANS.
WE HAD AN INITIAL PANEL ON CELL
AND GENE THERAPY AND KIND OF THE
ADVANCEMENTS THAT WE'RE HAVING
IN THE SPACE THERE FROM
DR. KEVIN FLANAGAN, CRAIG
MCDONALD AND MARUS.
THIS CONFERENCE CAME RIGHT ON
THE HEELS OF THE FIRST APPROVAL
OF A GENE THERAPY PRODUCT FOR
DUCHENNE MUSCULAR DYSTROPHY WITH
THE APPROVAL IN JUNE, SO I
THOUGHT IT WAS REALLY IMPORTANT
TO TALK ABOUT THAT AS WELL AS
THE OTHER ADVANCEMENTS THAT ARE
UNDERWAY IN BOTH OF THESE AREAS.
WE ALSO HAD RESEARCH ROW, WHICH
WAS A LITTLE BIT DIFFERENT FOR
US THIS YEAR, SO WE HAVE A LARGE
NUMBER OF COMPANIES THAT ARE IN
THE DUCHENNE AND BEGGAR SPACE,
ABOUT 35 ACTIVE CLINICAL TRIALS
AT A GIVEN TIME, SO THERE'S A
LOT OF INFORMATION THERE.
SO WE TRIED TO TARGET IT A
LITTLE BIT BETTER TO BREAKOUT SO
FAMILIES COULD FIND INFORMATION
ABOUT CLINICAL TRIALS THAT ARE
MAYBE A LITTLE BIT MORE RELEVANT
TO THEM, AND THEIR FAMILY
MEMBERS, SO THAT WAY YOU'RE NOT
NECESSARILY SITTING THROUGH
PRESENTATIONS THAT AREN'T SUPER
RELEVANT IF IT'S NOT FOR -- IF
IT'S ONLY FOR AMBULATORY
PATIENTS, SOMETIMES AS A
NON-AMBULATORY PATIENT YOU MAY
NOT WANT TO SIT THROUGH SOME OF
THOSE TALKS.
WE KIND OF BROKE IT UP TO GIVE
SOMEONE THE OPPORTUNITY TO SEE
REALLY RELEVANT MATERIAL.
AND WE HELD A NUMBER OF BREAKOUT
SESSIONS, SO ONE OF THEM WAS A
BECKER BREAKOUT SESSION BECAUSE
WE'VE SEEN SOME ADVANCEMENTS IN
THE PAST FEW YEARS WHERE OUR
BECKER POPULATION, WE'RE
STARTING TO SEE SOME CLINICAL
TRIALS THAT ARE BEING DEVELOPED
AND MOVE THROUGH THE PIPELINE IN
A WAY THAT WE HAVEN'T SEEN
BEFORE, AND THIS IS A
COMBINATION OF ADVANCEMENTS AND
THE NATURAL HISTORY THAT WE HAVE
FOR BECKER PATIENTS AS WELL AS
SOME EXCITING THERAPEUTIC
DEVELOPMENT.
AND THEN WE HAVE ALL OF OUR KIND
OF CARE SESSIONS THAT WE DO FOR
FAMILIES.
SO UPDATING THEM ON ADVANCEMENTS
IN CARDIAC CARE, GI CHALLENGES,
EVERYTHING INVOLVING THE
ENDOCRINE SYSTEMS, AND THEN, OF
COURSE, BEHAVIOR SESSIONS WHICH
REALLY ARE RELEVANT WHEN WE'RE
TALKING ABOUT A LOT OF OUR
DUCHENNE FAMILIES BECAUSE AS
I'LL TALK ABOUT IN SOME OF OUR
ENDOCRINE MEETINGS, A LOT OF
DUCHENNE PATIENTS ARE ON CHRONIC
STEROIDS, AND SO THIS DOES OR
CAN LEAD TO SOME ADDITIONAL
BEHAVIOR ISSUES AS WELL AS SOME
BEHAVIORAL OR DEVELOPMENT ISSUES
THAT COME ALONG AND A BYPRODUCT
OF THE DISEASE.
THEN WE ALSO HELD A GENE THERAPY
TOWN HALL AGAIN TO GIVE AN
OPPORTUNITY TO THE COMMUNITY TO
ASK QUESTIONS TO COMPANIES THAT
ARE DEVELOPING GENE THERAPY IN
THE SPACE AND THEN SOME OF OUR
EXPERTS THERE, SO WE HAD
DR. BEAR EE BERN GIVE A REALLY
GREAT OVERVIEW OF THE IMMUNE
SYSTEM AND KIND OF THE RESPONSE
THAT CAN OCCUR DURING GENE
THERAPY, WHICH IS -- IT'S A VERY
COMPLEX TOPIC BUT WE WANT TO
MAKE SURE FAMILIES ARE EDUCATED
FOR WHEN THEY PARTICIPATE IN
CLINICAL TRIALS.
AND OUR OPENING SPEAKER FROM
THAT WAS BUDDY CASSIDY, WHO WAS
THE PATIENT REPRESENTATIVE ON
THE ADVISORY COMMITTEE FOR
ELEBEDIS.
THIS WAS OUR LARGEST IN-PERSON
PMD EVENT.
WE HAD OVER 800 INDIVIDUALS ON
THE GROUND IN DALLAS.
WE HAD OVER A THOUSAND ATTENDEES
IN TOTAL, AND WE ARE LOOKING
FORWARD TO OUR 30TH ANNIVERSARY
IN ORLANDO NEXT YEAR.
WE'VE ALREADY HAD THE SAME
AMOUNT OF FAMILIES REGISTER FOR
IT SO I THINK IT'S GOING TO BE A
BIG EVENT AND A BIG CELEBRATION.
I WAS ALSO ASKED TO COVER SOME
OF OUR MORE SPECIALTY MEETINGS.
THESE ARE AIMED AT CLINICIANS,
RESEARCHERS, OTHER INDUSTRY
MEMBERS, AND SO WE HAD TWO
DIFFERENT SPECIALTY MEETINGS
TAKE PLACE IN THE PAST YEAR.
ONE OF WHICH WAS OUR CARDIAC
MEETING SO THIS IS A THREE-PART
SERIES.
OUR THIRD MEETING WILL BE IN
2024 IN PARTNERSHIP WITH A FEW
CARDIOLOGISTS.
WE HAVE AROUND 80 CLINICIANS AND
RESEARCHERS AND INDUSTRY
PARTICIPATE IN THIS EVENT.
THIS STARTED IN 2022, AS YOU
HEARD KIND OF IN THE EARLIER
TALKS FROM DR. BIANCHI THAT
HEART FAILURE IS THE LEADING
CAUSE OF MORTALITY IN DUCHENNE
AND WE DON'T HAVE CARDIAC END
POINT THAT CAN BE USED AS
PRIMARY OUT COME MEASURES IN
CLINICAL TRIALS, SO WELL HAVE
THIS GAP THAT WE NEED TO
ADDRESS.
WHEN WE TALK WITH THE FAMILY
MEMBERS, WE'RE ALWAYS SAYING
HEART IS A MUSCLE TOO.
SO THE FOCUS WAS TO GIVE US KIND
OF AN OVERVIEW OF OUR CURRENT
UNDERSTANDING OF CARDIAC END
POINTS.
WE HAD SOME PARTICIPATION FROM
MEMBERS OF THE FDA THERE, WHICH
WAS HELPFUL AS WE JUST KIND OF
START TO DISCUSS WHAT IS THE FDA
LOOKING FOR, WHAT ARE THE
OPINIONS AND THE DATA THAT IS
SUPPORTED FROM OUR CARD YOL JIS
CARDIOLOGISTSTO DEVELOP THESE E.
WE DISCUSSED TRYING TO GET A
BETTER UNDERSTANDING OF THE RISK
OF PROGRESSION AND THEN I THINK
IT REALLY IMPORTANTLY, TIMING OF
INTERVENTIONS.
WE DO HAVE CARE STANDARDS THAT
HAVE BEEN DEVELOPED ALONG WITH
THE CDC.
THOSE ARE CONSENSUS STANDARDS.
SO THERE'S ALWAYS KIND OF THE
LOWEST COMMON DENOMINATOR IN
TERMS OF HOW YOU'RE GOING TO USE
INTERVENTIONS AND SO A LOT OF
OUR CARDIOLOGISTS FEEL THAT HE
WITH CAN BE A BIT MORE
AGGRESSIVE SO THERE WERE
DISCUSSIONS IN SOME OF THE DATA
PRESENTED HERE FROM THE TIMING
OF SOME OF THOSE INTERVENTIONS.
AND THEN, OF COURSE, SOMETHING
THAT WAS REALLY RELEVANT AND
CONTINUES TO BE IS THE IMPACT OF
GENE THERAPY ON THE HEART.
MOST OF THE GENE THERAPY TRIALS
TO DATE IN THE DUCHENNE SPACE
ARE WITH THESE YOUNG AMBULATORY
PATIENTS, AND WE HAVE QUESTIONS,
OF COURSE, AROUND IS THE THERAPY
GETTING INTO THE HEART, IS IT
PROVIDING BENEFIT, IF YOU'RE
IMPROFFERRING THE SKELETAL
MUSCLE FUNCTION OF THESE
PATIENTS, IS THAT GOING TO
CONTRIBUTE TO FUTURE IMPACT ON
THE HEART IF IT'S NOT BEING
PROTECTED.
THE ULTIMATE OUTPUT FROM THIS
MEETING WAS AN INVESTMENT OF
PPMD OF $2 MILLION OVER THREE
YEARS TO SUPPORT THE EXPANSION
OF A DMD SUBGROUP IN THE ACTION
LEARNING NETWORK, A NATIONWIDE
PEDIATRIC CARDIOLOGY NETWORK.
AND SO THE GOAL THERE IS TO --
ONE OF THE -- THE MAIN GOAL IS
TO COLLECT PROSPECTIVE DATA ON
PATIENTS, SO TO DATE, THEY'VE
ENROLLED 500 PATIENTS IN THIS
STUDY.
THEY'RE DOING SOME OTHER THINGS
LIKE DEVELOPING CARDIAC-SPECIFIC
PROs, DEVELOPING EDUCATION
MATERIALS FOR PATIENTS.
AND THAT CARDIAC REPORT IS
AVAILABLE ON OUR WEBSITE AND I
CAN DROP A LINK IN THE CHAT
AFTERWARDS.
AND 2023, OUR MEETING WAS
FOCUSED ON KIND OF THE IMPROVING
CARE AND UNDERSTANDING OF
CARDIOMYOPATHY, SO WE HAD A LOT
OF DISCUSSION ABOUT THE CURRENT
PROTOCOLS, AND SO THIS CAME OUT
OF A LOT OF THE WORK FROM THE
ACTION NETWORK AROUND
HARMONIZATION OF PROTOCOLSS, SO
THAT WAY WE ARE CONSISTENTLY
COLLECTING DATA ON PATIENTS
ACROSS OUR CENTERS, TRYING TO
MAKE SURE AS WELL THAT THE WAY
WE'RE COLLECTING DATA WILL ALLOW
FOR KIND OF INTEROPERABILITY
DOWN THE LINE WHEN WE START TO
COMPARE DATASETS.
WE SHARED DATA ON SOME MORE
NOVEL MEDICATIONS THAT ARE
STARTING TO BE IMPLEMENTED IN
CARDIAC CARE FOR DUCHENNE AND
BECKER WITH ENTRESTO AND
SGL2 INHIBITORS.
DISCUSSIONS AROUND MONITORING
GENE THERAPY PATIENTS, AGAIN,
THIS WAS DONE IN APRIL SO BEFORE
THE APPROVAL OF ELEBITUS BUT
WITH HOW OUR CARE CENTERS ARE
SET UP TO MONITOR PATIENTS LONG
TERM AND OF COURSE REALLY
IMPORTANT TALKING ABOUT HEALTH
DISPARITIES ACROSS THE
LANDSCAPE.
SO WE HAVE ANOTHER MEETING
REPORT FOR THAT FORTHCOMING.
THEN IN 2024, WE ARE GOING TO
HAVE OUR NEXT MEETING IN
BALTIMORE, MARYLAND, AND IT'S
GOING TO BE A BIT MORE OF A
DISCUSSION TO INCLUDE SOME OF
THE BECKER AND CARRIERS.
WE DO HAVE NATURAL HISTORY DATA
THAT SHOWS THAT THERE ARE
CARDIAC MANIFESTATIONS IN SOME
CARRIERS OF DUCHENNE AND BECKER,
AND SO WE WANT TO MAKE SURE THAT
THOSE PATIENTS WERE ALSO BEING
LOOKED AFTER AND BEING PROVIDED
WITH QUALITY CARE.
THE OTHER SPECIALTY MEETINGS
THAT WE HELD WERE ON ENDOCRINE,
AND SO WE HAD TWO ENDOCRINE
MEETINGS THIS YEAR.
THE FIRST ONE WAS A SMALLER
MEETING THAT WAS HELD IN ROME,
ITALY WITH ABOUT 30 HEALTHCARE
PROFESSIONALS AND PATIENT
ADVOCATES FROM A COUPLE OF
DIFFERENT COUNTRIES.
AND LOOKING AT THIS CHALLENGE
FROM THE LONG TERM USE OF
CORTICOSTEROIDS SINCE THAT IS
THE BACKBONE, MOST PATIENTS WITH
DUCHENNE ARE CHRONICALLY ON A
CORTICOSTEROID AND THERE'S A
WHOLE HOST OF SIDE EFFECTS THAT
COME ALONG WITH THIS, ADRENAL
SUPPRESSION, LONG BONE
FRACTURES, FAT EMBOLISM
SYNDROME, AND SO THERE'S A LOT
OF AREA HERE FOR US TO TRY AND
ADDRESS AND IMPROVE, AND OF
COURSE WE HAD IN OCTOBER THE
APPROVAL OF AGARY, WHICH IS -- ,
ANOTHER CORTICOSTEROID, FOR
DUCHENNE.
SO THE PURPOSE OF THIS MEETING
WAS TO TALK THROUGH THE
PREVENTION OF THE FIRST EVER
FRACTURE.
AS YOU KNOW, FRACTURES ARE OFTEN
THE EVENT THAT LEADS TO LOSS OF
AMBULATION IN MANY OF THE BOYS,
AND THEN TRYING TO PREVENT
UNEXPECTED DEATH FROM
UNRECOGNIZED ADRENAL SUPPRESSION
AND CRISIS.
THAT SPURRED AND LED TO A
FOLLOW-ON MEETING IN OCTOBER OF
2023 WITH A SMALL COHORT OF
ENDOCRINOLOGISTS, AND THIS WAS
WITH DR. LEANNE WARD AT THE EURT
UNIVERSITY OF OTTAWA.
THE MAIN PURPOSE OF THIS WAS TO
IDENTIFIED ELEMENTS FOR AN
ENDOCRINOLOGY NATURAL HISTORY
STUDY.
THERE ARE CURRENTLY A NUMBER OF
WORK GROUPS ON WHAT ARE THE
COMMON ELEMENTS THAT WOULD NEED
TO BE COLLECTED FOR A BONE
HEALTH REGISTRY, AND AS THAT'S
DEVELOPED, LOOKING FOR WHAT THE
INFRASTRUCTURE WILL BE FOR KIND
OF RUNNING AND MAINTAINING THAT
REGISTRY.
AND OTHER TOPICS THAT CAME UP IN
THAT, YOU KNOW, THINGS LIKE
BIRTH IN PUBERTY, WEIGHT
MANAGEMENT, ADRENAL
INSUFFICIENCY, OSTEOPOROSIS AND
SEXUALITY AND FERTILITY, SO A
MEETING REPORT FOR THIS IS
FORTHCOMING AS WELL.
SO THE LAST THING I WAS TALKING
ABOUT TODAY IS JUST TO TALK
THROUGH A LITTLE BIT DIFFERENT.
THIS IS MORE AIMED AT KIND OF
THE SUPPORT SYSTEM AROUND
PATIENTS.
SO THIS IS OUR LIGHTHOUSE
PROJECT.
SO THIS WAS A PROJECT THAT CAME
ABOUT DURING THE PANDEMIC.
SO PAT FERLONG, OUR CEO,
PRESIDENT AND FOUNDER KIND OF
LAUNCHED THIS, WHERE THERE WAS
EIGHT WEEKS OF ABOUT 20 MOMS
MEETING AND TALKING ABOUT SELF
AND LANGUAGE THAT'S USED TO FORM
NARRATIVES AND CHALLENGES OF
BEING A CAREGIVER AND WHAT THAT
MEANS.
AND REALLY THE POWER OF LANGUAGE
AND HOW THAT DEFINES A LOT OF
HOW PEOPLE RESPOND TO
SELF-WORTH.
AND IT WENT SO WELL THAT THEY
CONTINUED FOR ANOTHER 37 WEEKS
AND THEY REALIZED THIS WAS
SOMETHING THAT REALLY SHOULD BE
OFFERED TO MORE FAMILIES.
SO THIS IS GUIDED BARRE CHEL
CALLENDAR'S ALLYSHIP PROGRAM,
SHE LOST A CHILD TO A RARE
DISEASE, SHE DOES A LOT OF
SPEAKING AND EDUCATION IN THESE
ALLYSHIP PROGRAMS.
SO SHE HELPS GUIDE THESE
MEETINGS WHICH WE'VE EXPANDED TO
A NUMBER OF COHORTS SO THERE IS
WOMEN PRIMARY CAREGIVERS, SOME
PRIMARY CAREGIVER GROUPS AS WELL
AS EXPANSION TO SPOUSES AND
PARTNERS OF INDIVIDUALS LIVING
WITH BECKER.
AND WE KEEP THESE IN SMALL
GROUPS SO ABOUT 20 INDIVIDUALS
PER GROUP TO TRY AND KEEP IT A
LITTLE BIT MORE INTIMATE AND THE
ABILITY FOR PEOPLE TO SHARE
OPENLY, AND THESE GROUPS MEET
EVERY OTHER WEEK FOR EIGHT
SESSIONS AND THEY TALK THROUGH
WELL-BEING, SENSE OF SELF, A LOT
OF PERSONAL REFLECTION.
AND JUST TRYING TO FIND WAYS TO
PROVIDE SUPPORT TO CAREGIVERS IN
OUR COMMUNITY THAT MAYBE THIS IS
OFTEN OVERLOOKED.
SO PART OF THIS AS WELL, IN
2022, WE HAVE THIS POWER OF US
SUMMIT WHICH WAS AGAIN FOCUSED
AROUND CAREGIVERS, GRANDPARENT,
SIBLINGS, THAT REALLY I THINK
AFFIRMED FOR US THE NEED TO
CONTINUE TO TRY AND REACH OUT TO
OUR COMMUNITY AND BUILD THESE
RESOURCES.
BECAUSE WHEN I ATTENDED THIS
EVENT, YOU HEARD A LOT OF REALLY
POWERFUL STORIES FROM A LOT OF
THESE FAMILIES ON WHAT IT MEANS
TO BE A CAREGIVER OR A SIBLING,
AND THEY DON'T ALWAYS HAVE A
PLACE TO SHARE THEIR STORIES AND
TO MAKE THOSE CONNECTIONS SO
WE'RE TRYING TO FACILITATE THAT
AND ALLOW THEM TO BUILD THEIR
OWN COMMUNITIES IN ADDITION TO
THE KIND OF BROADER COMMUNITY.
SO WE'RE GOING TO CONTINUE THIS
PROJECT AND CONTINUE TO EXPAND
TO OTHER GROUPS, BUT IT'S BEEN
REALLY WELL RECEIVED IN THE
COMMUNITY AND SO WE'RE LOOKING
FORWARD TO KIND OF BUILDING ON
THIS.
SO THAT WAS KIND OF THE
WHIRLWIND OF A COUPLE OF OUR
SPECIALTY MEETINGS AND
CONFERENCE, SO THANK YOU,
EVERYONE.
>> THANK YOU VERY MUCH, ERIC.
I THINK IN THE INTEREST OF TIME,
WE'RE RUNNING ABOUT 15 MINUTES
BEHIND, SO WE ARE GOING TO HOLD
THE QUESTIONS AND MOVE RIGHT
ALONG BECAUSE I'M SURE PEOPLE
ARE BEGINNING TO GET A LITTLE
HUNGRY IF THEY ARE ON THE EAST
COAST TIME ZONE.
SO THE NEXT SESSION OF OUR
MEETING WILL INCLUDE
PRESENTATIONS ON REGULATORY
APPROVALS OR PENDING REGULATORY
CONSIDERATIONS IN DUCHENNE
MUSCULAR DYSTROPHY.
SO I'M GOING TO TURN IT OVER TO
GLEN TO INTRODUCE THIS SESSION.
>> THANKS, DR. BIANCHI.
SO THE THEME OF THIS SESSION IS
RECENT ADVANCES IN DMD, AND THE
PRESENTATIONS WILL COVER
DIFFERENT REGULATORY ACTIVITIES.
SO THE MDCC CERTAINLY COVERS ALL
OF THE FORMS OF MUSCULAR
DYSTROPHY.
IT'S UNUSUAL FOR US TO FOCUS ON
ONE TYPE, IN THIS CASE,
DUCHENNE, SO WHAT WE'LL HEAR
ABOUT ARE RECENT REGULATORY
DECISIONS OR PENDING REGULATORY
DECISIONS THAT REALLY MARK THE
CULMINATION OF DECADES OF
RESEARCH AND DEVELOPMENT.
AND THE PRESENTERS WILL SHARE
SOME LESSONS LEARNED AND
EFFECTIVE STRATEGIES THAT HAVE
LED TO THESE ADVANCES.
SO THE GOAL OF THE SESSION ARE
REALLY TWOFOLD.
ONE, TO HIGHLIGHT THESE
ACCOMPLISHMENTS, BUT ALSO TO
CONSIDER HOW THESE REGULATORY
PATHS COULD BE EFFECTIVELY USED
IN, FOR EXAMPLE, FSHD RESEARCH
OR LIMB-GIRDLE MUSCULAR
DYSTROPHY OR OTHER FORMS OF
MUSCULAR DYSTROPHY BY LEVERAGING
THE KNOWLEDGE AND EXPERTISE OF
THE TRAILBLAZERS THAT WE'LL HEAR
FROM IN THIS SESSION.
SO JUST TO GIVE YOU AN IDEA OF
THE STRUCTURE OF THE SESSION,
FIRST WE'RE GOING TO HEAR A
CONVERSATION BETWEEN JENNIFER
AND LEANNA, JENNIFER'S FAMILY IS
PERSONS EXPERIENCED AND
PARTICIPATING IN A RECENT
CLINICAL TRIAL, THEN WE'RE GOING
TO HEAR FROM NIKI ARMSTRONG FROM
PARENT PROJECT MUSCULAR
DYSTROPHY, AND SHE'LL BE GIVING
US AN UPDATE ON NEWBORN
SCREENING.
WE'LL HEAR FROM BILL ROONEY AND
OREGON HEALTH SCIENCES
UNIVERSITY ON CLINICAL TRIAL
SIMULATION TOOL, THEN FROM
RAMONA FROM THE CRITICAL PATH
INSTITUTE, SHE'LL BE TALKING
ABOUT REGULATORY ACTIVITIES,
CRITICAL PATH, AND THE DUCHENNE
REGULATORY SCIENCE CONSORTIUM.
SO THAT'S KIND OF THE STRUCTURE.
WE'LL HAVE A LUNCH BREAK AFTER
THE FIRST PRESENTATION OR FIRST
DISCUSSION.
AND I'LL TURN IT BACK TO
DR. BIANCHI TO INTRODUCE THE
NEXT PRESENTERS.
>> OKAY.
WELL, WE THOUGHT THERE WOULD BE
NO BETTER WAY TO HIGHLIGHT THE
APPROVAL OF THE FIRST GENE
THERAPY FOR ANY FORM OF MUSCULAR
DYSTROPHY THAN TO INVITE SOMEONE
WHO HAS LIVED EXPERIENCE OF
PARTICIPATING IN THE TRIAL TO
SHARE THEIR THOUGHTS ON THIS
MOMENTOUS ACCOMPLISHMENT.
WE'D LIKE TO WELCOME
MS. JENNIFER HANDT.
MS. HANDT IS A PATIENT ADVOCATE.
SHE'S THE FOUNDER OF CHARLIE'S
CURE, AND SHE'S THE MOTHER OF
CHARLIE, WHO PARTICIPATED IN THE
EMBARK TRIAL FOR SAFETY AND
EFFICACY OF THE GENE THERAPY,
NOW CALLED ELEVIVIS IN DMD.
INSTEAD OF A PRESENTATION OR
STATEMENT TO THE COMMITTEE, WE
INVITED DR. LIANNA ORLANDO AND
HAVE A CONVERSATION LIKE A
FIRESIDE CHAT WITH JENNIFER.
IF THERE'S TIME AFTER THEIR
CONVERSATION, WE HOPE THAT
JENNIFER MAY BE OPEN TO
QUESTIONS FROM THE COMMITTEE OR
PEOPLE IN OUR AUDIENCE.
THANKS TO BOTH JENNIFER AND
LIANNA FOR PARTICIPATING IN OUR
MEETING TODAY.
>> THANK YOU SO MUCH FOR HAVING
US.
>> JENNIFER, WHY DON'T WE JUST
GET STARTED WITH YOU TELLING US
A LITTLE BIT ABOUT YOURSELF AND
YOUR FAMILY.
>> SURE.
FIRST, LET ME JUST START BY
SAYING IT'S GREAT TO GO SORT
AFTER ERIC TALKING ABOUT THE KEY
ISSUES IN DMD RIGHT NOW, BECAUSE
I THINK YOU'LL HEAR A LOT OF
THROUGH LINES IN OUR
CONVERSATION, WHETHER IT
CHARLIE'S CURE OR CURE DUCHENNE
OR PPMD, WE'RE ALL FOCUSED ON
THE SAME KIND OF PROBLEMS RIGHT
NOW, AND SO IT'S WONDERFUL TO
HAVE THIS OPPORTUNITY.
SO IT'S ME, MY FAMILY IS ME, MY
HUSBAND RICK, AND OUR TWO BOYS,
HENRY, WHO'S 13, HE DOES NOT
HAVE DMD, ALTHOUGH I LATER
LEARNED THAT I'M A CARRIER SO
THAT WAS A COIN FLIP THAT
FORTUNATELY HE GOT THROUGH.
AND CHARLIE, WHO'S 6, WHO DOES
HAVE DUCHENNE MUSCULAR
DYSTROPHY.
AND BEFORE HE WAS DIAGNOSED IN
2020, IT WAS NOT SOMETHING THAT
WAS EVER ON OUR RADAR, I WILL
JUST SAY.
AND IT ALSO KIND OF SO HAPPENS
THAT I'VE WORKED MY ENTIRE
CAREER IN HEALTH COMMUNICATION.
I SPENT SOME FORMATIVE YEARS IN
WASHINGTON DOING SOME LOBBYING
AND ADVOCACY, AND WORK A LOT IN
HEALTHCARE AND MEDICAL
COMMUNICATION.
SO IT'S KIND OF A STRANGE
FATEFUL KIND OF TRAINING FOR
WHERE I AM TODAY, I'M JUST
REALLY GRATEFUL FOR THE
OPPORTUNITY TO TALK TO YOU ALL
EARLY ON IN THE DIAGNOSIS
PROCESS.
THE FOUNDER OF CURE DUCHENNE
SAID TO ME ACTION IS THERAPY.
SO I TOTALLY AGREE WITH THAT,
AND TAKING ACTION BY TALKING TO
YOU TODAY IS THERAPEUTIC, SO
THANK YOU.
>> THANK YOU FOR THAT.
YOU KNOW, I WANTED EVERYONE TO
HEAR JUST -- TO APPRECIATE HOW
MUCH SCIENCE ACUMEN YOU HAVE,
BECAUSE I THINK THAT PROBABLY
SHAPED OR -- YOU HAVE MORE
EXPERIENCE WITH LOOKING AT
COMPLEX INFORMATION, CERTAINLY
SCIENTIFIC INFORMATION, AND IT
PROBABLY SHAPED YOUR PARTICULAR
JOURNEY IN DECISION-MAKING.
SO COULD YOU TELL US A LITTLE
BIT ABOUT WHEN CHARLIE FIRST
STARTED SHOWING SIGNS OF DMD AND
WHAT IT TOOK TO GET A DEFINITIVE
DIAGNOSIS?
>> YEAH, SO I'LL START BY SAYING
THAT OUR EXPERIENCE IS EXTREMELY
COMMON.
IF I TALK TO OTHER MOMS, IT'S
ALL THE SAME STORY.
IT'S THERE WERE THESE LITTLE
SIGNS, THERE WERE KIND OF THIS
LIKE SPIEDY SENSE AS PARENTS
THAT SOMETHING WAS NOT QUITE
RIGHT.
SO IN HIS FIRST YEAR, HE WAS
JUST SORT OF NOT MEETING
MILESTONES AND I WOULD SAY TO
THE PEDIATRICIAN, YOU KNOW, WE
HAVE CONCERNS AND SHE WOULD SORT
OF SAY, YOU KNOW, WHEN YOU HEAR
HOOVES, THINK OF HORSES, NOT
ZEBRAS, SO SHE HAD SEEN A LOT OF
PATIENTS OVER THE YEARS WHO HAD
DEVELOPMENTAL DELAYS AND IT'S
USUALLY NOTHING.
SO THEN IT'S LIKE YOUR SCIENCE
UNDERSTANDING OR MEDICAL
AWARENESS VERSUS YOUR INSTINCTS
AS A PARENT, LIKE YOU SORT OF
LIKE ARE LIKE, OKAY, I'D LIKE TO
BUY INTO THAT STORY AND GO ALONG
WITH THAT.
BUT THEN AS HE WASN'T WALKING
WHEN HE WAS TURNING 2, LATER AS
HE WAS TURNING 3, THERE WERE
JUST TOO MANY SIGNS TO IGNORE,
SO I SELF-REFERRED TO A
NEUROLOGIST TO GET THAT
DIAGNOSIS.
IT'S FUNNY WITH DMD, IT'S SUCH A
PROFOUNDLY IMPACTFUL DISEASE,
THERE'S SO MANY WAYS IN WHICH IT
AFFECTS MOBILITY AND OTHER
THINGS.
BUT AT FIRST IT'S VERY SUBTLE.
LIKE I KNOW A LOT OF FAMILIES
WHO SORT OF -- WITH ANOTHER
CONCERN AND THEN HAD A BLOOD
PANEL DRAWN AND IT TURNED OUT
LIVER ENZYMES WERE ELEVATED AND
THAT'S HOW THEY GOT THE
DIAGNOSIS.
SO THE SORT OF DIAGNOSTIC
ODYSSEY IS ONE OF THE THINGS
THAT I KIND OF WANT EVERYONE TO
UNDERSTAND, IS THAT IT TAKES A
WHILE TO GET THE DIAGNOSIS.
I THINK THE AVERAGE IS AGE 5,
WHEN REALLY THE DIAGNOSTIC IS SO
EASY.
IT'S A CK TEST, IF IT'S
ELEVATED, IT'S USUALLY MUSCULAR
DYSTROPHY AND THEN IT GOES FROM
THERE.
BUT IT WAS AN ODYSSEY AND IT DID
TAKE SOME TIME.
>> AND WHEN YOU FINALLY DID GET
THE DIAGNOSIS, WHAT WAS THAT
LIKE FOR YOUR FAMILY?
>> I MEAN, IT JUST IS LIKE IT'S
EARTH SHATTERING.
IT JUST -- EVERYTHING CHANGES IN
THAT MOMENT, YOU KNOW?
EVERYTHING.
YOUR THOUGHTS ABOUT THE FUTURE,
YOUR DAILY LIFE, EVERYTHING IS
IMPACTED.
I SORT OF FELT LIKE WHAT I COULD
DO IS EDUCATE MYSELF AND FIGURE
OUT -- AT THE SAME TIME,
DUCHENNE IS A TERRIBLE
DIAGNOSIS, BUT AT THE SAME TIME,
I WAS HEARTENED TO REALIZE THAT
THERE WAS SO MUCH GOING ON,
THERE WAS SO MUCH RESEARCH
HAPPENING, AND SO MANY THINGS IN
THE PIPELINE THAT COULD HELP
CHARLIE POTENTIALLY THAT THAT
SORT OF GAVE ME A LOT OF HOPE.
>> AND HOW DID YOU FIND OUT
ABOUT THE TRIAL?
>> SO I THINK IT'S KIND OF --
IT'S INTERESTING BECAUSE I THINK
A LOT OF PEOPLE SORT OF FEEL
LIKE THEIR CARE TEAM WILL MAKE
THEM AWARE OF TRIALS, AND IN
SOME WAYS, THAT DOES HAPPEN.
BUT I THINK IT ACTUALLY REQUIRES
A LOT OF HOMEWORK ON PARENTS'
PART.
I WAS JUST A SQUEAKY WHEEL.
I JUST FIGURED OUT WHERE THE
DIFFERENT GENE -- SO LET ME JUST
BACK UP FOR A SECOND.
SO IT BECAME OBVIOUS EARLY ON
THAT CHARLIE'S MUTATION WOULD
NOT BE AMENABLE TO ANY OF THE
EXON SKIPPERS THAT WO, SO IT BEE
CLEAR THAT THAT WAS OUR
REALLY -- LIKE OUR MAIN HOPE,
SORT OF HARNESSING WHATEVER
MEDICINE WAS OUT THERE FOR
CHARLIE RIGHT NOW.
SO ONCE THAT WAS A FOCUS FOR ME,
I DID SOME HOMEWORK, I FIGURED
OUT WHERE THE SITES WERE OPENING
FOR THE VARIOUS TRIALS, AND I
REACHED OUT, I HAD CONVERSATIONS
WITH MULTIPLE CENTERS BR
SETTLING ON WHERE WE ENDED UP
FOR EMBARK.
AND I JUST LIKEN TO IT'S A
LITTLE BIT FEELING LIKE YOU'RE
KIND OF PARADING YOUR KID AROUND
AS A CONTESTANT, LIKE, THIS IS
CHARLIE, HE WILL BE GREAT FOR A
TRIAL.
SO IT'S KIND OF AN INTERESTING
PROCESS, BUT AS A PARENT, YOU
DEFINITELY HAVE TO BE VERY
ACTIVE AND PROACTIVE, AND IT DID
OCCUR TO ME DURING THAT PROCESS
THAT I AM FAIRLY -- I HAVE A LOT
OF RESOURCES, WHAT ABOUT
FAMILIES WHO DON'T HAVE THOSE
RESOURCES?
SO THAT'S ONE THING THAT HAS
BEEN ON MY MIND THAT I JUST WANT
TO SHARE THAT I THINK THE ACCESS
TO THE CLINICAL TRIALS IS
DIFFICULT.
>> IN THE END, DID YOU END UP
PARTICIPATING IN THE CLINICAL
TRIAL AT THE SITE WHERE YOU GET
YOUR CARE OR WAS IT A DIFFERENT
SITE?
>> I DIDN'T, NO, THAT WAS NOT A
SITE FOR SEREPTA.
THERE WAS A LOT OF
DECISION-MAKING THAT WENT INTO
CHOOSING EMBARC.
ONE OF THE THINGS WAS THAT IT
WAS ONLINE AT THE RIGHT TIME,
BUT ALSO THAT THE MOST PATIENTS
WHO HAD RECEIVED GENE THERAPY
FOR DUCHENNE HAD RECEIVED THE
SEREPTA DRUG SO THAT WAS
REASSURING IN TERMS OF SAFETY.
SO OUR CARE SITE WAS NOT A SITE
FOR THE EMBARC TRIAL, SO I WAS
FOCUSED OND FIND ON FINDING SOMG
THAT COULD WORK FOR OUR FAMILY.
ULTIMATELY WE CHOSE THE SITE
THAT WE CHOSE BASED ON
CONFIDENCE IN THE PROVIDERS AND
JUST A GOOD FEELING ABOUT THE
WAY THAT THEY WERE GOING TO CARE
FOR CHARLIE.
>> AND HOW FAR DID YOU HAVE TO
TRAVEL THEN TO -- FOR THE
TREATMENT?
>> SO WE LIVE IN DARIAN,
CONNECTICUT OUTSIDE OF NEW YORK
CITY AND WE TRAVEL TO THE
UNIVERSITY OF ROCHESTER.
SO THAT WAS A FAIRLY SIGNIFICANT
JOURNEY TO MAKE, ESPECIALLY WHEN
THE TRIAL IS SUCH A COMMITMENT,
IT WAS WEEK AFTER WEEK THE FIRST
YEAR, UNFORTUNATELY THERE WAS A
SHORTAGE OF NURSES AVAILABLE TO
COME TO OUR HOUSE TO SORT OF
BRIDGE THE GAP AND SOLVE SOME OF
THOSE LOGISTICAL CONCERNS, I
THINK DUE TO COVID, SO THAT WAS
KIND OF A BARRIER, I WOULD SAY.
BUT YEAH, IT'S A COMMITMENT FOR
SURE.
>> THANK YOU FOR ALL OF THAT.
I THINK IT JUST REINFORCES WHAT
YOU WERE SAYING THAT YOU KIND OF
HAVE TO TAKE A LOT OF THINGS
INTO YOUR OWN HANDS, AND NOT ALL
FAMILIES HAVE THESE MEANS,
RIGHT, BECAUSE IT'S A BURDEN TO
THE FAMILY TO HAVE PEOPLE
TRAVELING, ESPECIALLY IF YOU
HAVE OTHER CHILDREN, AND IT'S A
BIG FOCUS FOR THE ENTIRE FAMILY,
CORRECT?
>> ABSOLUTELY.
YEAH.
BUT I MEAN, YOU KNOW, IT WAS A
DECISION-MAKING PROCESS BUT AT
THE END OF THE DAY, WITH WEIGHED
A LOT OF THINGS.
THERE WAS THE COST OF DOING
NOTHING, WHICH WE KNOW THE
NATURAL HISTORY OF THE DISEASE,
WE KNOW EXACTLY WHAT'S GOING TO
HAPPEN.
WE CERTAINLY WORRIED ABOUT AN
EXPERIMENTAL THERAPY, A TRIAL IS
ALWAYS SORT OF A RISK.
EVEN THOUGH SO MANY PATIENTS
HAVE BEEN DOSED, WE FELT
REASONABLY ASSURED BY THE
SAFETY, THERE WAS THAT DEATH
THAT WAS REFERENCED EARLIER, I
WAS REALLY HEARTENED BY THE FACT
THAT SO MANY OF THE SPONSORS HAD
COME TOGETHER AS DR. BONNEMANN
HAD REFERENCED EARLIER, AND
TRIED TO REALLY FIGURE -- ASSESS
OUT, WHAT WAS THE CAUSE OF THE
SAEs IN THOSE TRIALS AND HAVE
FIGURED OUT THAT IT WAS MOSTLY
EXONS THAT WERE JUST BEFORE
CHARLIE'S MUTATION, CHARLIE JUST
SQUEAKED THROUGH, HE'S 22 TO 39,
BUT JUST THE FACT THAT THAT HAD
HAPPENED AND SERIOUS
CONSIDERATION HAD BEEN MADE,
REALLY GAVE ME A LOT OF
CONFIDENCE.
SO ULTIMATELY IT WAS JUST A LOT
OF -- A LEAP OF FAITH, I WOULD
SAY.
>> IT'S LIKE YOU HAVE AN
HONORARY PH.D., RIGHT?
HOW DID YOU FIND OUT ABOUT --
ALL OF THIS SPECIFIC INFORMATION
IN REALTIME, THE COLLABORATION
BETWEEN THE COMPANIES THAT
DR. BONNEMANN TALKED ABOUT, YOU
KNOW, THEM SHARING THAT
INFORMATION OPENLY, THIS IS
PROOF IT GETS RIGHT TO THE
FAMILIES WHO NEED TO MAKE THOSE
DECISIONS.
HOW DO YOU FIND OUT ABOUT THIS
INFORMATION TO INFORM YOUR
DECISIONS?
>> I MEAN, I WOULD SAY MAINLY IN
TERMS OF THAT SPECIFIC PIECE OF
IT, I HAD LEARNED THROUGH CURE
DUCHENNE AND THROUGH PPMD, HAD
WEBINARS AND INFORMATIONAL
SESSIONS AND MAKE THEIR
SCIENTISTS AVAILABLE TO SHARE
THAT KIND OF INFORMATION.
SO I REALLY TURNED TO EXPERTS TO
TELL ME, IS THIS GOING TO BE
SAFE BASED ON EVERYTHING WE KNOW
ABOUT AAV AND THE TRANS GENE, IS
THIS GOING TO BE SAFE FOR
CHARLIE'S SPECIFIC MUTATION, AND
I FELT LIKE OVERALL THAT
CONFIDENCE DID OUT WEIGH ANY
CONCERN ABOUT RISK.
>> PERFECT.
SO MAYBE WE CAN GO BACK TO WHAT
WAS THE PROCESS LIKE FOR BEING
SCREENED AND SEEING IF CHARLIE
WOULD BE ACCEPTED INTO THE
TRIAL?
>> SO I KIND OF GO BACK TO THE
EARLIER COMMENT I MADE ABOUT
FEELING LIKE A CONTESTANT
BECAUSE THE SCREENING PROCESS IS
TWO DAYS, SO YOU TRAVEL TO THE
SITE, AND YOU GO THROUGH THIS
NECESSARY SCREENING PROCESS, AND
THE THING THAT REALLY WORRIED
MEMOS WAS THAT, YOU KNOW, THE
NSAA IS A VERY -- IT'S A
MULTIFACETED TEST, AND SO IF
CHARLIE AT ANY POINT DECIDED
THAT HE DIDN'T WANT TO DO ANY OF
THE ACTIVITIES, REMEMBER, WE'RE
TALKING ABOUT A -- YOU KNOW, AT
THE TIME HE WAS 4 YEARS OLD,
THEN WHAT?
WE WOULD NOT GET INTO THE TRIAL.
HE HAD NO IDEA AS A YOUNG CHILD
THE STAKES THAT WERE INVOLVED.
SO HERE I AM AS A MOM BEING LIKE
THIS IS THE MOST IMPORTANT GAME
SHOW OF OUR LIVES, YOU NEED TO
PERFORM, AND AND THAT SORT OF
CLUED IN TO ME THE LIMITS OF --
NOT LIMITS BUT THE CONCERNS
ABOUT NSAA AS A TOOL, BECAUSE
YOU ARE DEALING WITH THESE YOUNG
CHILDREN, AND COMPLIANCE IS KEY,
I MEAN, YOU ARE NOT GOING TO GET
A FAIR ASSESSMENT IF THE CHILD
JUST WON'T EVEN COMPLY.
SO IT WAS STRESSFUL.
I WILL SAY IT DEFINITELY -- WE
WERE LUCKY IN THAT TWO
RELATIVELY LOCAL SITES WERE
OPENING FOR SAREPTA, SO WE DID
HAVE KIND OF A CHOICE, AND THE
TEAM THAT WE WENT WITH JUST MADE
US FEEL SO CONFIDENT AND
COMFORTABLE AND JUST -- WE JUST
FELT LIKE WE'RE IN THE BEST
HANDS POSSIBLE, SO THAT HELPED A
LOT.
>> CAN YOU WALK US THROUGH THE
DAY WHEN CHARLIE ACTUALLY
RECEIVED THE THERAPY, HOW DID
THAT GO?
>> YEAH, I MEAN, IT'S
INTERESTING BECAUSE IT'S LIKE,
IT'S A LOT OF HURRY UP AND WAIT,
THE INFUSION TAKES A WHILE,
YOU'RE SORT OF SITTING THERE,
YOU'RE CONCERNED THAT YOUR CHILD
IS GOING TO, AGAIN, COMPLY AND
LET THE IV BE PLACED, STAY
STILL, ALL THOSE THINGS.
AND SO THERE WAS A LOT OF NERVES
AND EXCITEMENT.
I'LL JUST SAY I TOOK A VERY SORT
OF ANALYTICAL APPROACH TO
SETTING UP FOR THE TRIAL, BUT AT
THE END OF THE DAY, I WAS A MOM
WORRIED ABOUT MY KID, WORRIED
HOW IS HE GOING TO HAVE SIDE
EFFECTS, IS HE GOING TO HAVE ANY
SIGNS.
IT WAS A DOUBLE BLIND PLACEBO
CONTROLLED TRIAL, SO IS IT GOING
TO BE CLEAR TO US IF HE'S GOT
GOTTEN -- SO NO MATTER HOW MUCH
SORT OF RATIONALIZE IT AND THINK
IT'S THE RIGHT DECISION, IT'S
NOT ASPIRIN, RIGHT?
SO YOU'RE LIKE -- YOU'RE STILL
WATCHING IT.
BUT I WILL SAY THE MOMENT WHEN I
WAS SITTING THERE WATCHES THE
INFUSION GET IN, WHETHER IT WAS
WRONG OR NOT, I JUST GET LIKE
SOMETHING'S ON BOARD NOW THAT
IT'S GOING TO SLOW THE
PROGRESSION OF THE DISEASE THAT
WE KNOW OTHERWISE WOULD JUST
TAKE AWAY ABILITIES STEP BY
STEP, IT WAS REALLY THE FIRST
TIME I FELT LIKE I COULD EXHALE,
LIKE OKAY, I'VE DONE EVERYTHING
I CAN TO THIS MOMENT TO, LIKE,
HELP MY SON.
>> AND HOW DO YOU THINK THE
TREATMENT HAS AFFECTED HIS
ABILITIES?
HOW IS HE DOING NOW?
>> SO WE'VE DEFINITELY NOTICED
SOME IMPROVEMENTS WITH HIM.
I WOULD SAY MOST NOTABLY, HE NO
LONGER HAS THE GAWER SIGN, WHICH
TO ME, THAT'S LIKE THE HALLMARK
SYMPTOM OF DUCHENNE, IS THAT
SORT OF ASSISTING YOURSELF AS
YOU GET UP OFF THE FLOOR.
HIS MOVEMENTS SEEM MORE FLUID.
IT'S HARDER TO TELL I THINK HE
HAS DUCHENNE WHEN YOU WATCH HIM.
CLEARLY WITH PEERS, YOU WOULD
NOTICE SOMETHING IS A LITTLE
OFF, BUT STAIRS ARE EASIER, I
WOULD JUST SAY DAILY LIFE IS A
LITTLE BIT EASIER.
BUT AT THE SAME TIME, WE HAVE TO
BALANCE THAT HOPE AND OPTIMISM
AND RELIEF WITH, YOU KNOW, THE
FACT THAT HE STILL HAS DUCHENNE
AND WE JUST DON'T KNOW HOW LONG
THIS WILL LAST, YOU KNOW,
WHETHER WE CAN ALLOW HIM TO DO
MORE THINGS THAT HE WANTS TO DO.
I THINK CRYSTAL -- DR. CRYSTAL
PROUD IN HER TESTIMONY TALKED
ABOUT THE FACT THAT HER
SPAISHPATIENTS, SHE NOW HAS TO E
ABOUT BIKE SAFETY.
THAT WAS NOT A THING WITH
DUCHENNE BOYS BEFORE.
SO IT'S THE SAME THING IT'S SORT
OF LIKE AS A PARENT, DO WE ALLOW
HIM TO DO THE THINGS HE WANT TO
DO AND CAN DO, KNOWING THAT THAT
MUSCLE IS STILL BREAKING DOWN.
THERE WAS DEFINITELY A MOMENT
THIS WEEK WHERE HE WAS
PARTICIPATING IN AN AFTER-SCHOOL
PROGRAM WHERE, YOU KNOW, AT THE
END OF IT, HE WAS DRAGGING --
ESSENTIALLY CRAWLING UP AN
INCLINE.
SO HE STILL HAS DUCHENNE, SO
IT'S DEFINITELY A BALL ARRANGES
KBALANCE, AS WEAND ALL THE EXPES
WILL NOT LAST FOREVER, IT'S
DEFINITELY A RELIEF IN THE
MOMENT BUT ALSO A WHAT'S NEXT
KIND OF MENTALITY OF LIKE WE'RE
LOOKING TO HOW DO WE TAKE THIS
AMAZING VICTORY AND LEVERAGE TO
HOPEFULLY CREATE A LONG-TERM
SOLUTION FOR HIM.
>> SO WHAT WOULD YOU SAY --
WE'VE GOT A LOT OF RESEARCHERS
ON THIS CALL TODAY, AND WHAT
WOULD YOU WANT TO SAY TO THE
RESEARCHERS WHO CONTRIBUTED TO
THE DEVELOPMENT OF THIS
TREATMENT?
YOU KNOW, THE TEAMS CONDUCT THE
TRIALS?
>> YEAH.
I WOULD DEFINITELY LEA LEAD WITH
GRATITUDE.
AS A PARENT, IT IS -- IT'S FUNNY
BECAUSE WHEN YOU GET DIAGNOSED,
YOU'RE LIKE OKAY, I NEED TO FIX
THIS, I ALONE WILL FIX THIS, I
WILL, YOU KNOW, DO ALL THE
THINGS TO MAKE IT POSSIBLE.
AND THEN YOU REALIZE, WELL,
THAT'S NOT GOING TO HAPPEN, AND
THEN YOU JUST SORT OF REALIZE
THAT THERE ARE SO MANY SMART
MINDS WORKING ON THIS PROBLEM,
SO MANY SCIENTISTS AND OTHERS
WHO ARE, LIKE, COMPLETELY
DEVOTED TO SOLVING DUCHENNE, IT
JUST A -- YOU FEEL LIKE YOU CAN
LET OFF THE GAS A LITTLE AND
SAY, OKAY, HELP IS ON THE WAY.
SO THAT'S JUST SUCH A RELIEF,
BUT AT THE SAME TIME AS I SAID
BEFORE, YOU KNOW, WE KNOW THIS
ISN'T A CURE SO I WOULD SAY KEEP
GOING, PLEASE.
THERE ARE OTHER THINGS IN THE
PIPELINE THAT WE'RE WATCHING AND
HOPEFUL ABOUT, AND THIS IS AN
IMPORTANT CRITICAL FIRST STEP
AND WE'RE JUST HOPEFUL THAT IT
SORT OF SNOWBALLS INTO A
LONGER-TERM SOLUTION.
YOU KNOW, IT'S STRANGE AS A
PARENT ADVOCATE TO BE SORT OF
OUT THERE SAYING THIS IS
WONDERFUL, WE'RE SO GRATEFUL,
BUT AT THE SAME TIME, YOU KNOW,
WE ALSO KNOW IT'S NOT A CURE.
BUT THE THINGS THAT WE'RE SEEING
DAY TO DAY ARE MEANINGFUL, SO IT
JUST SHOWS HOW LITTLE -- HOW FEW
OPTIONS WE'VE HAD BEFORE THIS
MOMENT THAT WE'RE SO
TREMENDOUSLY GRATEFUL FOR A
SOLUTION, BUT AT THE SAME TIME
RECOGNIZING THAT WE NEED MORE
SOLUTIONS TO GET TO THE POINT
WHERE THE DISEASE IS COMPLETELY
TRANSFORMED.
>> SO WHAT ARE YOUR THOUGHTS ON
HOW AN APPROVAL OF GENE THERAPY,
YOU KNOW, YOU TALKED A LITTLE
BIT HOW IT AFFECT YOUR FAMILY.
HOW DO YOU THINK -- HOW DO YOU
THINK IT AFFECTS OTHER FAMILIES
WITH DUCHENNE OR THE DUCHENNE
COMMUNITY AT LARGE?
>> I MEAN, I THINK IT STARTS
WITH THE ACCESS TO THE TRIALS.
AS I MENTIONED, IT'S PRETTY HARD
TO -- YOU HAVE TO BE VERY
PROACTIVE AS A PARENT TO FIND AN
OPPORTUNITY TO PARTICIPATE IN
SUCH A TRIAL.
I THINK THAT, YOU KNOW, IN
REALTIME, IT AFFECTS THE WHOLE
FAMILY AND, AS I MENTIONED, THE
LACK OF AVAILABLE HOME NURSES,
THE FIRST YEAR OF THE TRIAL, WAS
REALLY CHALLENGING, AND WE ALSO
FOUND THAT A CHILD LIFE EXPERT
AVAILABLE TO CHARLIE DURING HIS
TREATMENT, DURING HIS TESTING,
DURING ANY KIND OF MEDICAL
INTERVENTION WAS REALLY HELPFUL.
BUT WE HAVE TO FIGHT FOR THAT,
ONLY BECAUSE THE STRUCTURE OF A
CLINICAL TRIAL IS VERY FIXED AND
DOESN'T SORT OF ALLOW FOR, LIKE,
THE SUPPLEMENTAL THINGS THAT
MIGHT MAKE IT EASIER FOR
PATIENTS AND FAMILIES TO
PARTICIPATE, WE ULTIMATELY WERE
ABLE TO GET THAT YOU IS PORT,
WHICH WE'RE SUPER GRATEFUL FOR.
AND THE OTHER THING I'LL JUST
SAY IS THAT AS CELEBRATORY WE
ARE ABOUT THE LIMITED APPROVAL
RIGHT NOW OF THE DRUG, YOU KNOW,
THERE ARE OTHER FAMILIES WHO ARE
STILL WAITING.
SO IT'S STILL SORT OF A MURKY
TIME I THINK IN THE FAMILY
LANDSCAPE IN TERMS OF LAKE SOME
OF US HAVE HAD ACCESS TO THE
TRIAL AND SOME OF US ARE STILL
WAITING SO IT'S A HOPEFUL TIME
BUT IT'S STILL A RECOGNITION WE
NEED MORE HELP.
>> WE TALK ABOUT IT ALL THE
TIME, THAT THERE'S ALREADY BEEN
SOME YEARS OF WHAT WE CALL THE
HAVES AND HAVE-NOTS, RIGHT, THE
EXON SKIPPING, INDIVIDUALS WITH
THOSE MUTATIONS AMENABLE TO
THOSE HAVING MORE OPPORTUNITIES,
AND NOW IT'S BEING EXTENDED,
RIGHT, WITH GENE THERAPY AND IT
GOING TO BE A REALLY -- IT'S A
PROMISING TIME, ALL OF THESE ARE
ADVANCES, BUT ALSO A CHALLENGING
TIME BECAUSE THERE'S GOING TO BE
SO MANY INDIVIDUALS LIVING WITH
THE DISEASE WHO ARE STILL
WAITING FOR US TO DO BETTER.
>> RIGHT.
ABSOLUTELY.
AND WE SORT OF NEED THAT
MOMENTUM, I THINK, TO REALLY
TRANSFORM.
THIS IS SUCH AN IMPORTANT FIRST
STEP AND NOW HE WITH NEED TO WEF
JUST CAPITALIZE ON IT.
>> EXACTLY.
WE'RE BUYING TIME AND WE STILL
NEED BETTER TRANSFORMATIVE
THERAPIES TO COME ALONG FOR MORE
INDIVIDUALS.
>> MM-HMM.
FOR SURE.
>> SO YOU KNOW, DO YOU HAVE ANY
OTHER THOUGHTS THAT YOU'D LIKE
TO SHARE WITH THE GROUP IN TERMS
OF NEEDS OR OPPORTUNITIES TO
HELP THE LIVES OF INDIVIDUALS
AND FAMILIES LIVING WITH
DUCHENNE?
>> I DO.
THANK YOU FOR ASKING THAT.
SO ONE OF THE ISSUES THAT I SEE
IS THE LACK OF SORT OF
SUBSPECIALISTS WHO ARE FOCUSED
ON DUCHENNE'S PERVASIVE IMPACT
ON A PATIENT AND A FAMILY.
I WAS SO HEARTENED TO SEE THAT
PPMD IS WORKING -- AND I'M SURE
CURE DUCHENNE IS AS WELL ON THE
CARDIAC ISSUES, THERE'S SO MUCH
WE DON'T UNDERSTAND STILL ABOUT
THE MECHANISMS OF THE CARDIAC
DECLINE IN DUCHENNE, EITHER HOW
THE TREATMENTS EITHER HERE OR ON
THE HORIZON CAN ADDRESS THOSE,
BUT THERE'S ALSO THE BEHAVIORAL
ISSUES OF DUCHENNE.
SO LIKE PEOPLE -- I TALK TO A
LOT OF FRIENDS AND OTHER
FAMILIES WHO ARE LIKE, OH,
PEOPLE JUST THINK IT'S LIKE YOUR
SON CAN OR CAN'T WALK.
IT'S LIKE SO MUCH MORE THAN
THAT.
BECAUSE DYSTROPHIN ACTS ON THE
BRAIN, THERE ARE SO MANY
ACKNOWLEDGED CONDITIONS THAT CAN
BE CO-MORBID ITS WITH DUCHENNE,
ADHD, AUTISM, LEARNING
DIFFERENCES, OCD AND FIXED
BEHAVIOR THAT MANIFEST EVERY
DAY.
THERE WAS JUST A FACEBOOK THIS
WEEK ON ONE OF THE DUCHENNE
BOARDS ABOUT PANTS AND HOW OUR
BOYS HAVE SENSORY ISSUES, THEY
DON'T WANT TO WEAR CERTAIN TYPES
OF PANTS SO WE'RE ALL TRYING TO
FIGURE OUT WHAT TYPES OF PANTS
OUR BOYS WILL WEAR EVERY DAY.
THAT SPHUF RE STUFF REALLY ACCUS
AND AFFECT A FAMILY.
WE HAD A PARTICULARLY TOUGH TIME
WITH CHARLIE WITH SOME OF HIS
FIXED BEHAVIORS THIS WEEK.
SO TO ME, THERE'S A NEED TO
CONSIDER THE HOLISTIC IMPACT OF
DUCHENNE ON A FAMILY.
I KNOW OF ONE EXPERT AT
NATIONWIDE WHO'S AMAZING, WHO
SPECIALIZES IN DUCHENNE
BEHAVIORS, BUT WE NEED MORE OF
THOSE.
WE NEED MORE THAN HERE'S THE
DIAGNOSIS, IT AFFECTS YOUR
CHILD'S BRAIN, AND ALSO WE'RE
GOING TO PUT YOUR CHILD ON DAILY
STEROIDS, WHICH WILL FURTHER
AFFECT YOUR CHILD'S BEHAVIOR,
BUT YOU DON'T -- WE CAN'T OFFER
YOU ANY HELP.
YOU KNOW, EVERY PARENT, I THINK,
FEELS LIKE I COULD REALLY USE AN
OWNER'S MANUAL WHETHER IT COMES
TO HAVING A BABY WITH DUCHENNE,
IT'S A THOUSAND TIMES MORE.
YOU NEED SOME GUIDANCE AND SOME
SUPPORT TO DEAL WITH SORT OF THE
DAILY IMPACT.
SO THAT'S JUST ONE -- THAT'S ONE
SORT OF OTHER AREA BEYOND
MOBILITY WHERE DUCHENNE HAS AN
IMPACT.
WE JUST MOVED TO A NEW HOUSE
BECAUSE WE WOULD ESSENTIALLY
HAVE TO HAVE REBUILT THE OTHER
HOUSE THAT WE WERE IN TO
ACCOMMODATE CHARLIE'S FUTURE
NEEDS AND WE JUST DIDN'T WANT TO
LIVE IN LIMBO ANYMORE, SO WE
MOVED.
THE STANDARDS OF CARE, I THINK
ARE A REAL POINT OF PRIORITY
THAT SHOULD BE LOOKED AT.
I THINK THAT WE'RE REALLY AT A
PIVOT POINT WHERE GENE THERAPY
IS NOW A THING AND I JUST FEEL
LIKE THERE NEEDS TO BE CONSENSUS
AROUND STANDARDS OF CARE,
ESPECIALLY FOR KID O KIDDOS WHOE
HAD THE GENE THERAPY, ARE WE
SWITCHING, ARE WE ABLE TO MOVE
ON FROM STEROIDS, THERE'S
ALREADY KIND OF A SPLIT IN TERMS
OF HOW PROVIDERS CONSIDER
STEROIDS AND REGIMENS.
>> YOU KNOW, JUST ON THAT --
>> LIKE I SAID -- WHAT'S THAT?
>> ON THAT POINT, I KNOW GLEN
HAS ORGANIZED TOPICS AROUND --
FOR THIS MEETING AROUND
REGISTRIES, AND I JUST THINK
THAT THAT KIND OF REAL WORLD
DATA IS GOING TO BE SO IMPORTANT
GOING FORWARD, AS WE HAVE
INDIVIDUAL, RIGHT, ON DIFFERENT
TYPES OF THERAPIES, AND SOME --
JUST TAKING THE STEROID, SOME
GOING OFF STEROIDS, SOME NOT,
AND ACTUALLY CAPTURING ALL OF
THAT GOING FORWARD SO THAT WE
CAN HAVE EVIDENCE TO ACTUALLY
INFORM THESE STANDARDS OF CARE.
>> ABSOLUTELY.
AND I THINK COMBINATION TRIALS
ARE GOING TO BE IMPORTANT IN
TERMS OF WHAT'S COMING DOWN THE
PIKE FOR THESE BOYS, BOYS WHO
HAVE ALREADY HAD THE GENE
THERAPY, YOU KNOW, CONSIDERING
HAVING MULTIPLE THINGS ON BOARD,
AND THEN THE ACCESS ISSUE, YOU
KNOW, ONCE THESE THINGS ARE
APPROVED, ARE PAYORS GOING TO
ALLOW OUR BOYS TO BE DOSED.
WE KNOW FOR SURE THAT THERE'S
ALREADY SOME PUSHBACK IN TERMS
OF BOYS WHO ARE ON THE EXON
SKIPPER, HAVE THE GENE THERAPY,
CAN THEY GO BACK TO THE EXON
SKIPPER, SO THAT'S A HUGE
CONSIDERATION.
IT'S A FINANCIAL CONCERN FOR
FAMILIES.
AND THEN LASTLY, I WOULD JUST
SAY THE NEWBORN SCREENING ISSUE
IS SUPER IMPORTANT.
I KNOW THERE'S GOING TO BE
DISCUSSION LATER ABOUT THAT.
THERE'S SOME MOMENTUM BUILDING
STATES.
I THINK THAT RUSS ABSOLUTELY
NEEDS TO ADD THIS TO THEIR
UNIVERSAL RECOMMENDATIONS TO
REALLY GET THAT OUT THERE TO THE
50 STATES.
SO IT'S KIND OF AN INTERESTING
POINT TO BE COMING IN RELATIVELY
NEW AS A PARENT OF A BOY WITH
DUCHENNE WHERE THINGS ARE
CHANGING AND I JUST THINK
THERE'S A LOT OF ALIGNMENT THAT
NEEDS TO HAPPEN.
>> SO I MEAN, THIS IS -- I THINK
YOU SAID IT PERFECTLY, THAT, YOU
KNOW, WE HAVE SOME REALLY GOOD
PROGRESS, SOME REALLY STRONG
FOOTHOLD, BUT THE WORK IS NOT
DOB, RIGHT?
DONE, RIGHT?
WE'RE NOT TAKING OUR FOOT OFF
THE GAS.
I'M JUST KEEPING AN EYE ON THE
TIME.
I DON'T KNOW IF THIS IS A GOOD
TIME TO OPEN UP TO MORE GENERAL
QUESTIONS FROM EVERYONE
PARTICIPATING?
>> SO THIS IS REALLY AN
INCREDIBLE DISCUSSION.
IT'S SO IMPORTANT FOR US TO
HEAR.
GLEN, I'M GOING TO ASK YOU WHAT
YOU WANT TO DO IN TERMS OF
TIMING.
WE HAVE A VERY BUSY OF A NOON AS
WELL.
>> YEAH, I THINK WE MAY BE ABLE
TO PICK UP A LITTLE BIT OF TIME
THIS AFTERNOON.
I CERTAINLY DON'T WANT TO CUT
THIS OFF.
THIS IS FASCINATING, REALLY
APPRECIATE JENNIFER AND LIANNA'S
PARTICIPATION.
PERHAPS IF THERE ARE QUESTIONS
FROM THE COMMITTEE OR QUESTIONS
FROM THE AUDIENCE?
>> ANDY?
>> MAYBE THIS COMMENT IS
ACTUALLY FOR YOU, DR. BIANCHI.
WHEN WE THINK ABOUT THE PROGRESS
IN THE GENOMIC AREA, RIGHT, AND
THE ADVANCEMENT OF SHORT READ
SEQUENCING AND LONG READ
SEQUENCING, WOULDN'T IT BE TIME
FOR NIH TO STEP UP AND SAY,
OKAY, SIMILARLY TO 15 YEARS AGO,
WHEN MASS SPEC MADE AN ENTRANCE
INTO NEWBORN SCREENING, WE
REALLY PUSH THE THIRD ACCESS OF
SCREENING TECHNOLOGY.
WE COULD PICK UP THESE DISEASES
OR MAJORITY OF THESE DISEASE, WE
WOULD FEED IN REGISTRIES AND WE
WOULD REALLY HAVE THE NEXT
GENERATION, RIGHT, OF
PHARMACEUTICAL DEVELOPM DEVELOPT
WOULD FOLLOW QUITE NATURALLY.
>> I AGREE WITH YOU.
I KNOW THAT FOR SOME OF THE WORK
THAT WE'RE DOING IN MY OWN
RESEARCH LABORATORY, WO WE'VE BN
EXPLORING RESOURCES AVAILABLE TO
US IN LONG READ SEQUENCING.
IT'S STILL A LITTLE EARLY.
I MEAN, THERE OBVIOUSLY ARE
PEOPLE IN THE ACADEMIC WORLD WHO
ARE BECOMING EXPERT IN THE
TECHNOLOGY.
I DON'T KNOW THAT WE'RE QUITE
THERE YET.
IN TERMS OF RESOURCES AT THE NIH
ITSELF.
BUT I AGREE WITH YOU THRA IS
GOI, THAT ISTHE WAY GOING FORWAE
CAN PINPOINT SOME OF THESE
VARIANTS.
DR. CRISWELL.
>> THANK YOU.
I JUST WANTED TO THANK JENNIFER
AND LIANNA SO MUCH FOR SUCH AN
AMAZING SESSION.
I'M LOOKING UP TO CONFIRM THAT
THIS HAS BEEN RECORDED, THANK
GOODNESS.
THIS HAS BEEN REALLY SPECIAL.
THANK YOU SO MUCH FOR SHARING
YOUR EXPERIENCE, JENNIFER IN
PARTICULAR.
>> THANK YOU.
THANK YOU FOR THE OPPORTUNITY.
>> RA RAMONA.
>> THANK YOU VERY MUCH FOR THIS
TESTIMONY.
THIS IS REALLY IMPORTANT TO BE
HIGHLIGHTED AND REALLY HIGHLIGHT
THE IMPORTANCE OF PATIENT
FOCUSED DRUG DEVELOPMENT.
SO THE QUESTION I HAVE FOR
JENNIFER IS, IF YOU HAD TO GIVE
A SUGGESTION TO THE COMMUNITY OF
DRUG DEVELOPERS, WHAT WOULD BE
YOUR SUGGESTION TO OPTIMIZE
CLINICAL TRIAL DESIGN TO INCLUDE
ADVICE OF PATIENTS AND
CAREGIVERS IN TRIAL DESIGN?
>> THAT'S A GREAT QUESTION
BECAUSE LIKE I SAID, I FEEL LIKE
WE'RE AT SUCH A PIVOT POINT
WHERE THINGS ARE NOT AS THEY
WERE.
AND I THINK CONSIDERING END
POINTS BEYOND NSAA IS AN
IMPORTANT FIRST STEP.
I THINK THAT PLATFORM TRIALS AND
COMBINATION TRIALS ARE REALLY
IMPORTANT AT THIS POINT IN TIME.
YOU KNOW, I THINK THIS IS A
NON-SCIENTIFIC COMMENT BUT I
JUST THINK AS A COMMUNITY, WE'VE
SEEN WHAT CAN HAPPEN WHEN
RESOURCES ARE PUT BEHIND A
CONDITION.
LOOK AT COVID-19 AND THE
EXISTING TECHNOLOGY THAT WAS
HARNESSED TO QUICKLY MEET AN
UNMET NEED.
THAT, TO ME, IS A PERFECT USE
CASE FOR DUCHENNE, WHERE, YOU
KNOW, IT'S BEEN -- WE'VE BEEN
AWARE OF THIS DISEASE FOR SO
LONG AND NOW WE HAVE TOOLS, SO
THERE'S KIND OF A SENSE IN THE
COMMUNITY LIKE WE HAVE WHAT WE
NEED TO SOLVE THIS AND WE NEED
KIND OF A MOONSHOT WITH WHAT'S
HAPPENED WITH CANCER AND OTHER
CONDITIONS TO REALLY SORT OF GET
BEHIND THIS.
SO THERE'S ALSO RECOGNITION THAT
SOLVING THIS PROBLEM OF GETTING
VIABLE NEXT GEN TREATMENTS TO
MUSCLE IS GOING TO BE TELLING
FOR SO MANY OTHER CONDITIONS.
LIKE IT'S A REALLY HARD PROBLEM,
AND IF WE SOLVE THIS REALLY HARD
PROBLEM, IT'S GOING TO TRICKLE
DOWN AND REALLY, I THINK, CHANGE
THE FACE OF SO MANY DISEASES OUT
THERE.
>> I AGREE.
DAN?
>> YES, HI.
THAT WAS AN EXCELLENT
DISCUSSION.
I HAVE THREE QUESTIONS FOR JEN.
ONE IS, WHEN YOU STARTED THIS
PROCESS, DID YOU SEE YOURSELF
GOING INTO A CLINICAL TRIAL OR
DID YOU SEE YOURSELF GOING INTO
A TREATMENT OR A DRUG?
-- MINDSET, DID YOU GO IN
THINKING I'M GOING TO GET MY SON
TREATED WITH THIS MEDICATION, OR
DID YOU GO IN THINKING, I'M A
PART OF A STUDY TO SEE WHETHER
THE DRUG WORKS OR NOT?
>> YEAH, THAT'S SUCH AN
INSIGHTFUL QUESTION.
SO I THINK WE WERE SO FORTUNATE,
AND I GIVE SO MUCH CREDIT TO THE
FAMILIES WHO WERE IN THE EARLIER
PHASES OF THE TRIAL.
WE WERE IN A PHASE THREE TRIAL.
SO WE ALREADY HAD A LOT OF
INFORMATION ABOUT WHAT THIS DRUG
MAY OR MAY NOT DO.
SO I THINK FOR US, IT WAS A
LITTLE BIT OF AN EASIER DECISION
IN THAT WE KNEW THAT IT PROBABLY
WOULD GIVE CHARLIE SOME BENEFIT.
AND ALREADY HAD A PRETTY DECENT
SAFETY RECORD.
SO IT MADE IT DEFINITELY EASIER,
PLUS KNOWING THAT WE WOULD GET
DRUG WITHOUT THE INSURANCE FILES
WE'VE SEEN ALREADY HAVE HAPPENED
SINCE THE LIMITED FDA APPROVAL
IT DEFINITELY MADE IT EASIER.
SO I WOULD SAY WE MORE
CONSIDERED THAT WE WERE GOING IN
FOR A TREATMENT ALTHOUGH IT WAS
STILL SOMEWHAT EXPERIMENTAL.
>> THEN FOLLOWING THAT, DID YOU
FIND YOURSELF AT ANY POINT DUE
TO FRUSTRATION WITH ACCESS AND
REALLY STRINGENT INCLUSION
CRITERIA FINDING YOURSELF
CHASING THE DIALOGUE OR THE
CRITERIA BY WHICH THE DRUG MAY
BE APPROVED THROUGH ADVOCACY?
SO DID YOU FIND YOURSELF REALLY
HAVING TO BE PROACTIVE IN COMING
UP WITH WAYS TO WORK WITH THE
FDA AND THE COMMUNITY TO GET THE
DRUGS APPROVED AND EXPANDED?
HOW MUCH EFFORT OR ACTIVITY DID
YOU OR DID YOU NOT HAVE TO PUT
INTO THAT CONSIDERATION?
>> SO AS I MENTIONED, YOU KNOW,
NSAA WAS A CONCERN IN TERMS OF
SCREENING INTO THE TRIAL.
I WAS WORRIED, YOU KNOW, WOULD
HE HAVE NEUTRALIZING ANTIBODIES,
WOULD HE PERFORM ON NSAA, WOULD
IT BE A BAD DAY, WOULD HE GET A
LOWER SCORE, WOULD HE -- YOU
KNOW, ALL THOSE THINGS THAT FELT
VERY LOOSE.
SO I DEFINITELY CONSIDERED THAT.
AND THEN I THINK ONLY NOW AM I
REALIZING HOW MUCH ADVOCACY
NEEDS TO BE DONE IN TERMS OF
LOOKING AT OTHER INSTRUMENTS TO
CONSIDER BOTH FOR SCREENING IN
TO A TRIAL AND FOR THOSE END
POINTS, I THINK WE'RE IN A
DIFFERENT DAY NOW WHERE PERHAPS
THERE ARE OTHER WAYS TO --
BECAUSE I THINK THERE'S A LITTLE
BIT OF A DISCONNECT IN THAT AS
PARENTS WE SEE EVERY DAY THE
IMPACT OF THIS TREATMENT ON OUR
BOYS AND IT'S A LITTLE BIT AT
ODDS WITH THE SORT OF CLINICAL
DISCUSSION OF THE NSAA.
SO I THINK NOW THERE'S AN
INCREASING REALIZATION OF
ADVOCACY TO MAYBE FIND SOME
OTHER TOOLS THAT MIGHT BE USE
USEFUL.
>> OKAY, BECAUSE I OFTEN
WONDER -- I THINK THIS AREA, THE
AAV VECTORS AND -- AND CRISPR, I
REALLY THINK -- AGNOSTIC
APPROACH BETWEEN THE PAYLOAD AND
THE DELIVERY.
SO I THINK WE NEED AS A
COMMUNITY TO HAVE AAV VECTOR --
AAV -- RA74 -- DUCHENNE, NOT SO
MUCH PERHAPS IN ADULTS, SO IN
TERMS OF LESSONS LEARNED FROM
SAREPTA 9001 FROM DUCHENNE IN
THE ADULT COMMUNITY, WE'RE SORT
OF AT A LOSS BECAUSE THERE
REALLY IS NO ACCESS TO SOMETHING
THAT COULD CAUSE NUMEROUS
PROBLEMS IN ADULTS.
SO THE THOUGHT OF DISCUSSION
WHAT IS THE CONSIDERATION WITH
THE -- VECTORS ACROSS ALL THE
DYSTROPHIES OR ARE THERE OTHER
NANOPARTICLE DELIVERY SYSTEMS,
AND I'M DI GRESSING.
IT'S A REALLY INTERESTING AREA
BUT I ALSO AM CONCERNED THAT WE
AS MOTHERS AND PATIENTS AND SONS
AND DAUGHTERS -- THE DUCHENNE
COMMUNITY.
THE KIDS ARE YOUNG, THE FAMILIES
ARE YOUNG, IT'S REALLY HARD.
SO WE MUST REMEMBER IT'S
PARTICULARLY DEVASTATING WHEN
YOU'RE 40 YEARS OLD AND YOU'RE
DIAGNOSED WITH NIATONICFSH, YOU
HAVE A -- AND A WIFE AND
EVERYTHING ELSE, BUT I OFTEN
WONDER WHETHER THE PATIENT
COMMUNITIES ARE TRYING TO COERCE
THE STANDARDS BY WHICH THE DRUG
WORKS.
SO THERE'S SO MUCH PRESSURE AND
SOME DESPERATION ON ALL OF TH
THE -- ALL OF OUR PARTS TO SEE
THESE DRUGS IN TRIAL AND USED.
I HAVE THIS NAGGING CONCERN THAT
FOR THREE DECADES OF WORK, THAT
WE'RE NOT DOING ENOUGH WORK ON
THE FRONT END, AND WHAT WE'RE
TRYING TO DO IS CHANGE THE SHAPE
NARRATIVE AROUND BY WHICH WE CAN
GET THESE DRUGS APPROVED.
THE PATIENT-REPORTED OUT COME,
WATCHING OUR KIDS GO THROUGH
DIFFERENT THRESHOLDS, SUCCESSES,
GRADES OF IMPROVEMENT OR FAILURE
IN ABILITY TO WALK, IN ORDER TO
GET OFF THE FLOOR, IN ORDER TO
DRESS YOURSELF, FEED YOURSELF,
ET CETERA, ET CETERA, ET CETERA.
AND I JUST -- I'M JUST ASKING,
JEN, FOR THE COMMUNITY HERE, HOW
ARE WE DOING, DO WE FEEL LIKE
WE'RE HAVING TO CREATE THE
STANDARD TO ALTERNATIVE
MECHANISM RATHER THAN THE DRUG
WORKS OR IT DOESN'T WORK.
WE'RE ALWAYS SITTING ON THIS
THRESHOLD, WE THINK IT'S -- FOR
THE NEXT FIVE YEARS.
SO IS IT JUST MY QUESTION TO YOU
OR -- DISCUSSION IS ARE WE DOING
THE RIGHT THING, AND DO WE NEED
BETTER MEASURES TO SHOW WHETHER
THE DRUGS ARE WORKING OR NOT
WORKING?
>> JEN, CAN YOU ANSWER?
>> YES.
>> SO I THINK THERE'S A LOT TO
KIND OF UNPACK THERE.
I THINK THAT AS I'VE SAID, I
THINK THERE ARE BETTER TOOLS TO
BE FOUND.
I THINK THAT THERE ARE CONCERNS
ABOUT MSAA.
I WILL JUST SAY THAT I THINK
THAT NO PARENT WILL PUT THEIR
CHILD IN A TRIAL THAT THEY DON'T
BELIEVE HAS SHOWN ITSELF TO BE
EFFICACIOUS IN HOWEVER WAY THEY
LOOK AT THAT, WHETHER IT BE
LIVED EXPERIENCE, WHETHER IT BE
THE DATA THAT'S ALREADY BEEN
REPORTED FROM EARLIER PHASES OF
THE TRIAL, I THINK THAT I
CERTAINLY WOULDN'T GO OUT ON A
LIMB AND SAY THAT WE HAVE SEEN
THINGS IN OUR SON THAT ARE
ENCOURAGING IF IT WEREN'T TRUE.
I WOULDN'T GO OUT AND ADVOCATE
FOR ANYTHING THAT WAS JUST SORT
OF WISHFUL THINKING.
I THINK THIS IS A MEANINGFUL
FIRST STEP AND I THINK EVERYONE
IN THE COMMUNITY RECOGNIZES THE
NEED FOR ALL THE STEPS TO COME.
>> THANK YOU.
AND DAN, IN THE INTEREST OF
TIME, WALTER DID WRITE AN ANSWER
IN THE CHAT BOX, AND WE'LL TAKE
BRAD'S QUESTION OR COMMENT AS
THE LAST ONE BEFORE THE LUNCH
BREAK.
>> THANK YOU.
SO JENNIFER, I'M WONDERING IF
YOU COULD, GIVEN YOUR EXPERIENCE
IN SORT OF THE COMPLICATED, YOU
KNOW, PATH THAT IT TOOK YOU TO
GET YOUR SON INTO THE TRIAL,
WHAT DO YOU THINK COULD BE DONE
TO MAKE ENROLLMENT IN CLINICAL
TRIALS EASIER, WHICH, GIVEN THAT
DMD HAS A FAIRLY LARGE
POPULATION AS MUSCULAR
DYSTROPHIES GO, BUT FOR TYPES OF
MUSCULAR DYSTROPHY WHERE THE
POPULATIONS ARE MUCH SMALLER,
BEING ABLE TO RECRUIT ENOUGH
PEOPLE TO FILL THE TRIAL IS EVEN
MORE OF A CHALLENGE.
>> YEAH, SO I DEFINITELY HEAR
YOUR POINT.
I MEAN, I THINK THERE'S ALWAYS
GOING TO BE AN ELEMENT OF, YOU
KNOW, NOT EVERY BOY OR FAMILY
WHO WANTS TO GET INTO A DUCHENNE
TRIAL CAN.
IT'S JUST A MATTER OF NUMBERS.
BUT I THINK THERE'S A LITTLE BIT
OF EDUCATION AND CONNECTION THAT
NEEDS TO BE MADE BETWEEN
FAMILIES AND SPONSORS, SPONSOR
SITES, TO ALERT FAMILIES OF THE
OPPORTUNITY.
I THINK THAT IT'S INCUMBENT UPON
FAMILIES TO GO TO
CLINICALTRIALS.GOV AND FIGURE IT
OUT FOR THEMSELVES, OR RELY ON
THEIR CARE TEAM WHO, YOU KNOW,
FRANKLY MIGHT BE OVERWHELMED
WITH CARE AND NOT PAYING
ATTENTION OR NOT BE AWARE IF
THEY'RE NOT A SITE ON A CERTAIN
DRUG AND ALL OF THE SITES THAT
ARE INVOLVED IN A CERTAIN PHASE
OF A TRIAL.
SO I JUST THINK, PARTLY BECAUSE
I'M A PROFESSIONAL COMMUNICATOR,
I THINK THERE NEEDS TO BE SOME
OTHER COMMUNICATION MECHANISM BY
WHICH FAMILIES CAN UNDERSTAND IF
THEIR CHILD AND THEIR CHILD'S
MUTATION, AMBULATORY STATUS,
WHATEVER CRITERIA MIGHT BE MAT
MATCHED WITH A CERTAIN SITE THAT
MIGHT BE OPENING UP OR ACTIVELY
RECRUITING FOR A CERTAIN
POTENTIAL TREATMENT OR PHASE
1 TRIAL.
>> THANK YOU.
>> I KNOW PPMD DOES THIS AS
WELL.
WE HAVE ONE-ON-ONE MEETINGS WITH
FAMILIES TO SORT OF, YOU KNOW,
NAVIGATE, AND SOME OF THAT IS --
SOME OF THAT INFORMATION IS
EVERGREEN, RIGHT, IF YOU HAVE A
MUTATION THAT EXON SKIPPING IS
NEVER GOING TO ADDRESS, BUT SOME
OF THAT CHANGES MONTH TO MONTH
AS NEW TRIALS ARE INITIATED AND
SO YOU'RE TRYING TO GIVE THEM A
SNAPSHOT OF WHERE THINGS ARE.
AS WELL AS WHAT TO BE KEEPING AN
EYE ON.
BUT IT IS, IT HAS TO BE A
CONTINUOUS PROCESS, AND I AGREE
THAT OUR COMMUNITIES, WE NEED TO
FIND ADDITIONAL WAYS TO ACTUALLY
MAKE ALL OF THAT EASIER FOR
INDIVIDUALS TO ACCESS.
>> WELL, I'D LIKE TO THANK BOTH
OF YOU.
I WISH WE HAD MORE TIME BECAUSE
THIS IS SO IMPORTANT, AND FROM
MY PERSPECTIVE, JEN, THE
QUESTIONS THAT YOU RAISED ABOUT
THE LONG-TERM EFFECTS OF
TREATMENT ARE SO IMPORTANT.
I MEAN, WE'RE REALLY MOVING INTO
THE YO UNKNOWN, AND, YOU KNOW,
QUESTIONS ABOUT LONG TERM
HEALTH, FERTILITY, YOU KNOW,
NEXT GENERATION TYPES OF
CHANGES.
I MEAN, SO WE'LL PROBABLY HAVE
YOU COME BACK.
I THINK --
>> I'D LOVE TO.
>> THAT WILL BE THE SOLUTION.
SO I BELIEVE WE HAVE A LUNCH
BREAK.
WE'RE RUNNING ABOUT 22 MINUTES
BEHIND, GLEN, WHAT'S THE RETURN
TIME?
>> SO I THINK WE PROBABLY CAN
MAKE UP SOME TIME A LITTLE BIT
IN THE AFTERNOON, SO LET'S GO
AHEAD AND TAKE A 30-MINUTE
BREAK.
SO RETURN AT 1:30.
AND IF YOU ORDERED LUNCH HERE,
THE LUNCHES ARE IN THE KITCHEN
DOWN HERE WITH YOUR NAME ON IT.
AGAIN, PLEASE HELP YOURSELF TO
FRUIT AND THERE'S LACROIX IN THE
COOLER.
SO WE'LL RESUME AT ABOUT 1:30.
>> THANK YOU.
>> I HOPE EVERYBODY HAD A GOOD
LUNCH BREAK.
WELCOME BACK.
IN THE NEXT SESSION, WE'LL BE
DISCUSSING STRATEGIC PLANNING.
NOPE, SORRY, I'M ON THE WRONG
PAGE.
WELCOME BACK.
NEXT WE'LL HAVE THREE
PRESENTATIONS ON THE THEME OF
PATHWAYS TO REGULATORY
APPROVALS.
THE FIRST IS A PRESENTATION FROM
MS. NIKI ARMSTRONG OF THE PARENT
PROJECT MUSCULAR DYSTROPHY ON
PROGRESS IN NEWBORN SCREENING.
NIKI.
>> THOUSAND THANK YOU FOR THE
INTRODUCTION AND OPPORTUNITY TO
SPEAK TODAY.
AS YOU SAID, MY NAME IS NIKI
ARMSTRONG, ASSOCIATE VICE
PRESIDENT OF COMMUNITY RESEARCH
AND GENETIC SERVICES AT PPMD,
AND I'M A GENETIC COUNSELOR BY
TRAINING AND I'M GOING TO BE
TALKING ABOUT OUR PROGRESS ON
NEWBORN SCREENING FOR DUCHENNE.
SO AS GLEN MENTIONED EARLIER,
NEW BORE SCREENING IS SOMETHING
PPMD HAS BEEN WORKING ON VOR A
VERY LONG TIME, AT THIS POINT
MORE THAN 10 YEARS, BUT I THINK
IT'S IMPORTANT WHEN STARTING A
CONVERSATION ON NEWBORN
SCREENING THAT WE PUT IT IN CON
FLEX OF HOW COMPLEX THE NEWBORN
SCREENING SYSTEM IS IN THE U.S.
NEWBORN SCREENING HAS BEEN AN
INCREDIBLY SUCCESSFUL PUBLIC
HEALTH INITIATIVE, BUT IT IS
ALSO INCREDIBLY VARIABLE.
AND THAT IS BECAUSE NEWBORN
SCREENING IS A STATE-BASED
PROGRAM.
SO EVERY STATE GETS TO DECIDE
WHICH CONDITION THAT EACH BABY
BORN IN THAT STATE SHOULD BE
SCREENED FOR.
AND YOU CAN SEE IN THAT MAP
THERE TO THE LEFT, THE DARKER
COLORS ARE STATES THAT ARE
SCREENING FOR MORE CONDITIONS,
LIGHTER COLORS ARE STATES
SCREENING FOR FEWER CONDITIONS.
EVERY STATE DECIDES HOW THEY
DETERMINE WHETHER ADDITIONAL
CONDITIONS SHOULD BE ADDED TO
THEY'RE STATE NEWBORN SCREENING
PROGRAM AND ALSO HOW THEY WANT
TO DO NEWBORN SCREENING.
SO PRETTY MUCH EVERY STATE
RECOMMENDS A SAMPLE BE COLLECTED
BETWEEN 24 AND 48 HOURS OF AGE
BUT SOME STATES ALSO RM AN
ADDITIONAL SAMPLE AT 7 TO 14
DAYS OF AGE.
SOME STATES ONLY DO A
BIOCHEMICAL SCREENING, SOME
STATES DO DNA SCREENING.
THERE'S A HUGE AMOUNT OF
VARIABILITY ABOUT HOW NEWBORN
SCREENING HAPPENS IN THE U.S.
SO THERE IS A LONG HISTORY OF
NEWBORN SCREENING PILOTS FOR
DUCHENNE.
YOU CAN SEE HERE IT DATES BACK
ALMOST 50 YEARS.
BUT THERE'S BEEN A CLUSTERING OF
PILOTS IN THE MORE RECENT YEARS.
ALL THE PILOTS HIGHLIGHTED IN
RED ARE PILOTS THAT USE AN FDA
AUTHORIZED ASSAY AND I'LL TALK
MORE ABOUT THAT.
AT THIS POINT, MORE THAN
2 MILLION NEWBORNS WORLDWIDE
HAVE BEEN SCREENED FOR
DUCHENNE'S AND AT LEAST ONE
PLACE, TAI WAN, TAIWAN, IS SCREL
BABIES WITHIN THAT PARTICULAR
REGION.
THE MORE RECENT NEWBORN
SCREENING PROGRAMS IN THE U.S.
ARE OUTLINED HERE.
SO PPMD SPONSORED A PILOT IN
NEW YORK STATE THAT RAN FROM
2019 TO 2021, SO TWO YEARS'
TIME, AND IN THAT TWO YEARS'
TIME, ALMOST 37,000 BABIES WERE
SCREENED.
WE THEN IDENTIFIED FOUR MALES,
THREE WITH DUCHENNE AND ONE WITH
BECKER AS WELL AS ONE FEMALE
CARRIER WITHIN THAT GROUP.
AND AT THE SAME TIME, THE RTI
MDA PROGRAM WAS ONGOING IN NORTH
CAROLINA THROUGH THEIR EARLY
CHECK AND NEWBORN SCREENING.
THAT PROGRAM WRAPPED UP OVER THE
SUMMER AND THEY SCREENED MORE
THAN 13,000 BABIES AND
IDENTIFIED TWO BOYS WITH
DUCHENNE.
BOTH THE PPMD AND THE RTI
PROGRAMS WERE VERY TRADITIONAL
CONSENTED NEWBORN SCREENING
PILOTS, MEANING EVERY FAMILY
THAT PARTICIPATED, PARTICIPATED
IN A RESEARCH STUDY WITH A
NUMBER OF PARAMETERS IN PLACE,
INCLUDING FULLY INFORMED
CONSENT.
THE THIRD PROGRAM THERE ON THE
RIGHT, THE CURE DUCHENNE PROGRAM
IN BOSTON, MASSACHUSETTS WAS
HAPPENING AT BRIGHAM AND
WOMEN'S, STARTED IN TWEB 2021 S
ONGOING.
IT'S A SUPPLEMENTAL NEWBORN
SCREENING PROGRAM RATHER THAN A
CONSENTED PILOT.
EVERY FAMILY HAS THE OPTION TO
OPT IN BUT IT IS NOT A RESEARCH
STUDY.
AT THIS POINT THEY SCREENED MORE
THAN 20,000 BABIES, HAVE NOT
IDENTIFIED ANY MALES BUT HAVE
IDENTIFIED FOUR FEMALE CARRIERS.
THE BOTTOM LINE IS WE HAVE HAD A
NUMBER OF DUCHENNE PILOTS IN A
NUMBER OF YEARS THAT WERE
SUCCESSFUL IN IDENTIFYING
CHILDREN WITH DUCHENNE'S.
SO WHAT ARE OUR NEXT STEPS?
SO GETTING TO UNIVERSAL NEWBORN
SCREENING FOR DUCHENNE, ONE OF
THE KEY STEPS IS GETTING
DUCHENNE ON THE RECOMMENDED
UNIFORM SCREENING PANEL.
I THINK MOST OF THIS BODY IS
FAMILIAR WITH THE RECOMMENDED
UNIFORM SCREENING PANEL OR THE
RUSP AS WE FONDLY CALL IT.
IT'S THE LIST OF DISORDERS THAT
THE SECRETARY OF THE DEPARTMENT
OF HEALTH AND HUMAN SERVICES
RECOMMENDS FOR EACH STATE.
SO WHILE THE STATES GET TO MAKE
THE ULTIMATE DECISION, THE
FEDERAL GOVERNMENT DOES PUT
TOGETHER A LIST OF CONDITIONS
THAT THEY RECOMMEND EVERY STATE
SCREEN FOR.
THIS LIST IS REVIEWED BY THE
ADVISORY COMMITTEE ON HERITABLE
DISORDERS IN NEWBORNS AND
CHILDREN.
SO GETTING ON THE RUSP FOR
DUCHENNE HAS A NUMBER OF
BENEFITS.
ONE OF THE KEY BENEFITS IS THAT
THERE IS RUSP ALIGNMENT
LEGISLATION IN 11 STATES NOW,
AND WHAT THAT MEANS IS THOSE
STATES HAVE STATE LEGISLATION IN
PLACE THAT SAYS WHEN A CONDITION
GETS ON THE RUSP, THAT STATE
WILL EITHER AUTOMATICALLY BEGIN
SCREENING FOR THAT CONDITION OR
WILL START A INDEPENDENT REVIEW
PROCESS TO START SCREENING FOR
THAT CONDITION.
AND EVEN IN STATES, WHICH IS THE
MAJORITY OF STATES, THAT DO NOT
HAVE R USP ALIGNMENT
LEGISLATION, BEING ON THE RUSP
REALLY LENDS VALIDITY, IT SAYS
THAT A CONDITION HAS BEEN
THROUGH A VERY THOROUGH ROUX VEE
PROCESS AND WE KNOW THERE ARE
BENEFITS TO SCREENING, AND IT
ALSO PROMPTS STATES TO START
CONSIDERING THAT CONDITION AS A
POTENTIAL ADDITION IN THEIR
STATE.
SO THE RUSP PROCESS IS LONG AND
INTENSE, AND IS SOMETHING THAT
PPMD AND OUR PARTNERS HAVE BEEN
WORKING ON FOR A NUMBER OF
YEARS.
SO WE ACTUALLY INITIALLY
SUBMITTED THE RUSP PACKAGE BACK
IN JUNE OF 2022.
FOR THOSE WHO AREN'T FAMILIAR,
YOUR NOMINATION PACKAGE CONSISTS
OF AN ACTUAL NOMINATION FORM
WHICH IS A SERIES OF QUESTIONS
THAT YOU ANSWER.
EVERY ANSWER YOU PROVIDE HAS TO
HAVE LITERATURE CITED, AND THEN
YOU SUBMIT THAT INITIALLY TO
HRSA, WHO REVIEWS IT FOR
COMPLETENESS.
THEY MAKE SURE ALL THE QUESTIONS
ARE ANSWERED AND THAT THERE'S
CITATIONS FOR EVERY QUESTION.
AFTER THAT STEP IS COMPLETE, IT
GOES TO A WORK GROUP WITHIN THE
ACHDND THAT'S CALLED NOMINATION
AND PRIORITIZATION WORK GROUP.
THAT GROUP IS A SUBSET THAT
REVIEWS THE PACKAGE LOOKING AT
SOME KEY QUESTIONS TO MAKE SURE
THAT PACKAGE IS ANSWERING THOSE
KEY QUESTIONS AND THE
INFORMATION IS NEEDED TO MOVE ON
TO NEXT STEPS.
AT THAT POINT, THE NOMINATION
AND PRIORITIZATION WORK GROUP
PRESENTS WHAT THEY FOUND AFTER
LOOKING AT THE PACKAGE TO THE
WHOLE COMMITTEE AND THEN THE
COMMITTEE VOTES.
FOR THOSE OF YOU WHO HAVE BEEN
FOLLOWING DUCHENNE NEWBORN
SCREENING, YOU WILL LIKELY BE
AWARE THAT THERE WAS A NO-VOTE
IN FEBRUARY OF 2023.
SO THE COMMITTEE FELT THERE
WASN'T ENOUGH EVIDENCE TO MOVE
THE PACKAGE FORWARD.
VERY SOON AFTER THAT NO-VOTE,
THE COMMITTEE REACHED OUT TO US
AND ASKED US TO MAKE SOME MINOR
MODIFICATIONS WITHIN THE PACKAGE
AND RESUBMIT.
SO THAT WAS SUBMITTED AT THE
BEGINNING OF THIS SUMMER AND
DURING THE AUGUST 2023 MEETING,
THE COMMITTEE VOTED YES TO MOVE
THE DUCHENNE PACKAGE FORWARD TO
EVIDENCE REVIEW.
SO THAT'S WHERE THE DUCHENNE
PACKAGE IS RIGHT NOW, AND I'LL
TALK A LITTLE BIT MORE ABOUT THE
EVIDENCE REVIEW PROCESS IN A
MINUTE.
REVIEW IS LEGISLATED TO BE NINE
MONTHS.
AT THE END OF THE EVIDENCE
REVIEW PROCESS, THE COMMITTEE
THEN GATHERS TOGETHER AND
DISCUSSES ALL THE THINGS THAT
HAVE BEEN FOUND THROUGH THE
EVIDENCE REVIEW AND VOTES.
RIGHT NOW WE'RE EXPECTING THAT
VOTE TO BE IN MAY OF 2024,
ALTHOUGH THINGS ARE ALWAYS
SUBJECT TO CHANGE.
IF THE COMMITTEE VOTES YES, THE
PACKAGE IS THEN MOVED ON TO THE
SECRETARY OF HEALTH AND HUMAN
SERVICES, WHO MAKES THE FINAL
DECISION ON WHETHER OR NOT TO
ADD THE CONDITION TO THE RUSP.
THIS PROCESS IS NEVER FAST.
THE VAST MAJORITY OF CONDITIONS
TAKE MORE THAN 24 MONTHS.
SO EVIDENCE REVIEW IS A LITTLE
BIT DIFFERENT THAN SOME OF THE
OTHER STEPS BECAUSE DURING
EVIDENCE REVIEW, THERE'S
ACTUALLY AN INTERNAL GROUP THAT
WORKS ON THE PACKAGE.
AND THAT GROUP CONSISTS OF A
NUMBER OF PEOPLE THAT ARE
ACTUALLY SITTING WITHIN THE
ACHDNC AS WELL AS A NUMBER OF
FEDERAL COMMITTEES.
A KEY PIECE OF THAT GROUP IS
CALLED THE TECHNICAL EXPERT
PANEL.
THAT INCLUDES REPRESENTATIVES
FROM THE NOMINATORS, SO IN
DUCHENNE'S NOMINATORS THAT WAS
PPMD AND THE MDA, AS WELL AS
CLINICAL EXPERTS AND EXPERTS
INVOLVED IN THE NEWBORN
SCREENING PILOTS FOR THAT
CONDITION.
SO THAT GROUP HAS THE JOB OF
COLLECTING THE DATA, CREATING A
FINAL REPORT, AND THEN
PRESENTING THAT REPORT BACK TO
THE ACHDNC.
THAT REPORT HISTORICALLY
INCLUDES A SYSTEMATIC EVIDENCE
REVIEW, SO THE EXTERNAL GROUP
ACTUALLY DOES ANOTHER LITERATURE
REVIEW OUTSIDE OF WHAT WAS
ALREADY PROVIDED TO THEM IN THE
NOMINATION PACKAGE.
AND THEN THERE'S ALSO A
COMPONENT WHERE THERE IS
DECISION ANALYSIS MODELING, SO
ESSENTIALLY THINKING ABOUT THERE
ARE 4 MILLION BABIES ROUGHLY
BORN IN THE U.S. EVERY YEAR.
WHAT WOULD HAPPEN IF WE HAD
NEWBORN SCREENING FOR ALL
4 MILLION OF THOSE BABIES, WHAT
WOULD WE SEE AS OUTCOMES, WHAT
WOULD WE EXPECT THAT TO LOOK
LIKE?
HE THTHEN THE LAST IS A PUBLIC H
SYSTEM IMPACT ASSESSMENT, COULD
YOU START SCREENING FOR DUCHENNE
AND WHAT KIND OF WOULD IT TAKE
TO GET YOU IN THE RIGHT PLACE TO
BE TO DO MORE SCREENING.
THERE HAVE BEEN CONVERSATIONS AT
THE MOST RECENT MEETINGS ABOUT
ALTERING THE WAY THIS IS SET UP,
ESPECIALLY THE PUBLIC HEALTH
ASSESSMENT.
IT'S BEEN -- THE INFORMATION IS
GATHERED FROM THOSE ASSESSMENTS
HASN'T NECESSARILY BEEN THAT
USEFUL IN SOME OF THE PAST
REVIEWS SO THE COMMITTEE IS
LOOKING AT HOW TO BETTER DO
THAT.
SO IT MIGHT BE DIFFERENT IN THE
FUTURE.
BECAUSE THIS IS TYPICALLY A NINE
MONTH EVIDENCE REVIEW PROCESS,
AND THE COMMITTEE USUALLY MEETS
QUARTERLY, THAT MEANS THAT EACH
CONDITION IS TI TYPICALLY DISCUD
OVER A TOTAL OF THREE MEETINGS
AT THE COMMITTEE.
SO DUCHENNE WAS DISCUSSED IN
NOVEMBER OF 2023, WE EXPECT TO
BE ON THE AGENDA FOR
JANUARY 2024, AND THEN AGAIN MA.
WHEN WE WOULD EXPECT THE VOTE TO
OCCUR.
SO THE RUSP IS -- IT'S A LOT BUT
IT'S ALSO JUST THE BEGINNING.
ONCE THE CONDITION IS ON THE
RUSP, YOU STILL HAVE TO GO BACK
TO THE STATES AND GET DUCHENNE
ADDED TO THE NEWBORN SCREENING
PANELS IN EVERY STATE.
EACH STATE DIFFERS ON HOW YOU DO
THAT PROCESS.
SOME STATES ENTIRELY USE
LEGISLATION.
SOME STATES HAVE ADVISORY PANELS
OR COMMITTEES THAT ARE SET UP
THAT ESSENTIALLY HAVE THEIR OWN
REVIEW PROCESS FOR EACH
CONDITION.
AND SOME STATES USE A
COMBINATION, WHERE THEY MIGHT
HAVE AN ADVISORY COMMITTEE OR A
REVIEW PANEL, BUT THEN THEY
REQUIRE LEGISLATION FOR THE
FUNDING THAT NEEDS TO HAPPEN TO
ADD A NEW CONDITION TO THEIR
NEWBORN SCREENING.
SO IT'S A COMPLICATED PROCESS
THAT, AGAIN, VARIES FROM STATE
TO STATE.
I JUST WANT TO TALK A LITTLE
ABOUT THE DETAILS OF HOW
DUCHENNE NEWBORN SCREENING IS
HAPPENING.
IN ALL CASES WHAT WE SUBMITTED
AS PART OF OUR RUSP NOMINATION
PACKAGE IS THAT THE FIRST TIER
SCREEN WOULD BE CK-MM, THE
MUSCLE ISOFORM OF CREATINE
KINASE.
IT IS SIGNIFICANTLY ELEVATED IN
DUCHENNE, AND IT IS AN FDA
AUTHORIZED KIT THAT IS RUN ON
THE REVVITY'S GSP MACHINE, WHICH
ARE COMMONLY USED IN ALL THE
NEWBORN SCREENING LABORATORIES
IN THE U.S.
SO THAT MAKES IT VERY
CONVENIENT.
IF A BABY HAS AN ELEVATED CK-MM,
THERE ARE REALLY TWO PRIMARY
ALGORITHMS THAT WE'VE SEEN
STATES TALK ABOUT USING.
THE FIRST IS IF THERE'S AN
ELEVATED CK-MM, THE NEXT STEP IS
THE DMD DNA TESTING WHICH WOULD
CONFIRM THE DIAGNOSIS.
THE OTHER OPTION THAT SOME
STATES ARE CONSIDERING IS GOING
FROM CK-MM TO A REPEAT CK-MM
COLLECTED SOMETIME AFTER A WEEK
OF AGE, AND THEN IF THAT SECOND
REPEAT CK-MM IS ELEVATED, THEN
THE DNA TESTING FOR DMD WOULD BE
PERFORMED.
THE REASON FOR THAT SECOND CK-MM
IS THAT ONE OF THE PRIMARY
CAUSES OF FALSE POSITIVES IN
NEWBORN SCREENING FOR DUCHENNE
IS ACTUALLY BIRTH TRAUMA.
SO WHEN YOU THINK ABOUT HOW
DIFFICULT LABOR AND DELIVERY CAN
BE ON A BABY, IT CAN CAUSE
ELEVATIONS IN CK-MM THAT
ACTUALLY DROP REALLY QEKLY.
QUICKLY SO
BY DAY 4 OF LIFE, THOSE
ELEVATIONS DROP.
IF YOU DO A REPEAT SAMPLE OR
YOU'RE A STATE THAT COLLECTS TWO
SAMPLE, ON THAT SECOND SAMPLE,
WE'RE GOING TO LOSE ALL THE
BABIES THAT HAD FALSE POSITIVE
ELEVATIONS RELATED TO BIRTH OR
DELIVERY TRAUMA.
AT THIS POINT, WE HAVE TWO
STATES WHO HAVE MANDATED NEWBORN
SCREENING FOR DUCHENNE, AND
WE'LL START LIKELY IN 2024, OHIO
AND NEW YORK.
AND THEN WE HAVE A THIRD STATE,
MINNESOTA, WHOSE ADVISORY
COMMITTEE WHO HAS APPROVED
DUCHENNE NEWBORN SCREENING BUT
IT'S UNDER FINAL STATE
COMMISSIONER REVIEW.
WE'RE HOPEFUL THAT IN EARLY
2024, THE STATE COMMISSIONER
WILL SIGN OFF ON THAT IN
MINNESOTA.
I DO WANT TO TALK A LITTLE BIT
ABOUT HOW DIFFERENT STATES ARE
APPROACHING THIS, JUST SO YOU
AGAIN CAN SEE HOW IT MIGHT VARY
FROM STATE TO STATE.
OHIO IS MANDATED TO START IN
MARCH OF 2024.
THEIR PROPOSED ALGORITHM STILL
UNDER DISCUSSION IS THAT THEY'RE
GOING TO DO A CK-MM, THEN
THEY'RE GOING TO DO A REPEAT
CK-MSM M IS THE FIRST IS
ELEVATED, THAT REPEAT WILL
HAPPEN ABOUT TWO TO FOUR WEEKS
OF AGE.
IF THAT REPEAT REMAINS ELEVATED,
THAT BABY WILL BE CONSIDERED TO
HAVE A POSITIVE NEWBORN
SCREENING, AND AT THAT POINT,
WOULD BE REFERRED TO A NEWBORN
SCREENING FOLLOW-UP SPECIALIST,
WHICH IN THE STATE OF OHIO IS
GOING TO BE EITHER A NEUROLOGIST
OR GENETICIST.
AT THAT POINT, THE NEWBORN
SCREENING FOLLOW-UP SPECIALIST
WILL MAKE THE DECISION ABOUT
WHAT GENETIC TESTING TO DO, BUT
WE WOULD ASSUME THAT IT WOULD BE
DMD DNA, BUT THEY MAY ALSO
CONSIDER SOME ADDITIONAL
NEUROMUSCULAR GENES FOR OTHER
MUSCULAR DYSTROPHIES.
THAT'S OHIO'S CURRENT PLAN.
MINNESOTA, WHICH AGAIN IS STILL
UNDER REVIEW BY THE STATE
COMMISSIONER, BUT THEIR ADVISORY
COMMITTEE ACTUALLY RECOMMENDED
AN ALGORITHM AS PART OF THEIR
REVIEW PROCESS.
AND THE RECOMMENDED ALGORITHM
BASED ON THEIR ADVISORY
COMMITTEE IS THAT IN THE EVENT
OF AN ELEVATED CK-MM, THAT WOULD
GOING DIRECTLY TO DMD DNA
GENETIC TESTING AND THEY WOULD
ONLY REPORT OUT PATHOGENIC OR
LIKELY PATHOGENIC VARIANTS IN
THE DMD GENE.
AT THE FINDING OF A PATHOGENIC
VARIANT IN THE DMD GENE, THAT
BABY WOULD BE REFERRED TO A
NEWBORN SCREENING FOLLOW-UP
SPECIALIST, WHICH AGAIN WOULD BE
EITHER A NEUROLOGIST OR
GENETICIST WITHIN THAT STATE.
SO AS I MENTIONED BEFORE, WE
HAVE THREE STATES THAT ARE VERY
FAR ALONG IN THE PROCESS, BUT
THERE ARE A NUMBER OF OTHER
STATES WHERE WE'RE AT, I WOULD
SAY SORT OF ENTRY LEVEL, WHERE
THE STATES HAVE HAD SOME
INTEREST IN DUCHENNE NEWBORN
SCREENING AND WE'VE HAD MEETINGS
WITH THE STATE ADVISORY
COMMITTEES OR INDIVIDUALS ON THE
STATE ADVISORY COMMITTEES.
AND THOSE STATES ARE HIGHLIGHTED
IN THE LIGHT BLUE HERE.
THERE'S A LOT OF WORK LEFT TO BE
DONE TO GET TO UNIVERSAL
DUCHENNE NEWBORN SCREENING.
SO WE CAN SEE HIGHLIGHTED IN
ORANGE, WE HAVE OUR STATE
EFFORTS SUPPORTING STATES THAT
ARE INTERESTED IN ADVOCACY AT
THE STATE LEVEL.
WE HAVE OUR CONTINUED EFFORTS TO
GET ON THE RUSP AND HOPEFULLY
THAT WILL HAPPEN IN 2024.
AND THEN WE HAVE THE OTHER
PIECES THAT WE REALLY NEED TO
HAVE IN PLACE TO SUPPORT AS
NEWBORN SCREENING BECOMES MORE
BROADLY AVAILABLE.
ONE OF THE KEY PIECES IS FAMILY
EDUCATION AND SUPPORT.
WHAT I NEGLECTED TO PUT ON THIS
SLIDE IS ACTUALLY PROVIDER
EDUCATION AND SUPPORT, SO WE
REALLY NEED TO PROVIDE A LOT
MORE EDUCATION FOR OUR
PEDIATRICIANS WHO -- NEWBORN
SCREENING FOR DUCHENNE WILL BE
BRAND NEW TO THEM, SO MAKING
SURE THEY ARE COMFORTABLE AND
FAMILIAR.
AND WE ALSO NEED TO BETTER
DEVELOP EARLY CARE GUIDELINES
FOR BABIES IDENTIFIED ON
DUCHENNE NEWBORN SCREENING.
PPMD HOSTED A MEETING LOOKING AT
CARE FROM ZERO TO 3 EARLY IN
2023 AND WE WANT TO FOLLOW UP
WITH THAT WITH MORE CLEAR
GUIDELINES TO HELP PROVIDERS AS
THESE BABIES ARE IDENTIFIED.
AND THAT'S IT.
SO THANK YOU VERY MUCH AND I'M
HAPPY TO TAKE QUESTIONS.
>> THANK YOU VERY MUCH, NIKI.
DO WE HAVE QUESTIONS?
>> IT LOOKS LIKE THERE'S ONE IN
THE CHAT FROM BRAD WILLIAMS?
>> PLEASE.
>> SO THE QUESTION ABOUT DO WE
HAVE A PROPORTION OF BABIES WITH
HIGH CK THAT WOULD HAVE MUSCULAR
DYSTROPHIES OTHER THAN DUCHENNE
IS A REALLY GOOD ONE.
SOME OF THAT'S GOING TO DEPEND
ON WHAT THAT PARTICULAR STATE
CHOOSES AS THE CUTOFF.
THE CK ELEVATIONS IN DUCHENNE
ARE MUCH HIGHER THAN MOST OF THE
OTHER MUSCULAR DYSTROPHIES.
SO IF A STATE CHOOSES A HIGHER
CUTOFF, OUR LIKELIHOOD OF
IDENTIFYING OTHER MUSCULAR
DYSTROPHYs IS ACTUALLY GOING
TO BE MUCH LESS.
THAT BEING SAID, WHEN WE LOOK AT
THE PILOTS THAT HAVE BEEN
CONDUCTED THUS FAR, THE NEW YORK
STATE PILOT DIDN'T IDENTIFY ANY
OTHER MUSCULAR DYSTROPHIES.
THE PILOT IN THE BOSTON BRIGHAM
PROGRAM HAS ALSO NOT IDENTIFIED
ANY OTHER MUSCULAR DYSTROPHIES.
HOWEVER, THE NORTH CAROLINA RTI
PROJECT DID IDENTIFY ONE BABY
WITH A CONGENITAL -- WELL, WITH
A SORT OF -- IT LOOKS LIKE
AUTOSOMAL DOMINANT MYOTONIA
SYNDROME BUT THE AFFECTED PARENT
IS DOING VERY WELL SO THAT WAS
JUST A LITTLE BIT -- BUT NO
OTHER.
>> JENNIFER IS VOLUNTEERING
CHARLIE'S CK LEVEL, WHICH WAS
EXTREMELY HIGH AT THE TIME OF
HIS DIAGNOSIS.
NEXT WE'RE GOING TO HAVE
DR. BILL ROONEY FROM OREGON
HEALTH AND SCIENCES UNIVERSITY.
HE'S GOING TO TELL US ABOUT THE
DEVELOPMENT OF A CLINICAL TRIAL
SIMULATION TOOL THAT IS
CURRENTLY UNDER REVIEW BY THE
FDA AND THE EMA.
BILL.
>> SORRY TO INTERRUPT,
DR. BIANCHI.
I THINK THERE WAS A QUESTION
FROM MICHAEL GOLDSTEIN.
>> YEAH, IF I COULD FOR JUST A
MINUTE, I DON'T WANT TO -- I
KNOW THAT WE'RE RUNNING A LITTLE
SHORT ON TIME BUT -- AND I ALSO
REALIZE THAT THIS IS LIKELY
ELEMENTARY, MY INQUIRY FOR A LOT
OF THE RESEARCHERS AND THOSE
THAT HAVE A MUCH GREATER DEPTH
OF KNOWLEDGE THAN I DO, BUT I
WAS HOPING THAT MAYBE THERE
COULD JUST BE A BRIEF DISCUSSION
PERHAPS ON SOME OF THE
DIFFERENCES, BECAUSE IT'S VERY
RELEVANT FROM MY SEAT, THE
DIFFERENCES IN THE COURSE OF
CARE AND POTENTIAL OUTCOMES
BEYOND THE KIND OF OBVIOUS
PLANNING OF THESE NEWBORN
SCREENINGS AND THE
IDENTIFICATION AS A NEWBORN IN
COMPARISON TO A DIAGNOSIS AT AGE
2, AND IF THERE IS A SIGNIFICANT
OUT COME DIFFERENCE, IF WE COULD
HAVE MAYBE JUST -- IF I COULD
GET A BRIEF SYNOPSIS OF LIKE THE
NEXT STEPS.
>> SURE.
AND FROM A DUCHENNE PERSPECTIVE,
I THINK IT'S IMPORTANT TO KEEP
IN MIND THAT THE TYPICAL AGE OF
DIAGNOSIS OF DUCHENNE IS BETWEEN
4 AND 5, AND AT THAT POINT, KIDS
HAVE SIGNIFICANT MUSCLE DAMAGE
ALREADY.
WHICH IS IRREVERSIBLE.
THE OTHER PIECE TO RECOGNIZE IS
THAT WHILE THE AVERAGE AGE IS
BETWEEN 4 AND 5, WE KNOW THAT
THERE ARE KIDS -- THE KIDS THAT
COME FROM UNDERSERVED
COMMUNITIES, THE KIDS WHO HAVE
OTHER DIAGNOSES SUCH AS AUTISM,
WHICH IS MORE COMMON IN
DUCHENNE, THOSE KID ARE EVEN
LATER TO DIAGNOSIS.
WHICH IS A HUGE ISSUE WHEN THE
CARE IS SUPPOSED TO THE AT LEAST
START BY AGE 4 BUT WOULD YOU
HOPE EVEN EARLIER THAN THAT, AND
ESPECIALLY IT'S BECOME AN ISSUE
BECAUSE OF THE LEVITIS APPROVAL
WHICH IS FOR 4 TO 5-YEAR-OLDS
AND GIVEN THE NUMBER OF KIDS
DIAGNOSED AFTER 5 SINCE THE
AVERAGE AGE IS 5, THOSE KIDS ARE
NO LONGER ELIGIBLE FOR LEVITIS
BECAUSE OF THEIR AGE OF
DIAGNOSIS.
SO FROM THAT PERSPECTIVE, IT'S
REALLY IMPORTANT WE'VE GOT
SIGNIFICANT MUSCLE DAMAGE AT THE
TIME OF DIAGNOSIS AND THE EXON
SKIPPING THERAPIES ARE APPROVED
FOR ALL AGES, SO CHILDREN WHO
ARE ELIGIBLE FOR THE EXON
SKIPPING THERAPIES, AND THAT'S
ABOUT 30% OF DUCHENNE'S, CAN
START THOSE AT ANY AGE.
WE'RE AWARE OF A -- IN A FAIR
NUMBER OF KIDS THAT ARE STARTING
RIGHT BEFORE OR AROUND AGE 1 AT
THIS POINT, I WOULD SAY ONE OF
THE BIGGEST ISSUES HAS BEEN THAT
DIAGNOSIS DOESN'T TYPICALLY
OCCUR IN BABIES, SO IT'S VERY
HARD TO COLLECT SIGNIFICANT
AMOUNTS OF DATA ABOUT TREATING
BABIES TO KNOW WHAT THE LONG
TERM IMPACTS ARE.
THE OTHER PIECE THAT'S REALLY
COMPLICATED IS THE FACT THAT
DUCHENNE HAS A REALLY SLOW
PROGRESSION.
SOME OF THE VERY COMMON OUT COME
MEASURES THAT WE USE, ESPECIALLY
IN REAL WORLD DATA LIKE LOSS OF
AMBULATION DOES TAKE FOWRP OR 1R
LONGER YEARS TO SEE, SO IT'S
BEEN DIFFICULT TO MEASURE FROM
THAT PERSPECTIVE.
>> THANK YOU.
THAT'S VERY INFORMATIVE.
THANK YOU.
>> OKAY.
THANK YOU AGAIN TO MS. ARMST
MS. ARMSTRONG, AND WE'RE GOING
TO GO OVER TO BILL ROONEY, WHO
IS ALL -- HE'S ONLINE AND HE'S
GOT HIS SLIDES DIALED UP SO
WE'RE OVER TO YOU, BILL.
>> OKAY, THANK YOU.
CAN EVERYBODY HEAR ME OKAY?
>> WE CAN HEAR YOU PERFECTLY.
>> OKAY.
THANK YOU.
WELL, I'D LIKE TO THANK GLEN
NUCKOLLS FOR THE OPPORTUNITY TO
PRESENT.
THIS IS WORK THAT WAS STARTED
ACTUALLY IN 2010.
IT'S AN NIH-FUNDED PROJECT
THROUGH NIAMS AND NINDS.
AND MORE RECENTLY, WE'VE TEAMED
WITH C-PATH, RAMONA
BELFIORE-OSHAN IS IN THE
AUDIENCE AND SHE HAS BEEN REALLY
GREAT TO WORK WITH TO MOVE SOME
OF THESE BIOMARKERS FORWARD TO A
CLINICAL TRIAL SIMULATION TOOL.
SO I'LL JUST REVIEW SOME OF THAT
NOW.
SO THERE'S REALLY AN UNMET NEED
FOR CLINICAL TRIAL SIMULATION
TOOLS.
IMAGING IN ITSELF DOESN'T CURE
DISEASE.
BUT THESE IMAGING MEASURES ARE
SENSITIVE AND THEY CAN REALLY
HELP ASSIST TRIAL DESIGN IN THE
SENSE THAT THESE SENSITIVE
BIOMARKERS ARE NONINVASIVE, THEY
CAN TRACK DISEASE IN BOTH
AMBULATORY AND NON-AMBULATORY
INDIVIDUALS, AND THEY'RE REALLY
AN ADJUVANT THAT CAN BE USED TO
ACCELERATE DRUG DISCOVERY.
SO BOTH THE U.S. FOOD AND DRUG
ADMINISTRATION AND EMA HAVE
STATED A PRIORITY TO DEVELOP
IMPROVED UNDERSTANDING OF
DISEASE PROGRESSION IN RARE
DISEASE.
AND THIS UNMET NEED REMAINS TO
BETTER UNDERSTAND THE
RELATIONSHIP BETWEEN DISEASE --
LONGITUDAL DISEASE DYNAMICS AND
CLINICALLY MEANINGFUL OUT COME
MEASURES.
AND MRI HAS A NUMBER OF THEM I
WILL DESCRIBE THE FACT FRACTION
MEASURE TODAY.
TO ACHIEVE THIS, HIGH QUALITY
NATURAL HISTORY STUDIES THAT
TRACK SENSITIVE BIOMARKERS OVER
APPROPRIATE TIME SCALES CAN BE
USED TO GENERATE MATHEMATICAL
MODELS OF DISEASE PROGRESSION
AND IT'S THESE MATHEMATICAL
MODELS AND RELATED STATISTICAL
APPROACHES WHICH FORM THE KERNEL
FOR THE CLINICAL TRIAL
SIMULATION TOOL.
REALLY THIS WAS THE POINT OF THE
IMAGING DMD, NOW IMAGING NMD
TRIAL.
SO JUST A BRIEF BACKGROUND ON
THIS.
THIS IS A TRIAL THAT WAS
ESTABLISHED IN 2010.
IT'S CURRENTLY FUNDED THROUGH
2025.
THIS IS A NATURAL HISTORY STUDY,
OVER 1200 SUBJECT VISITS HAVE
OCCURRED SINCE 2010.
WITH LONGITUDAL DATA GOING OUT
TO 10 YEARS IN SOME INDIVIDUALS.
THERE ARE 50 AGE MATCHED
CONTROLS.
WE'VE UTILIZED QUANTITATIVE MRI
AND MRS, AND THEN IN ADDITION TO
THAT, MULTIPLE FUNCTIONAL AND
STRENGTH MEASURES.
AND THIS IS A TRIAL THAT'S
STARTED WITH THREE PRINCIPAL
SITE.
THE MAIN SITE IS IN GAINESVILLE
UNDER THE LEADERSHIP OF THE
PROJECT VI, AND IN PORTLAND,
OREGON AT MY INSTITUTION, OREGON
SCIENCE AND HEALTH UNIVERSITY,
AND AT CHILDREN'S HOSPITAL OF
PHILADELPHIA.
SO MAGNETIC RESONANCE
SPECTROSCOPY PROVIDES A MEASURE
OF MUSCLE FAT FRACTION, AND IN
THE SLIDE UP HERE, YOU CAN SEE
WITH MY POINTER, YOU CAN SEE A
HEALTHY CONTROL.
THIS MUSCLE DOESN'T HAVE A LOT
OF BRIGHTNESS IN THE
INTRAMUSCULAR SPACE.
THIS IS A HEALTHY CONTROL, AND
OVER HERE ARE JUST THREE YEARS
FOR A YOUNG BOY WITH DUCHENNE
MUSCULAR DYSTROPHY STARTING AT .
YOU CAN REALLY SEE THE
BRIGHTNESS IN THE MUSCLE.
THAT'S JUST AN INDICATION OF THE
FAT.
SO WE CAN QUANTIFY THAT FAT WITH
A TECHNIQUE CALLED SPECTROSCOPY.
THERE ARE A FEW SPECTRUMS SHOWN
HERE.
YOU CAN SEE A VERY INTENSE PEAK
FROM WATER IN THE HEALTHY
CONTROL AND A REALLY SMALL PEAK
FROM FAT.
IN THE DMD BOY, YOU CAN SEE THE
WATER PEAK IS DIMINISHED, THE
FAT PEAK INCREASED AND THAT FAT
PEAK INCREASES WITH TIME.
SO WE CAN QUANTIFY THAT AND USE
THAT AS A BIOMARKER FOR DISEASE
PROGRESSION.
SO THE INVOLVEMENT IN THE
DISEASE IS SHOWN HERE.
IN THE EARLY PHASE, RATE OF
MUSCLE LOSS IS LOW DUE TO A LOW
CUMULATIVE INJURY AND A
FUNCTIONAL REPARATIVE PROCESS.
IN THE MIDDLE RANGE, THE RATE OF
MUSCLE LOSS IS HIGH.
WHEN MUSCLE CELLS ARE ABUNDANT
AND A CUMULATIVE INJURY EXCEEDS
REPARATIVE CAPACITY.
IN THE LATE PHASE, MUSCLE IS
LOST SO THERE'S JUST NOT A LOT
OF ABSOLUTE MUSCLE LEFT.
AND THE ACTUAL PROGRESSION OF
THE FAT SIGNAL DECREASES.
SO WE HAVE THIS GAUSSIAN-LIKE
BEHAVIOR FOR DISEASE
PROGRESSION, WHICH IS LOW IN THE
EARLY YEARS, GOES THROUGH A
MAXIMUM AND THEN DECLINES.
SO THE FAT DOESN'T DISAPPEAR.
SO THE INTEGRATION OF THAT
GAUSSIAN-LIKE FUNCTION IS A
SIGMOID FUNCTION.
SO HERE AGAIN, ON THE LEFT
PANEL, WE'RE SHOWING THAT CHANGE
IN FAT FRACTION PER UNIT TIME,
AND IT HAS THIS OVERALL GAUSSIAN
SHAPE.
THE INTEGRATION OF THIS GAUSSIAN
SHAPE IS SHOWN HERE.
THIS IS A TOTAL ACCUMULATED
MUSCLE FAT, AND IT TAKES ON THIS
SIGMOID-LIKE FUNCTIONAL FORM.
AND AGAIN, INITIAL DISEASE
PROGRESSION, GOES THROUGH
MAXIMUM DECLINES AS MUSCLE IS
LOST.
WE CAN USE THESE MEASURES AS I
MENTIONED EARLIER, WE FOLLOWED
SOME OF THESE BOYS FOR UP TO 10
YEARS, SO MANY, MANY STUDIES.
A LOT OF INFORMATION IN THIS
SLIDE.
THIS IS JUST TO SHOW YOU THE
VARIABILITY.
ONE OF THE OTHER THINGS IS THE
DISEASE PROGRESSION OF DMD IS
HIGHLY VARIABLE.
SOME INDIVIDUALS PROGRESS VERY
QUICKLY, SOME, VERY, VERY
SLOWLY.
THIS MODELING CAN CAPTURE THAT
DIVERSITY IN DISEASE
PROGRESSION, AND IT'S SHOWN HERE
FOR THE VASTUS LATERALIS.
THERE'S A SOLID LINE THAT GOES
THROUGH THOSE DATA POINTS AND
THAT'S THE MATHEMATICAL MODEL.
THE OVERALL BEHAVIOR IS SHOWN
HERE.
AGAIN, WE SEE THESE SPAGHETTI
PLOTS SHOWING A LOT OF
VARIABILITY IN THE INDIVIDUAL
DISEASE PROGRESSION.
THE GROUP AVERAGE, POPULATION
AVERAGE IS SHOWN BY THAT SOLID
LINE AND, AGAIN, IT TAKES ON
THAT SIG MOI DAL FUNCTION.
WE CAN DO THIS FOR ANY MUSCLE IN
THE BODY.
THIS IS JUST SHOWING A NUMBER OF
DIFFERENT SKELETAL MUSCLES AND
HOW RAPIDLY THEY'RE PROGRESSING.
YOU CAN SEE THE MUSCLES CLOSER
TO THE TRUNK PROGRESS VERY
QUICKLY.
THEY START WITH VERY LOW FAT AND
THEY PROGRESS QUICKLY.
AGES HERE ON THE X AXIS.
SO THE VAST KSUS LATERALIS
PROGRESS VERY QUICKLY, OTHERS
MUCH MORE SLOWLY.
ONE THING I'D LIKE TO ILLUSTRATE
HERE IS THIS IS AN OPPORTUNITY
FOR FOLLOWING HOW MUSCLES AND
DISEASE IS PROGRESSING OVER A
LONG PERIOD OF TIME, ESSENTIALLY
OVER 20-PLUS YEARS HERE.
SO IT'S OPPORTUNITY TO FOLLOW TO
POTENTIALLY ENROLL INDIVIDUALS
NOT AMBULATORY INTO TRIAL AND
STILL BE ABLE TO FOLLOW THE
DISEASE PROGRESSION.
ONE OTHER POINT THAT THESE
MEASURES ARE SENSITIVE TO
THERAPEUTIC TREATMENT.
HERE THIS IS JUST SHOWING DATA,
AGAIN, ON FAT FRACTION.
NOW FOR THE SOLEUS MUSCLE UNDER
TWO CONDITIONS, WITHOUT STEROIDS
AND WITH STEROIDS.
SO WHAT YOU CAN SEE IS, IN THE
CASE WITHOUT STEROIDS, THE
DISEASE PROGRESSION IS FURTHER
TO THE LEFT, SO MORE
ACCUMULATION OF DISEASE AT
YOUNGER AGE, AND THEN IN THE
STEROID-TREATED, IT PUSHES
THINGS OUT BY SEVERAL YEARS.
SO IT'S IMPORTANT THAT THESE
MEASURES -- THESE FAT FRACTIONS
ARE RESPONSIVE AND SENSITIVE TO
INTERVENTION.
HERE I'M PLOTTING A POSITIVE
MEASURE OF ONE OF THE PARAMETERS
PULLED OUT OF THE MODELING WITH
THE AGE AT LOSS OF AMBULATION.
WE SEE VERY STRONG MODULATIONS.
THESE MEASURES ARE TRACKING
CLINICALLY IMPORTANT MILESTONES
IN FUNCTION.
MORE RECENTLY, WE'VE TEAMED WITH
SARAH KIM AND HER PEOPLE AT
UNIVERSITY OF FLORIDA, AND THE
MODELING HAS REALLY BECOME MUCH
MORE SOPHISTICATED NOW AND WE'VE
DEVELOPED THESE COVARIATE --
THESE MULTIVARIATE MODELS TO
CAPTURE THE DISEASE ACTIVITY.
THERE'S A PUBLICATION THAT CAME
OUT EARLIER THIS YEAR THAT'S
REFERENCED HERE, BUT THINGS HAVE
REALLY ADVANCED VERY QUICKLY.
I JUST WANT TO POINT OUT THAT
THE APPROACH THAT WE TAKE IS
COMPREHENSIVE AND RIGOROUS.
SO WE START BY THESE EXTENSIVE
DATASETS, AND AGAIN, THIS WAS
FUNDED THROUGH THE NIH, THE
IMAGING TRIAL, A LOT OF HIGH
QUALITY DATA COLLECTED OVER TIME
IN ITS NATURAL HISTORY, AND WE
FORMAT THE DATA, SPLIT IF WE'RE
GOING TO DO VALIDATION ANALYSIS,
WHICH WE ALWAYS DO, AND THEN WE
CAN GO THROUGH AND ESTABLISH
BASE MODELS, WHICH WE START WITH
UNIVARIATE MODELS, AND THEN MOVE
TO MULTIVARIATE.
WE BRING IN COVARIATES.
WE GO THROUGH MODEL VALIDATION
SO WE SPLIT THE TATA IN THE DATE
SURE THE OVERALL MODEL IS
GENERALIZABLE.
THE LAST STEP WHICH WE'RE
WORKING ON NOW IS THE
DEVELOPMENT AND INCORPORATION OF
THESE MODELS WHICH FORM THE
KERNEL FOR CLINICAL TRIAL
SIMULATION TOO.
SIMULATION TOOL.
SO THE KEY COMPONENTS IS HAVING
SOME IDEA, OF SOME OF THE
DISEASE TRAJECTORY, THE
PROGRESSION, AND WE HAVE THAT
FROM OUR NATURAL HISTORY DATA.
THEN OTHER INPUTS TOLL THE
CLINICAL TRIAL, THE
PHARMACEUTICAL WILL HAVE SOME
TRIAL DESIGN CONSIDERATION AND
THEY CAN PUT IN THINGS LIKE
TRIAL DURATION, THE NUMBER OF
INDIVIDUALS EXPECTED TO DROP
OUT, INTRINSIC CHARACTERISTICS
OF THE TRIAL POPULATION, AND
THEN THE ASSUMED BEHAVIOR,
ASSUMED THERAPEUTIC EFFECT OF
THE DRUG.
SO ALL OF THESE THINGS ARE
IMPORTANT AND THEY'RE COMPONENTS
OF THE CLINICAL TRIAL SIMULATION
TOOL, BUT UNDERLYING IS THE
ENGINE THAT'S DRIVING THIS
DISEASE PROGRESSION MODEL WHICH
WE GET THROUGH THESE NATURAL
HISTORY STUDIES.
SO THE CLINICAL TRIAL SIMULATION
TOOL, IT'S A PROCESS.
YOU HAVE REAL DATA, YOU SAW ALL
OF THE TRAJECTORIES I SHOWED FOR
A SINGLE MUSCLE.
WE HAVE THAT FOR MULTIPLE
MUSCLES, MULTIPLE INDIVIDUALS.
SO THAT'S THE REAL DATA.
WE CAN GET ESTIMATES WITH OUR
MAMATHEMATICAL MODEL.
FROM THOSE ESTIMATES, WE CAN
CREATE VIRTUAL INDIVIDUALS
THROUGH DIFFERENT MONTE CARLO
AND SAND S SOCASTIC PROPERTIES.
SO ALL OF THIS PROVIDES A VERY
POWERFUL BACKGROUND FOR
IMPROVING THE ABILITY TO RUN
CLINICAL TRIALS.
SO ULTIMATELY THE INTENT IS TO
BENEFIT THE DMD COMMUNITY, SO AT
SOME POINT THESE WILL BE
AVAILABLE TOOLS TO THE
COMMUNITY.
AND AN EXAMPLE OF THAT TOOL
DEVELOPED BY SARAH KIM'S TEAM IS
SHOWN HERE.
AGAIN, THIS IS THE GRAPHICAL
USER INTERFACE, BUT IT SHOWS THE
BEHAVIOR OF SOME BIOMARKER UNDR
CONDITIONS INPUT FROM THE USER,
AND DRIVING, AGAIN, ON THAT
KERNEL OF THE NATURAL HISTORY
DATA THAT IS SO IMPORTANT FOR
ESTABLISHING THESE MODELS.
BUT THESE ARE QUANTITATIVE
DISEASE PROGRESSION MODELS.
WE NEED TO KNOW SOMETHING ABOUT
BASELINE POPULATION FEATURES SO
THERE'S SOME SLEK SHOUL SELECTIE
INTERESTED IN AN AGE RANGE,
STEROID TREATED/NON-STEROID
TREATED OR OTHERS, THESE CAN BE
INCORPORATED INTO THESE
SIMULATIONS.
OF COURSE THERE HAS TO BE
SOMETHING SAID ABOUT THE ASSUMED
DRUG EFFECT AND YOU CAN OPTIMIZE
DIFFERENT TRIAL DESIGN
PARAMETERS WITH THIS TYPE OF
TOOL.
SO TO SUMMARIZE, THE MRS FAT
FRACTION IS A SENSITIVE AND
NONINVASIVE MEASURE OF DUCHENNE
MUSCULAR DYSTROPHY PROGRESSION.
THE NON-LINEAR MIX EFFECT
MODELING PROVIDES A ROBUST AND
RELIABLE APPROACH TO
CHARACTERIZE THE NATURAL HISTORY
OF MUSCLE INVOLVEMENT IN DMD.
MRS FAT FRACTION DETECTS
THERAPEUTIC EFFECTS OF
CORTICOSTEROIDS ON DISEASE
PROGRESSION AND PROVIDES
PROGNOSTIC INFORMATION ON
FUNCTIONAL OUTCOMES.
THE MRS FAT FRACTION BIOMARKER
AND MATHEMATICAL MODELING
PROVIDES THE KERNEL FOR A DMD
CLINICAL SIMULATION TOOL.
SO WE'RE CURRENTLY IN THE
SUBMISSION PROCESS WITH BOTH THE
FDA AND EMA AND THINGS ARE
MOVING FORWARD.
WE EXPECT GOOD THINGS IN 2024.
BUT THEY ARE IN PROGRESS AND
UNDER REVIEW.
AND AGAIN, THE ULTIMATE GOAL IS
TO PROVIDE A CTS TOOL FOR THE
DMD COMMUNITY, SO UTILIZING
THESE SENSITIVE BIOMARKERS TO
REALLY ACCELERATE DRUG DISCOVERY
AND TO EXPAND THESE TRIALS TO A
LARGER NUMBER OF INDIVIDUALS
WITH MUSCULAR DYSTROPHY, I THINK
ULTIMATELY IS GOING TO BE VERY
IMPORTANT.
SO AGAIN TO SUMMARIZE, DISEASE
TRAJECTORY MODELING AND A CTS
TOOL.
NATURAL HISTORY STUDIES ARE
FUNDAMENTALLY IMPORTANT IN
CREATING THESE TOOLS.
AND THEN THERE'S A LOT OF
MATHEMATICS AND PROCESS THAT
GOES ON BEHIND THE SCENES.
BUT ULTIMATELY, THESE DATASET
ARE GOING TO BE PUT TO USE AND
OPEN TO THE PUBLIC.
AGAIN WITH THE INTENT OF
ACCELERATING DRUG DISCOVERY AND
MOVING THINGS MORE QUICKLY
THROUGH THE PIPELINE, AS SILICON
VALLEY LIKES TO SAY, FAIL FASTER
AND IDENTIFY THOSE THERAPIES
THAT ARE REALLY EFFECTIVE AND
MOVE ON THERE MORE QUICKLY.
WITH THAT, I'D LIKE TO JUST
ACKNOWLEDGE THE IMAGING DMD
TEAM.
THIS IS WHAT THEY LOOKED LIKE IN
2017.
IT'S BEEN A VERY PRODUCTIVE
GROUP OF INDIVIDUALS, AND IT'S
BEEN A LOT OF FUN TO WORK WITH
THEM, BUT OF COURSE NONE OF THIS
WOULD BE POSSIBLE WITHOUT THE
PARTICIPANTS AND THEIR FAMILIES,
SO WE REALLY APPRECIATE THEIR
CONTRIBUTIONS TO THESE STUDY,
AND THEN ALL OF THE FUNDING THAT
GOES ON.
THE DEVELOPMENT OF THE CLINICAL
TRIAL SIMULATION TEAM, SARAH KIM
AT THE UNIVERSITY OF FLORIDA,
LAKE NONA, AND THEN THE C-PATH
GROUP HAS BEEN JUST
INDISPENSABLE IN MOVING THIS
FORWARD AND WE'RE REALLY
THANKFUL.
AND WITH THAT, I WILL END THERE.
AND HAPPY TO TAKE ANY QUESTIONS.
>> BILL, THANK YOU VERY MUCH.
THERE'S A NICE COMMENT IN THE
CHAT BOX FROM JEN HANDT.
I ALSO WANTED TO SAY THAT THIS
INFORMATION INDIRECTLY ANSWERS
SOMETHING THAT JUNE ASKED
EARLIER ABOUT WHY PEOPLE WHO ARE
NOT AMBULATORY ARE EXCLUDED, AND
PART OF IT MIGHT HAVE TO DO WITH
THE FACT THAT THERE AREN'T
BIOMARKERS TO ASSESS THE EFFECTS
OF TREATMENT, BUT YOUR DATA
WOULD SUGGEST THAT EVEN FOR
PEOPLE WHO ARE NON-AMBULATORY
THAT WE COULD FOLLOW THEM AND WE
COULD MEASURE THE EFFECTS OF
TREATMENT.
SO THAT PROVIDES A LOT OF HOPE,
I THINK, FOR THE FUTURE GOING
FORWARD.
>> YEAH, I COMPLETELY AGREE.
A LOT OF THE CLINICAL TRIALS
CURRENTLY ARE BASED ON
AMBULATORY CHARACTERISTICS, AND
OF COURSE INDIVIDUALS WITH THIS
DISEASE LOSE THE ABILITY TO
AMBULATE IN THEIR EARLY TEENS,
AND THAT THEN -- YOU KNOW,
THEY'RE NOT GOOD CANDIDATES FOR
THESE TRIALS.
SO HAVING MEASURES THAT SPAN A
MUCH LARGER RANGE IN THE DISEASE
PROCESS OPENS UP TRIALS FOR
THESE NON-AMBULATORY
INDIVIDUALS, WHICH I THINK IS
REALLY IMPORTANT.
RARE DISEASE IS ALWAYS HARD,
THERE LIMITED SOURCE.
SO YOU WANT TO BE ABLE TO BE AS
INCLUSIVE AS POSSIBLE AND THAT'S
POSSIBLE WITH THESE MEASURES.
>> GREAT.
THANK YOU SO MUCH FOR YOUR WORK.
I'M JUST LOOKING BECAUSE I'VE
GOT TWO PAGES HERE OF HANDS, I
SEE DR. KOROSHETZ HAS RAISED HIS
HAND.
>> I WAS JUST WONDERING, THE
SPAGHETTI PLOT PASSED PRETTY
QUICKLY BUT IT LOOKED TO ME LIKE
THE VARIABILITY IS IN THE AGE OF
ONSET BUT THE SLOPES LOOK PRETTY
CLOSE TO BE IDENTICAL.
IS THAT TRUE?
>> YEAH.
IT'S -- THAT'S -- SO THE
SLOPE -- IN THE MODELING, THERE
ARE THREE PRINCIPAL PARAMETERS
WE PULL OUT.
THAT KIND OF AGE AT HALF MUSCLE
INVOLVEMENT, AND THE SLOPE OF
THAT.
SO THERE IS A FAIR AMOUNT OF
VARIABILITY IN THE SLOPE.
IT MAY NOT HAVE BEEN EASY TO SEE
WITH THAT SPAGHETTI PLOT.
BUT THERE IS A FAIR AMOUNT OF
VARIABILITY IN THE DISEASE
PROGRESSION.
IT'S KIND OF HOW TALL THAT
GAUSSIAN FUNCTION IS, OR HOW
NARROW IT IS, IF THE AREA IS
CONSERVED.
BUT WE DO SEE A LOT OF
VARIABILITY IN BOTH THAT TIME AT
50% MUSCLE INVOLVEMENT, BUT ALSO
THE SLOPE AT THAT TIME POINT.
AND TREATMENT OF DISEASE COULD
MODIFY BOTH OF THOSE, AND WE
EXPECT TO MODIFY.
THAT'S BASICALLY WHAT
CORTICOSTEROID TREATMENT WAS
FOUND TO DO, TO MODIFY BOTH THE
SLOPE AND THEN THE AGE AT 50%
FAT FRACTION.
>> GREAT, THANK YOU.
LET'S GO TO GLEN.
>> THANKS, BILL.
GREAT TALK.
I SAW A RECENT PRESENTATION FROM
KEVIN FLANAGAN, AND HE'S
IDENTIFIED SOME ADDITIONAL
GENETIC MODIFIERS OF THE
DUCHENNE PHENOTYPE IN ADDITION
TO LTBP4 AND THROMBUS -- AND I
KNOW SOME OF THOSE ARE REALLY
CONNECTED WITH AGE OF LOSS OF
AMBULATION.
SO I'M CURIOUS, WOULD IT BE
ABLE -- WOULD YOU BE ABLE TO
INCORPORATE MODIFIER GENOTYPES
INTO YOUR MODELING AND HOW
MANY -- I DON'T KNOW HOW
FREQUENT THOSE DIFFERENT
GENOTYPES ARE AND WHETHER YOU'RE
GOING TO HAVE SUFFICIENT POWER
TO PUT IT INTO YOUR SYSTEM.
>> IT'S A GREAT QUESTION AND ONE
WE WERE VERY INTERESTED IN.
WE DID TAKE A CLOSE LOOK AT
THAT.
DESPITE HAVING PRETTY GOOD
NUMBERS IN THIS RARE DISEASE
NATURAL HISTORY STUDY, WE
WEREN'T SUFFICIENTLY POWERED TO
PULL OUT A LOT OF GENETICS BUT
IT'S SOMETHING WE'RE KEEPING AN
EYE ON.
WITH EACH ADDITIONAL DATASET, WE
GET A LITTLE BIT CLOSER TO BEING
ABLE TO DO THAT.
WE SEE SOME CLUSTERS IN SOME
DIFFERENT GENETIC MARKERS THAT
LOOK PROMISING, BUT IT WILL --
WE DO EXPECT TO BE ABLE TO
INCLUDE THOSE AT SOME POINT.
>> GREAT.
LET'S GO TO DR. CRISWELL.
>> THANK YOU.
I JUST WANTED TO ECHO THE
COMMENTS BY DR. BIANCHI AND
OTHERS.
I REALLY APPLAUD THIS WORK.
IT'S SO EXCITING, SO IMPORTANT,
AND THE APPROACH YOU'RE TAKING
IS SO SOPHISTICATED.
REALLY, REALLY THRILLED TO HEAR
ABOUT THIS PROGRESS.
THANK YOU SO MUCH FOR SHARING
THAT.
>> THANK YOU.
IT'S BEEN FUN.
THANK YOU.
>> OKAY, LAST, WE HAVE A
QUESTION FROM CAROL
TAYLOR-BURDS.
DO YOU WANT TO COME OFF MUTE AND
ASK IT YOURSELF?
>> SURE, I CAN DO THAT.
VERY NICE PRESENTATION AND GREAT
TO SEE THE MODELING BEING DONE.
JUST CURIOUS, WHAT'S THE
FREQUENCY OF THE IMAGING
ASSESSMENTS?
>> SO FREQUENCY IS YEARLY.
THERE ARE SUBSETS THAT WE DID A
LITTLE BIT MORE FREQUENTLY, BUT
OVERALL, EVERYONE WAS IMAGED
ABOUT EVERY 12 MONTHS.
>> THANK YOU.
>> WONDERFUL.
AND THERE'S BEEN SOMEWHAT OF A
SEGUE TO OUR NEXT SPEAKER, WHO
IS DR. RAMONA BELFIORE-OSHAN,
WHO WAS LISTED AS A COLLABORATOR
OF DR. ROONEY'S, AND SHE IS AT
THE CRITICAL PATH INSTITUTE.
SHE'S GOING TO TELL US ABOUT
COLLABORATIVE STRATEGIES TO
ACCELERATE MEDICAL PRODUCT
DEVELOPMENT AND THE REGULATORY
REVIEW PROCESS.
SO DR. BELFIORE-OSHAN, OVER TO
YOU.
>> THANK YOU.
THANK YOU SO MUCH FOR THE INVITE
AND THANK YOU TO THE COMMITTEE
FOR YOUR ATTENTION TODAY.
SO AS ANTICIPATED, I WILL GO
OVER SOME OF THE OVERVIEW
RELATED TO THE DUCHENNE
REGULATORY SCIENCE CONSORTIUM AT
CRITICAL PATH INSTITUTE, AND HOW
WE BUILD CASE STUDY OF THEIR
TREATMENT SOLUTION TO REALLY
ENHANCE DRUG DEVELOPMENT FOR
DUCHENNE AND POTENTIALLY OTHER
DYSTROPHINNOPATHIES AND UPDATED
GOALS AND COLLABORATIONS AND
DATA SHARING TOGETHER WITH SOME
OF THE MOST RECENT C-PATH'S
REGULATORY SUCCESS SUMMARY.
SO THOSE LESS FAMILIAR WITH THE
CONSORTIUM, WE ARE A
PUBLIC-PRIVATE PARTNERSHIP
GENERATED IN 2015 BY
COLLABORATION BETWEEN THE
CRITICAL PATH INSTITUTE AND
PARENT PROJECT MUSCULAR
DYSTROPHY.
SO THIS WAS REALLY MEANT TO COME
TOGETHER WITH ALL THE
STAKEHOLDERS FROM INDUSTRY,
ACADEMIA, CLINICAL RESEARCH,
NON-PROFIT FOUNDATIONS, PATIENT
ADVOCACY AND -- INITIAL FORM OF
THE CRITICAL PATH INSTITUTE INTO
THIS PRECOMPETITIVE SPACE WHERE
WE COULD REALLY ALL BUILD
TOGETHER DRUG DEVELOPMENT TOOLS
AS NEUTRAL CONVENER THAT WILL BE
NEXT AVAILABLE TO THE ENTIRE
COMMUNITY AND FREELY.
SO OUR ORIGINAL MISSION WAS
FOCUSED ESSENTIALLY IN
GENERATING THE PLATFORM AND
STANDARDIZING DATA SHARED IN A
WAY WE COULD AGGREGATE DATA FROM
MULTIPLE SOURCES AND THEN REALLY
APPLY THIS DATA WHICH ADVANCED
ANALYTICS COMES FROM AGGREGATION
INTO DRUG DEVELOPMENT TOOLS TO
REALLY ACCELERATE DRUG
DEVELOPMENT AND REDUCE THE
NUMBER OF PATIENTS NEEDED TO
DEMONSTRATE EFFICACY OF NEW
THERAPY.
THE MODEL COMES FROM THE
UTILIZATION OF CORE COMPETENCIES
THAT ARE PART OF THE CRITICAL
PATH INSTITUTE IN GENERAL, BUT
OF COURSE APPLIED TO THE
DUCHENNE REGULATORY SCIENCE
CONSORTIUM, LOOKING AT MODELING
AND ANALYTICS SO IN THOLGOLOGIES
THAT GO INTO MEDICAL MODELING,
REGULATORY SCIENCE WHICH
EMBRACES ALL OF THESE CORE
COMPETENCIES AND APLAYS TO ALL
OF THEM.
CLINICAL OUT COME ASSESSMENT,
GENERATION OF NOVEL BIOMARKERS
AND DATA MANAGEMENT AND DATA
STANDARDS AS CORE COMPETENCIES
SEEM AT THE BASIS OF WHAT WE DO
AS A DATA-DRIVEN EFFORT.
THIS IS A VERY LONG TIMELINE
THAT I SHOW FROM 2015 TO 2023
TODAY, BUT REALLY JUST TO
PROVIDE A SENSE OF HOW LONG THE
EFFORTS GO THROUGH AND REALLY
EXTEND THE TIMELINE THAT IS
NEEDED TO DEVELOP THESE TOOLS.
BUT REALLY HOW THIS INITIATIVE
IS ONLY POSSIBLE THANKS TO THE
COLLABORATION OF MANY, MANY
STAKEHOLDERS THAT CAME TOGETHER
AND REALLY ENGAGED INTO A
COMMUNITY-WISE EFFORT, SO HERE I
HIGHLIGHTED SOME OF THE
REGULATORY SUCCESSES AND
MILESTONES, MOST RECENTLY
RELATED TO THE CLINICAL TRIALS
TOOL DEVELOPED BY THE INTERNAL
TEAM FOCUSED ON THE FIVE END
POINTS COMMONLY USED IN CLINICAL
TRIALS FOR DUCHENNE MUSCULAR
DYSTROPHY.
TO PROVIDE A CASE EXAMPLE OF HOW
THIS WORKS AND WHAT'S THE
PROCESS, ESSENTIALLY AS
MENTIONED, WE DO START FROM DATA
AND DATA ARE COMING FROM
MULTIPLE SOURCES.
SO REALLY THE DATA SHARING
PROCESS IS A KEY POINT OF OUR
COLLABORATIONS.
THE CHAMPIONS THROUGHOUT THESE
YEARS THAT HAVE REALLY HELPED
THE COMMUNITY ADVANCE THE
ANALYTICAL POWER REALLY COMING
FROM THE DATA CUSTODIANS THAT
HAVE PUT THEIR DATA AVAILABLE TO
THE ENTIRE COMMUNITY OR EVEN
JUST TO THE ANALYTICAL TEAM AT
CRITICAL PATH TO AGGREGATE THE
DATA IN A STANDARDIZED AND VERY
SOPHISTICATED PROCESSES AS SHOWN
BY DR. ROONEY PREVIOUSLY OF
MODELING OR REALLY GENERATION OF
ANALYTICAL TOOLS THAT HAVE
IMPLEMENTED KNOWLEDGE ALSO
BIOMARKERS AND COS DEVELOPMENT.
SO THIS IS ONLY IMPACTFUL FOR
THE ADVANCEMENT OF DRUG
DEVELOPMENT TOOLS AND CLINICAL
TRIAL DESIGN, BUT REALLY ALSO
INFORMS THE NEAR TERM INPUT
COMING OUT FROM THE DATA THAT
WILL BE GENERATED TOMORROW.
SO THE DATA THAT WAS SHARED WITH
THE CRITICAL PATH INSTITUTE WERE
VERY HELPFUL TO GENERATE
THERAPEUTIC USER GUIDE WHICH WAS
PUBLISHED FIRST IN 2017 IN
COLLABORATION WITH CDISC, THE
COLLABORATION FOR DATA
STANDARDS, CLINICAL DATA
INSTITUTE STANDARD AND
CONSORTIUM, INTEGRATED STANDARDS
CONSORTIUM, ESSENTIALLY THE
MECHANISM FOR WHAT WE WERE ABLE
TO AGGREGATE DATA FROM MULTIPLE
SOURCES.
AND AS DR. ROONEY SHOWED BEFORE,
REALLY AGGREGATING THIS DATA
FROM MULTIPLE SOURCES INCLUDING
OBSERVATIONAL AND CLINICAL TRIAL
DATA HAS ALLOWED US TO PERFORM
SOPHISTICATED MODELING AND
GENERATION OF MULTIMODAL MODELS
INCORPORATED IN THE OUTPUT THAT
REALLY AMPLIFIES UNDERSTANDING
OF DISEASE PROGRESSION, THE
TRAJECTORY RATE OF POTENTIAL
PREDICTORS AND THE GENERATION OF
SOMETHING THAT CAN BE ALSO
USER-FRIENDLY FOR THE COMMUNITY
ALL TO UNDERSTAND HOW CLINICAL
TRIAL DESIGN CAN BE OPTIMIZED.
SO HERE I SUMMARIZED SOME OF THE
STEPS AND IMPORTANCE HIGHLIGHT
ON WHY REGULATORY ENDORSEMENT OF
THESE TOOLS IS REALLY KEY FOR
THE ENTIRE COMMUNITY.
AND THE NEWS FROM THE 2022
SUPPORT LETTER THAT WE RECEIVED
FROM THE EMA SO THE SAME TOOL
THAT IS ORGANIZED FOR THE
DEVELOPMENT OF DISEASE
PROGRESSION MODELS OF FIVE
FUNCTIONAL ASSESSMENTS AND
RESPIRATORY END POINT INCLUDING
CLINICAL TRIALS FOR DUCHENNE IS
CURRENTLY ALSO UNDER THE
SUBMISSION AND REVIEW AT THE
FDA, AND THE TOOL IS REALLY
MEANT TO PROVIDE EARLY
INDICATION ON HOW TO SIMULATE
INCLINIC TRIAL DESIGN.
SOME OF THE UPDATED GOALS AND
COLLABORATIONS I WANTED TO SHOW
TODAY IS REALLY COMING FROM THE
ANNOUNCEMENT AND EXPANSION OF
OUR DATASET.
SO THE DATABASE FOR DUCHENNE
MUSCULAR DYSTROPHY GROWTH HAS
ALLOWED US TO ALSO PERFORM NEW
ANALYTICS AND AGGREGATE ENOUGH
DATA FOR THE SUBMISSION OF A
QUALIFICATION PACKAGE FOR A
SAFETY BIOMARKERS OF GLDH AS
SAFETY BIOMARKER DAILY IN
INDIVIDUALS WITH UNDERLYING
MUSCLE DAMAGE, INCLUDING, OF
COURSE, DUCHENNE MUSCULAR
DYSTROPHY, BUT ALSO OTHER
DYSTROPHIES IN GENERAL.
ADDITIONAL EFFORTS HAVE BEEN
REALLY RELEVANT TO THE SUPPORT
OF THE DEVELOPMENT OF A MASTER
PROTOCOL FOR DUCHENNE PLATFORM
TRIAL AS WELL AS THE
COLLABORATION WITH IMAGING NMD
FOR MODEL BASED CLINICAL TRIAL
SIMULATION TOOL AND MOST
RECENTLY REALLY THE COMMUNITY
HAS COME TOGETHER TO ENGAGE
INITIALLY FOCUSED ON CARDIAC
DMD, AS WE KNOW IS UNDERLYING
CAUSE OF DEATH IN DUCHENNE AND
WE REALLY ARE TRYING TO ADVANCE
KNOWLEDGE OF THE TOOLS, OUTCOMES
AND END POINTS THAT ARE
CURRENTLY AVAILABLE AND WE CAN
IMPLEMENT INTO THESE DISEASE
PROGRESSION MODELS NEXT.
SO REALLY THE EVALUATION ALSO OF
HOW READY ARE SOME OF THE
MARKERS AVAILABLE IN FLUID
BIOMARKERS AND UNDERSTANDING IF
WE CAN IMPLEMENT THE KNOWLEDGE
AND PROGRESSION OF THIS
KNOWLEDGE INTO THE APPLICATION
FOR DRUG DEVELOPMENT TOOLS.
HOW WOULD HE WE DO THIS, OF COUS
BASED ON DATA SHARING, SO REALLY
DATA SHARING IS KEY FOR US TO
HAVE SUCCESSFUL PATHWAY FORWARD,
AND APPLICATION OF QUANTITATIVE
METHODOLOGIES, AI, MACHINE
LEARNING, ANALYTICS THAT ARE
LOOKING AT DIGITAL HEALTH
TECHNOLOGIES AND DIGITALLY
MEASURED OUTCOMES AND HOW WE CAN
IMPLEMENT THOSE TO UNDERSTANDING
BERT THE TRIAL DESIGN AND THE
SEPTEMBERIZATHECENTRALIZATION O.
AS WE LEARN MORE ABOUT DUCHENNE,
WE KNOW THAT WE CAN APPLY THE
SAME LEARNINGS TOWARDS OTHERS'
THERAPEUTIC AREAS, SO WE ARE
LOOKING AT COLLABORATIONS FOR
EXPANSIONS ON OUR KNOWLEDGE ON
PROJECT-SPECIFIC TASK FORCE FOR
OTHER SPACES IN THE
NEUROMUSCULAR DISORDERS.
THIS IS JUST A TABLE SHOWING
REALLY THE EFFORT IMPACT
DIRECTION WHERE WE GO FROM A
CLINICAL TRIAL SIMULATION TO THE
IMPACT REALLY DIRECTLY GOES TO
TRIAL DESIGN BUT ALSO INDIRECTLY
TO THE PATIENT POPULATION BY
ANNOUNCING THE TRIAL DESIGN AND
POTENTIALLY REDUCING THE NUMBER
OF PLACEBO NEEDED IN TRIALS,
COLLABORATION WITH THE CDISC FOR
STASTANDARDIZATION IS HELPING
UNDERSTAND HOW IMPORTANT WILL BE
TO START UTILIZING MRI IMAGING
EARLY ON IN INDIVIDUALS WITH
DUCHENNE MUSCULAR DYSTROPHY TO
REALLY DETECT EARLY ON PROCESSES
OF FIBROSIS IN THE CARDIAC
MUSCLE.
AND OF COURSE THE PROCESS OF
QUALIFICATION OF A SAFETY
BIOMARKER THAT ALLOWS
DISCRIMINATION OF TARGETS FOR
DRUG EFFECT WILL IMPROVE OUR
SAFETY IN DMD TRIALS BUT ALSO
OTHER TRIALS RELATED TO MUSCLE
DAMAGE DISEASES AND WHENEVER WE
SEE AN INCREASE OF CK.
SO THIS IS REALLY MEANT TO BE A
COMMUNITY EFFORT, AND THIS IS A
VERY CROWDED SLIDE BUT REALLY IT
MEANT TO SHOW THE NUMBER OF
STAKEHOLDERS INVOLVED AND THE
WAY WE SET UP THE CONSORTIUM IS
TO HAVE A MAIN COORDINATING
COMMITTEE MEETING, AND THEN
REALLY SUBDI V SUBDIVISIONS OR
SUBCOMMITTEES ARE FOCUSED ON
MORE SPECIFIC TOPICS FOR
MODELING AND SIMULATION,
CARDIAC, ADD OCC PUBLICATION AND
IN THE NEAR FUTURE A FLUID
BIOMARKER FOCUS GROUP.
SO REALLY SHARING ALL THE
INFORMATION, KNOWLEDGE AND
RESOURCES WILL BRING US TO SHARE
OUR SUCCESSES FOR TOMORROW.
HERE ARE SOME HIGHLIGHTS FROM
2023 PUBLICATIONS, AND REALLY
MAKING THIS A WORLDWIDE
COLLABORATION.
SO WE HAVE COLLABORATORS IN
EUROPE.
WE JUST HAVE INTEGRATION
STAKEHOLDERS IN CANADA, JAPAN,
CHINA, AND WE'RE LOOKING FORWARD
TO REALLY EXPAND OUR RESOURCES
TO EMBRACE THIS GLOBAL COMMUNITY
IN THE ENTIRE -- WORLDWIDE.
SO THE DUCHENNE REGULATORY
SCIENCE CONSORTIUM IS PART OF
THE C-PATH RARE AND ORPHAN
DISEASE PROGRAM.
WE WERE ALSO ABLE TO HAVE SOME
CROSS LEARNINGS ACROSS MULTIPLE
DISEASES INCLUDING ALS AND OTHER
NEUROLOGICAL, NEURODEGENERATIVE
DISEASES IN THE RARE SPACE, SO
REALLY THIS HAS BEEN KEY FOR US
TO DEVELOP A MECHANISM SYSTEM
FOR HIGHLIGHTING OUR POWER FOR
COLLABORATION AND THE NEED FOR
SUCH PRECOMPETITIVE
COLLABORATION TO ADVANCE DRUG
DEVELOPMENT IN THE RARE DISEASE
SPACE.
AS YOU CAN SEE THE NUMBER OF
STAKEHOLDERS IS REALLY EXTEN
EXTENSIVE, BUT THIS IS THE
ENTIRE COMMUNITY FOR -- AND
BEYOND.
I WOULD LIKE TO HIGHLIGHT SOME
OF C-PATH'S REGULATORY SUCCESSES
COMING UP FOR TODAY TO REALLY
SHOW THE POWER OF PRECOMPETITIVE
COLLABORATION OF THE COMMUNITY
AND HOW MUCH IT WOULD TAKE TO
INDIVIDUAL STAKEHOLDERS TO
INVEST IN REGULATORY ENDORSEMENT
AND HOW IMPORTANT IT WOULD BE TO
COME TOGETHER IN A
PRECOMPETITIVE SPACE TO ADVANCE
THE DRUG DEVELOPMENT FASTER.
THE SAME IS RELEVANT TO THE EMA
SUBMISSION, THE CRITICAL PATH
INSTITUTE HAS A GREAT NUMBER OF
LETTERS OF SUPPORT AND
QUALIFICATION OPINIONS, WHICH
REPRESENTS THE 23.5% OF THE
TOTAL COMBINED OF OTHER
ORGANIZATIONS.
THIS WAS ONLY POSSIBLE THANKS TO
AN INCREASE OF 135% OF OUR DATA
SHARING PROCESSES IN THE PAST
FIVE YEARS.
SO WE ARE EXTREMELY GRATEFUL TO
ALL THE DATA CUSTODIANS THAT
REALLY WERE READY TO ADVOCATE
FOR THE -- OF THE DATA AND
THE -- THAT ARE SHARING THAT
TRANSFORMATION AND CURATION
AND -- FOR DELIVERY OF THESE
DATA TO THE ENTIRE COMMUNITY IN
THE FORM OF A DRUG DEVELOPMENT
TOOL THAT WOULD ADVANCE
EFFECTIVELY THE DRUG DEVELOPMENT
FOR RARE DISEASE AND NON-RARE
DISEASES.
WITH THIS, I WILL THANK YOU AND
SEE IF YOU HAVE ANY QUESTIONS.
THANK YOU, EVERYONE.
>> THANK YOU SO MUCH, RAMONA.
I THINK THERE'S ONE COMMENT OR
QUESTION IN THE CHAT BOX.
>> THANK YOU FOR A GREAT
PRESENTATION.
THIS IS HUIQING LI, PROGRAM
DIRECTOR FROM THE NATIONAL HEART
LUNG BLOOD INSTITUTE.
I'M VERY GLAD TO SEE DATA
SHARING RELATED PRESENTATIONS
FROM THE MUSCULAR DYSTROPHY
COMMUNITY.
I'M REALLY CURIOUS, I MISSED
THIS, HOW TO ACCESS TO THE
DATASET, AND IF I'M INTERESTED,
HOW TO JOIN THE WORKING GROUP,
CARDIAC-SPECIFIC WORKING GROUP.
THANK YOU.
>> SURE.
SO THE DECISION MADE ON THE
SHAREABILITY LEVEL OF EACH OF
THE INDIVIDUAL DATASETS IS
REALLY UP TO THE DATA CUSTODIAN,
SO WE HAVE A VERY ESTABLISHED
PROCESS FOR DATA SHARING WITHIN
THE CRITICAL PATH INSTITUTE,
WHICH THE LEGAL AGREEMENT FOR
DATA SHARING WOULD ALLOW THE
DATA CUSTODIAN TO DECIDE HOW
BROADLY OR CONFIDENTIALLY THE
DATA CAN BE SHARED.
SO WITHIN OUR DATABASE, WE HAVE
24 DATASETS CURRENTLY.
NINE OF THOSE ARE SHAREABLE IN
OUR PLATFORMS, AND TWO MORE ARE
GOING TO BE SHAREABLE NEXT,
AFTER A PROCESS OF EMBARGO
RELEASE -- APPLIED.
SO ONE ADDITIONAL NOTE HERE IS
THAT A DATA CUSTODIAN CAN CHOOSE
TO LIMIT THE USE OF DATA
TEMPORARILY WHILE ALREADY
INITIATING PROCESSES OF CURATION
AND TRANSFER OF THE DATA INTO
THE PLATFORM WHILE THEY ARE
WAITING FOR PUBLICATIONS TO COME
OVER.
SO IT'S REALLY UP TO THE DATA
CUSTODIAN TO MAKE THE FINAL
DECISION ON HOW THE DATA CAN BE
SHARED, AND WE HAVE TWO
PLATFORMS THAT CURRENTLY HOST
DMD DATA, THE CODER PLATFORM
YOU'LL FIND ON OUR WEBSITE, I
THINK I PUT THE LINKS IN THE
SLIDE BUT I'LL BE HAPPY TO SHARE
IN THE CHAT RIGHT AFTER THE
LINK, AND THE RDCA DATA PLATFORM
WHICH HOSTS THE RARE DISEASE --
DATA ANALYTIC PLATFORM, HOSTING
ALL DATA FOR THE RARE DISEASES
IN CRITICAL PATH INSTITUTE.
AND WE HAVE SOME OF THE DATA
ALSO SHARED IN THE RDC PLATFORM
AS WE ARE -- ALL THE DUE SHIN
SHEN DATA WILL BE SOON PART OF
THE PLATFORM.
SO YOU WILL FIND SOME OF THE
INFORMATION THERE AND FOR THE
PROCESS OF MEMBERSHIP OF THE
CONSORTIUM, WE HAVE A STRUCTURE
IN PLACE FOR DEPENDING ON THE
NATURE OF THE STAKEHOLDER, WE
HAVE A FEE MEMBERSHIP FOR
INDUSTRY AND ALSO NON-PROFITS
JOINING AS WELL AS ADVISERS FROM
ACADEMIA, SO I'LL BE HAPPY TO
GET BACK TO YOU ON SOME OF THE
PROCESSES TO JOIN THE EFFORTS
AND THE WORKING GROUPS.
>> THANK YOU.
CAROL TAYLOR-BURDS HAS HER HAND
UP.
>> THANKS.
GREAT PRESENTATION.
I'M JUST CURIOUS, DO YOU KNOW
HOW MANY OFF THE TOP OF YOUR
HEAD ARE ACADEMICS USING THE
MODELING TOOLS AS WELL OR IS IT
PRIMARILY INDUSTRY?
>> IT IS CERTAINLY A DRUG
DEVELOPMENT TOOL, SO IT REALLY
INFORMS CLINICAL TRIAL DESIGN,
BUT WE DO HAVE AN EXTENSIVE
NUMBER OF ACADEMIC INSTITUTIONS
THAT AS MAIN POINT OF CONTEXT
FOR CLINICAL TRIAL SITE ARE
REALLY TRYING TO GET AS MUCH
FROM US AS THEY CAN, SO YOU CAN
TELL THERE IS INTEREST IN THE
DEVELOPMENT FROM A RESEARCH
POINT OF VIEW, AND THEN THE
APPLICATION IN CLINICAL RESEARCH
FROM THE DRUG DEVELOPERS.
SO IT'S REALLY -- IT'S HARD TO
SAY HOW MANY, BUT IT'S PRETTY
MUCH AT LEAST ONE INDIVIDUAL
FROM EACH OF THESE INSTITUTIONS'
MEMBERS HAVE APPROACHED THE
TOOL.
>> GREAT.
OKAY, GLEN, OVER TO YOU.
>> YES, I'M CURIOUS, WHAT IS THE
PROCESS BY WHICH CRITICAL PATH
SELECTS A NEW DISEASE AREA TO
BUILD SUCH A CONSORTIUM AROUND?
AND PERHAPS RELATED TO THAT
QUESTION IS, WHAT'S THE FUNDING
STRUCTURE?
WHO PAYS FOR THIS AND HOW MUCH
DOES IT COST?
>> SO I'D BE HAPPY TO PROVIDE
SOME OF THE DETAILS.
YOU KNOW, WE HAVE MANY
CONVERSATIONS WITHIN THE SPACE
ON HOW WE CAN -- YOU KNOW, NEW
AREAS CAN APPROACH CRITICAL PATH
INSTITUTE, AND IT REALLY DEPENDS
ON THE DIFFERENT POINTS.
ONE OF THEM IS CERTAINLY THAT
READINESS OF THE AREA IN TERMS
OF PIPELINE, HOW MUCH DATA IS
BEING COLLECTED AND GENERATED,
AND BECAUSE EVERYTHING IS REALLY
A DATA-DRIVEN EFFORT, WE WILL
NEED TO START FROM DATA TO BUILD
NEW KNOWLEDGE AND SO REALLY IT
IS IMPORTANT TO LOOK AT THE
REGULATORY READINESS FROM A
POINT OF VIEW OF WHAT'S --
MAKING SURE WE HAVE A DEFINED
UNMET NEED AND GAP IN THE SPACE,
BUT ALSO MAKING SURE THAT WE
HAVE ENOUGH DATA TO WORK WITH TO
THEN EXTRAPOLATE NEW INFORMATION
TO ENHANCE THE SPACE.
THEN REALLY THIS COMES, IN THE
CASE OF DUCHENNE, THERE WAS AN
INITIATIVE, REALLY THE ENTIRE
COMMUNITY CAME TOGETHER AND --
PSM PMD AND CRITICAL PATH
INSTITUTE AS CO-FOUNDERS,
GENETIC -- CONSORTIUM, BUT FOR
OTHER CASES, WE HAVE OTHER
SPACES WHERE THE EVALUATION OF
THE READINESS WAS PERFORMED
DURING A PERIOD OF PRECONSORTIUM
STATUS IN WHICH THE EVALUATION
OF READINESS WAS PERFORMED
ACROSS MULTIPLE STAKEHOLDERS, SO
YOU WILL HAVE THE INDUSTRY
GENERATING DATA, THE ADVOCACY
GROUPS AND THE REGULATORY
AGENCIES UNDERSTANDING WHETHER
THERE WAS ENOUGH READINESS FOR
THAT LAUNCH OF A CONSORTIUM.
WE ARE FOCUSING ON TASK FORCES
NOW BECAUSE WE UNDERSTAND THAT
FOR THOSE AREAS, THE THEY ARE LS
READY TO HAVE A FORMALIZED
CONSORTIUM.
THERE ARE STILL SOME QUESTIONS
AND PROJECT FOCUSED OR PROJECT
SPECIFIC EFFORTS THAT COULD HELP
UNDERSTANDING OF TRIAL DESIGN IN
THE FUTURE, SO WE'RE TRYING TO
WORK WITH SOME OF THE COMMUNITY
IN THE NEURON NEW NEUROMUSCULARO
UNDERSTAND THE PROCESS IN THE
FORM OF A TASK FORCE THAT HAS A
SPECIFIC OBJECTIVE AND QUESTION
TO BE ADDRESSED.
AND THE COST IS REALLY -- THE
INDUSTRY MEMBERS HAVE A FEE AND
CONTRIBUTES TO THE CONSORTIUM
DEVELOPMENT, AND THIS IS A
PUBLIC PRIVATE PARTNERSHIP
BECAUSE WE HAVE INDUSTRY FEES,
WE HAVE FUNDING FROM THE FDA
COMING -- THE CRITICAL PATH
INSTITUTE AND THIS IS PRETTY
MUCH THE ORGANIZATIONAL
STRUCTURE WHERE -- IN THE CASE
OF PPMD, WE HAVE ALSO GREAT
SUPPORT FROM THE ORGANIZATION,
SO THIS IS MEANT TO BE A
MULTI-STAKEHOLDER EFFORT BECAUSE
IT REALLY COMES FROM EVERY
SOURCES AND COST AND SHARED
EFFORTS FROM ALL OF THESE
PARTIES.
>> THANK YOU.
>> OKAY.
JUST CHECKING THE OTHER PAGE FOR
HANDS.
I DON'T SEE THEM.
SO I'M GOING TO TURN IT OVER TO
GLEN NOW FOR A QUICK SUMMARY OF
THIS REGULATORY SESSION.
>> THANKS, DR. BIANCHI.
SO I WANTED TO TRY TO JUST KIND
OF WEAVE THESE TOPICS TOGETHER
AND PROVIDE -- THANKS.
I WANTED TO JUST TRY TO WEAVE
THESE TOPICS TOGETHER AND
PROVIDE KIND OF A BRIEF SUMMARY
OF THE SESSION.
SO WHAT WE'VE HEARD HERE IS
ABOUT THEMES RELATED TO DUCHENNE
AND REGULATORY APPROVAL, BUT I
THINK REALLY AT THE HEART OF
THIS AND THEME THAT'S VERY
COMMON TO MDCC MEETINGS IS THAT
PATIENT-CENTERED RESEARCH IS
WHAT WE'RE REALLY TRYING TO
FOCUS ON HERE, AND THROUGH
PATIENT-CENTERED RESEARCH, WE
CAN LEAD TO THINGS LIKE EARLY
SCREENING AND DIAGNOSIS THAT
NIKI WAS TELLING US ABOUT, AND
ALSO EFFECTIVE TREATMENTS,
CERTAINLY FIRST GENERATION
TREATMENTS THAT EVENTUALLY LEAD
TO HOPEFULLY FUTURE GENERATIONS
AND A CURE EVENTUALLY.
SO SCREENING AND DIAGNOSIS IS
ALSO A REALLY IMPORTANT ASPECT,
NAD TO HAVING KIND OF THE DIRECT
BENEFIT FROM PATIENTS AND MAY BE
NEATBNECESSARY DETERMINING WHEN
THEY'RE ELIGIBLE FOR APPROVED
DRUGS.
YOU ALSO NEED A COHORT OF
GENETICALLY WELL CHARACTERIZED
PATIENTS IN ORDER TO PARTICIPATE
IN CLINICAL TRIALS SO THAT CAN
ALSO BE FACILITATED BY NEWBORN
SCREENING AND EARLY DIAGNOSIS,
AND THERE'S CERTAINLY A PUSH FOR
TRYING TO GET EARLIER AND
EARLIER INTERVENTION WHERE
PATIENTS MAY BE MOST RESPONSIVE
TO TREATMENTS.
SO BEFORE YOU GET TO THIS POINT,
DECADES EARLIER, IT REALLY COMES
DOWN TO THINGS LIKE NATURAL
HISTORY STUDIES, AND VALIDATED
OUT COME MEASURES AND BIOMARKERS
THAT MUST BE INVESTED IN AND
DEVELOPED THROUGH THE RESEARCH
COMMUNITY.
BILL WAS TELLING US A REALLY
EXCELLENT EXAMPLE OF TAKING THE
NATURAL HISTORY DATA FROM MRI
AND FUNCTIONAL OUT COME MEASURES
TO BUILD THE CLINICAL TRIAL
SIMULATION TOOL.
AND SO THAT REALLY CONTRIBUTES
TO OPTIMIZING TRIAL DESIGN.
CERTAINLY YOU ALSO NEED
INNOVATIVE CANDIDATE
THERAPEUTICS, THAT'S CERTAINLY A
LOT OF WHAT WE DO AT NIH, IS
SUPPORTING EARLY DISCOVERY,
PRE-CLINICAL TRANSLATION,
HOPEFULLY EVENTUALLY GETTING TO
CANDIDATE THERAPEUTICS THAT CAN
GO INTO CLINICAL TRIALS.
YOU KNOW, I THINK A REALLY
IMPORTANT ASPECT OF THE OPTIMIZE
TRIAL DESIGN THAT FEEDS BACK
INTO THIS PATIENT-CENTERED
RESEARCH CONCEPT IS THAT WITH
REALLY EFFECTIVE CLINICAL TRIAL
DESIGNS, THEN WE CAN INCREASE
THE LIKELIHOOD OF SUCCESS OF
CLINICAL TRIALS AND IMPORTANTLY
WE COULD ALSO PERHAPS REDUCE THE
BURDEN OF PARTICIPATION IN
TRIALS FOR PATIENT.
BY THINGS LIKE REDUCING THE
DURATION OF THE TRIAL, OR
PERHAPS DECREASE THE NUMBER OF
PATIENTS OR THE PROPORTION OF
PATIENTS THAT NEED TO BE IN A
CONTROL GROUP.
SO IN THIS DIAGRAM THAT I'VE
BEEN PUTTING TOGETHER HERE,
REALLY THE ARROWS, MANY OF THEM
REPRESENT REGULATORY ASPECTS,
EITHER REGULATORY FROM A FEDERAL
GOVERNMENT STANDPOINT OR STATE
GOVERNMENTS, AND WHAT RAMONA HAD
TOLD US ABOUT IS WHAT IS
NECESSARY AND REALLY FACILITATES
ALL OF THIS WORKING TOGETHER IS
PEOPLE COLLABORATING, HAVING
DATA STANDARDS, AND HAVING A
SHARING OF DATA AND AN ABILITY
TO REALLY MINE THAT DATA TO
ADVANCE IT.
SO WHAT WE'VE HEARD HERE IS
EXAMPLES FROM THE DUCHENNE
FIELD, BUT THESE THEMES REALLY
RESONATE, I THINK, WITH ALL THE
FORMS OF DYSTROPHY, AND EVEN
OTHER RARE DISEASES AND DISEASES
BEYOND THE MISSION OF OUR
COMMITTEE.
SO I THINK -- I HOPE WE'VE TRIED
TO ACCOMPLISH THE GOAL OF THIS
SESSION BY NOT ONLY HIGHLIGHTING
THESE ADVANCES IN DUCHENNE, BUT
ALSO TO MAKE EACH OF US THINK
ABOUT HOW CAN WE USE THESE
PATHWAYS THAT HAVE BEEN
DEMONSTRATED SUCCESSFUL IN
DUCHENNE, HOW CAN WE APPLY THEM
TO FSHD, LIMB-GIRDLE, OR OTHER
FORMS OF MUSCULAR DYSTROPHY.
AND I'LL LEAVE IT THERE, YOU
KNOW, I THINK OPEN THIS SESSION
UP FOR EITHER ADDITIONAL
QUESTIONS FOR THE PRESENTERS OR
OVERALL COMMENTS.
>> I'M NOT SEEING ANY QUESTIONS.
I HAVE A FEELING THAT PEOPLE MAY
WANT JUST A LITTLE BREAK RIGHT
NOW.
JUST TO REFRESH THEMSELVES FOR
THE LAST PART OF THE SESSION.
SO WE ARE RUNNING ABOUT
6 MINUTES BEHIND.
WE PICKED UP SOME TIME.
SO SHALL WE HAVE EVERYBODY COME
BACK AT 2:51, SO 10 MINUTES FROM
NOW?
THAT'S GOOD.
OKAY. MINI BREAK.
THE CONGRESSIONALLY DIRECTED
MEDICAL RESEARCH PROGRAM ON
THEIR STRATEGIC PLANS, AND THEIR
LONG TERM GOALS.
WE ALSO DISCUSSED THE RENEWAL OF
THE MDCC ACTION PLAN FOR THE
MUSCULAR DYSTROPHIES.
WE WOULD NOW LIKE TO LEVERAGE
THE EFFORTS OF STRATEGIC
PLANNING BY OUR MEMBER
ORGANIZATIONS AND OTHER PATIENT
GROUPS TO INCORPORATE OR LINK
THEIR PLANS TO THE RENEWED
ACTION PLAN.
TODAY, WE'LL CONTINUE THE
SESSION FROM OUR PREVIOUS
MEETING WITH SOME PRESENTATIONS
FROM THE MUSCULAR DYSTROPHY
ASSOCIATION, AND THE PARENT
PROJECT MUSCULAR DYSTROPHY.
OUR FIRST PRESENTER IN THE
SESSION IS DR. ANGELA LEK, THE
VICE PRESIDENT FOR RESEARCH WITH
THE MDA.
ANG THAT, ANGELA, OVER TO YOU.
>> HI.
SORRY.
LET ME JUST GET THIS UP AND
RUNNING.
SCREEN 2.
YOU CAN SEE THAT?
>> WE JUST NEED IT IN
PRESENTATION MODE.
>> YES.
DOES THAT WORK?
>> PERFECT.
>> GREAT.
ALL RIGHT.
THANK YOU FOR INVITING ME HERE
TODAY AND ALLOWING ME TO FILL IN
ON BEHALF OF SHARON HESTERLEE.
HIGH NAME IS ANGELA LEK, I'M THE
VICE PRESIDENT THE RESEARCH AT
MDA.
SO MDA IS AN UMBRELLA
ORGANIZATION COVERING OVER 300
MUSCULAR DISEASES IN OUR
PORTFOLIO.
OUR OVERALL MISSION IS TO ENSURE
THAT PATIENTS -- THE PATIENTS
WHO WE SERVE LIVE LONGER AND
MORE INDEPENDENT LIVES.
SO WE STRIVE TO ACHIEVE THIS BY
FOUR PILLARS.
OOUR CARE CENTER NETWORK,
ADVOCATING FOR THE NEEDS AS WELL
AS PROVIDING COMMUNITY
EDUCATION, AND IN ADDITION OF
OUR ACTIVITIES AND EVENTS
THROUGH OUR NETWORK OF
VOLUNTEERS, AND PROVIDE A WEALTH
OF RESOURCES TO SUPPORT
EDUCATION AND ADAPTIVE LIFESTYLE
CHOICES WITH A VARIETY OF OUR
MULTIMEDIA PLATFORMS BELOW HERE.
SO TODAY I'LL BE TOUCHING ON
MDA'S STRATEGIC INITIATIVES FOR
RESEARCH.
HEALTH, QUALITY OF LIFE AND
HEALTHCARE SERVICES, AS WELL AS
ADVOCACY.
SO WE BEGIN WITH RESEARCH.
WE'VE BEEN THE BIGGEST FUNDER OF
NEUROMUSCULAR DISEASE RESEARCH.
WE OFFER GRANTS TO CATER TO
DIFFERENT STAGES OF DRUG DEVELOP
DEVELOPMENT AS YOU CAN SEE ON
THE LEFT.
TO BOTH ACADEMIA AND EARLY STAGE
COMPANIES.
OUR ACTIVE GRANT PORTFOLIO
CHANGES A LOT FROM YEAR TO YEAR,
AND IS LARGELY DICTATED BY THE
INPUT OF OUR GRANT REVIEW
COMMITTEE.
BUT AS YOU CAN SEE, WE CURRENTLY
HAVE MANY ACTIVE GRANTS IN THE
MUSCULAR DYSTROPHIES COVERING
DMD, BMD, LIMB-GIRDLE, MYOTONIC,
FSHD, CMDs.
WE MAKE AWARDS OF DIFFERENT
SIZES.
AN EXAMPLE OF A BIG AWARD IS ONE
THAT SUPPORTS SHARED RESOURCES
AND INFRASTRUCTURE FOR A
CLINICAL TRIAL NETWORK OF
MUSCULAR DYSTROPHY SITES HEADED
BY JOE STATLIN.
AN EXAMPLE OF A STANDARD
SCREENING RESEARCH -- --
RESEARCH PROJECT IS TO LOOK AT
MOBILIZING MUSCLE STEM CELLS FOR
DMD HEADED BY MICHAEL RUDNICKI.
SO INTEREST IN PRE-CLINICAL
RESEARCH IS NOT LIMITED TO
TRANSLATIONAL PROJECTS BUT WE
ALSO SEEK TO ANSWER BASIC
SCIENCE QUESTIONS ABOUT DISEASE
MECHANISM.
RECENTLY WE'VE ALSO LAUNCHED THE
KICK START PROJECT PROGRAM WHICH
IS OUR IN-HOUSE DRUG DEVELOPMENT
PROGRAM FOR ULTRA-RARE DISEASES
AMENABLE TO GENE REPLACEMENT
THERAPY.
SO WE FEEL THERE IS A ROLE FOR
NON-PROFITS TO KICK START AND
DE-RISK DRUG DEVELOPMENT FOR
DISEASES THAT HAVE A HIGH
BARRIER FOR COMMERCIALIZABILITY.
SO THE PILOT PROJECT, WE HAVE
SELECTED A CO CONGENITAL --
SYNDROME.
LESS THAN 300 PEOPLE IN THE
U.S., WHO SUFFER FATAL EPISODES
OF APNEA DUE TO MUTATIONS IN THE
CHAT GENE.
WE WORK CLOSELY WITH AN ACADEMIC
P.I. AT UC DAVIS, RICARDO MA
MASELLI.
WE CAN DEVELOP A BLUEPRINT FOR
HOW NON-PROFITS CAN PLAY AN
ACTIVE ROLE AND HELP DE-RISK THE
EARLY STAGES OF DRUG DEVELOP M.
SO FOR THIS PROGRAM, WE HAVE
ASSEMBLED AN ADVISORY COMMITTEE
COMPOSED OF KEY LEADERS FROM
INDUSTRY AND ACADEMIA WHO HAVE
HELPED SELECT OUR FIRST
INDICATION TO FOCUS ON.
WE HAVE A CORE PROJECT TEAM WHO
MEET WEEKLY AND CONSULTANTS WITH
SPECIFIC EXPERTISE AND WE HAVE A
LIST OF ACTIVITIES THAT OUR KICK
START PROGRAM COVERS AND WHAT WE
DEEM ESSENTIAL FOR ADVANCING
GENE THERAPY INDICATIONS THROUGH
THE DRUG DEVELOPMENT PIPELINE.
OUR INTENTION IS TO SET UP OUR
KICK START PROJECTS FOR SUCK
SUCCESSFUL FOLLOW-ON FUNDING
FROM LARGER SOURCES WHO CAN HELP
THEM CARRY OUT ID ENABLING
STUDIES INTO PHASE ONE CLINICAL
TRIALS.
SO ANOTHER ONE OF OUR STRATEGIC
GOALS IN RESEARCH IS TO ADDRESS
THE LACK OF DIVERSITY IN THE
INVESTIGATORS THAT WE FUND.
SO AFTER SURVEYING THE
ECOSYSTEM, WE DISCOVERED THAT
THE BEST STAGE FOR US TO
ALLOCATE INVESTMENT IS IN THE
UNDERGRADUATE LEVEL BEFORE WE
BEGIN TO SEE A DROPOFF IN
DIVERSITY AND REPRESENTATION OF
CANDIDATES WHO SEEK TO PURSUE
FURTHER RESEARCH IN
NEUROMUSCULAR DISEASES.
SO DIVERSITY HERE, WHEN WE TALK
ABOUT LACK OF DIVERSITY IS USING
THE NIH DEFINITION OF
UNDERREPRESENTED RACIAL AND
ETHNIC GROUPS, AS WELL AS
INDIVIDUALS WITH DISABILITY AND
FROM OTHER DISADVANTAGED
BACKGROUNDS.
SO THIS YEAR WE PILOTED A SUMMER
UNDERGRADUATE RESEARCH PROGRAM
SUPPORTING FOUR STUDENTS TO
PURSUE A RESEARCH INTERNSHIP AT
FOUR VOLUNTEER SITES WITH
ASSIGNED MENTORS.
THESE STUDENTS, WE HAVE ALSO
FUNDED FOR THEM TO ATTEND THE
ANNUAL CONFERENCE TO PRESENT
POSTERS OF THEIR SUMMER PROJECTS
AND THEY WILL ATTEND A CAREER
DEVELOPMENT AND MENTORING
WORKSHOP THAT WILL REMAIN
INVOLVED WITH THE PROGRAM NEXT
YEAR, ALSO THROUGH ME MENTORSHIF
THEIR NEXT COHORT.
SO FAR SURVEYS FROM THE STUDENTS
AND THEIR MENTORS ALL POINT TO
KEY SUCCESSFUL METRIC OF THIS
PROGRAM, WHICH IS TO BROADEN
THEIR RESEARCH EXPERIENCE AND
INTEREST IN NEUROMUSCULAR
DISEASES.
SO ANOTHER BIG RESEARCH PRIORITY
IN MDA IS THAT WE CONTINUE TO
GROW AND EXPAND OUR MOVR
DATABASE, PATIENT REGISTRY.
FOR THOSE WHO ARE UNAWARE, MOVR
COLLECTS LONGITUDINAL CLINICAL
CENTER DATA FOR ALS, BMD, DMD,
FSHD, LGMD, POMPE AND SMA.
WE HAVE PLANS TO GROW THIS
NUMBER AND ADD MORE SITES BUT SO
FAR WE HAVE ENROLLED CLOSE TO
5,000 PATIENTS AND COLLECT DATA
AT EACH ONE OF THEIR CLINIC
VISITS IN AN OBSERVATIONAL STUDY
TO MONITOR THEIR DISEASE
PROGRESSION AND DISEASE --
ANSWER DISEASE-SPECIFIC
QUESTIONS.
DON'T ANSWER, I MEAN COLLECT.
AS WELL AS SERVE AS AN EXAMPLE
AS WHAT MEDICATION THEY'RE
TAKING OR WHAT ASSISTIVE DEVICE
THEY MAY BE USING.
AND WE'D LIKE TO ENCOURAGE IN
THE COMING YEARS MORE ACADEMICS
TO MAKE USE OF THE DATA WE HAVE
COLLECTED TO ANSWER THEIR
SPECIFIC RESEARCH QUESTIONS.
AND ALSO TO ENGAGE WITH MORE
COMPANIES IN THE SPACE WHO CAN
APPLY TO USE OUR MOVR DATA TO
HELP WITH CLINICAL TRIAL DESIGN
AND MATCHING.
SO WE HAVE EXPANDED OUR MOVR
PLATFORM TO PROMOTE REMOTE DATA
COLLECTION, WHICH CAN BE THEN
PREFERABLY MAPPED BACK WITH EACH
AS THEY MOVE ALONG THE -- WE ARE
PILOTING THIS FOR ALS IN
PARTNERSHIP WITH MT FARMER IN A
DECENTRALIZED STUDY DESIGN WHICH
INCLUDES COLLECTING MONTHLY
SURVEYS AND MAPPING FINE MOTOR
ASSESSMENTS AND HAND DEXTERITY
USING A TABLET, AS WELL AS USING
A FITBIT TO MONITOR DAILY
ACTIVITY AND SLEEP.
SO ONE OF THE FIRST ASSESSMENTS
WE WILL BE MONITORING -- WE'RE
PERFORMING IS TO SEE WHETHER
THESE ACTIVITY MONITORS
CORRELATE WITH DISEASE
FUNCTIONAL OUTCOMES DETERMINED
IN THE CLINIC SETTING, SUCH AS
THE ALS FRS SCORE, AND IF SO, IT
MEANS THAT THE DATA COLLECTION
PROCESS IN MOVR DOES NOT HAVE TO
BE LIMITED TO THE CLINICAL
SETTING AND THAT CONTI CONTINUOA
COLLECTION MONITORING IN A REAL
WORLD SETTING IS, IN FACT,
POSSIBLE, SO WE'VE PICKED ALS AS
OUR FIRST INDICATION, BUT
HOPEFULLY WE CAN EXPAND THIS TO
OTHER MUSCULAR DYSTROPHIES.
SO ANOTHER RESEARCH PRIORITY IS
TO CONTRIBUTE PROACTIVELY TO
TRANSLATION OF GENETIC THERAPIES
USING AIDS-F AAVs.
TO OPENLY CHARASH EUS IMPORTANT
FOR THE TRANSLATION OF GENETIC
THERAPIES.
A MEETING REPORT SUMMARIZING THE
DISCUSSIONS AND RECOMMENDATIONS
ARE PUBLISHED IN A PEER REVIEWED
JOURNAL AND THEN WE ALSO
FUNDRAISE AROUND THE IMPORTANT
TOPICS RAISED IN THIS MEETING,
SUCH AS HOW TO BETTER UNDERSTAND
AND MITIGATE ANTITRANS GENE
SAFETY CONCERNS IN DMD GENE
THERAPIES.
SO WHILE AAVs REPRESENT THE
MOST PROMPT NENT METHOD FOR
DELIVERING GENE THERAPIES, MDA
HAS PARTNERED TO INVESTIGATE THE
REPURPOSING AFTER AN PROVED DRUG
FOR MYASTHENIA GRAVIS CALLE CALD
VYVGART, AS WELL AS EXPLORING
THE POTENTIAL ABILITY FOR
REDOING WITH A SECOND GENE
THERAPY.
SECONDLY BY OUR VENTURE
PHILANTHROPY PROGRAM WE'VE MADE
AN INVESTMENT IN MYOSANA BASED
OUT UFT UNIVERSITY OF WASHINGTON
WORK ON NON-VIRAL DELIVERY
ALTERNATIVES FOR GENE THERAPY.
IN TERMS OF HEALTHCARE NEEDS, WE
CONTINUE TO GROW OUR CARE CENTER
NOTE WORK WITH OVER 150 SITES
AROUND THE U.S.
THESE ARE SITES THAT HELP
SUPPORT PATIENTS GET THE
SPECIALIZED CARE THEY NEED FOR
THEIR RESPECTIVE NEUROMUSCULAR
DISEASES AS WELL AS ENABLING
INFRASTRUCTURE FOR CLINICAL
TRIALS AND NATURAL HISTORY
STUDIES.
SO OTHER WAYS WE SUPPORT QUALITY
OF LIFE AND HEALTHCARE NEEDS ARE
PROVIDING A HEALTHCARE CENTER,
FAMILY AND COMMUNITY SUPPORT
CHANNEL, GENE THERAPY SUPPORT
NETWORK, OUR CARE CENTER SUPPORT
NETWORK, MEDICAL EDUCATION TO
HEALTHCARE PROVIDERS, AS WELL AS
A VARIETY OF COMMUNITY EDUCATION
AND ENGAGEMENT PROGRAMS, AND I
WILL SHOWCASE SOME OF THESE IN
THE NEXT FEW SLIDES.
SO AS WE'VE DISCUSSED THE FIRST
GENE THERAPY WAS APPROVED
EARLIER THIS YEAR AND IT'S
ANTICIPATED THAT MANY MORE WILL
FOLLOW IN THE NEXT FEW YEARS.
WE ARE INVESTING IN STRATEGIES
TO HELP WITH READINESS AT OUR
CARE CENTER SITES, SWELL WITHIN
OUR PATIENT COMMUNITY.
WE'RE WORKING TO DEVELOP A
VIRTUAL RESOURCE PLATFORM FOR
OUR CARE SITES AND WE HAVE
ESTABLISHED A GENE TEAM WITH
SPECIALISTS WHO DEAL DIRECTLY
ONE-ON-ONE WITH OUR PATIENT WHO
HAVE QUESTIONS AND ARE SEEKING
RESOURCES ON GENE THERAPY.
SO OUR GENE THERAPY NETWORK
OBJECTIVES ARE TO EQUIP OUR CARE
CENTERS TO DELIVER NEARLY
APPROVED GENE THERAPIES AND
THROUGH OUR PLATFORM WE ARE
DISSEMINATING CHECKLISTS OF
RESOURCES, PERSONNEL SUPPORTIVE
CARE TEAMS NEEDED, PROTOCOLS FOR
POST DOSING MONITORING, FILE
BEIINGFOR REIMBURSEMENTS AS WELS
EDUCATIONAL RESOURCES FOR
PATIENT AND CAREGIVERS TO ALIGN
EXPECTATIONS, HOW TO PREPARE FOR
PRE AND POST INFUSION LOGISTICS,
AND MONITORING FOR SIGNS OF
ADVERSE EVENTS.
SO TO ADDRESS QUALITY OF LIFE
NEEDS, MDA INVESTS IN A VARIETY
OF RECREATION NAP PROGRAMS.
THE SO YOU MAY HAVE HEARD OF OUR
WELL-KNOWN SUMMER CAMPS FOR
CHILDREN BUT RECENTLY MDA ALSO
INTRODUCED FAMILY GETAWAYS WHERE
PATIENTS AND THEIR FAMILIES CAN
PARTICIPATE IN MEANINGFUL WRECK
RATIONAL EXPERIENCES, SO I
BELIEVE THEY'VE LAUNCHED FOUR
SESSIONS IN O OREGON, PUERTO RI,
TEXAS, NORTH CAROLINA.
POSITIVE QUALITY OF LIFE
MEASURES SUCH AS MAKING A NEW
FRIEND, TRYING SOMETHING NEW FOR
THE FIRST TIME AND FEELING MORE
CONFIDENT HAVE BEEN NOTED IN
SURVEYS FROM PARTICIPATING
INDIVIDUALS IN OUR RECREATIONAL
PROGRAMS.
SO IN TERMS OF ADVOCACY, OUR
STRATEGIC INITIATIVES FALL UNDER
THESE THREE CATEGORIES.
ACCESS TO CARE IS WHERE WE SEEK
TO ENSURE A ACCESS TO ANYTHING
THAT CAN BENEFIT THE HEALTH OF
OUR COMMUNITY.
THESE ARE THE FOUR AREAS WE
EXPECT TO PRIORITIZE IN THE
PORTFOLIO OVER THE NEXT FOUR
YEARS, SHORTENING DIAGNOSTIC
ODYSSEY AND NEWBORN SCREENING
AND GENETIC TESTING.
ACCESS TO GENETIC MEDICINES AND
A GUARANTEE OF ACCESS TO
AFFORDABLE HEALTH INSURANCE.
THE SECOND IS ACCELERATING
THERAPEUTIC DEVELOPMENT IS THE
AREA IN WHICH WE TRY TO GET MORE
AND BETTER THERAPIES TO OUR
COMMUNITY MORE QUICKLY.
THIS INCLUDES WORKING WITH FDA,
INDUSTRY AND CONGRESS TO ENSURE
THAT THE DRUG DEVELOPMENT
ECOSYSTEM, PARTICULARLY FOR GENE
THERAPIES, IS WORKING OPTIMALLY.
AND THE THIRD IS WHERE WE TRY TO
BREAK DOWN THE SOCIETAL BARRIERS
THAT PREVENT PATIENTS FROM
LEADING LIVES THAT THEY WISH TO
LEAD.
AND THIS INCLUDES ACCESSIBILITY
CHALLENGES, PARTICULARLY IN
TRANSPORTATION, ACCESS TO
BENEFITS, EMPLOYMENT, EDUCATION,
AND FINANCIAL SECURITY.
OUR ANNUAL AND CLINICAL
SCIENTIFIC MEETING IS IN ORLANDO
NEXT YEAR, ALSO WITH A VIRTUAL
OPTION.
THIS TYPICALLY DRAWS A CROWD OF
ABOUT 1,500 MAYBE.
THIS MEETING IS TARGETED TOWARDS
HEALTHCARE PROFESSIONALS,
RESEARCHERS AND CLINICIANS IN
THE NEUROMUSCULAR DISEASE SPACE.
EXAMPLE SESSIONS INCLUDE
SPECIFIC DISEASE FOCUSED ONES,
AS WELL AS SESSIONS THAT COVER
CLINICAL CONSIDERATIONS IN
STREAMLINING CARE.
WE ALSO HOLD SPECIFIC CAREER
DEVELOPMENT SESSIONS, MEANINGFUL
CARE CENTER DIRECTORS, AND
GATHERING FOR PARTNER
ORGANIZATIONS TO DISCUSS
ADVOCACY COLLABORATIONS.
SO I WANT TO END SUMMARIZING OUR
RESEARCH INITIATIVES.
WE HAVE MOSTLY RECOVERED FROM
THE IMPACTS OF THE COVID
PANDEMIC, WE HAVE NOT YET OPENED
ALL OUR GRANT CATEGORIES AND ARE
PRIORITIZING THE MOST IMPACTFUL
ONES MAKING SURE OUR YOUNG AND
EARLY STAGE INVESTIGATORS REMAIN
SUPPORTED.
WE ARE OPEN TO COLLABORATIVE
FUNDING OPPORTUNITIES THROUGH
PARTNERSHIPS AND COFUNDING
PROJECTS WITH OTHER ADVOCACY
ORGANIZATIONS.
I SPOKE ABOUT A MOVR REGISTRY IN
WHICH WE CONTINUE TO EXPAND AND
ADD MORE INDICATIONS.
OUR VENTURE PHILANTHROPY PROGRAM
WE'RE BEGINNING TO SEE EARLY
INVESTMENTS LEADING TO DRUG
APPROVAL SUCH AS GAMRY, AS IT'S
CALLED, AND WE ARE BEING
PROACTIVE IN AREAS OF READINESS
IN GENE THERAPY AS WELL AS
INCREASING DIVERSITY IN
REPRESENTATION IN OUR FIELDS AND
WE'RE EXCITED ABOUT OUR NEW KICK
START PROGRAM AS WELL AS TO HOST
OUR ANNUAL CONFERENCE IN ORLANDO
NEXT YEAR.
SO WITH THAT, I'D LIKE TO THANK
EVERYONE FOR THEIR SUPPORT AND
PLEASE REACH OUT IF YOU HAVE ANY
COLLABORATIVE IDEAS OR
SUGGESTIONS.
THANK YOU.
>> THANK YOU SO MUCH, ANGELA.
I SEE THERE'S ALREADY A QUESTION
IN THE CHAT BOX.
FOR YOU FROM
MARIE PIERRE.
>> OKAY.
ARE DATA COLLECTED AVAILABLE TO
ENTITIES INSTITUTION -- YES, YOU
MEAN THE DATA COLLECTED BY MOVR?
YES, YES, DEFINITELY ARE.
ARE YOU ABLE TO EMAIL ME AND I
WILL CONNECT YOU TO OUR MOVR
TEAM?
HOW DO YOU -- OH, YES, SO IF YOU
APPLY TO ACCESS THE DATA, WE
WILL CROSS-REFERENCE THAT WITH
OUR DATA GOVERNANCE POLICY TO
MAKE SURE THAT IT'S ALLOWABLE
FOR USE FOR YOUR PARTICULAR
STUDY.
BUT THE DATA CAN BE ACCESSED AND
DEIDENTIFIED SO WE CAN
DEFINITELY GIVE YOU ACCESS TO
THAT.
>> I WAS JUST WONDERING HOW DO
YOU FACILITATE FOR DIFFERENT
INVESTIGATORS THAT MAY BE
INTERESTED IN ACCESSING THAT
DATA, DEPENDING ON THE DIFFERENT
STAGE THEY ARE, THE RESEARCH --
>> SO I CAN'T REALLY HEAR YOU.
>> I WAS ASKING THE QUESTION FOR
GENERALLY HOW DIFFERENT
INVESTIGATORS, DEPENDING ON THE
STAGE OF THE RESEARCH AND HOW DO
YOU MAKE THAT DATA AVAILABLE FOR
THEM?
BECAUSE I THOUGHT IT WAS A GREAT
IDEA THAT ALL THE PATIENT DATA
IS BEING COLLECTED, BUT ACCESS
AND HOW DO YOU USE IT DOWN THE
LINE IS ALSO --
>> YEAH, YES.
SO INVESTIGATORS WILL APPLY TO
USE THE DATA IN DIFFERENT WAYS.
THEY CAN ASK US TO PERFORM
ANALYSIS.
THEY CAN HAVE THE DATA
THEMSELVES, OR WE HAVE A
VIRTUAL -- LIKE A VISUALIZATION
PLATFORM IN WHICH THEY CAN PLAY
AROUND WITH THE DATA AND THEIR
BASIC KIND OF ALSO SCRIPTS TO
HELP YOU ANALYZE THE DATA AND
GET WHAT YOU NEED.
BUT IF YOU -- WE CAN LET YOU
KNOW, YOU KNOW, INVESTIGATORS
CAN TELL US WHAT KIND OF -- WHAT
INTERESTS THEM AND WE CAN HAVE A
CONVERSATION AND WE CAN HELP
THEM GET WHAT THEY NEED.
>> THANK YOU, ANGELA.
NOW THERE'S A QUESTION FROM MY
GOOD COLLEAGUE DR. WALTER
KOROSHETZ.
>> HI, ANGELA.
JUST WONDERING IF YOU CAN ANSWER
THIS, I WAS WONDERING WHAT
PEOPLE THINK THE PENETRANCE OF
THE CURRENT GENE THERAPY WILL
BE, AND HOW THAT WILL AFFECT THE
TRIALS OF FUTURE THINGS COMING
UP.
>> PENETRANCE INTO -- CAN YOU
BETTER DEFINE WHAT YOU MEAN BY
PENETRANCE?
>> I'M GUESSING THAT IF 100% OF
THE PEOPLE ARE ON THE APPROVED
GENE THERAPY, THEY WILL NOT BE
ELIGIBLE FOR A NEW GENE THERAPY.
>> OH, RIGHT, RIGHT, RIGHT.
I SEE WHAT YOU MEAN.
YES, THAT IS DEFINITELY THE CASE
RIGHT NOW FOR AAV GENE
THERAPIES.
HAVING SAID THAT, THERE ARE MANY
ACTIVE STRATEGIES NOW TO -- THE
AAV ANTIBODIES, AND I BELIEVE IN
THE NEXT FIVE YEARS, WE'RE GOING
TO BE SEEING SOME OF THEM
EMPLOYED AND ALLOWING
INDIVIDUALS TO BE RE-DOSED WITH
AAV THERAPIES.
THERE ARE LOTS OF PROMISING
THINGS IN THE PIPELINE THAT
WE'VE SEEN.
>> RELATED TO THE CONGENITAL
MYASTHENIA PROGRAM, SO IT'S A
VERY RARE DISEASE.
ARE YOU ANTICIPATING THAT IT
WOULD EVENTUALLY BE
COMMERCIALIZED, OR IF NO ONE
PICKS IT UP, DO YOU HAVE ANY
PLANS TO MAKING IT AVAILABLE?
>> YEAH, SO WE DEFINITELY HAVE
PLANS TO -- IF POSSIBLE, TO
COMMERCIALIZE, BUT IT IS
DIFFICULT IN THE CURRENT
ECONOMIC, YOU KNOW, LANDSCAPE
FOR RARE DISEASES.
IT COULD POSSIBLY WELL BE THAT
SOME GENE THERAPIES FOR
ULTRA-RARE DISEASES MAY JUST
REMAIN AS AN OPEN IND AND ACCESS
TO IT WILL BE LIMITED TO JUST
ONE SITE, BUT THAT'S
DEFINITELY -- WE'RE HOPING THAT
WE WILL DE-RISK THE PROGRAM
ENOUGH AND GET ENOUGH DATA THAT
IT WILL SUFFICIENTLY INTEREST A
BIOTECH PARTNER TO TAKE IT ALL
THE WAY.
>> OKAY.
THANK YOU.
SO NOW WE ARE GOING TO HAVE A
RETURN ENGAGEMENT FOR DR. ERIC
CAMINO.
YOU'VE HEARD HIM EARLIER IN THE
DAY.
HE'S THE VICE PRESIDENT FOR
RESEARCH AND CLINICAL INNOVATION
WITH PPMD AND HE'S GOING TO TELL
US ABOUT THEIR GOALS AND
STRATEGIC PLANS.
>> THANK YOU.
SO I JUST WANTED TO START, I
TALKED EARLIER A LITTLE BIT
ABOUT PPMD BUT JUST FOR ANYONE
UNFAMILIAR, WE WERE FOUNDED IN
1994.
OUR APPROACH IS TO REALLY TRY TO
ADDRESS DUCHENNE AND BECKER
MUSCULAR DYSTROPHY THROUGH
FUNDING OF RESEARCH THROUGH OUR
ADVOCACY EFFORTS, THROUGH CARE
AND EDUCATION.
AND SO I'M NOT GOING TO TALK AS
MUCH ABOUT SOME OF OUR CARE
PROGRAM TODAY.
WE DO HAVE 37 CERTIFIED DUCHENNE
CARE CENTERS ACROSS THE NATION.
AND THOSE ARE CENTERS WHERE WE
HAVE KIND OF VETTED THEM AND
THEY'VE GONE THROUGH A PROCESS
TO ENSURE THAT THEY ARE
DELIVERING THE MULTIDISCIPLINARY
CARE THAT IS OUTLINES IN THE
CARE STANDARDS.
WITH THAT PROGRAM IN CARE, WE'VE
ALSO LAUNCHED A PILOT PROGRAM AT
U. PENN FOR A CARRIER CLINIC
SPECIFIC TO CARRIERS OF DUCHENNE
AND BECKER MUSCULAR DYSTROPHY.
SO SINCE OUR FOUNDING, WE'VE
FUNDED OVER 55 MILLION-DOLLARS
IN RESEARCH AND DEVELOPMENT.
WE ESTABLISHED THE DUCHENNE
REGISTRY WHICH I'M GOING TO TALK
ABOUT A LITTLE BIT.
WE HAVE THE LONGEST RUNNING
ADVOCACY CONFERENCE IN RARE
DISEASE AND HELPED TO GET FOUR
PIECES OF LEGISLATION SIGNED
INTO LAW.
SO WHERE I'M GOING TO START
TODAY IS ON THE DUCHENNE
REGISTRY AND KIND OF WHAT OUR
THOUGHTS ARE FOR THE EVOLVING OF
THIS AND DATA COLLECTION.
SO THE DUCHENNE REGISTRY HAS
BEEN AROUND FOR 15 YEARS.
WE HAVE AROUND 5700 TOTAL
REGISTRANTS GLOBALLY.
THIS IS ALL PATIENT-REPORTED
DATA, SO TYPICALLY IT'S
CAREGIVERS OF THE CHILDREN BUT
SOME OF THE ADULTS THEMSELVES
ARE IN THE REGISTRY.
AND THERE'S A SERIES OF MODULES
THAT THEY -- AND SURVEYS THAT
THEY COMPLETE TO ENTER DATA.
AND WITH THAT, THEY ENTER
GENETIC TEST REPORTS AND SO
THESE GENETIC TEST REPORTS ARE
CURATED BY THE GENETIC
COUNSELORS THAT WE HAVE ON
STAFF, SO NIKI ARMSTRONG, WHO
YOU HEARD EARLIER TODAY, IS ONE
OF THOSE GENETIC COUNSELORS.
WE RECENTLY PUBLISHED OUR
15-YEAR REGISTRY REPORT FOR THE
COMMUNITY.
FOR US THIS WAS REALLY IMPORTANT
AS A WAY TO HELP SHOW THE
COMMUNITY WHAT THEY'RE DOING.
IT'S A NICE GIVE-BACK.
IT'S IMPORTANT, WE FEEL, THAT
PATIENTS UNDERSTAND WHAT THE USE
IS AND SO TO DATE, IT'S BEEN
USED FOR RECRUITMENT IN 82
CLINICAL TRIALS AND 100 RESEARCH
STUDIES.
WE HAVE A NUMBER OF INDUSTRY
PARTNERS WHO HAVE ACCESSED THIS
DATA.
WE HAVE 13 PUBLICATIONS THAT
HAVE BEEN USED FROM REGISTRY
DATA.
SO THE REGISTRY REPORT, IT'S
AVAILABLE ON PPMD'S WEBSITE BUT
WE TRY TO PULL THIS INTO SOME
FAMILY FRIENDLY LANGUAGE
EXPLAINING ALL OF THE DIFFERENT
THINGS THAT ARE CAPTURED IN
THERE, MAKING SOME GRAPHS THAT
REALLY HELP EXPLAIN THIS AND I
ALWAYS THINK THERE'S SOME REALLY
INTERESTING DATA THAT COMES OUT
OF THIS.
FOR INSTANCE, SEEING THE
DIFFERENT TRENDS OVER THE PAST
KIND OF SETS OF FIVE YEARS IN
TERMS OF STEROID USE, WE CAN SEE
IN THE PAST FIVE YEARS, WE'VE
HAD THIS CHANGE WHERE MORE
NON-AMBULATORY PATIENTS ARE
CONTINUING TO STAY ON STEROIDS,
WHEREAS THAT PREVIOUSLY IS
SOMETHING THAT WOULD DECLINE.
AND ONE OF THE IMPORTANT ASPECTS
OR THE THINGS THAT WE'RE LOOKING
TO DO TO BUILD ON THIS REGISTRY
AND PATIENT-REPORTED OUTCOME IS
FOLD SOME OF THE DATA THAT WE'RE
COLLECTING FROM THE DUCHENNE
REGISTRY INTO OUR DUCHENNE
OUTCOMES RESEARCH EXHIB INTERCH.
SO THE OUTCOMES RESEARCH
INTERCHANGE, WE OFTEN REFER TO
IT AS DORI, WAS LAUNCHED IN 2019
WITH THE IDEA OF COMBINING OUR
PATIENT-REPORTED DATA WITH
CLINICIAN REPORTED DATA FROM
APPROVED THERAPIES, AND
ELECTRONIC HEALTH RECORDS.
SO TRYING TO BUILD A WAREHOUSE
WHERE WE CAN PULL IN ALL OF THIS
DIFFERENT DATA.
SO CURRENTLY, OUR OUTCOMES
RESEARCH INTERCHANGE HAS OUR
DUCHENNE REGISTRY DATA.
WE HAVE DATA FROM OUR EHR STUDY
WITH FLOWING INTO THAT.
THERE'S 10 CENTERS
PARTICIPATING.
I'LL TALK ABOUT THOSE SLIDES IN
A SECOND, NOT ALL OF THEM HAVE
DATA FLOWING AT THE MOMENT.
THEN WE HAVE DATA FROM SAREPTA'S
EVOLVE REGISTRY WHICH IS FOR
THEIR THREE APPROVED
EXON-SKIPPING THERAPIES, SO IT'S
THEIR POST MARKET SURVEILLANCE
DATA FLOWING INTO THE
INTERCHANGE AS WELL.
SO WE HOPE THIS IS A TOOL THAT
CAN BE USED AS WE CONTINUE TO
HAVE APPROVALS IN THE DUCHENNE
SPACE.
SO ALL OF THE DATA IN HERE IS
SECURED.
EVERYBODY WHO'S CONTRIBUTING
DATA OWNS THEIR OWN DATA, SO
DATA SAFETY, PRIVACY IS
OBVIOUSLY PARAMOUNT, AND THERE'S
GATE KEEPING SO THAT YOU CAN'T
ACCESS DATA THAT DOESN'T BELONG
TO YOU.
THIS IS KIND OF OWE SCHEMATIC OF
HOW THIS TYPICALLY FLOWS.
YOU HAVE THESE INDIVIDUAL TYPE
OF DATA MARTS, WHETHER IT'S
RPROs OR THE DATA FROM SITES
FROM THE ELECTRONIC HEALTH
RECORD, AND ALL OF IT CAN BE
PULLED INTO THIS INTERCHANGE
HUB, AND EVENTUALLY USED FOR
DOING SOME RESEARCH AND
ANALYTICS AND WE'RE HOPEFUL THAT
THIS ALLOWS US TO REALLY GET A
BETTER GRASP OF THE DISEASE AND
UNDERSTANDING AS WE HAVE
APPROVED THERAPIES KIND OF WHAT
IS HAPPENING AND WHAT THE CHANGE
IN OUR NATURAL HISTORY LOOKS
LIKE.
SO AS PART OF THIS I MENTIONED
WE HAVE AN ELECTRONIC HEALTH
RECORD STUDY.
SO WE HAVE BEEN WORKING TO SET
UP EXTRACTION OF ELECTRONIC
HEALTH RECORDS AUTOMATED FROM
SOME OF OUR CERTIFIED DUCHENNE
CARE CENTERS.
SO THESE ARE THE FIRST COHORTS
IN OUR EHR STUDY, SO ARKANSAS
CHILDREN'S HIGHLIGHTED IN RED
THERE HAS DATA -- THEY'RE
CONSENTING PATIENTS AND WE HAVE
DATA FLOWING INTO THE
INTERCHANGE.
AND THEN DUKE IS THE OTHER SITE
THAT IS ACTIVELY CONSENTING
PATIENTS AND DATA SHOULD BE
FLOWING SOON, AND THEN ALL OF
THE OTHER SITES MARKED ON THIS
MAP ARE AT SOME STAGE OF KIND OF
CONTRACTING AND SETTING UP THE
DATA INFRASTRUCTURE.
BUT REALLY WHAT WE'RE WORKING TO
DO IS TRY AND TAKE SOME OF THE
BURDEN OFF OUR CLINICIANS AND
OUR NETWORK FROM HAVING TO
HAND-ENTER DATA AS WE HAVE
DIFFERENT POST MARKET STUDIES
ONGOING, SO TAKING THE DATA
RIGHT FROM THE EHR INTO THE
INTERCHANGE, THEN WE HAVE
ANOTHER PROJECT ONGOING WITH
THIS, LOOKING AT NATURAL
LANGUAGE PROCESSING BECAUSE WE
KNOW THAT A LOT OF THE IMPORTANT
DATA ENDS UP IN THE NOTES, SO WE
WANT TO MAKE SURE THAT WE CAN
GET TO THAT.
WE DON'T WANT THAT DATA TO BE
LOST SO WE HAVE AN ONGOING
PROJECT TO TRY AND TEASE OUT
SOME OF THAT AS WELL.
AND SO THIS IS JUST A SNAPSHOT
OF THE CURRENT DRUG DEVELOPMENT
PIPELINE IN DUCHENNE.
SO WE CURRENTLY HAVE SEVEN
APPROVED THERAPIES, FOUR OF
WHICH ARE EXON SKIPPING, SO
MUTATION-SPECIFIC THERAPIES THAT
COVER ABOUT 30% OF OUR
POPULATION.
TWO CORTICOSTEROIDS AND THEN THE
GENE THERAPY PRODUCT, AND THEN
WE'RE HOPEFUL COME MARCH THAT WE
WILL HAVE OUR EIGHTH APPROVAL
WITH JI VIF STAT, PADUFA DATE
GOT PUSHED TO MARCH.
WE ARE STARTING TO HAVE THIS
REALLY ROBUST PIPELINE MOVE FROM
A LOT OF CLINICAL TRIALS TO
APPROVALS, AND THAT IS GOING TO
ALTER A NUMBER OF THINGS.
IT'S GOING TO ALTER THE CLINICAL
TRIAL LANDSCAPE, WE HAVE WORK TO
DO TO MAKE SURE THAT PATIENTS
HAVE ACCESS TO ALL OF THESE
THERAPIES IF THEY ARE AVAILABLE
FOR THEM.
AND THEN OF COURSE UNDERSTANDING
WHAT COMBINATION THERAPY LOOKS
LIKE AND IS IT SAFE AND HOW ARE
WE TRACKING PATIENTS.
SO PART OF THIS EVOLVING
LANDSCAPE RECENTLY LED US TO
UPDATE THE GUIDANCE FOR DRUG
DEVELOPERS THAT PPMD HELPED TO
LADY ELEADEARLY IN 2014 THAT LEE
FDA'S DEVELOPMENT OF THAT
GUIDANCE.
SO WE WERE KIND OF LOOKING AND
REALIZED THIS WAS GETTING TO BE
A BIT OUT OF DATE IN TERMS OF
THE ALL OF THE ADVANCEMENTS THAT
HAD GONE UNDERWAY.
SO WE OPTED IN 2021 TO START
UPDATING THIS GUIDANCE.
MANY OF THE INDIVIDUALS ON THIS
CALL IN THE DUCHENNE SPACE
PARTICIPATED IN THIS PROCESS AND
WE'RE GRATEFUL FOR IT AND THIS
IS JUST KIND OF AN OVERVIEW OF
THE STRUCTURE.
WE BROUGHT BACK OUR STEERING
COMMITTEE FOR IT AND WE HAD VERY
SPECIFIC WORKING GROUPS FOR A
NUMBER OF DIFFERENT AREAS THAT
WE UPDATED, AND TWO OF THOSE NEW
AREAS THAT WE HAD TO ADD TO THIS
GUIDANCE WAS CARDIAC, BECAUSE
THAT WAS NOT IN THE INITIAL
GUIDANCE, AND GENE THERAPY.
AS THAT IS, AGAIN, A REALLY
EVOLVING SPACE IN OUR FIELD.
SO WE WENT THROUGH THE PROCESS
OF UPDATING THIS, LIKE I SAID, A
LOT OF GREAT CONTRIBUTION.
WE DID SUBMIT TO THE FDA.
THEY'RE NOT CURRENTLY GOING TO
UPDATE THEIR GUIDANCE, SO WE ARE
ACTUALLY GOING TO PUBLISH THE
ENTIRE DOCUMENT.
AND THEN WE'VE TALKED WITH OUR
STEERING COMMITTEE ABOUT USING
THIS AS A LIVING DOCUMENT MOVING
FORWARD, SO RATHER THAN HAVING
EVERY FIVE TO SEVEN YEARS THIS
KIND OF MAMMOTH TASK OF UPDATING
ALL OF THE SCIENCE THAT'S GOING
ON, WE WANT TO BE ABLE TO BE A
BIT MORE NIMBLE AND LOOK AT
AREAS AS THEY ARE EVOLVING AND
SEE IF WE CAN PROVIDE GUIDANCE
AND TURN AROUND MORE QUICKLY.
SO RAMONA AND BILL BOTH TALKED
ABOUT THESE DRUG UTILITY TOOLS
THAT ARE BEING DEVELOPED, THESE
MODELING SIMULATION TOOLS.
AS THOSE ARE APPROVED, WE WANT
TO MAKE SURE WE INCORPORATE HOW
DO YOU USE THOSE, HOW DO DRUG
DEVELOPERS COMING INTO THE SPACE
BETTER DESIGN CLINICAL TRIALS.
SO THAT'S KIND OF OUR THOUGHT
WITH THE GRAY DANCE DOCUMENT.
AS WE CONTINUE TO MOVE FORWARD.
ANOTHER AREA THAT WE CONTINUE TO
WORK IN IS WITH OUR DUCHENNE
DEVELOPMENT ROUNDTABLE.
THIS IS A PRECOMPETITIVE SPACE.
WE HAVE A NUMBER OF COMPANIES
THAT ARE WORKING IN DUCHENNE AND
BECKER COME TOGETHER TO TALK
ABOUT CHALLENGES IN DRUG
DEVELOPMENT.
AND THIS HAS BEEN A REALLY GREAT
SOURCE FOR US FOR LAUNCHING
PROGRAMS THAT PPMD HAS WORKED ON
SUCH AS SOME OF THE NEWBORN
SCREENING PILOT THAT WE DID IN
NEW YORK STATE, THE ICD-10 CODE,
SOME OF OUR PATIENT PREFERENCE
STUDIES, EVEN SOME OF THE WORK
WITH THE PLATFORM TRIAL DESIGN.
AND SO THIS IS AN AREA THAT
WE'RE CONTINUING TO UTILIZE THIS
GROUP OF STAKEHOLDERS TO TRY AND
ADDRESS CHALLENGES THAT
EVERYBODY FACES.
SO WE HAD SOME REALLY GREAT
RECENT MEETINGS.
REANTLY ON IMAGING BIOMARKERS
AND CLINICAL TRIALS, SOME OF THE
WORK THAT'S GOING ON FROM THE
IMAGING DND GROUP AND SHOWING
HOW THAT CAN BE BEST UTILIZED
FOR TRIAL DESIGN.
AND THEN MORE RECENTLY, JUST
THIS PAST NOVEMBER, WE HAD A
MEETING ON ACCESS AND TRIAL
DESIGN FOR COMBINATION THERAPY.
AGAIN, TRYING TO LOOK AHEAD AND
RECOGNIZE THAT A LOT OF PATIENTS
IN OUR COMMUNITY ARE GOING TO
HAVE ACCESS TO THERAPIES THAT
RESTORE DYSTROPHIN IN SOME FORM,
WHETHER THAT'S EXON SKIPPING OR
A MICRO DYSTROPHIN OR OTHER
THERAPIES.
SO WHAT DOES THAT DO TO THE
TRIAL LANDSCAPE IF A NUMBER OF
OUR PATIENTS ARE ON THESE
THERAPIES, HOW DOES THAT CHANGE
NATURAL HISTORY, HOW DO WE THINK
ABOUT DESIGNING CLINICAL TRIALS
SO WE CAN STILL ENROLL AND
ENSURE ACCESSIBILITY OF TRIALS
TO PATIENTS.
AND THEN FROM THE PAYOR SIDE,
HOW DO WE MAKE SURE THAT WE'RE
COLLECTING RELEVANT DATA TO SHOW
THAT THESE DRUGS CAN BE USED IN
COMBINATION, THAT THEY'RE SAFE,
THAT THEY'RE EFFICACIOUS, AND
THAT THEY'RE COVERED.
AT THE END OF THE DAY, HAVING A
BUNCH OF APPROVED THERAPIES IF
YOU DON'T HAVE ACCESS TO THEM,
THAT'S A PROBLEM AND THAT'S
SOMETHING WE WANT TO MAKE SURE
WE'RE KEEPING AN EYE TOWARDS.
AND THEN SOME OF THE MEETINGS
THAT WE'RE LOOKING TO HOLD KIND
OF IN THE NEXT YEAR, WE HEARD A
LITTLE BIT ABOUT STRIDE -- 95TH
PERCENTILE STRIDE VELOCITY,
TRYING TO GET A BETTER
UNDERSTANDING OF WHAT THOSE ARE
AND HOW WE CAN UTILIZE THEM.
THEN AS WELL SOME OF THE
ADVANCEMENTS WE'VE SEEN IN THE
PRE-CLINICAL MODELS AND HOW WE
CAN IMPROVE TRANSLATION OF
DRUGS.
THEN ONE BIG PIECE WE'VE WORKED
ON FOR A NUMBER OF YEARS HAS
BEEN THE DUCHENNE PLATFORM
TRIAL.
I KNOW THAT WAS SOMETHING JEN
MENTIONED IN HER DISCUSSION WITH
LIANNA WAS LOOKING AT PLATFORM
TRIALS IN COMBINATION THERAPIES.
SO WE HAVE BEEN WORKING ON THIS
PLATFORM TRIAL ORIGINALLY, WE
HAD A BIG STAKEHOLDER MEETING IN
2019.
WHERE WE TOOK IN FEEDBACK ABOUT
A MASTER PROTOCOL.
WE TOOK THAT TO THE FDA AND GOT
SOME REALLY GREAT FEEDBACK IN
MARCH OF 2021 AND HAVEN'T BEEN
ABLE TO IMPLEMENT THAT, SO WE
HAVE A PROTOCOL IN HAND.
NOW, WHEN THIS WAS BEING WORKED
ON, THE LANDSCAPE WAS A BIT
DIFFERENT AND I THINK OUR
ORIGINAL INTENTION WAS THIS WAS
GOING TO BE A LANDING SPOT FOR A
LOT OF SMALL MOLECULES THAT WERE
TARGETING MORE DOWNSTREAM
ASPECTS OF DUCHENNE.
AND WE ARE NOW LOOKING AND
INVESTIGATING IS THIS SOMETHING
THAT COULD BE UTILIZED AS WE TRY
TO GET A BETTER UNDERSTANDING ON
POTENTIAL COMBINATION THERAPIES.
SO THIS IS SOMETHING WE'RE GOING
TO CONTINUE TO WORK WITH OUR
PARTNERS AND CRITICAL PATH
INSTITUTE HAS BEEN REALLY
HELPFUL IN THE DESIGN HERE AS WE
CONTINUE TO EXPLORE THIS.
I DID WANT TO TALK A LITTLE BIT
ABOUT SOME OF OUR ADVOCACY
EFFORTS.
SO EVERY YEAR WE HAVE OUR
ADVOCACY MEETING AT D.C. .
THIS YEAR IT GOING TO BE
MARCH 3RD THROUGH FIFTH AND IT
IS A REALLY GREAT FAMILY EVENT.
WE HAVE A LOT OF FAMILIES THAT
COME TO D.C. , AND IT'S NICE TOO
BECAUSE IT PROVIDES FAMILIES AN
OPPORTUNITY WHO MAYBE AREN'T THE
PRIMARY CAREGIVERS TO INTERACT
AND FEEL LIKE THEY'RE
CONTRIBUTING, SO WE GET A LOT OF
GRANDPARENTS, A LOT OF SIBLINGS
THERE.
AND THEY GO, THEY GET TO MEET
THEIR REPRESENTATIVES, TELL
THEIR STORIES, AND HELP US AS WE
ASK FOR APPROPRIATIONS.
SO A NUMBER OF THINGS THAT WE'VE
BEEN WORKING ON THE PAST FEW
YEARS IN PARTNERSHIP WITH A
NUMBER OF OTHER GROUPS IN THE
RARE DISEASE SPACE.
THINGS LIKE THE BENEFIT ACT,
WE'RE GOING TO CONTINUE TO WORK
AND SUPPORT NEWBORN SCREENING IN
ADDITION TO THE RUSP AND STATE
IMPLEMENTATION AS NIKI WAS
TALKING ABOUT.
WE'RE GOING TO, AGAIN, TRY TO
WORK AND ENSURE COMBINATION
THERAPY ACCESS FOR FAMILIES.
OUR ADULT ADVISORY COMMITTEE HAS
BEEN WORKING WITH OUR DIRECTOR
OF ADVOCACY ON A NUMBER OF
DISABILITY AND INCLUSION
POLICIES.
AND THEN WE ARE PILOTING SOME
STATE LEVEL ADVOCACY TRAINING
WITH OUR CONNECT GROUP FAMILY
LEADERS.
SO IN STATES WE HAVE SOME OF OUR
LOCAL COMMUNITY THAT ARE THERE
TO HELP FACILITATE COMMUNITY AND
CONNECTION AND SOME OF THEM HAVE
EXPRESSED MORE INTEREST IN
INTERACTING WITH THEIR STATE
LEGISLATION AND SO WE'RE HOPING
TO TRAIN THEM TO ADVOCATE AT
THAT STATE LEVEL.
NOW I WANTED TO TOUCH A LITTLE
BIT ON SOME MORE OF OUR
RESEARCH-SPECIFIC TOPICS.
SO AT PPMD, WE FUND BASIC
RESEARCH, PRE-CLINICAL RESEARCH,
SOME CLINICAL TRIALS, WE'VE
STARTED TO DO SOME VENTURE
PHILANTHROPY, BUT OUR CURRENT
STRATEGY, WE HAVE KIND OF THREE
MAIN INITIATIVES WHERE THE
MAJORITY OF OUR FUNDING, OUR
RESEARCH FUNDING IS GOING,
ALTHOUGH LIKE I SAID, WE DO KIND
OF GO OUTSIDE OF THIS AS WELL.
SO WE HAVE OUR GENE THERAPY
INITIATIVE THAT WAS LAUNCHED IN
2017.
AND THIS WAS LAUNCHED WITH THE
INITIAL FUNDING THAT WE PROVIDED
TO DR. JERRY MENDELL FOR THE
FIRST SYSTEMIC DELIVERY OF MICRO
DYSTROPHIN WHICH LED TO THE
LICENSING WITH SAREPTA AND THIS
APPROVAL THAT WE HAD IN JUNE.
MORE RECENTLY, WE HAD SOME
AWARDS AS ANGELA JUST TALKED
ABOUT, WE WERE REALLY GREAT TO
WORK TOGETHER WITH MDA AND CURE
DUCHENNE TO WORK ON THIS
REPURPOSING STUDY OF VYVGART.
-- WE PROVIDED SOME BRIDGE
FUNDING TO DR. CARRIE MICELI ON
SOME CHARACTERIZATION OF
DYSTROPHIN RESTORATION FOR
INDIVIDUALS.
SOME ADDITIONAL SUPPLEMENTAL
FUNDING TO THE UNIVERSITY OF
FLORIDA AND THAT WELLSTONE
CENTER AND THEIR COLLABORATORS
TO SUPPORT SOME POSTDOCTORAL
FELLOWS AND EXPANSION OF SOME
ANIMAL COLONIES AS THEY EXPLORE
NOVEL MICRO DYSTROPHINS IN
COMBINATION THERAPY AND THE
IMPACT OF GENE THERAPY ON THE
HEART.
AND A COLLABORATION WITH
DUCHENNE U.K. TO DR. NAGARAJU TO
LOOK AT SOME INVESTIGATION
IMPROVED THERAPIES FOR
INTERACTING AND MODULATING THE
INNATE IMMUNITY.
AND WE'RE GOING TO CONTINUE TO
INVEST IN STRATEGYINGS THAT LOOK
TO INCREASE SAFETY FOR PATIENTS,
WAYS WE CAN ENHANCE DELIVERY SO
BOTH VIRAL AND NON-VIRAL,
EXPLORING NOVEL TRANS GENES.
ANGELA MENTIONED -- WE ALSO
PROVIDED SOME FUNDING TO, SO
TRYING TO REALLY MAKE SURE THAT
WE'RE IDENTIFYING THESE
POTENTIAL STRATEGIES THAT MIGHT
BE ABLE TO ENSURE MORE PATIENTS
CAN RECEIVE ACCESS TO THERAPY.
AS PART OF THIS AS WELL IS SOME
OF OUR BENEFIT RISK WORK THAT
WE'VE BEEN DOING, SO WE JUST
RECENTLY THIS YEAR COMPLETED OUR
UPDATED BENEFIT-RISK STUDY SO
THIS IS SOMETHING WE HAD
CONDUCTED IN 2017, PRIOR TO THE
FIRST SYSTEMIC DOSE OF GENE
THERAPY.
LOOKING AT BENEFIT RISK IN OUR
POPULATION.
NOW THAT WE'VE HAD MULTIPLE
TRIAL, WE'VE HAD TWO DEATH IN
THE DUCHENNE SPACE AND THERE'S
BEEN DEATHS IN OTHER GENE
THERAPY TRIALS.
WE WANTED TO GET A BETTER GRASP
OF OUR COMMUNITY'S OUTLOOK ON
GENE THERAPY SO WHI WE CONDUCTED
THESE STUDIES LOOKING AT -- AS
WELL AS MAXIMUM ACCEPTABLE RISK
OF DEATH AND PUBLICATIONS FOR
THIS ARE FORTHCOMING, BUT WHAT
WE DID FIND IS EVEN WITH
EVERYTHING ELSE GOING ON, OUR
COMMUNITY CONTINUES TO HAVE A
REALLY HIGH RISK TOLERANCE FOR
GENE THERAPY.
WHICH WAS IMPORTANT AND WE
SUBMITTED AS PART OF THE
ALZHEIMER'S DISEASE COM FOR
ELEVITIS.
THE OTHER TWO MAIN RESEARCH
INITIATIVES ARE OUR CARDIAC
INITIATIVE.
WHEN I WAS TALKING ABOUT THE
SPECIALTY MEETINGS OF THE
FUNDING WE PROVIDED TO THE
ACTION NETWORK, SO THIS
$2 MILLION OVER THREE YEARS TO
HELP GENERATE MORE DATA ON
CARDIAC NATURAL HISTORY IN
DUCHENNE HELPED HARMONIZE
PROTOCOLS AND DEVELOP OUTCOME
MEASURES AND THEN WE HAVE A
BIOMARKERS INITIATIVE AS WELL,
AND THERE'S A NUMBER OF PROJECTS
THAT WE FUNDED UNDER BOTH OF
THESE.
I JUST PULLED OUT TWO OF THE
BIGGER EXAMPLES AND THE PROTEIN
BIOMARKERS, WE DID THIS PROTEIN
MAPPING PROJECT WHERE TRYING TO
LEVERAGE SAMPLES THAT HAVE BEEN
COLLECTED FROM SOME OF THESE
LONG RUNNING NATURAL HISTORY
STUDIES, SO 10 YEARS OF IMAGING
DMD DATA, DOING SOME BIG
PROTEOMIC ANALYSIS ON THIS.
WITH THIS PROJECT, WE'RE JUST
COMING TO PUBLICATION ON IT NOW
BUT WE WANT TO MAKE SURE THAT
THESE DATASETS ARE MADE PUBLICLY
AVAILABLE FOLLOWING THE WAY
OTHER RESEARCHERS, MEMBERS OF
INDUSTRY CAN HAVE ACCESS AND TRY
TO ANSWER ADDITIONAL RESEARCH
QUESTIONS AND HELP MOVE THE
FIELD FORWARD.
SO THAT WAS JUST KIND OF A
SNAPSHOT OF SOME OF THE AREAS
THAT WE'RE WORKING IN COMING UP.
SO HAPPY TO TAKE ANY QUESTIONS.
>> THANK YOU SO MUCH, ERIC.
THERE'S ALREADY A QUESTION FROM
BRAD IN THE CHAT.
>> SO THAT IS -- WE STARTED TO
DO -- I THINK IT'S ACTUALLY
SOMETHING WE NEED TO DIVE INTO,
THE IMPACT OF THE ICD-10 CODES.
SO WE HAD DONE SOME INITIAL LOOK
AT THAT BUT I THINK THAT'S
SOMETHING THAT WE DO NEED TO
INTERROGATE A BIT MORE CLOSELY
TO UNDERSTAND THE IMPACT.
>> GREAT.
AND THERE IS A COMMENT FROM
DR. CRISWELL, THERE'S ALSO
ANOTHER QUESTION FROM ANDY.
>> SO WHEN YOU SAY -- SO
MONETIZING OUR INTERFACE, SO CAN
I ASK SPECIFICALLY?
WHICH PIECE?
>> SO RIGHT WHERE YOU PULL
SELF-REPORTED DATA AND DATA FROM
THE EHRs, THAT'S OF CLEAR
LEHIGH MONETARY VALUE, RIGHT, IN
THE DEVELOPMENT PROCESS.
DO YOU USE THAT -- THIS HIGH
VALUE PIECE, RIGHT, TO THINK
ABOUT OFFSETTING THE COST OF
THESE SUPER EXPENSIVE THERAPIES
WHEN THEY WILL HIT THE MARKET?
>> SO I THINK WITH THAT, MOST OF
WHAT WE DO IN TERMS OF -- IF
THERE IS AS WE UTILIZE THINGS
LIKE THE REGISTRY AND THERE IS
SOME MONETIZATION OF THAT WITH
OUR INDUSTRY PARTNERS, TYPICALLY
THAT GOES INTO FUNDING FUTURE
RESEARCH, SO WE HAVEN'T LOOKED
AT IT AS SOMETHING TO OFFSET THE
COST OF THAT, AND THAT'S
TYPICALLY NOT AN AREA THAT PPMD
REALLY GETS INTO IN TERMS OF THE
DRUG PRICING AND THE IMPACT KIND
OF WITH THAT.
I MEAN, I THINK OUR HOPE WOULD
BE THAT WE JUST CONTINUE TO
ACCELERATE THERAPY DEVELOPMENT,
BUT THAT PIECE IS A LITTLE BIT,
I THINK, BEYOND OUR SCOPE OTHER
THAN CONTINUING TO ADVOCATE AND
WORK WITH OUR PARTNERS ON THE
HILL TO ENSURE THAT WE HAVE FAIR
DRUG PRICES AND THAT FAMILIES
ARE BEING COVERED I AND THAT
MEDICAID IS WORKING TO COVER
THOSE.
AND EVEN WITH THE REALLY HIGH
PRICES, I DO THINK ONE THING
THAT'S BEEN REALLY GREAT, SOME
OF THE WORK FROM PROJECT -- OR
FROM LITTLE HUR QUEUE LEASE,
THEY'RE A GROUP THAT HELPS WITH
SOME OF THESE INSURANCE KIND OF
BATTLES, AND THEY'VE BEEN ABLE
TO OVERTURN I THINK ALL 11
DENIALS THAT HAPPENED WITH THE
GENE THERAPY WITH ELEFT TLEVETIE
ARE SEEING FAMILIES GETTING
ACCESS AND COVERAGE.
>> ANY OTHER QUESTIONS?
SEEING NONE, THANK YOU, ERIC,
FOR BOTH OF YOUR PRESENTATIONS
TODAY.
OH, A LATE-BREAKING QUESTION IN
THE CHAT BOX, IF YOU COULD SEE
THAT.
>> SO YEAH, DO YOU ENVISION
NATURAL HISTORY STUDIES WOULD
INCLUDE RESPIRATORY DECLINE,
RESPONSIVE TRAJECTORY OF DECLINE
AT GENE THERAPY, IMPACT OF
THORACIC CAGE ISSUES ON LUNG
FUNCTION, ET CETERA.
I THINK THIS GOES INTO WHAT I
WAS TALKING ABOUT ALMOST IN THE
EARLIER SESSION, IS THAT I THINK
WE WANT TO MAKE SURE THAT WE'RE
TRACKING AND GETTING A BETTER
UNDERSTANDING OF WHAT ARE THE
LONG-TERM IMPACTS OF THESE GENE
THERAPIES ON CARDIOPULMONARY
FUNCTION BECAUSE TO DATE, THE
MAJORITY OF PATIENTS TREATED
WITH GENE THERAPIES HAVE BEEN IN
THIS YOUNG 4 TO 7 AMBULATORY
RANGE.
WE DO HAVE A HANDFUL OF PATIENT
THAT HAVE BEEN TREATED THAT ARE
OLDER AND NON-AMBULATORY BUT
IT'S NOT A LOT OF DATA.
AND SO I THINK WE NEED TO MAKE
SURE THAT WE ARE TRACKING IT IN
A WAY THAT ALLOWS US TO ANSWER
THESE TYPE OF QUESTIONS AND MAKE
SURE THAT WE DON'T END UP 10
YEARS DOWN THE ROAD WONDERING
WHAT THE IMPACT WAS, AND IF THIS
DOES SHIFT SOME OF THAT NATURAL
HISTORY, YOU KNOW, HOW ARE WE
RESPONDING IN TERMS OF CLINICAL
TRIAL DESIGN, AND THERE'S ALWAYS
A PUSH FOR EXTERNAL CONTROLS AND
WE NEED TO MAKE SURE THAT OUR
DATA IS CONTEMPORARY.
SO I THINK THESE ARE IMPORTANT
QUESTIONS AND I HOPE THAT WE'RE
BEING THOUGHTFUL IN HOW WE'RE
SETTING UP TO CAPTURE THIS DATA
SO THAT WE CAN ANSWER THOSE
QUESTIONS.
>> OKAY.
SO LET ME AGAIN SAY THANK YOU
FOR BOTH OF YOUR EXCELLENT
PRESENTATIONS.
AND NOW WE'RE GOING TO HAVE GLEN
PROVIDE AN UPDATE ON THE RENEWAL
OF THE MDCC ACTION PLAN.
GLEN.
>> THANK YOU.
SO YOU MAY RECALL FROM THE APRIL
MDCC MEETING THIS YEAR WE
DECIDED IT WAS PROBABLY ABOUT
TIME TO RENEW THE STRATEGIC PLAN
FOR THIS COMMITTEE WHICH IS
CALLED THE ACTION PLAN FOR THE
MUSCULAR DYSTROPHIES.
SO WE'RE COMING UP ON 10 YEARS
SINCE THE PREVIOUS PLAN WAS
RELEASED.
AND I JUST WANTED TO GIVE YOU
KIND OF A BRIEF UPDATE ON THE
PROGRESS THAT WE'VE MADE SINCE
THEN.
SO THIS SLIDE SHOWS KIND OF THE
ORG CHART FOR ACTIVITIES RELATED
TO THE RENEWAL OF THE ACTION
PLAN.
SO EVENTUALLY THE DRAFT PLAN
WILL COME BACK TO THIS COMMITTEE
FOR VOTING ON PROBABLY IN THE
SPRING OF 2025 TO KIND OF HELP
WITH THE EVERYDAY OR EVERY-MONTH
DECISION-MAKING RELATED TO IT.
WE'VE CREATED A STEERING GROUP
WHICH IS COMPOSED OF SOLITARY
MEMBERS FROM MDCC AS WELL AS
OTHER ADVOCACY GROUP AND NIH
STAFF.
AND CURRENTLY WE'RE WORKING ON
CREATING THESE WORKING GROUPS
THAT WILL BE ON TOPICS SPECIFIC
TO SECTIONS OF THE ACTION PLAN.
SO THIS IS THE MEMBERSHIP OF THE
STEERING GROUP.
REALLY APPRECIATE EVERYONE'S
HELP THAT'S BEEN MEETING WITH
THIS GROUP.
WE'VE MET, I GUESS LIKE THREE
TIMES NOW TO T THROUGH THE SUMMD
INTO THE FALL.
ONE OF THE THINGS THAT WE TALKED
ABOUT, BOTH AT OUR LAST MDCC
MEETING AND THROUGH THE STEERING
GROUP IS HOW BROAD ARE WE GOING
TO MAKE THIS, YOU KNOW, AND DO
WE JUST STICK WITH THE TYPES OF
MUSCULAR DYSTROPHY THAT ARE
LISTED IN THE FEDERAL
LEGISLATION, THE MD CARE ACT, OR
ARE WE OPEN TO OTHER THINGS, AND
I DON'T THINK THAT WE NEED TO
COME UP WITH A, YOU KNOW, REALLY
SHARP DEFINITION OF MUSCULAR
DYSTROPHY THAT I THINK THE
FEELING WAS, YOU KNOW, CERTAINLY
ALL OF THE DYSTROPHIES LISTED
TRADITIONALLY THOUGHT OF AS
MUSCULAR DYSTROPHIES AND IN THE
LEGISLATION BUT ALSO WE'RE OPEN
TO INCLUDING RELATED MUSCLE
DISEASES THAT HAVE SIMILAR
GENETICS, SIMILAR
PATHOPHYSIOLOGY, CLINICAL
PRESENTATION, THIS SORT OF
THING.
BUT THERE SEEM TO BE PRETTY
CLEAR THOUGHTS THAT WE WOULDN'T
TRY TO INCORPORATE OTHER
CONDITIONS THAT RESULT FROM LIKE
A NEURONAL METABOLIC OR
AUTOIMMUNE MECHANISMS.
SO FOR EXAMPLE, SMA, POMPE,
MYASTHENIA GRAVIS IS REALLY NOT
WITHIN THE MISSION OF THIS
COMMITTEE OR THE ACTION PLAN.
I DON'T THINK THAT THIS IS
REALLY -- YOU KNOW, I THINK ONCE
WE GET TO THE OBJECTIVES IN THE
ACTION PLAN, THEY'LL BE BROAD
ENOUGH THAT THEY COULD QUITE
POSSIBLY BE APPLICABLE TO OTHER
DISEASE AREAS, BUT WE WANTED TO
MAKE IT KIND OF CLEAR WHAT WE
CONSIDER OUR -- WE'VE ALSO
DEVELOPED SOME KIND OF DRAFT
DEFINITIONS FOR DIFFERENT
WORKING GROUPS, SO WE'RE GOING
TO HAVE MECHANISMS OF DISEASE
WHICH IS KIND OF OBVIOUS.
PRE-CLINICAL THERAPY DEVELOPMENT
WHICH WOULD REALLY COVER
EVERYTHING FROM KIND OF
SCREENING ASSAYS UP THROUGH
PROOF OF CONCEPT IN ANIMAL
MODELS AND IND-ENABLING STUDIES,
SO ANYTHING YOU NEED TO KIND OF
TAKE A PRODUCT UP TO BEFORE YOU
GET TO A CLINICAL TRIAL.
AND THEN WE'RE GOING TO HAVE A
SECTION ON CLINICAL STUDIES, AND
BY CLINICAL IN THIS CASE, WE
MEAN PATIENT ORIENTED STUDIES
WHERE THEY SAY THERE WAS A
RESEARCHER AND THERE'S A STUDY
PARTICIPANT IN THE SAME ROOM AT
THE SAME TIME, AND BOTH OF THEM
ARE LIVE.
AND THIS WILL COVER EVERYTHING
FROM CLINICAL TRIAL READINESS,
BIOMARKERS, OUT COME MEASURES,
AS WELL AS CLINICAL TRIALS, BUT
ALSO THINGS LIKE EPIDEMIOLOGIC
STUDIES AND BEHAVIORAL STUDIES
AND SO FORTH.
AND THEN WE'LL HAVE A WORKING
GROUP ON HEALTH, QUALITY OF
LIFE, ACCESS TO CARE AND
SERVICES.
AND THIS WILL INCLUDE THINGS
LIKE DEVELOPMENT, ZOO IT'S
CERTAINLY RESEARCH TOPICS, BUT
ALSO IMPLEMENTATION O OR
EVALUATION OF POLICIES OR
EDUCATION PROGRAMS, WOULD
INCLUDE THINGS LIKE PROMOTING
INDEPENDENT LIVING, INTEGRATION
IN THE EDUCATION SYSTEM OR THE
WORKFORCE, AS WELL AS ACCESS TO
CARE AND SERVICES AND
IMPLEMENTATION OF NEWBORN
SCREENING, THAT SORT OF THING.
SO IN ADDITION TO THOSE, THE
TOPICS THAT ARE REALLY FOR EACH
OF THOSE FOUR WORKING GROUPS,
EACH OF THE WORKING GROUPS IS
ALSO GOING TO TALK ABOUT
WORKFORCE DEVELOPMENT AND
TRAINING WITHIN THEIR AREA,
OPPORTUNITIES FOR COLLABORATION
AND PARTNERSHIP, DATA AND
RESOURCE SHARING, AND THEN DEIA
ISSUES AS IT FITS INTO WHATEVER
ITS PRE-CLINICAL RESEARCH, IF
IT'S CLINICAL RESEARCH, ACCESS
TO CARE AND SERVICES AND SO
FORTH.
SO WE HAVE SUCCESSFULLY
RECRUITED ALL OF THE CO-CHAIRS
FOR OUR WORKING GROUPS, SO
MECHANISMS OF DISEASE IS GOING
TO BE CO-CHAIRED BY
EMANUELAGUSSONI AND LEE SWEENEY,
CLINICAL STUDIES BY KATHERINE
MATHEWS AND RICHARD FINKEL,
HEALTH, QUALITY OF LIFE AND
ACCESS TO CARE AND SERVICES BY
ANNIE KENNEDY AND PAUL MELMEYER.
WE'RE IN THE PROCESS OF GETTING
RECOMMENDATIONS FROM OUR
CO-CHAIRS, WE HAD
RECOMMENDATIONS FROM OUR
STEERING GROUP OF WHO SHOULD BE
ON THESE WORKING GROUPS.
WE'RE ANTICIPATING THAT EACH
WORKING GROUP WILL BE ABOUT
EIGHT MEMBERS PLUS THE
CO-CHAIRS, AND WE'RE CONSIDERING
THINGS LIKE EXPERTISE ACROSS
MULTIPLE TYPES OF MUSCULAR
DYSTROPHY, TRIED TO GET A
BALANCE OF MUSCULAR DYSTROPHY, A
BALANCE OF GENDER, RACE,
ETHNICITY, GEOGRAPHIC
DISTRIBUTION, CAREER STAGES SO
WE'RE NOT ALL JUST RECRUITING
THE MOST EXPERIENCED PEOPLE BUT
GETTING GOOD IDEAS FROM MID
CAREER AND APPROPRIATE BROAD
THINKERS AT THAT LEVEL.
AND SO THE PLAN IS TO HAVE THOSE
WORKING GROUPS, GIVE THEM A
CHARGE.
FIRST THING WE WANT TO DO IS
HAVE THEM REVIEW PROGRESS ON THE
2015 ACTION PLAN, AND I THINK
THE WAY WE'VE DECIDED TO DO THIS
IS, YOU KNOW, WITH HELP FROM NIH
STAFF AND SOME PEOPLE THAT WE'LL
REACH OUT TO, WILL DRAFT KIND OF
ONE OR TWO SENTENCES SUMMARIZING
PROGRESS ON EACH OF THE 81
OBJECTIVES.
THIS IS NOT A REVIEW ARTICLE,
WE'RE NOT PUTTING REFERENCES
INTO IT, WE'RE NOT TRYING TO
DOCUMENT ALL THE PROCESS IN THE
MUSCULAR DYSTROPHIES FOR THE
PAST 10 YEARS.
WE'RE JUST TRYING TO SUMMARIZE
KIND OF BRIEFLY HOW HAVE THINGS
GONE FOR THIS OBJECTIVE.
AND THEN WE'LL ASK THE WORKING
GROUPS TO KIND OF REVIEW THAT
DRAFT DOCUMENT AND ADD
ADDITIONAL DETAIL IF THEY FEEL
NECESSARY.
WE FIGURE THAT WILL KIND OF
PRIME THEM INTO THINKING ABOUT,
WELL, OKAY, THAT'S WHERE WE ARE
NOW, WHERE SHOULD WE BE GOING,
AND THEN WE REALLY WANT EACH
WORKING GROUP TO DISCUSS AND
DEVELOP CONSENSUS ABOUT THREE TO
FOUR BROAD PRIORITIES.
AND IN PARTICULAR, THEY'RE NOT
SAYING THIS IS ALL WE NEED TO
WORK ON.
THEY WANT TO SAY THESE ARE BROAD
AREAS THAT RISE TO THE TOP, THAT
WE FEEL VERY STRONGLY, YOU KNOW,
SHOULD BE EMPHASIZED.
SO THE 2015 ACTION PLAN
OBJECTIVES ARE STILL VERY
IMPORTANT.
YOU KNOW, WE'LL POINT OUT THAT
MANY OF THEM ARE CERTAINLY NOT
COMPLETED YET.
THEY'RE AT A MUCH KIND OF HIGHER
RESOLUTION THAN WHAT WE'RE
THINKING THESE BROAD PRIORITY
WILL BE, AND SO THE RENEWED
ACTION PLAN WILL SAY CONTINUE TO
LOOK AT THE OBJECTIVES IN THE
2015 ACTION PLAN, THERE'S STILL
A LOT TO BE DONE THERE.
BUT WE RILEY WANTED OUR WORKING
GROUPS TO RECOMMEND THESE, YOU
KNOW, BROADER AND HIGHER LEVEL
PRIORITIES.
JUST A COUPLE OF EXAMPLES, IT'S
REALLY GOING TO BE UP TO THE
WORKING GROUPS TO DECIDE WHAT
THEY WANT TO PRIORITIZE, BUT I
CAN IMAGINE, FOR EXAMPLE, THE
PRE-CLINICAL WORKING GROUP MAY
WANT TO PRIORITIZE DEVELOPMENT
OF GENE-BASED THERAPIES.
AND THAT CAN INCLUDE AAV GENE
DELIVERY, ANTISENSE
OLIGONUCLEOTIDE, GENOME EDITING,
THINGS WE HEARD FROM CARSTEN
THIS MORNING ABOUT IMMUNOLOGIC
OBSTACLES TO GENE-BASED
THERAPIES.
AN EXAMPLE IN THE CLINICAL
STUDIES AREA IS PERHAPS
FACILITATE THE DESIGN OF PATIENT
FOCUSED CLINICAL TRIALS.
SO HAVING VALIDATED OUTCOME
MEASURES THAT ARE IMPORTANT TO
PATIENTS, APPROPRIATE DIVERSITY
OF THE TRIAL PARTICIPANTS,
STRATEGIES SUCH AS REMOTE DATA
COLLECTION, OR DIGITAL HEALTH
END POINT TO REDUCE THE BURDEN
OF TRIAL PARTICIPATION, SO
AGAIN, IT'S UP TO THEM TO
DECIDE, YOU KNOW, WHAT THEY
THINK THE PRIORITIES ARE, AND
JUST GIVING THESE AS EXAMPLES OF
WHAT WE'RE ENVISIONING AS KIND
OF THE BREADTH OF THE OBJECTIVES
THAT THEY MAY WANT TO INCLUDE.
SO THIS IS THE TIMELINE OF HOW
WE'RE DOING FOR THE ACTION PLAN,
SO, YOU KNOW, PRESENTED THE
PLANS AT THE LAST MDCC MEETING.
WE'VE NOW GOT OUR STEERING
GROUP, WE'RE WORKING ON
ASSEMBLING OUR WORKING GROUPS,
WE'RE GOING TO CHARGE THEM AND
START SCHEDULING MEETINGS.
WE'RE ANTICIPATING ABOUT THREE
MEETINGS WITH THE INDIVIDUAL
WORKING GROUPS.
MOSTLY ONLINE IF WE FEEL THAT
THERE'S A NEED TO KIND OF MEET
TOGETHER IN PERSON TO DEVELOP
CONSENSUS, WE CAN CERTAINLY DO
THAT.
ON AN INDEPENDENT TRACK TO THE
WORKING GROUPS, WE'D LIKE TO
HAVE A MEETING WITH INDUSTRY
RESEARCHERS, YOU KNOW, MDCC IS A
FACA COMMITTEE SO WE HAVE TO BE
VERY CAREFUL ABOUT THE
APPEARANCES OF ANY INDUSTRY
GROUP INFLUENCING, YOU KNOW, OUR
DECISION-MAKING, SO WE WOULD
HAVE A TRANSPARENT MEETING WITH
ANY INDUSTRY PEOPLE THAT WANT TO
PARTICIPATE AND GET THEIR VIEWS
BECAUSE IT'S CERTAINLY REALLY
IMPORTANT FOR ADVANCING THE
FIELD.
AND THEN PROBABLY FOR THE FALL
MEETING IN 2024, FALL MDCC
MEETING, WE'LL HAVE THE WORKING
GROUP CO-CHAIRS, YOU KNOW, COME
AND TALK ABOUT THE PRIORITIES
THAT WE'VE DEVELOPED, WE'LL PUT
IT OUT FOR PUBLIC COMMENT, FINAL
EDIT, AND THEN ANTICIPATE THE
MDCC CONSIDERING IT FOR A VOTE
IN SPRING MEETING OF 2025.
AND THEN WE CAN GO TO IC
ADVISORY COMMITTEE MEETINGS,
ADVISORY COUNCIL MEETINGS, AND
PROVIDE UPDATE IF THAT'S
DESIRED.
FOR THE LAST TIME IN 2015, WE
ALSO PUBLISHED A JOURNAL ARTICLE
JUST KIND OF DESCRIBING THE MDCC
AND THE ACTION PLAN, WE CAN
CONSIDER DOING THAT AGAIN THIS
TIME.
SO THAT'S KIND OF WHERE WE ARE
NOW, AND HAPPY TO TAKE ANY
QUESTIONS.
>>
>> DOES THE MATH ADD UP?
OKAY.
>> I HAD ONLY ONE QUESTION.
IN TERMS OF THE PROGRESS ON
PREVIOUS 81 OBJECTIVES, SO IF
YOU WANTED TO KEEP IT SHORT,
RIGHT, SO YOU COU TSH THEY COULD
FOCUS MORE ON THE FUTURE, I'M
GUESSING, AND I THINK THAT'S A
GOOD IDEA.
BUT I DO THINK -- I WAS THINKING
THAT SINCE IT'S GOING TO BE SO
SHORT, TO HAVE REFERENCES IS
PROBABLY WORTH IT.
YOU'RE NOT GOING TO GIVE AN
EXHAUSTIVE VIEW, BUT IF IT'S
ONLY A COUPLE OF SENTENCES, THEN
I WOULD THINK THAT IT WOULD BE
VALUABLE TO HAVE A LIST OF
REFERENCES FOR EACH ONE SO THAT
PEOPLE KNOW, YOU KNOW, WHAT'S IN
THERE.
>> OKAY.
SO YOU KNOW, I THINK THAT SOME
OF THE OBJECTIVES WOULD HAVE
HUNDREDS AND HUNDREDS OF
REFERENCES.
, YOU KNOW, OF THE
WORK THAT'S BEEN DONE OVER THE
PAST 10 YEARS.
IT MAY BE KIND OF CHALLENGING.
WE CAN, YOU KNOW, DATA-MINE THAT
FROM WHEN NIH HAS FUNDED, BUT
THERE ARE OTHER FUNDING
ORGANIZATIONS.
YOU KNOW, THAT WOULD
EXPONENTIALLY, I THINK, INCREASE
THE WORKLOAD FOR THIS.
>> IF YOU TRY AND BE
COMPREHENSIVE, -- THERE MUST BE
SOME MEAT TO IT.
>> THE REFERENCES, A REVIEW
ARTICLE OF THE -- FOR THE LAST
10 YEARS.
OKAY.
THANKS, MAYBE WE'LL CHAT ABOUT
THAT MORE AT THE STEERING
COMMITTEE.
>> DR. CRISWELL?
>> THANKS VERY MUCH FOR THAT
SUMMARY.
I'M SO PLEASED TO HEAR HOW MUCH
PROGRESS HAS BEEN MADE ALREADY.
AND I'M GRATEFUL TO THOSE WHO
HAVE AGREED TO BE CO-CHAIRS AND
ALL THE WORKING GROUP MEMBERS.
THIS IS REALLY IMPORTANT.
I ALSO APPRECIATE AND I THINK
IT'S HIGHLY APPROPRIATE TO
UNDERSTAND THE T THE STRATEGIC S
FOR THE ADVOCACY AND THINK ABOUT
HARMONIZING, ALIGNING WITH THEM
SO THAT THERE'S SOME SORT OF AT
SOME LEVEL CONSENSUS STATEMENT
FROM THIS BROADER RESEARCH
COMMUNITY, SO I'M REALLY LOOKING
FORWARD TO SEE HOW THIS EVOLVES.
THANKS, GLEN, AND EVERYBODY ELSE
WHO'S BEEN THINKING ABOUT THIS
ALREADY.
>> WONDERFUL.
WE'RE WAITING FOR MI MORE
QUESTIONS OR COMMENTS ON THE
PROPOSED PLAN GOING FORWARD.
ALL RIGHT.
WELL, I CAN'T BELIEVE IT, BUT WE
ARE JUST ABOUT ON TIME.
I REALLY WANT TO THANK ALL OF
OUR PRESENTERS TODAY.
I WANT TO THANK THE CONTRACTORS
WHO HAVE REALLY HELPED IN TERM
OF RUNNING A VERY SMOOTH HYBRID
MEETING.
I WANT TO THANK GLEN NUCKOLLS
AND HIS STAFF FOR THEIR ENORMOUS
PREPARATION FOR THIS MEETING.
I MEAN, WE'VE PACKED IN A LOT OF
INFORMATION.
SOME OF THE KEYWORDS THAT I HAVE
WRITTEN DOWN AS WE'VE GONE
THROUGH THE MEETING TODAY, WE
TALKED A LOT ABOUT CLINICAL
TRIALS AND INCLUSIVITY AND
SPECIFICALLY RESTRICTIONS ON WHO
CANNOT PARTICIPATE IN CLINICAL
TRIALS, SO HOPEFULLY THAT'S
SOMETHING THAT WILL BE ADDRESSED
GOING FORWARD.
WHETHER IT IS RESTRICTION BY AGE
OR RESTRICTION BY MOBILITY, I
THINK THAT'S REALLY IMPORTANT.
WE TALKED ABOUT CLINICAL END
POINTS, AND HOW IMPORTANT IT IS
TO DEVELOP RELIABLE AND VALID
END POINTS.
WE ALSO TALKED ABOUT THE LONG
TERM IMPACT OF THERAPY, WHICH --
WE'RE ALL PIONEERS IN THE SPACE,
AND THERE'S GOING TO BE A
KNOWLEDGE GAP ABOUT THE
LONG-TERM EFFECTS OF THERAPY.
WE TALKED ABOUT DATA SHARING,
WHICH IS CLEARLY IMPORTANT
ACROSS NIH.
WE TALKED ABOUT REGULATORY
REVIEW, AND VERY IMPORTANTLY, WE
TALKED ABOUT PATIENT-CENTERED
RESEARCH AS EXEMPLIFIED BY THE
LIVED EXPERIENCE OF JEN AND HER
SON.
I HOPE THAT WE'LL HEAR MORE OF
THOSE KINDS OF EXPERIENCES.
MY ONLY REGRET WAS WE DIDN'T
HAVE ENOUGH TIME TO REALLY ASK
MORE QUESTIONS ABOUT THE WHOLE
EXPERIENCE.
AND IT WILL BE WONDERFUL TO HEAR
ABOUT THE EXPERIENCE IN SOMEONE
WHO PERHAPS IS LESS MEDICALLY
SAVVY, JUST TO HEAR HOW THAT
EXPERIENCE GOES.
SO I REALLY WANT TO THANK,
AGAIN, ALL THE PRESENTERS.
I THINK IT'S BEEN AN INCREDIBLE
MEETING.
IT'S, AGAIN, MY PRIVILEGE TO
CHAIR THIS COMMITTEE FOR THE
LAST FOUR YEARS.
I'M HANDING OVER THE ACTION PLAN
TO DR. CRISWELL TO CHAIR, AND I
KNOW SHE'S GOING TO DO A
FANTASTIC JOB.
AND I SPEAK FOR MYSELF AND
DR. KOROSHETZ THAT WE ARE
AVAILABLE TO HELP YOU ALONG THE
WAY, AND IT'S JUST -- YOU KNOW,
FOR THOSE OF US WHO STARTED IN
GENETICS, FOR EXAMPLE, WHEN IT
WAS ALL ABOUT DIAGNOSIS.
I MEAN, IT'S JUST AN INCREDIBLE
PRIVILEGE TO BE ABLE TO SEE THE
PROGRESS AND THE CHALLENGES WITH
REGARD TO THERAPY.
BUT WE DO HAVE THERAPY, SO
THAT'S REALLY, REALLY EXCITING.
SO WITH THAT, I'M GOING TO HAND
IT OVER BACK TO GLEN, IF HE
WANTS TO HAVE ANY FURTHER
REMARKS AND THEN WE WILL LET
EVERYBODY GO AND I WANT TO WISH
EVERYONE A VERY HAPPY HOLIDAY,
HOLIDAYS, WHATEVER YOU'RE
CELEBRATING, AND A VERY HEALTHY
NEW YEAR FOR ALL.
SO GLEN, OVER TO YOU.
>> THANKS, DR. BIANCHI, AND
THANKS FOR CHAIRING THIS AND
PREVIOUS MEETINGS.
SO WE HAVE NOT YET SELECTED THE
DATE FOR OUR NEXT MEETING, WHICH
WILL BE SOMEWHERE PROBABLY
APRIL, MAY-ISH 2024, BUT WE'RE
WORKING ON A DATE FOR THAT.
IF ANYBODY HAS SUGGESTIONS FOR
TOPICS THAT YOU THINK WE SHOULD
COVER, THEN PLEASE SEND THE
IDEAS TO ME.
AND WITHOUT FURTHER ISSUES, YOU
KNOW, THANKS, EVERYBODY.
THANKS FOR PARTICIPATING IN OUR
MEETING.
>> THANK YOU.
HAVE A GOOD HOLIDAYS.