>>WELCOME TO NIH ALS WORKSHOP
HAS HELPED UNDERSTAND THE
BIOLOGY AS WELL. AS YOU CAN
SEE HERE THERE'S OTHER
INSTITUTIONS THAT FUND ALS.
THERE'S $40 MILLION AS WELL
THAT IS CONGRESSIONALLY
MANDATED. NEXT SLIDE PLEASE.
A NEW DEVELOPMENT WAS THE NIH
COMMON FUND. AND THEN WE SET
UP AN ACCELERATED SCIENCE
PROGRAM WITH ALS. AND IT'S
REALLY KIND OF OUT OF THE BOX
PROJECTS AT VICKSBURG THERE'S
TISSUE THAT I SHOULD SAY IS
THAT HAVE ALLOWED THIS TYPE OF
ANALYSIS TO BE DONE ON CELLS
WHICH COULD REALLY MAKE THE
PROBLEMS WORSE AND EXPAND THE
MOTOR NEURONS. AND SEVER THE
COURT WHICH ARE MORE EFFECTIVE
IN THIS OFTEN OPENS UP THE
POSSIBILITY OF HAVE TO
INTERVENE IN THIS TYPE OF
MANNER IN ALS IN THE FUTURE.
THERE'S ALSO THE FUTURE
LOOKING AT MACRO CROWDING AND
ALS. THIS IS IDENTIFIED AS
SOMETHING IS COMMON IN BOTH
THE GENETIC FORM OF ALS.
THOSE FINDINGS EXPAND TO THE
NONGENETIC FORM ARE REALLY
BEING HEAVILY THERE'S
HOMEOSTASIS IN THE CELLS. AND
THEY CAN TRY TO THIS PATHWAY.
AND FINALLY UNIVERSITY OF
MICHIGAN WAS DISCUSSING THIS
LOOKING AT ENVIRONMENTAL
EXPOSURES WITH ALS DISEASE
RISK. AS WE MENTIONED THEY
WERE LEARNING A LOT ABOUT THE
GENETIC FORMS BUT WHAT IS
DRIVING ALS FOR PEOPLE WHO DO
NOT HAVE THIS HAS ALWAYS BEEN
A MAJOR, MAJOR GAP IN
KNOWLEDGE AND WE ARE HOPING TO
EXPLORE THIS GAP. THERE'S
DARK MATTER OF ENVIRONMENTAL
EXPOSURE THAT LEADS TO THESE
CONDITIONS. NEXT SLIDE
PLEASE. WE HAVE THE CREATE
SOURCE AND WHICH IS WHICH IS
LOOKING AT ALS AND KIND OF A
NATURAL HISTORY STUDY TRYING
TO LOOK AT THE DIFFERENCE
PHENOTYPES AND LOOKING AT
BETTER CLINICAL OUTCOMES,
SUBTYPING WITH DIFFERENT FORMS
OF ALS AND LOOKING AT
DEVELOPING BIOMARKERS.
THERE'S NOW A FILAMENT LIGHT
THAT SHOWS THE POTENTIAL
BIOMARKER LINKED TO THE
DISEASE. AND FOR THE VALUE OF
THE THINGS PAN OUT THOSE
THINGS THAT REDUCE THE
FILAMENT LIGHT LEVELS ARE
POTENTIALLY USEFUL IN LIMITING
THE PROGRESSION OF THE
DISEASE. THIS IS SOMETHING
THAT HAS TO BE PROVEN FOR SURE
BUT IT IS VERY HELPFUL
DEVELOPMENT. OF COURSE THE
CREATIVE NETWORK IS PART OF
THE RARE DISEASE NETWORK HERE
AT AND IH. NEXT SLIDE. THE
CREATE CONSORTIUM WAS ALSO
LOOKING AT DIVERSE POPULATION
AND THEN GOING INTO SOUTH
AFRICA. SOMETIMES CONDITIONS
YOU CAN KIND OF HAVE AN
EPIPHANY BY SETTING A
PARTICULAR POPULATION WHERE IF
YOU CAN IDENTIFY A PARTICULAR
CORE OF ALS AND AN
ENVIRONMENTAL CORE FOR
INSTANCE IN SOUTH AFRICA.
THIS COULD THEN BE TESTED IN
THE UNITED STATES. OR
ACTUALLY NEW GENETICS
UNDERPINNING FROM ALS AS IT IS
WITH THE DIVERSE POPULATION
LIKE THIS WILL BE POTENTIALLY
HELPFUL. NEXT SLIDE. GETTING
BACK TO WHAT WE HAD BEEN
SAYING THE LAST COUPLE OF
MINUTES IS THAT TEN-15% OF ALS
IS FAMILIAL AND THERE'S 13 OR
EXCUSE ME 30 MUTANT GENES HAVE
IDENTIFIED SO FAR. THE
FINDING OF A GENETIC MUTATION
REALLY OPENS UP THE DOOR TO
GET INTO THE DETAILS OF THE
BIOLOGY OF THE DISEASE. THERE
YOU CAN STUDY FOR THE
BEGINNING OF THE STAGES TO SEE
WHAT THAT DOES TO MOTOR NEURON
CELLS AND THERE YOU CAN LOOK
AT CELLS THAT HAVE BEEN TURNED
INTO MOTOR NEURONS FROM SKIN
CELLS TAKEN FROM PEOPLE AND
THE GENETICS REALLY OPENED THE
DOOR TO USE THE TOOLS OF
SCIENCE TO UNDERSTAND THE
DISEASE. IT ALSO LEADS TO
THERAPIES AND THAT IS WHERE
SOME OF THE BIGGEST
BREAKTHROUGHS MAKE FOR
EFFECTIVE THERAPIES AND MAY BE
COMING IN THE NEAR FUTURE.
BUT AGAIN, THE MAJORITY
TEN-20% ARE FAMILIAL WHICH
LEADS 85% WHICH ARE NOT. AND
THAT WOULD CAUSE A SPORADIC,
NON- FAMILIAR, SO TRYING TO
UNDERSTAND WHAT ARE THE
NONGENETIC FACTORS THAT CAUSE
ALS AND CONTINUE ITS
PROGRESSION, AS I MENTIONED,
THE REAL CHALLENGE LOOKING
FORWARD. THIS IS SIMPLY NO
PROBLEM WITH ALS IS A PROBLEM
WITH MOST NEUROLOGICAL
DISEASES. WE HAVE RECENTLY
STARTED A NEW OFFICE FOR THIS
TOXICOLOGY STUDY AND THE GOAL
IS TO ADVANCE THE
UNDERSTANDING OF THE NON-
INHERITED FACTORS COLLECTIVELY
CALLED THE NEURAL DISPOSABLE.
THAT COULD BE FACTORS IN THE
ENVIRONMENT LIKE TOXICS AND AN
INTERPLAY BETWEEN SOMETHING IN
THE ENVIRONMENT IN A
PARTICULAR GENE THAT PEOPLE
HAVE. OR THERE COULD BE
BEHAVIORAL FACTORS AS WELL
THAT CONTRIBUTE TO THIS MIX OF
GENE ENVIRONMENT INTERACTIONS.
NEXT SLIDE PLEASE. THERE ARE
A NUMBER OF GENE -BASED
THERAPIES COMING, WHEN
MENTIONED. THE GENETIC WAYS
TO WHICH OF THESE THAT CAUSE
TROUBLE CAN BE BLOCKED. THERE
IS THE ANSWER I SENT NUCLEAR
TIDE ARE SUPER OXIDE THIS ALS.
THERE'S ANTIRACIST ANTISENSE
NUCLEAR TIDE FOR THE SC NINE
OH RF 72 LATE, WHICH IS THE
MOST COMMON GENETIC FORM. AND
THEN THERE IS THE ANTI- CENSUS
WELL FOR THE OTHER LINK OF ALS
WHICH IS LESS COMMON GENETIC
FORM AND ANOTHER MICRO RNA FOR
THE SOD ONE LINKED ALS FROM
THIS COMPANY. SO THE AAS
THOSE ARE WALKING OR THE IDEA
IS TO BLOCK THE BAD EFFECTS OF
THESE MUTATED GENES. AS YOU
CAN SEE HERE ONE OF THE
BIGGEST PUSHES IN THE ALS
TREATMENT IS THE HOPE OF THESE
WOULD HAVE HIGH EFFECT SIZES.
ALTHOUGH THERE ARE STILL LOTS
OF QUESTIONS ABOUT HOW THESE
WORK AND HOW YOU GET INTO THE
CELLS THAT YOU NEED TO GET
THEM INTO AND HOW OFTEN DO YOU
HAVE TO TREAT? OR THE
POTENTIAL TOXICITIES OF THESE
TYPES OF THERAPIES. IN
PARTICULAR, THE NERVOUS
SYSTEM. THERE'S A LOT TO
LEARN BUT THIS IS THE KIND OF
THING THAT WE FIGURE OUT THE
ISSUES IT SHOULD REALLY WORK
FOR THESE CONDITIONS. OR AT
LEAST THAT'S WHAT WE THINK.
NEXT SLIDE. WE HAVE FOR THE
FORMS OF ALS AND OTHER REALLY
WHERE GENETIC DISORDERS, AS I
MENTIONED, THERE'S 30 GENES
FOR ALS. WE TALKED ABOUT ASO
TREATMENTS FOR THREE OF THOSE
30. THE OTHERS, MANY OF WHICH
ARE EXTREMELY RARE. SO, WE DO
NOT CURRENTLY HAVE COMPANIES
GOING AFTER THE TREATMENTS.
WE HAD THIS NETWORK WHICH IS
BEING SET UP NOW FOR WHAT WE
CALL ULTRA RARE GENETIC
DISORDERS, SUCH AS SOME OF
THESE RARE FORMS OF ALS. THEY
DEVELOP NOT JUST ASO BUT GENE
DEVELOPING TREATMENTS FOR
THESE TYPES OF DISORDERS.
THIS IS NOW OPEN AND WERE
HOPING TO GET APPLICATIONS TO
TRY SOME OF THESE THERE
APPEARS WITH SOME OF THE ULTRA
RARE FORMS OF ALS. NEXT
SLIDE. THIS ONE IS AGAIN
SOMETHING THAT WE THINK IS
IMPORTANT TO HELP PEOPLE WITH
ALS. IF WE REALLY CANNOT
PREVENT THE PROGRESSION AND
ONE OF THE BIGGEST PROBLEMS IS
COMMUNICATIONS AS TIME GOES
ON. SO, WHEN THE BRAIN
INITIATIVE AND STUDIES ARE
GOING ON WHERE GRIDS OF
ELECTRODES ARE PLACED OVER THE
PART OF THE BRAIN THAT IS PART
OF PRODUCING SPEECH. IT TURNS
OUT IF ONE IS PARALYZED AND
CANNOT MOVE THE MUSCLES ONE
CAN STILL TRY TO SPEAK AND
ACTIVATE THIS PART OF THE
BRAIN. IN THIS STUDY THEY
WERE ABLE TO USE THE
ELECTRICAL ACTIVITY THAT COMES
OUT OF THE BRAIN WHEN SOMEONE
SPEAKS TO CREATE LANGUAGE ON A
COMPUTER. SO, IT IS BASICALLY
BYPASSING THE NERVES FROM THE
BRAINS TO THE MUSCLES AND
GOING STRAIGHT FROM THE BRAIN
TO THE COMPUTER TO GENERATE
SPEECH WE WOULD REALLY LIKE TO
STOP THE DISEASE FROM EVER
GETTING TO THIS PLACE BUT I
THINK THAT WE ALWAYS HAVE TO
THINK ABOUT INVESTING AND NOT
JUST THE FUTURE TREATMENTS BUT
ALSO HOW TO BEST HELP PEOPLE
WHO HAVE THIS DISEASE NOW
BEFORE THESE TREATMENTS BECOME
EFFECTIVE. NEXT SLIDE PLEASE
AS YOU PROBABLY KNOW,
PRESIDENT BIDEN ON
DECEMBER 201st, SIGNED THE
ACCELERATED AXIS FOR CRITICAL
THERAPIES ACT. AND IH IS
GEARED UP TO FIND AND EXPAND
ACCESS AND STUDY WITH A DRUG
THAT IS CURRENTLY IN TRIALS ON
THE HEEL OF THE ALS PLATFORM.
THIS WILL ALLOW FOR PEOPLE WHO
DO NOT QUALIFY FOR THE
CLINICAL TRIALS OR OUT OF THE
CLINICAL TRIALS TO BE TREATED
WITH THIS DRUG. ACTIVE ALS
ALSO CALLED FOR A
PUBLIC-PRIVATE PARTNERSHIP
BETWEEN THE FDA AND THE NIH
AND WE HAVE BEEN WORKING THERE
AND WERE VERY EXCITED ABOUT
THIS NEW PARTNERSHIP. IT WILL
BE ORCHESTRATED THROUGH THE
CLINICAL PATH FOR RARE
NEURODEGENERATIVE DISEASES AND
THIS IS THE CRITICAL PATH
INSTITUTE THAT THE FDA HAS
BEEN WORKING FOR A NUMBER OF
DECADES NOW. THEY CAN BE ABLE
TO BRING THE FDA AND NIH
PATIENT COMMITTEES AND
ADVOCACY OVER THIS
PHARMACEUTICAL COMPANY IN THE
BIO TEXT ALTOGETHER WORKED OUT
HOW TO MAKE THE PROCESS OF
THERAPY DEVELOPMENT AND
APPROVAL OF EFFECTIVE
THERAPIES MORE STREAMLINED.
THIS CAN BRING ALL THE DATA
TOGETHER FROM ALL OF THE
DIFFERENT SOURCES FROM WHERE
WE START AND THEN ANALYZE THAT
DATA AND THEN WE CAN TO MOVE
THINGS FORWARD IN THE FUTURE
BASED ON WHAT HAS BEEN DONE IN
THE PAST. I THINK THAT MIGHT
BE ONE OF OUR FIRST ATTEMPTS
HERE. IT IS ALWAYS FOCUSED ON
PATIENT AND DRUG DEVELOPMENT
TO HELP PATIENTS. THE FDA
ALSO SUPPORTS WORKING WITH
THEM ON THE RARE GENETIC
DISEASE PROGRAM. THEY HAVE
FUNDED AND JUST LAUNCHED A
NATURAL HISTORY STUDY IN ALS.
THEY ALSO ARE STUDYING OTHER
TOOLS IN ALS WITH THIS
PARTNERSHIP. COMING UP AFTER
THE STRATEGIC PLAN THERE WILL
BE A NATIONAL ACADEMY OF
SCIENCES STUDY AND RESEARCH
CARE AND SERVICES FOR ALS.
THIS WAS COMMISSIONED BY NIH.
THIS GROUP WILL THEN
IDENTIFYING KEY ACTIONS FOR
THE PUBLIC, PRIVATE, AND
NONPUBLIC SECTORS. THIS WILL
BUILD UPON THE RESEARCH
PRIORITIES YOU HEAR ABOUT
TODAY. AND THAT INCLUDE
RECOMMENDATIONS FOR CARE AND
SERVICES AS WELL AS THE PLAN
THAT YOU HEAR TODAY WHICH IS
FOCUSED ENTIRELY ON RESEARCH
DEVELOPMENT THERAPY PROGRAMS.
THEY WILL HAVE A COMMITTEE,
SOMETIMES UP TO 15 EXPERTS.
AND THEN THE SCIENCE OF ALS
AND DEVELOPMENT REGULATION BUT
WILL ALSO INCLUDE PEOPLE WHO
HAVE LIVED WITH ALS, PEOPLE
WHO CARE FOR PEOPLE WITH ALS
AND PEOPLE WITH GENETIC RISKS
WITH THE DISEASE. IT WILL
WORK ON DELIVERY SUPPORT AND
ACCESS AND ARE LOOKING FOR
NOMINATION OF PEOPLE FOR THIS
GROUP AN ILLNESS OR IF YOU
KNOW SOMEBODY WHO'D BE
INTERESTED, PLEASE SUBMIT
NOMINATIONS BY NOVEMBER 4th
ON THIS WEBSITE LISTED. WE
WILL TRY TO PUT THIS IN THE
CHAT SO IT WILL BE AVAILABLE
THROUGHOUT THE MEETING TODAY.
NEXT SLIDE. SO, NOW WERE
GOING TO HEAR FROM THE
STRATEGIC PLAN AND THIS BEGAN
AS A PUBLIC REQUEST
INFORMATION AND RECEIVED OVER
100 RESPONSES AND LOOKED AT
THE FORMS AND THE DRAFT
PRIORITIES HAVE BEEN MET ON
SEVERAL OCCASIONS AND
INDIVIDUALLY AND ONE GROUP AT
A TIME. AND THEY ALSO MET
WITH ALL OF THE DIFFERENT
GROUPS AND TRADED THEIR
THOUGHTS BACK AND FORTH. WERE
GOING TO HEAR IF THE SCIENCE
PEOPLE IN THE TRANSLATIONAL
SCIENCE AND MOVING THE
DISCOVERIES TO THERAPIES IN
THE CLINICAL GROUP AND THE
QUALITY OF LIFE GROUP AND THEN
A SPECIAL GROUP FOCUSING ON
HOW TO BE FORGED MORE
EFFECTIVE PARTNERSHIPS AND
COLLABORATIONS IN THE FUTURE?
WE ASKED FOR THEM WE ASKED
THEM TO BE CRITICAL AND MAKE
COMPREHENSIVE LIFTS FOR
STRAIGHT TO THE TOP THEIR TOP
THREE PRIORITIES IT'S REALLY
IMPORTANT CERTAINLY FOR ANY
AGENCY SUCH AS US TO HAVE A
SENSE OF WHAT RISES TO THE
TOP? THOSE ARE KIND OF THE
THINGS THAT YOU WOULD GO AFTER
FIRST. NOW HERE AT THE PUBLIC
WORKSHOP AND THEN AFTER THIS
THERE WILL BE A PUBLIC
COMMENT. THAT WILL BE OPEN
FOR ABOUT ONE MONTH. SO, THE
COMMENTS THAT COME IN WILL BE
USED BY THE GROUP TO REVISE
PRIORITIES AND THEN BRING A
FINAL VERSION TO THE ADVISORY
COUNCIL AND THE FIRST WEEK OF
FEBRUARY 2023. NEXT SLIDE. I
WOULD LIKE TO THINK ANYONE WHO
HAS WORKED ON THIS. AS I
MENTIONED THERE'S A LOT OF
PEOPLE ON THIS LIST AND SOME
PEOPLE HAVE ALS AND SOME
PEOPLE CARE WITH PEOPLE WITH
ALS AND SOME PEOPLE HAVE SPENT
DECADES TRYING TO DEVELOP A
BETTER TREATMENT FOR THIS
DISEASE. WE'VE BEEN INVOLVED
IN MANY DIFFERENT DISEASE
RELATED COMMUNITIES. THE ALS
DISEASE RESEARCH COMMITTEE IS
REALLY A SPECIAL GROUP AND
THEN DEDICATION WHICH IS
MOTIVATED BY THE URGENCY OF
THE DISEASE AND THE PEOPLE
THEY KNOW THAT HAVE THE
DISEASE AND TRY TO TAKE CARE
OF. IT'S REALLY UNMATCHED.
SO THANK YOU VERY MUCH FOR
EVERYONE'S HELP FROM THIS
EXPERIENCE TO GROUP IN PUTTING
TOGETHER THIS STRATEGIC PLAN.
NEXT SLIDE. AS THE PLAN COMES
IN THE NIH WILL REVIEW THE
PORTFOLIO THAT WE HAVE LOOKING
FOR PRIORITIES AND THAT WE
HAVE A NUMBER OF LEVERS THAT
WE CAN PULL. WE CAN PUSH
PEOPLE TO LOOK AT TOPICS THAT
HAVE COME OUT OF THIS. I
SUSPECT THERE WILL BE A LOT OF
INTEREST IN MOVING THE SEARCH
FROM THE COMMUNITY AND THESE
TOPICS. WE HAVE THE ABILITY
TO USE SPECIAL PROGRAM
PRIORITY FUNDING TO MOVE SOME
OF THESE THINGS FORWARD. WE
CAN MODIFY CURRENT PROGRAMS
AND DEVELOP NEW FUNDING
OPPORTUNITIES AND WE CAN HOLD
WORKSHOPS AND WORK WITH THE
PUBLIC BY PARTNERSHIP TO MOVE
THINGS FORWARD. WE WANT TO
START BY MENTIONING THAT
PEOPLE WHO HAVE GOOD IDEAS FOR
ALS RESEARCH YOU DON'T HAVE TO
WAIT. AND I DS IS OPEN TO
APPLICATIONS INTO THREE TIMES
A YEAR THEY COME IN SO IF
YOU'RE INTERESTED CONTACT THE
PROGRAM OFFICIALS TO HELP YOU
FIND THE RIGHT PROGRAM THROUGH
THE GRANT APPLICATION. WITH
THAT, I WOULD LIKE TO AGAIN
SAY THANKS EVERYBODY FOR
LISTENING. THANK YOU TO THE
FOLKS WHO WORK SO HARD ON THIS
AND TURN IT BACK TO ROBERT
BROWN'S AUNT RITA SET THE
CHAIRS OF THE ORTHOPEDIC
GROUP.
>>: THANK YOU VERY MUCH
WALTER I'M A NEUROLOGIST AT
THE UNIVERSITY OF
MASSACHUSETTS WITH
LONG-STANDING EXPERIENCE
THINKING ABOUT ASPECTS OF ALS,
CAUSE, AND THERAPY. I MUST
SAY IT'S A GREAT PRIVILEGE TO
BE IN ALS PHYSICIAN AND IT'S A
GREAT PRIVILEGE TO BE PART OF
THIS CAUSE TODAY. IT IS
INCREDIBLY EXCITING TIME FOR
THOSE OF US IN ALS RESEARCH.
THERE ARE MORE TO USE WALTER'S
TERM, APART FROM THE TOOLSET
IN SCIENCE ON THE TABLE NO USE
FOR THINKING AND IT'S
INCREDIBLY EXCITING TO BE PART
OF THIS PROCESS WITH THE NIH
TRYING TO ESTABLISH THE MOST
IMPORTANT PRIORITY FOR ALS
INVESTIGATIONS AND RESEARCH,
NEXT SLIDE PLEASE. I'M GONNA
TAKE THE LIBERTY OF GOING
THROUGH VERY BRIEFLY THE NEXT
FEW MINUTES OF THE COMMON
ELEMENTS THAT MOTIVATED OUR
THINKING OF THESE ELEMENTS IN
OUR OVERALL PROGRAM. I WANT
TO BEGIN A WORD ABOUT ALS
ITSELF. WE DO KNOW THIS IS A
DISEASE AND THE BRAIN MORE
NEURONS AND WE KNOW THAT IT
STARTS INSIDIOUSLY WITH VOCAL
PARALYSIS WHICH THEN SPREADS
WIDELY. NOW, THE IMPLICATION
OF THAT IS THAT IS
REGRETTABLY, A LONG TIME
BEFORE PEOPLE HAVE AN
ESTABLISHED DIAGNOSIS. THE
TIME. NOW IS UPWARDS OF ONE
YEAR IN THE UNITED STATES AND
IN EUROPE. THIS IS ONE OF THE
ISSUES THAT WE HAVE TO ADDRESS
TO MAKE THE DIAGNOSIS OR
RAPID. IT'S ALSO THE CASE
THAT SOME CASES ARE ASSOCIATED
WITH ATYPICAL FRONTAL TEMPORAL
DEMENTIA THAT WILL COME UP
DURING THE DAY. NEXT SLIDE
PLEASE. THE STRIKING
PATHOLOGY IN THIS DISEASE AS
WE ALL KNOW IS THE LOSS OF THE
MOTOR NEURONS AND AS MOTOR
NEURONS UNPLUG THERE IS MUSCLE
WASTING AND WEAKNESS, AS SHOWN
IN THE TOP FIGURES HERE.
YOU'VE HEARD THE DOCTOR
MENTIONED THE KEY ELEMENTS OF
VIRTUALLY ALL KEYS OF ALS IS A
DYSFUNCTION OF ALL PROTEINS
AND VARIOUS TYPES WHICH ARE
MIS- LOCALIZED TO WREAK HAVOC.
AS WELL AS A POINT THAT WERE
BEGINNING TO UNDERSTAND THAT
THESE CELLS THAT ARE ACTIVATED
IN THIS DISEASE AND IN A SENSE
AS IT GOES IT TAKES A VILLAGE
TO KILL A MOTOR NEURON AND
DISCUSSES WHAT WE CALL MICRO-
NARRATION WHICH IS PART OF THE
PROCESS. I'M GOING TO SIMPLY
REITERATE WHAT THE DOCTOR SAID
WHICH IS THE HUGE ELEPHANT IN
THE ROOM. EVERY TIME YOU HAVE
AN ALS DISCUSSION IT IS SO
SPORADIC, NON- FAMILIAL ALS.
WHAT CAUSES IT? WE DON'T KNOW
BUT WE HAVE IDEAS. WE DO TO
THE 10% OF CASES ARE FAMILIAL
AND SO BECAUSE OF THAT IN THE
EVOLUTION OF GENETICS IT'S
IMPOSSIBLE TO IDENTIFY MANY
ALS GENES. THESE HAVE BEEN
NICELY SUMMARIZED BY MANY
PEOPLE, INCLUDING DOCTOR HARMS
IN THE FIGURE IN THE REFERENCE
ON THE RIGHT. HERE'S THE KEY
POINT. WE ARE ALREADY
LEARNING THAT SOME OF THE
GENES THAT CAUSE FAMILIAL ALS
ARE ALSO IMPLICATED IN
SPORADIC ALS. NEXT SLIDE.
BUT ARE ALSO LEARNING IS THAT
WE ARE CAREFULLY ANALYZING DUE
TO MOTOR NEURONS IN
SURROUNDING CELLS WE FIND THAT
IT'S INCREDIBLY COMPLEX. YOU
CAN SEE THIS SHOWN HERE IN
YELLOW WHICH IS PURPLE GOING
TO THE MUSCLE ON THE RIGHT.
LOOK AT IT CAREFULLY AND NO
MATTER WHAT YOU'RE LOOKING AT
IT WILL BE ABNORMAL IN ALS.
THIS IS DOWNSTREAM *
DOWNSTREAM, DEVASTATING,
PATHOLOGICAL EVENTS THAT ARE
VERY IMPORTANT IN
UNDERSTANDING THIS DISEASE AND
ON THE UPSIDE PROVIDE
POTENTIAL POTENTIAL
INTERVENTION. NEXT SLIDE. I
WANT TO EMPHASIZE TWO-POINT AS
WALTER SAID, IT'S A BIT
DISCOURAGING PERHAPS WE ARE
NOT FURTHER ALONG IN THE
PATHWAY TO THERAPY. THERE ARE
FOUR APPROVED DRUGS, UNTIL
RECENTLY ARE APPROVED. AND
THAT IS PERHAPS NOT AS GOOD AS
WE WOULD LIKE. BUT WHAT I
WOULD LIKE TO EMPHASIZE ON THE
UPSIDE IS THAT THERE IS A HUGE
PIPELINE NOW OF POTENTIAL ALS
THERAPIES INVOLVING, NOT JUST
CONVENTIONAL DRUGS, BUT ALSO
BIOLOGICAL REAGENTS,
ANTIBODIES AND AS WALTER SAID,
THE NUCLEOTIDES AND CELL
THERAPIES AS WELL. BUT MORE
IMPORTANTLY OR AS IMPORTANTLY,
THERE ARE SOME NEW MODELS FOR
HOW TO DO DRUG TRIALS. I
THINK IT WAS AN APPROPRIATE
NOTICE TO UNDERTAKE THIS
ORGANIZATION AS WERE NOT GOING
TO DO THIS OVER THE NEXT
TRANSLATE THE BASIC SENSITIVE
CLINIC. THIS REQUIRES THAT WE
ALSO HAVE A BETTER
INFRASTRUCTURE. THERE'S A LOT
OF EFFORTS IN COLLECTING BIO
SAMPLES FROM PEOPLE LIVING
WITH ALS. THEIR SPINAL FLUID,
BLOOD, THE LOT IS BIO SAMPLES
REALLY ALLOW THE RESEARCHERS
TO BETTER UNDERSTAND THE
DISEASE. THIS SHOULD BE
STRUCTURED IN A MORE ORGANIZED
WAY AND THIS IS ONE OF THE
PRIORITIES OF THIS GROUP HAS
COME UP WITH. AND FINALLY IT
WOULD BE IMPORTANT TO GET MORE
STRUCTURED SUPPORT IN ORDER TO
UTILIZE ALL OF THE INFORMATION
TO REALLY ENABLE THE TRIALS
THAT WE EVENTUALLY WANT TO GET
TO. AND AGAIN, TO FOSTER THE
COLLABORATION BETWEEN INDUSTRY
AND ACADEMIC INSTITUTIONS
WHICH REALLY MAKE THIS
TRANSLATION HAPPENED TO THEN
MOVE FORWARD TO GO INTO
CLINICAL TRIALS. THIS IS OUR
THIRD WORKING GROUP OF THE DAY
IF I COULD HAVE THE NEXT
SLIDE. THIS IS THE GROUP
TRYING TO THIS GROUP IS
CHAIRED BY TIM AND THE
PRIORITIES OF CANADA'S GROUP
THAT ARE REALLY DEFINED TO GET
A BETTER IDEA OF ALS NATIONAL
HISTORY AND THIS WAS BROUGHT
UP BY WALTER EARLIER IN HIS
INTRODUCTION. WE SEE THIS IS
A VERY IMPORTANT TOPIC OF HOW
WE CAN BETTER RUN CLINICAL
TRIALS IF WE HAVE THIS
INFORMATION THAT WE COULD
GATHER THROUGH THESE NATIONAL
HISTORY STUDIES? OF COURSE,
WE WANT TO MAKE SURE THAT WE
HAVE TREATMENTS FOR PEOPLE
LIVING WITH ALS AT ALL STAGES
ACROSS THE DISEASE SPECTRUM.
FOR THOSE THAT ARE
PRESYMPTOMATIC AND POTENTIALLY
GENETIC MUTATION CARRIERS.
FOR THOSE THAT HAD JUST
DEVELOPED THE DISEASE AND FOR
THOSE THAT ARE WAY INTO THE
DISEASE WE HAD TO FIGURE OUT
WAYS THAT WE CAN TARGET ALL OF
HIS PATIENT POPULATIONS AND
THAT WE FIND TREATMENTS THAT
ARE SPECIFICALLY SUITABLE FOR
NO MATTER WHICH STAGE OF THE
DISEASE YOU ARE AT WE WILL
HAVE A TREATMENT FOR YOU. WE
HAVE TO KEEP THAT IN MIND.
AND WITH THAT IN MIND IT IS
ALSO THIRDLY IMPORTANT THAT WE
DEFINED HOW DOES ALS MANIFEST
EARLY ON? IT IS A START
TEN-YEARS PRIOR TO DISEASE
ONSET? 20-YEARS PRIOR TO
THAT? ARE THERE WAYS FOR US
TO UNDERSTAND HOW THAT
HAPPENS? THIS IS AN IMPORTANT
PRIORITY FOR US TO BETTER
UNDERSTAND WHEN COULD
POTENTIALLY THERAPEUTIC
INTERVENTION WITH PATIENTS AT
THE EARLY SIGNS OF THE
DISEASE, EVEN THOUGH THERE'S
NO OBVIOUS SYMPTOMS YET
VISIBLE WITH PEOPLE LIVING
WITH THIS DISEASE. THESE ARE
THE MAJOR THREE TOPICS THAT
WERE GOING TO DISCUSS TODAY.
IT'S INTERESTING AND IMPORTANT
TOPIC THAT WE ALSO APPRECIATE
WAS PUT TOGETHER FROM THE
COMMITTEE MEMBERS THAT EITHER
LIVE WITH ALS OR HAVE TAKEN
CARE OF PATIENTS WITH ALS IS
THE NEXT SESSION. AND IF I
COULD HAVE THE NEXT SLIDE.
THIS IS REALLY WHAT WE CALL
THE LIVED EXPERIENCE TO PANEL.
THIS WAS SUPPORTED STRONGLY BY
THE CHEERS OF THIS PANEL,
WHICH IS LANE AND ELLEN
PHILLIPS WHO THOUGHT THIS
WOULD BE AN IMPORTANT PART OF
THIS WORKSHOP IN ORDER FOR US
TO BETTER UNDERSTAND WHY ARE
WE DOING THIS? WHY ARE WE
SITTING BEHIND OUR DESKS AND
TRYING TO UNDERSTAND HOW WE
CAN TACKLE THIS DISEASE? WE
NEED TO HEAR FROM THE PEOPLE
WHO HAVE LIVED WITH THE
DISEASE AND THE PEOPLE WHO
TAKE CARE OF THE PEOPLE THAT
HAVE THIS DISEASE. I REALLY
APPRECIATE LANE AND ELLEN IT
IS EFFORTS WITH THIS AND I
WOULD LIKE TO INTRODUCE OUR
TWO COMMITTEE MEMBERS. THEY
PUT THIS TOGETHER AND I HOPE
AND LOOK FOR MORE FORWARD TO
THE PANEL DISCUSSION.
>>: GOOD MORNING
EVERYONE. COULD YOU PUT THE
FIRST SLIDE UP? THE TITLE
SLIDE PLEASE, THANK YOU. GOOD
MORNING TO EVERYBODY OUT
THERE! AS YOU CAN TELL I HAVE
ALS, EVEN HERE IN MY SPEECH.
WHAT WE WANT TO DO THIS
MORNING IS GIVE YOU INSIGHT
INTO THE WORLD AS I WOULD CALL
IT. I CALL THIS AN ALS
EXPERIENCE EXPERTS. THOSE
PEOPLE WITH ALS, ALS
CAREGIVERS AND ALS GENE
CARRIERS HAVE HAD AND CONTINUE
TO HAVE INVOLVEMENT IN THE ALS
STRATEGIC PLANNING PROCESS.
AS RITA MENTIONED, THIS
SESSION WILL BE MODERATED BY
MYSELF. IT ALSO ELLEN. CAN
YOU PUT UP THE FIRST SLIDE
PLEASE. NEXT SLIDE. THIS IS
OUR PANEL. AS YOU CAN SEE,
THEY ARE NINE, ALS EXPERIENCE
EXPERTS ON THIS PANEL. AND
INDEED THERE ARE TWO OTHER
PEOPLE WHO ARE ALS EXPERIENCED
EXPERTS WHO ARE INVOLVED IN
THE PLANNING PROCESS. THEY
ARE BOTH COCHAIRS OF
COMMITTEES AND WILL BE
SPEAKING LATER. SO, A TOTAL
OF 11 OUT OF 52, 52 BEING
NONPERSONNEL BUT 11 WERE
PEOPLE WITH ALS EXPERIENCED
EXPERTS. THAT IS
UNPRECEDENTED WITH A FEDERAL
AGENCY BY DEVELOPING A
STRATEGIC PLAN. WE CAN TALK
MORE ABOUT THAT LATER TODAY OR
TOMORROW. WE DO HAVE A SECOND
PANEL TOMORROW. WITH THAT,
LET ME GIVE YOU A 22nd
BACKGROUND OF MY ALS. I WAS
INITIALLY DIAGNOSED WITH P ALS
IN 2017. THAT WAS CHANGED TO
ALS IN NOVEMBER OF 2020. MY
TRAINING PHYSICIAN, HIS NAME
WAS ALREADY MENTIONED THIS
MORNING, DOCTOR MATTHEW HARMS
AT COLUMBIA UNIVERSITY. WITH
THAT I'M GOING TO TURN IT OVER
TO ELLEN TO COORDINATE THE
INTRODUCTIONS OF OUR PANEL AND
THE BACKGROUND AND HERSELF.
>>: THANK YOU IT'S BEEN A
PLEASURE WORKING WITH YOU ON
THIS PROJECT. YOU HAVE A LOT
OF ENERGY AND YOU'RE CERTAINLY
SMART AND I LOOK AT YOU AS A
MENTOR FOR WHAT WE HAVE DONE
HERE TODAY. MY NAME AS YOU
HEARD. CURRENTLY PHILADELPHIA
ALS ASSOCIATION I'M ALSO A
FORMER TRUSTEE OF THE NATIONAL
ALS ASSOCIATION. I CONSIDER
MYSELF A PATIENT ADVOCATE
HAVING LOST MY HUSBAND ALAN TO
ALS IN 1980 FOUR, WHICH SEEMS
LIKE THE DARK AGES. HE WAS 36
AND OUR DAUGHTER AMY WAS THREE
AT THE TIME. OUR NEUROLOGISTS
WAS DOCTOR KENNETH FISCHBECK,
YOU MAY RECOGNIZE THAT NAME.
I LEARNED MORE ABOUT ALS OVER
THE YEARS BY HAVING THAT
PRIVILEGE OF SERVING ON THE NI
NDS COUNCIL, THE FDA ADVISORY
COMMITTEE ON CENTRAL AND
PERIPHERAL NERVOUS DISORDERS,
AND THE INAUGURAL DEPARTMENT
OF DEFENSE ALS RESEARCH GROUP.
NOW I SPEND MY TIME IT IS
FUNDRAISING FOR OUR CHAPTER
WHICH INCLUDES WORKING WITH
THE PHILADELPHIA PHILLIES. I
REFRAINED FROM WEARING MY
JERSEY. THEY HAVE RAISED OVER
$20 MILLION FOR PATIENT CARE
AND RESEARCH. A WORLD SERIES
CHAMPIONSHIP THIS IS INCREASE
THAT AMOUNT SIGNIFICANTLY. I
WOULD LIKE TO INTRODUCE OUR
PANEL AND THEY WILL INTRODUCE
THEMSELVES. BUT I WILL CALL
ON THEM. GWEN PETERSON.
>>: HELLO. MY NAME IS
GWEN PETERSON. I WAS
DIAGNOSED AT 30 TWO-YEARS OLD
IN 2018 AND IT'S REALLY GOOD
TO BE HERE, THANK YOU.
>>: ED RAPA.
>>: THANK YOU. MY NAME
IS ED AND I AM THE FORMER
CATERPILLAR GROUP PRESIDENT
AND ANNOUNCED MY RETIREMENT AT
THE END OF 2015 WHEN I WAS
DIAGNOSED DIAGNOSED WITH ALS.
IN THE PALS TOLD ME YOU GOT A
CHOICE YOU CAN STAY BETTER AND
YOU CAN STAY ENGAGED I AM
OPTING FOR THE LATTER. AND
THIS IS WHERE WE BRING
TOGETHER FOR ALS LARGEST
REPOSITORY DATA AND IPS CELLS
GATHERED IN THE HISTORY OF THE
DISEASE AND THEY'RE PUTTING ON
AN OPEN-SOURCE PLATFORM AND
MAKE IT AVAILABLE TO
RESEARCHERS AROUND THE WORLD
FOR FREE. NO, IT'S NOT
SELLING TRACTORS BUT IT'S
MEANINGFUL WORK AS IS
PARTICIPATION IN THE NIH
EFFORT THAT WERE DISCUSSING
TODAY. THANK YOU, COOPER.
>>: COOPER [INDISTINCT]
SORRY WELL, MY TOTALLY BLUE.
I GUESS THE BACKGROUND DIDN'T
WORK FOR ME OR SOMETHING.
MAYBE I SHOULD TURN OFF MY
CAMERA SO LET'S NOT
DISTRACTING. MY NAME IS
COOPER PENNER, I AM A CURRENT
PHD STUDENT AT THE UNIVERSITY
OF PENNSYLVANIA AND I WORK
WITH IP SC DERIVED NEURONS TO
BASICALLY STUDY THE
PATHOGENESIS OF ALS AND I WORK
IN THE CLINIC EVERY WEEK
HELPING FAMILIES NAVIGATE
CAREGIVING. I CARED FOR MY
MOM FOR THREE-YEARS WHILE SHE
WENT THROUGH HER JOURNEY WITH
ALS AND I MYSELF AM A CARRIER.
SO I LIVE WITH THIS DISEASE
EVERY DAY. I'M REALLY
GRATEFUL TO BE HERE ANYMORE
AND GRATEFUL THAT SO MANY
PEOPLE HAVE SIGNED UP AND HAVE
JOINED US. LOOKING FORWARD TO
THE CONVERSATION.
>>: THANK YOU COOPER.
ANDREA.
>>: GOOD MORNING I AM
ANDREA PAUL SPACKMAN AND I
LOST MY MOTHER SALLY TO ALS IN
2010 THREE-YEARS AFTER HER
DIAGNOSIS. I WAS ONE OF HER
PRIMARY CAREGIVERS AND TRULY
THIS WAS A PROFOUND EXPERIENCE
THAT CHANGED MY LIFE IN MANY
WAYS ALSO CHANGE MY CAREER
TRAJECTORY. SHORTLY AFTER SHE
DIED AND LEFT A 30 YEAR CAREER
INVESTMENT IN MANAGEMENT AND
THEN BEGAN TO SERVE AS A BOARD
MEMBER FOR THE ASSOCIATION FOR
A COUPLE OF YEARS AND I CAN AS
CEO OF THE OLDEST INDEPENDENT
ALS GROUP IN THE COUNTRY. I'M
ALSO ON THE BOARD OF DIRECTORS
AND DO LOTS OF OUTREACH FOR
OTHER ORGANIZATIONS. I AM
REALLY HONORED TO BE PART OF
THIS GROUP AND THAT WERE DOING
TODAY. THANK YOU.
>>: THANK YOU ANDREA,
ALLISON.
>>: GOOD MORNING. MY
NAME IS ALLISON I'M SURVIVING
SPOUSE OF ALS HAVING LOST MY
HUSBAND 20-YEARS TO ALS AND
EARLY 2016. AFTER A VERY
QUICK AND DEVASTATING 380 DAY
JOURNEY FROM DIAGNOSIS TO
GAINING HIS WINGS. AS WITH
MANY OF US WHO HAVE
EXPERIENCED THIS UP CLOSE AND
PERSONAL, THE PERSON I WAS
LEFT TO THE PERSON I LOVED. I
HAD A SUCCESSFUL CAREER AND
TECHNOLOGY I CHOSE TO GO BACK
TO SCHOOL AND CITY CLINICAL
RESEARCH ADMINISTRATION. FOR
THE PAST SIX-YEARS OR SO I
FOUND MY HOME AND FOREVER
FAMILY IN THE ALS COMMUNITY.
I WORK AS PART OF THE PATIENT
TEAM AT THE MASSACHUSETTS
GENERAL HOSPITAL AND ICE ON
THE RECURSION AND RETENTION
EXPANDED ACCESS AND PATIENT
ADVISORY COMMITTEES FOR THE
TRIALS. I'M ALSO VERY
INVOLVED WITH THE ALS
CONSORTIUM SERVING AS A
PATIENT LIAISON TO THE
EXECUTIVE LEADERSHIP TEAM, THE
COCHAIR OF THE PATIENT
EDUCATION ADVOCACY COMMITTEE
AND I ALSO SIT ON THE
RETENTION AND RECRUITMENT
COMMITTEES. FINALLY, SERVE AS
A MEMBER OF THE BOARD OF
DIRECTORS AND THE ARIZONA
CHAPTER OF THE ALS
ASSOCIATION. I PARTICIPATED
IN THE CDM RP THAT
CONGRESSIONALLY DIRECTED
MEDICAL RESEARCH PROGRAM AS A
CONSUMER REVIEWER. I WAS PART
OF THE OPPORTUNITIES FOR
COLLABORATIONS AND
PARTNERSHIPS WORK GROUP AND A
VERY HAPPY TO BE HERE WITH A
LOT OF MY FRIENDS ON THE
PANEL. THANK YOU FOR HAVING
ME.
>>: THANK YOU ALLISON. I
DON'T THINK THAT NADIA IS HERE
YET, SHE SENT AN E-MAIL THAT
SHE PROBABLY WILL NOT BE ON
UNTIL 11:00 A.M. I AM
ASSUMING, UNLESS SHE SPEAKS UP
WE WILL GET HER AFTER A LITTLE
LATER IN OUR PORTION. THAT
BRINGS US TO STEVE.
>>: GOOD MORNING
EVERYBODY, MY NAME IS STEVE
KOWALSKI AND I WAS DIAGNOSED
IN AUGUST OF 2017, WITH
SPORADIC ALS. MY FIRST
SYMPTOM WAS THE INABILITY TO
USE MY TOES IN MY RIGHT FOOT
WHICH IS CLASSICALLY KNOWN AS
THE BEGINNING OF DROP FOOT IN
THIS DISEASE. I LIVE IN
BOSTON MASSACHUSETTS WITH
THREE OF MY CHILDREN WHO LIVED
THERE AS WELL AND HELP TAKE
CARE OF ME WITH MAINLY MY
MOBILITY ISSUES. I RETIRED
AFTER 30 FOUR-YEARS IN HIGH
TECH AND I CAN SAY NOW MY
FULL-TIME JOB AS ALS ADVOCACY.
THANK YOU FOR THIS OPPORTUNITY
TO PARTICIPATE.
>>: THANK YOU EVERYONE.
>>: NEXT SLIDE ASLEEP
NEXT SLIDE PLEASE. GO AHEAD.
>>: HERE I GO. THIS IS A
QUESTION FOR EVERYONE AND WE
WILL GO AROUND AGAIN WHAT WERE
YOUR THOUGHTS AND FEELINGS
ABOUT ALS RESEARCH BEFORE?
COMPARE THIS TO AFTER THE
DEVELOPMENT OF THE NIH
BACKSLASH AND I NDS STRATEGIC
PLAN? WE WILL START AGAIN.
>>: ALL RIGHT, SO MY MY
THOUGHTS AND FEELINGS ABOUT
ALS REACH SEARCH THAT COMPARED
AFTER THE DRAFT PLAN REALLY AT
THE MOST BASIC LEVEL HAVE NOT
CHANGED. WE DON'T KNOW A LOT
ABOUT ALS AND CERTAINLY THIS
DRAFT PLAN IS DESPERATELY
TRYING TO GET US THERE.
AGAIN, A BASIC LEVEL THE MORE
WE KNOW ABOUT ALS THE CLOSER
WE ARE GOING TO GET TO HAVING
DISEASE MODIFYING THERAPIES
AND WHAT I MEAN BY THAT ARE
THERAPIES THAT EITHER HALT
PROGRESSION OR REVERSE
SYMPTOMS. TO DO THAT PATIENT
PARTICIPATION IN THE RESEARCH
IS MISSION-CRITICAL I JUST
WANT TO SAY THAT WE CAN HAVE A
BLOCKBUSTER DRUG FOR ALS THEY
HAD THE BEST STUDY DESIGNED IN
THE WORLD BUT IF YOU DON'T
HAVE PATIENTS WHO PARTICIPATE
IT IS SORT OF MOOT. SO, THOSE
ARE MY BASIC THOUGHTS AND I
WILL STOP THERE.
>>: THANK YOU. I WILL
REPEAT THIS FOR EACH SPEAKER,
WHAT WERE YOUR THOUGHTS AND
FEELINGS ABOUT ALS RESEARCH
BEFORE COMPARED TO AFTER THE
NIGHT H/AND I NDS ALS
STRATEGIC PLAN?
>>: I WOULD SAY PRIOR TO
THE STRATEGIC PLAN I WAS A BIT
FRUSTRATED BY THE FRAGMENTED
NATURE OF ALL OF THE EFFORTS
IN THIS ALS SPACE TAUGHT ME
THE GREAT INNOVATION WITH
GREAT COLLABORATION AND WHILE
THIS POSITIVE EXAMPLES
HISTORICALLY THIS HAS NOT BEEN
THE MOST COOPERATIVE FIELD.
IT REMINDS ME OF RECOVERING
BUT I WILL REMIND THE GROUP IS
NOT FOR THE FAINT OF HEART.
STRATEGY DEVELOPMENT IS
RELATIVELY BUSY BUT
IMPLEMENTATION IS THE HARD
PART. THIS IS NOT WITHOUT
HOPE THIS OVER THE NEXT FEW
DAYS OR TO HEAR A LOT ABOUT
INITIATIVES MAKE A DIFFERENCE
IN THE DISEASE. THE NIH CAN
TRULY PUT SOMETHING LIKE THIS
IN PLACE AND DRIVE EXECUTION
AS A PATIENT IT DOES BRING
HOPE.
>>: THANK YOU ED. WERE
GOING TO ADDRESSES FOR COOPER.
WHAT ARE YOUR THOUGHTS AND
FEELINGS ON ALS RESEARCH
BEFORE COMPARED TO AND AFTER
THE DEVELOPMENT OF THE NIH/AND
IND AS ALS STRATEGIC PLAN.
>>: GOOD MORNING.
THINKING ABOUT THIS QUESTION
LAST NIGHT AND THOUGHTS REALLY
RETURNED TO MY MOM AS THEY SO
OFTEN DO. AND AFFORD A LOT OF
LESSONS CARING FOR HER AND ONE
OF WHICH WAS THE IDEA OF ALS
TIME WHICH IS SOMETHING I FEEL
LIKE I'M LIVING WITH THE NOUN
I THINK A LOT OF THE FOLKS WHO
LIVE WITH THIS DISEASE OR CARE
WITH FOLKS WITH THIS DISEASE
WILL UNDERSTAND. WE COULD
TALK A LOT ABOUT HOW TIME
EXPANDS AND CONTRACTS IN THE
FACE OF A HORROR LIKE ALS, BUT
FOR ME THE MOST SALIENT
DIMENSION OF TIME AND ENOUGH
OF IT. HORRIBLE TRAGIC THING
IN SOME WAYS SOME PEOPLE WHO
LIVE WITH DISEASES SUPERPOWERS
IN SOME WAYS AND WHEN YOU SEE
AND LIVE WITH THIS MOST
NIGHTMARISH DISORDER THAT FEW
COULD EXPERIENCE AS FAR AS I'M
CONCERNED, YOU HAVE A
DIFFERENT APPRECIATION FOR
SPEED AND PERHAPS A DIFFERENT
HUMILITY AND GRACE. AND AS I
GOT TO UNDERSTAND THE NIH
UNDERSTANDS THAT THE VALUE OF
THE TIME AND PEOPLE WHO LIVE
ON ALS TIME INTO THIS
IMPORTANT DECISION-MAKING
PROCESS IS A GOOD DEAL OF FEAR
AND IS A GOOD DEAL OF HOPE I
DO THINK WERE ON TIME .4 OF
THE EXPONENTIAL GROWTH CURVE
UP. BUT COME AWAY FEELING
SIMILAR BUT WITH AN
APPRECIATION OF EFFECT FOR
WHAT THIS PROCESS LOOKS LIKE
WHEN FOLKS LIKE US ARE
INCORPORATED DIRECTLY INTO THE
CONVERSATION. AND WHAT THEY
BRING TO THE TABLE AND I THINK
WE HAVE PRODUCED A MEANINGFUL
DOCUMENT AND HOW IT SERVED OUR
COMMUNITY WELL AND I'M
GRATEFUL FOR THAT.
>>: THANK YOU. ANDREA
ARE YOU OKAY WITH ME NOT
REREADING THE STATEMENT?
>>: I HAVE IT THANK YOU.
I WOULD SAY THAT MY EXPERIENCE
IN ALS RESEARCH OVER THE LAST
TEN-YEARS IS THAT I OBSERVED
THE FUNDING SYSTEM
PREDOMINANTLY INCENTIVIZE
SILOS. THAT WAS CERTAINLY IS
TRUE WITH BASIC SCIENCE SPACE.
BUT COLLABORATION THE
COLLABORATION OF DATA WAS MORE
INFREQUENT THAN EXPECTED IT TO
BE. AND THIS WAS DUE TO THE
NATURE OF THE GRANTING
PROCESS. I'VE SEEN SOME OF
THAT CHANGE AND RESEARCH IN
YEARS BUT IT WAS NOT CHANGING
QUICKLY ENOUGH TO HELP PEOPLE
LIVING WITH ALS. I BELIEVE
THE CHANGE HAS BEGUN TO TAKE
PLACE AS MORE OPPORTUNITIES
HAVE ARISEN WITH PEOPLE
GETTING ALS TO GET INVOLVED.
WHERE THEY ARE WITH THIS PLAN
TODAY REALLY SHOWS A WIDE
RANGE OF OBJECTIVES THAT WE
DESCRIBED DESIGNED TO
ACCELERATE RESEARCH TO MOVE
MORE QUICKLY IN TRANSLATIONAL
RESEARCH AND THE ESTABLISHMENT
OF DATA PLATFORMS AND RESEARCH
LANDSCAPES THAT WILL FOSTER
COOPERATION. I BELIEVE THAT
IS THE ANY WORK WE NEED TO DO
HERE. I BELIEVE WE NEED TO
OPERATIONALIZE HIS PLAN AND
I'M READY.
>>: THANK YOU. STEVE.
>>: YES, SO MY OPINION ON
RESEARCH PRIOR TO THIS
PLANNING EFFORT TODAY HAS
CHANGED SLIGHTLY. I QUICKLY
BECAME A RESEARCH PARTICIPANT
AND MANY RETRIALS ARE
QUALIFIED FOR. I QUICKLY
LEARNED THAT THE CLINICAL
TRIALS ARE EXTREMELY COMPLEX.
THE VENUE AND THE COMPLEXITY
OF THE DISEASE LIKE AL SS AND
AT TIMES FROM A PATIENT'S
PERSPECTIVE VACANCY RATHER
DAUNTING. SO, INSTEAD OF
BEING FEARFUL THAT I HAVE
LEANED IN AND BECOMING
INVOLVED IS HELPED EDUCATE ME
ALONG THE WAY IT IS BUT A FIVE
YEAR JOURNEY OF LEARNING
THROUGH THE PROCESS OF BEING
ENGAGED IN RESEARCH. WHAT I
HAVE LEARNED IS THAT RESEARCH
IS INFORMED AND WILL HELP
RESEARCH CLINICIANS AND PROFIT
AND NONPROFIT SPONSORS.
DOCTOR BROWN BENCH OF THE PIE
PLATE OF CURRENTLY EXISTS THAT
IS GETTING LARGER AND IS IN
NEED OF EXPERTISE AND
GUIDANCE. I THINK IN MANY
WAYS ALSO AT KELLS ON THIS
PANEL HAVE CONTRIBUTED TO HELP
HUMANIZE THAT PROCESS AND
FOSTER FURTHER COOPERATION AND
IS TRAPPED THERE GREAT
INVESTMENT.
>>: THANK YOU STEVE.
ALLISON.
>>: THANK YOU. BECAUSE
OF MY INVOLVEMENT IN OR WITH
DIFFERENT ORGANIZATIONS WITHIN
THE ALS COMMUNITY I TEND TO
HAVE A VERY HOLISTIC VIEW OF
THE ALS RESEARCH LANDSCAPE.
WHEN I SIT DOWN OF THE VIRTUAL
TABLE WITH NUMBERS OF ALL OF
THESE LARGE ORGANIZATIONS
WITHIN THE COMMUNITY I WASN'T
REALLY SURPRISED TO HEAR THAT
WE ACTUALLY HAVE QUITE A BIT
IN COMMON. WE TALKED ABOUT
OUR PRIORITIES AND OUR GOALS
AND THERE IS TOO MUCH ERROR IN
A STRONG COLLABORATION AMONGST
US THAT REALLY REINFORCE THE
DESIRE TO CREATE MEANINGFUL
SOLUTIONS TO FINDING REAL
ANSWERS AND TO NOT RE-CREATING
OR DUPLICATING EFFORTS. WE
TRULY CAME IN FOR SESSIONS
WITH AN ABUNDANCE OF HOWEVER,
I THINK I SHARE ON THIS ONE MY
CONCERN COMING OUT OF THIS IS
THAT AN ABUNDANCE OF IDEAS
REQUIRES AN ABUNDANCE OF
FUNDING AND RESOURCES TO TURN
INTO REALITY. I'M TRULY NOT
SURE WITH THE FUNDING WILL
COME FROM OR HOW PEOPLE GO
ABOUT MAKING GOOD JOB OF
WORKING TOGETHER AND
ARTICULATE OUR DIVISIONS AND
WE KNOW THAT REALISTICALLY WE
NEED TO ACKNOWLEDGE THAT HER
VISION ALONE WILL NOT GET US
TO WHERE WE NEED TO BE SAID
THAT PIECE OF TURNING GREAT
IDEAS INTO GREAT REAL CHANGES
IS STILL A LITTLE UNCERTAIN
FOR ME. I'M HOPEFUL, ANXIOUS,
AND LOOKING FORWARD TO SEEING
WHERE THE STRATEGIC PLAN GOES.
>>: THANK YOU ALLISON. I
DON'T BELIEVE THAT NADIA HAS
ARRIVED YET. THERE YOU ARE.
OKAY, NADIA. HAVE YOU SEEN
THE PEOPLE ARE RESPONDING TO?
AND ALSO INTRODUCE YOURSELF
PLEASE.
>>: HI EVERYBODY, I AM
NADIA AND IT IS MY PLEASURE TO
BE HERE. I APOLOGIZE, I HAD
TO DROP THE KIDS OFF AT
SCHOOL. LIFE GOES ON AS WE
TRY TO FIGHT ALS. IT'S MY
PLEASURE TO BE HERE AND I'VE
BEEN SO INVOLVED IN ADVOCACY
THE LAST FEW YEARS I LOST MY
HUSBAND TO A FAST, PROGRESSIVE
FORM OF ALS IN 2020. TO MY
SURPRISE, THERE WAS A GENETIC
COMPONENT TO IT ALTHOUGH WE
WERE TO SHARE A FAMILY HISTORY
AT THAT POINT. I AM GRATEFUL
FOR THE NIH EFFORTS AND I
THINK THAT MY UNDERSTANDING OF
RESEARCH BEFORE THIS MEETING
I'VE LEARNED A LOT. SPENT
FAST LEARNING IN THE PAST
COUPLE OF MONTHS WITH PEOPLE
WHO ARE ARE WORKING ON A
CONCERTED EFFORT TO CHANGE. I
THINK BEFORE I HAD THIS GROUP
AND I THINK THEY'RE EVEN MORE
COMPLICATED BUT NOW I'M GLAD
THERE'S A CONCERTED EFFORT
FROM MANY DIFFERENT PARTIES.
I DO THINK THAT YOU TAKE. WE
NEED THE RESEARCH AND ACADEMIC
PERSPECTIVE AND MANY OF THE
VOICE OF PATIENTS AND
CAREGIVERS AS WELL. THIS WAS
A MOST EXCITING ABOUT. I
THINK BE ON MY OWN PERSONAL
PERSPECTIVE IT'S GOING TO
MATTER IS HOW THE COMMUNITY
RESPONSE TO WHAT WE SHARE IN
THE NEXT TWO-DAYS AND THE
STEPS THAT COME OUT OF THAT.
THOSE ARE THE THINGS ARE GOING
TO BE IMPACTFUL. I AM HOPING
THAT ANOTHER PRODUCT FROM THE
NEXT TWO-DAYS WILL BE THAT THE
PATIENT AND CAREGIVER
COMMUNITY WILL CONTINUE TO
ADVOCATE FOR A VERY STRONG
SCIENCE. THAT'S WHAT WE NEED
TO REALLY MAKE A DIFFERENCE IN
ALS AND IN THE FUTURE. THERE
ARE THINGS ALREADY IN PLACE
THAT ARE MOVING FORWARD AND
THERE'S MANY CLINICAL TILES
TRIALS AND GREAT RESEARCH IS
HAPPENING. WHAT WERE GOING TO
NEED MORE FOR ALS AND WE HAVE
TO CONTINUE TO ADVOCATE FOR
STRONG SCIENCE AND CONCERTED
EFFORTS TO MAKE THAT HAPPEN.
>>: THANK YOU.
>>: GO AHEAD ELLEN YOU
CAN ANSWER THE QUESTION
YOURSELF. YES AND THEN YOU
CAN.
>>: IT'S HARD TO BE BRIEF
WHEN MY HUSBAND DIED IN 1984.
SO, I HAVE SEEN A LOT BEFORE
OBVIOUSLY NOT GOING TO GO
THROUGH EVERY YEAR OR EVEN THE
AID BUT THERE'S A COUPLE OF
THINGS THAT STAND OUT AND ONE
IS IN THE LATE 1980s THE ALS
ASSOCIATION HAVE APPLICANT CJ
AND A BUNCH OF US WENT TO NIH,
KNOCKED ON THE DOOR AND SAID
HE WAS THE PERSON IN CHARGE OF
THE ALS RESEARCH HERE? AND
AFTER A TIME A GENTLEMAN CAME
OUT AND HE SAID, WHAT ARE YOU
DOING FOR ALS? HE SAID
NOTHING, NO ONE IS INTERESTED.
HE COULD'VE HAD A LITTLE MORE
POLISH TO THE ANSWER BUT WHAT
I FOUND THAT HE MEANT WAS THAT
NO ONE WAS APPLYING FOR
GRANTS. AND THEREFORE HE
DEDUCED THAT NO ONE IS
INTERESTED. THROUGHOUT THIS
TIME I REMEMBER SAYING TO
MYSELF WHEN MY DAUGHTER WAS
THEN AS I SAID, SHE WAS THREE
WHEN MY HUSBAND DIED. WHEN HE
WOULD GET OLDER I KEPT HOPING
AND A FEW MORE YEARS. THERE
WOULD BE SOME TYPE OF DRUG OR
CURE. I REALIZED EVERY FEW
YEARS I MOVED UP WITH THE HOPE
THAT WHEN SHE IS TEN, WHEN SHE
IS 16 AND TIME HAD FLOWN BY
AND THERE STILL NOT HOPE THAT
WE NEED AND THE CONCRETE
DRUGS. BUT HAVING SERVED ON
THIS I CAN SEE THE LANDSCAPE
CHANGE. I'M SO IMPRESSED WITH
EVERYONE WHO HAVE PARTICIPATED
WITH THE AMOUNT OF DETAIL IN
THE AMOUNT OF GRIT ALL OF THE
THINKING THIS THROUGH AND VERY
HOPEFUL. AND ONLY TYPE TIME
WILL TELL.
>>: THANK YOU. THIS IS
IMPRESSIVE AND MAJOR GROUP OF
PEOPLE. NOT JUST THE ALS
EXPERIENCE EXPERTS, BUT
EVERYBODY INVOLVED. I HAVE
SEEN TIME AND AGAIN PEOPLE
CARING ABOUT WHAT WE HAVE TO
SAY. THAT IS SO IMPORTANT.
MY THOUGHTS HAVE BEEN
MENTIONED AND TEARING DOWN
SILOS AND REDUNDANCIES IS SO
IMPORTANT THIS PLAN WHICH I
CALL A ROADMAP I HOPE THIS
ROADMAP WILL RESULT IN A
SYNERGISTIC OPPORTUNITY. I
REALLY HOPE THAT I'M
OPTIMISTIC. EVEN THOUGH I
HAVE ALS I'M STILL AN
OPTIMIST. AND I THINK THIS
PLAN WILL LEND ITSELF TO MORE
SYNERGISTIC OPPORTUNITIES.
WITH THAT THANK YOU. GOING TO
HAVE ANOTHER SESSION TOMORROW
MORNING WITH THE SAME AMAZING
GROUP OF PEOPLE. AND WITH
THAT LIKE TO TURN THE MEETING
OVER TO THE COCHAIRS WHO ARE
DOING EXCEL UNIT RESEARCH ON
THE BIOLOGY BEHIND ALS FOR OUR
NEXT ACTION. CAN WE TURN THE
SLIDE PLEASE? THANK YOU.
>>: THANK YOU EVERYONE ON
THE LIVED EXPERIENCE PANEL.
WE WANT TO REMIND WORKSHOP
ATTENDEES THAT THEY MAY ENTER
QUESTIONS INTO THE ZOOM
QUESTION AND ANSWER BOX. OR
THEY CAN FILL OUT THE QUESTION
AND ANSWER FORM ON THE
WEBSITE. GOING TO BE TALKING
ABOUT THE ACCELERATING
RESEARCH ON THE BIOLOGY BEHIND
ALS WORKING GROUP. CAN I HAVE
THE NEXT SLIDE PLEASE. I AM
WORKING AT KING'S COLLEGE
LONDON AS A NEUROLOGIST. MY
COCHAIR IS FROM HARVARD
MEDICAL SCHOOL AT
MASSACHUSETTS GENERAL
HOSPITAL. WE HAVE MANY
MEMBERS IN OUR WORKING GROUP
WILL BE INTRODUCING THEM IN
MORE DETAIL AFTER THE
PRESENTATION. BUT TO QUICKLY
NAME THEM TO HAVE THE NEXT
SLIDE PLEASE. SO, OUR THREE
PRIORITIES OF YOU ALREADY
HEARD ARE: TO UNLOCK SPORADIC
ALS TO IDENTIFY NEW
THERAPEUTIC TARGETS ACROSS
ANCESTRIES. AND PRIORITY TWO:
IS TO UNDERSTAND THE MOLECULAR
MECHANISMS UNDERLYING CLINICAL
HETEROGENEITY IN ALS. THE
THIRD PRIORITY: IS TO HARNESS
EMERGING TECHNOLOGIES TO
UNCOVER NEW DISEASE MECHANISMS
AND MECHANISMS OF ALS. I WILL
GO THROUGH EACH OF THOSE AND
EXPLAIN IN MORE DETAIL WHAT WE
MEAN. IF YOU HAVE THE NEXT
SLIDE PLEASE. THE FIRST
PRIORITY TO UNLOCK SPORADIC
ALS. IF YOU HAVE A LOOK AT
THE DIAGRAM ON THE RIGHT:
THIS IS A PIE CHART SHOWING
THE CONTRIBUTIONS OF FAMILIAL
ALS AND SPORADIC ALS AND
GENETIC NONGENETIC FORMS OF
ALS. THE BLUE SHADING IS
PEOPLE WOULD SPORADIC ALS,
PEOPLE WITH NO OBVIOUS FAMILY
HISTORY. AND THE RED IS
PEOPLE WITH FAMILIAL ALS,
PEOPLE WITH A FAMILY HISTORY
OF THE DISEASE. AND YOU CAN
SEE ALONG THE TOP THAT I HAVE
BRACKETED THE TWO LARGE
SEGMENTS IN BLUE AND RED.
THOSE ARE PEOPLE WITH SPORADIC
ALS AND FAMILIAL ALS FOR THAT
IS UNKNOWN AND JANE. TO BE OF
SOME UNDERSTANDING OF WHAT'S
CAUSING IT AND THOSE PEOPLE.
C. THEN IF YOU CAN SEE THE
SMALL SLIVER OF RED ON THE
RIGHT AND THEN THE MUCH LARGER
BLUE SPORADIC ALS SECTION,
THAT IS PEOPLE WHO HAVE NO
KNOWN GENE. WE HAVE VERY
LIMITED UNDERSTANDING OF WHY
THOSE PEOPLE HAVE DEVELOPED
ALS. WHAT WE WANT TO DO IS
UNDERSTAND HOW TO UNLOCK THIS
VERY LARGE SEGMENTS WHERE WE
HAVE VERY LIMITED
UNDERSTANDING OF THE CAUSE OF
ALS. ONE WAY TO DO THAT IS TO
ENCOURAGE CLOSE COLLABORATION
BETWEEN SCIENTISTS IN THE LAB
AND CLINICIANS TO UNDERSTAND
HOW TO SUBGROUP ALS. BECAUSE
ALS IS NOT ONE DISEASE AND WE
KNOW THAT VERY CLEARLY. IT'S
ACTUALLY LOTS OF DIFFERENT
CONDITIONS, BUT UNDERSTANDING
HOW TO BREAK IT DOWN AND HOW
TO CHOP UP THE DIFFERENT
GROUPS OF ALS AND SAY THIS IS
ONE GROUP AND ANOTHER GROUP
AND TO UNDERSTAND HOW TO
UNDERSTAND THE CAUSES IN THOSE
GROUPS IS ACTUALLY VERY
CHALLENGING TASKS AND WE HOPE
THAT THE COLLABORATION WITH
CLINICIANS AND TOP SCIENTIST
TO ENCOURAGE THAT. WE CAN GET
DIFFERENT VIEWS OF HOW THE
CLINICAL PATTERNS MATCH UP
WITH GOING ON IN THE
LABORATORY. WE ALSO NEED TO
DEVELOP WAYS AND SHARE VIEWS
WITH DIFFERENT TYPES OF DATA
THAT DESCRIBES ALS. OBVIOUSLY
THERE'S CLINICAL PATTERNS OF
ALS THAT WE KNOW. FOR EXAMPLE
WHERE IT BEGINS AND TELL THAT
FAST PROGRESSES AND WHETHER IT
IS INVOLVED THINKING AS WELL,
ET CETERA. THERE'S LOTS OF
DIFFERENT WAYS TO DESCRIBE IT
CLINICALLY. BUT IS ALSO OTHER
TYPES OF LABORATORY DATA THAT
WE CAN USE TO DESCRIBE ALS,
SUCH AS GEN X, TRANSCRIPT
METRICS AND ENVIRONMENTAL RISK
FACTORS. AND WE HAVE TO NOTE
THAT WHEN ONE RESEARCH GROUP
USES CERTAIN TERMS OR USES
CERTAIN DATATYPES THOSE ARE
UNDERSTANDABLE BY END OF A
GROUP. FOR EXAMPLE, WHEN
SOMEONE SAYS THIS IS THE AGE
OF ONSET FOR ALS, WHAT DO THEY
MEAN? THEY MEAN THE SITE OF
FIRST WEAKNESS? DID ANYONE
FORKED FLICKERING FIRST
HAPPENED? WHAT IS THE
DEFINITION? WE HAVE TO USE
SOME KIND OF COMMON
TERMINOLOGY TO ALLOW SHARING.
WE ALSO HAVE TO WIDEN OUR
UNDERSTANDING TO USE THESE
DIFFERENT WEE MIXES ET CETERA.
THE STATES TO INCLUDE
UNDERSTUDIED GROUPS AND THOSE
ARE GROUPS THAT ARE BASICALLY
ALL OF OUR RESEARCH AT THE
MOMENT HAS BEEN DONE AND
PEOPLE OF NORTH EUROPEAN
ANCESTRY. WE NEED TO INCLUDE
EVERYBODY BECAUSE HE
UNDERSTUDIED GROUPS HAVE MANY
OF THE BIOLOGICAL ANSWERS THAT
WE NEED AND MANY OF THE
ENVIRONMENTAL ANSWERS THAT WE
NEED TO UNLOCK SPORADIC ALS.
THE OTHER REASON WE NEED TO
INCLUDE UNDERSTANDING THESE
GROUPS IS BECAUSE TREATMENT IS
APPLIED TO PEOPLE OF MORE
EUROPEAN ANCESTRY MAY NOT
APPLY TO PEOPLE OF OTHER
ANCESTRIES. AND SO, THERE'S A
VERY IMPORTANT REASON TO
GENEALOGY. AND THE OTHER
ASPECT THAT IS VERY IMPORTANT
TO UNLOCK HIS PRODUCT ALS IS
TO DEVELOP NEW WAYS TO MODEL
ALS IN THE LAB AND MAKE
INTRODUCE REFLECTIVE AND
PATHOLOGY. AT THE MOMENT
NEARLY ALL MODELS INVOLVE
USING GENES THAT ARE BEING
CHANGED IN SOME WAY. SO, SOME
GENE MUTATIONS IMPORTANT FOR
ALS PEOPLE WITH THIS GENETIC
BASIS FOR ALS HAD REMODELED
THE LAB CORRECTLY. THAT IS A
CHALLENGING ISSUE BUT IT'S
IMPORTANT WHEN WE MUST
RESOLVE. THE NEXT SLIDE
PLEASE. THE SECOND PRIORITY
IS TO UNDERSTAND THE MOLECULAR
MECHANISMS UNDERSTANDING THE
CLINICAL HETEROGENEITY IS THE
DIFFERENCES IN THE WAY TO ALS
PRESENTS. ADVANTAGES AND AGE
OF ONSET, CLINICAL FEATURES
AND PROGRESSION RATES. AGAIN
IF YOU LOOK AT THE DIAGRAM ON
THE RIGHTS, YOU CAN SEE THERE
IS A DNA WITH A DOUBLE HELIX
IN THE RED STAR INDICATING A
MUTATION. AND THERE IS A
PERSON WHO HAS SOME RISK
FACTORS THAT WILL PUSH THEM
TOWARDS DEVELOPING ALS OR
FRONTOTEMPORAL DEMENTIA OR
BOTH. THERE'S ALSO SOME
RESILIENCE FACTORS THAT
PREVENT FROM DEVELOPING THOSE
CONDITIONS. THERE'S A BALANCE
BETWEEN THESE RISK FACTORS IN
HIS CONTRIBUTION FOR TIME
BECAUSE WE KNOW THE ALS RISK
INCREASES AS TIME GOES ON AS
SOMEONE AGES. THIS
CONTRIBUTIONS FROM EPIC
GENETICS IS THE WAY THAT DNA
IS MAPPED. THEY CAN EITHER BE
INHERITED OR TRANSMITTED FROM
ENVIRONMENTAL CHANGES. AND
FINALLY, THERE'S LIFETIME
ENVIRONMENTS. HOW DO THEY FIT
INTO THIS ISSUE VERSUS
RESILIENCE FACTORS.
UNDERSTANDING WHY DO SOME
PEOPLE DEVELOPED ALS, SOME
FROM TEMPORAL DEMENTIA, AND
SOME BOTH AND WHY SOME NOTES
NEVER DEVELOP EITHER, EVEN
WITH THE SAME GENETIC CAUSE IS
CRUCIAL. WE ALSO NEED TO
UNDERSTAND ALS ONSET THAT WILL
FEED DIRECTLY INTO
UNDERSTANDING UNDERSTANDING
ALS INTO GENE CARRIERS. AND
THIS IS A RISK FACTOR THAT'S
NOT MODIFIABLE WITH
MANIPULATION SOME KIND OF
THERAPY THEN WHEN IT'S CAUSED
ALS BUT IT'S IMPORTANT TO HAVE
THE NEXT SLIDE PLEASE? DO
UNCOVER NEW DISEASE MECHANISMS
ALS THIS INCREASES OUR
UNDERSTANDING OF ALS. FOR
EXAMPLE IF WE LOOKED AT
FILAMENTS FOR 20 OR 30 YEARS
AGO WE MIGHT'VE HAD THIS IDEA
THAT NEURAL FILAMENTS WOULD BE
IMPORTANT TO MEASURE THE
ACTIVITY THEY HAVE TODAY.
THEY DID NOT EXIST. THEY CAN
MEASURE AN UNDERSTANDING HOW
NEW TECHNOLOGIES CAN ALS IS
VITAL WE NEED TO MAKE IT
EASIER TO COLLABORATE FOR
PEOPLE THAT NEED TO KNOW HOW
TO USE THESE TECHNOLOGIES WE
CONSTRAINTS RESEARCHERS AND
NEW TECHNOLOGIES. THAT'S THE
END OF THE PRESENTATION SO I'M
GOING TO HAND OVER TO MY
COLLEAGUE.
>>: THANK YOU VERY MUCH I
WOULD LIKE TO TALK ABOUT THE
WORKING GROUP TO JOIN US FOR
THIS CONVERSATION AND TO
RETURN YOUR CAMERAS.
[INDISTINCT] I'M GOING TO CALL
YOUR NAMES.
>>: HELLO I AM SAMMY AND
I'M A NEUROLOGIST AND
NEUROSCIENTIST AT THE
UNIVERSITY OF MICHIGAN. I SEE
PEOPLE IN THE COGNITIVE
DISORDER CLINIC THAT FOCUS ON
THIS AND JUST AS THIS WAS
BROUGHT UP BEFORE THERE'S A
GREAT DEAL OF OVERLAP BETWEEN
FRONTOTEMPORAL DEMENTIA IT IS
AND ALS AND THAT'S WHAT
RESEARCH FOCUSES ON. IT'S A
REAL PLEASURE TO BE HERE
TODAY.
>>: THANK YOU.
>>: GOOD MORNING EVERYONE
AND THANK YOU FOR HAVING ME.
MY NAME IS SALLY AND I AM THE
NEW ASSISTANT PROFESSOR AT
MONTRÉAL AND I STUDIED THE MIX
OF ALS AND I'M HAPPY TO ANSWER
ANY QUESTIONS HERE TODAY.
THANK YOU VERY MUCH.
>>: GOOD MORNING
EVERYONE, I AM A
NEUROSCIENTIST AT JOHN HOPKINS
UNIVERSITY AND THE DIRECTOR OF
[INDISTINCT] WHICH IS A
CLINICAL RESEARCH INTEGRATED
PROGRAM I'M ALSO GRATEFUL AND
HONORED TO BE HERE TODAY WITH
MANY PEOPLE COMING FROM ALL
WALKS OF LIFE. I'M ALSO
APPROACHING WITH HOPE FOR THE
FUTURE.
>>: I WOULD LIKE TO ECHO,
SINCE I AM VERY GRATEFUL FOR
THE OPPORTUNITY FOR
PARTICIPATING IN THIS WORKING
GROUP AND HIS EFFORTS. I AM A
PLEDGE OF THE COLUMBIA OF
UNIVERSITY AND THE DEPARTMENT
OF NEUROLOGY AND AT THE YORK
GENOME CENTER WHERE I DIRECT
THE CENTER FOR GENOMICS AND
NEURAL GENERATIVE DISEASE. IN
THE BASIC RESEARCHER WHO WORKS
ON ALS AND I ALSO SUPPORT A
LARGE INTERNATIONAL
CONSORTIUM.
>>: YES, MOVE YOUR
CAMERA.
>>: I GUESS I'M CURSED OR
SOMETHING. I MET YOU AND I AT
THE PROGRAM HERE MY WORK IS
ALL COMPUTATIONAL WORK WITH
INTRACRANIAL RECORDINGS AND
NOW I HAVE [INDISTINCT]. IN
LOOKING AT DISEASE AND
[INDISTINCT] AS EVERYONE ELSE
THAT IS VERY GRATEFUL TO BE
HERE IN A VERY GRATEFUL FOR
THE BRILLIANCE OF THIS PANEL.
>>: HELLO I AM AT THE
MAYO CLINIC IN JACKSONVILLE,
FLORIDA. I AM A PROFESSOR.
MY PROGRAM FOCUSES ON
UNDERSTANDING THE MECHANISMS
ASSOCIATED WITH ALS AS WELL AS
HEAVY EMPHASIS ON DEVELOPING
NOVEL BIOMARKERS FOR THE
DISEASE. I ECHO MY COLLECTS
AND IT'S A PRIVILEGE TO BE
WORKING ON THE RECOMMENDATIONS
AND PRIORITIES AND PRESENTING
ANSWERING ANY QUESTIONS IN
TODAY'S SESSION.
>>: I MICHAEL WARD I'M A
NEUROLOGIST INVESTIGATOR AT
THE NIH IN BETHESDA, MARYLAND.
I SEE PATIENTS WITH SPECTRUM
DISORDERS IN CLINIC AND LEAD A
RESEARCH TEAM INTO
UNDERSTANDING WHAT THE BASIC
MECHANISMS ARE BEHIND DISEASE.
I ALSO CO- LEAD THE
NEURODEGENERATIVE DISEASE
INITIATIVE HERE WHICH IS A
PUBLIC, PRIVATE PARTNERSHIP TO
MAKE A LARGE REPOSITORY OF
STEM CELL MODELS OF ALS AND TO
SHARE WITH THE BROAD RESEARCH
COMMUNITY. I'M DELIGHTED TO
BE HERE TODAY. I WANT TO
THANK ALL OF YOU WOULD FOR
YOUR WORK IN THE INTERSECTION
OF THIS PLAN. WE HAVE HAD ANY
COMMUNITY DISCUSSIONS THAT
HAVE LED TO PRIORITIES OF THAT
WERE JUST DESCRIBED. IN THE
FROM THE NEXT 15 MINUTES WERE
TO DISCUSS THE DISEASES AND
[INDISTINCT] ONE OF THE FIRST
THINGS THAT PROMOTING
COLLABORATIONS BETWEEN BASIC
AND CLEAN RESEARCHERS IS
REALLY A CRUCIAL STEP TO OUR
ADVANCE UNDERSTANDING
MECHANISMS WITH ALS. AND SO
MANY OF THE PANEL LIKE TO
ELABORATE ON THIS?
>>: WE ARE IN NEED OF
THIS COOPERATION AND TO
SUMMARIZE WILLIE THIS IS A
DISEASE FOR WHAT WE WILL BE
DOING BECAUSE WE KNOW THE
DISEASE IS HETEROGENEOUS, BOTH
SPORADIC NOT FAMILIAL AND
UNFAMILIAR FORMS. AND IN THIS
IS INDIFFERENT TO PATIENTS AND
THIS IS DIFFERENT ET CETERA.
SO FOR US TO UNDERSTAND WHAT
ARE THE CAUSES UNDERLINED HIS
THESE DIFFERENCES AND WE NEED
ORGANIC AND FREQUENT
COMMUNICATION BETWEEN THE
RESEARCHERS INTO THE
CLINICIANS CAN TELL US HOW THE
PATIENTS HAVE A SPECIFIC
MUTATION THAT CAN MANIFEST IN
PROGRESS. SO WHEN LOOKING FOR
THE GENES AND THE SPECIFIC
GROUP OF PATIENTS AND WE KNOW
EXACTLY WHAT MAKES THE
PATIENTS WHO THEY ARE. AND WE
NEED AN ORGANIC COMMUNICATION
AND THE BASIS OF THE FINDINGS
FROM THE BASIC RESEARCH AND
THIS IS TAILORED FOR THESE
GROUP OF PATIENTS. I WOULD
LIKE TO SAY THAT THERE ARE
CURRENTLY ONGOING AND IN RED
STATES AND ELSEWHERE WERE THEY
TALK ABOUT THE GRADING OF THE
CONSORTIUM AND THE NIH NETWORK
IS ALS AND THE TARGET ALS BIO
MARKETS PROGRAM. BUT NOW
OUTLINING OUR PRIORITIES AND
OUR COMMITTEE FELT THAT WE
NEEDED TO STRESS THAT THERE IS
THE NEED TO SET THIS APPROACH
EVERYWHERE. THE NATURE CENTER
AND THEN ENCOURAGE CLINICIANS
TO TALK TO THE RESEARCHERS AND
VICE VERSA BECAUSE THIS
APPROACH REALLY FORMS THE
BASIS FOR EFFICIENT EXECUTING
OF A PLAN THAT MY COLLEAGUES
THAT HAVE BEEN DISCUSSING IN A
MINUTE. IN THE DEVELOPING AND
ASSISTING THE TRUE MEANING OF
SPORADIC ALS FOR INSTANCE, AND
CREATE INFORMATION FOR THIS
DISEASE ET CETERA. WE NEED TO
UNDERSTAND THIS BETWEEN CLINIC
AND BASIC RESEARCHER IT IS
ROLLOUTS TO ONE: UNDERSTAND
THE DISEASE AND TWO: TO
DEVELOP TRIALS CLINICALLY THAT
ARE A SPECIFIC SUBGROUP OF
PATIENTS. I WOULD ALSO LIKE
TO ADD THAT WE CAN HAVE THE
BEST RESEARCH MODELS IN THE
LAB BUT IF WE DO NOT INVOLVE
THE PATIENTS EARLY ON AND
THEREFORE, BRING THE CLINICAL
RESEARCH I DON'T THINK WE CAN
GO AS FAR.
>>: THANK YOU. AS YOU
JUST SAID. WERE GOING WITH
GREAT CLINICAL INFORMATION.
GOING TO MAKE A DIFFERENCE.
AND IN THAT SENSE IT COULD BE
REALLY BROADLY SHARED AND THEY
LOOKING AT PLATFORMS AND MAYBE
DESCRIBE THE CHALLENGES YOU'VE
HEARD TODAY THAT ALX IS A
COMPLEX DISEASE IS CLINICALLY
HETEROGENEOUS IN THE MANIFEST
DIFFERENTLY AND ALSO
GENETICALLY COMPLEX. YOU CAN
HAVE MUTATIONS THAT ARE RARE
AND HAVE A LARGE REFLECT AND
THEN HAVE SEVERAL MUTATIONS
THAT COMBINE AND EACH OF THEM
HAVE SMALL EFFECTS. IT IS
ALSO A RELATIVELY RARE DISEASE
AND IN ORDER TO GET THE LARGE
NUMBER OF SAMPLE SIZES THAT
YOU NEED FOR PEOPLE TO WORK
TOGETHER TO COMBINE THESE
SAMPLES NEED TO BRIDGE THE
PARTNERSHIP OF DIFFERENT
CENTERS. AND WE CAN TALK
ABOUT EVERYBODY STUDIES THESE
DIFFERENTLY. IF HE WANTED TO
STUDY THE RELATIONSHIP BETWEEN
HOW A PARTICULAR BIOMARKER
CORRELATES WITH A PARTICULAR
TYPE OF DISEASE PROGRESSION,
AND EMPLOY NEW TECHNOLOGIES TO
STUDY THESE BIO SAMPLES FROM
NATIONS LIKE THESE, AND THEN
HOW THIS RELATES TO THEIR
GENOTYPE WE NEED TO BE ABLE TO
COLLECT ALL OF THE INFORMATION
AND ALL OF THE SAMPLES IN A
WAY THAT YOU CAN COMPARE
ACROSS DIFFERENT SCIENCE. IN
THE LAST EIGHT-TEN-YEARS THERE
HAS BEEN A SEA CHANGE IN HOW
WE HAVE APPROACHED THIS IN THE
ALS COMMUNITY. THERE'S ABOUT
HALF A DEGEN LARGE, MULTI-
CENTER AND MULTINATIONAL
EFFORTS. WE'VE LEARNED A LOT
THROUGH DOING THIS ABOUT WHAT
IT TAKES FOR WHAT IS THE
MINIMUM AMOUNT OF INFORMATION
THAT YOU NEED, AND HOW IT
NEEDS TO BE COLLECTED AND HOW
IT NEEDS TO BE PUT TOGETHER.
>>: WE LOST TO EMILY IN
YOUR LAST SENTENCE.
>>: IS BETTER?
>>: MUCH BETTER.
>>: THANK YOU.
>>: WE NEED TO
INCORPORATE ALL THIS
INFORMATION TO THE QUESTIONS
THAT WE ARE ASKING. IT'S ONE
THING TO KNOW THAT CITIES LIKE
THEM ARE HAPPENING AND IT'S
ANOTHER TO MAKE THIS
INFORMATION WIDELY
DISSEMINATED. THE LARGE
STUDIES THAT WE KNOW UP TO
EACH OTHER AND WORKED OUT WAYS
TO SHARE INFORMATION THE NEXT
CHALLENGE BEFORE US AND HOW TO
INCORPORATE OTHER UNDERSTUDIED
GROUPS AND TO BUILD ON WHAT
WE'VE LEARNED SO FAR ABOUT
DOING A LARGE MULTINATIONAL
EFFORTS.
>>: THANK YOU SO MUCH.
IT'S A GREAT SEGUE TO THE NEXT
QUESTION I WANTED TO PUT UP
HERE. THIS IS THE ASPECT THAT
WE WANTED TO HIGHLIGHT
PRIORITIES AND THIS FREQUENTLY
COMES UP WITH CORRECT
KNOWLEDGE AND IS BASED ON DATA
FROM PEOPLE OF EUROPEAN
ANCESTRY AND THEN FOR PEOPLE
WITH YEAST EUROPEAN ANCESTRY.
IT'S NOT SPECIFIC TO ALS
RESEARCH FOR OUR COMMUNITY
NEEDS THIS TO CHANGE AND
RESEARCH ACROSS ANCESTRIES.
SO SALLY WOULD YOU MIND
DESCRIBING THIS ISSUE AND THEN
TALK ABOUT ALS RESEARCH.
>>: ABSOLUTELY BEFORE I
ANSWER THIS QUESTION I WILL
ADDRESS WHY THIS EVENT HAPPENS
BECAUSE CERTAINLY WHEN YOU GET
THE DATA SET WE DO CLINICIANS
ARE NOT ONLY SEEING THOSE OF
EUROPEAN ANCESTRY. WHAT
HAPPENS IS CLINICIANS COLLECT
ALL THE DATA. THEY SAY ARE
YOU EUROPEAN * EUROPEAN
ORANGE? WHAT HAPPENS AT THE
GENETIC LEVEL WHEN YOU GO TO
IMPUTE GENETIC INFORMATION AND
FILE ALL OF THESE POPULATIONS
ACROSS THE MAP YOU SEE THE
MAJORITY OF PARTICIPANTS
THEMSELVES THAT ARE JUST BEING
IN BASIC RESEARCH STUDIES TEND
TO BE OF EUROPEAN DESCENT.
THERE'S A LOT OF DIFFERENT
STUDIES AS TO WHY THAT HAPPENS
AS WELL. BUT WHAT HAPPENS AT
THE GENETIC LEVEL IS WHEN
YOU'RE TRYING TO MAKE A
HOMOGENEOUS POPULATION BECAUSE
YOU WANT TO COMPARE APPLES TO
APPLES. SO YOU CAN KEEP IT
SIMPLE THIS WAY. IF YOU ARE
INCORPORATING DIFFERENT
ETHNICITIES FOR EXAMPLE, THOSE
FROM SOUTH AMERICA OR AFRICA,
YOU'RE GOING TO SEE A SIGNAL
THAT IS ENRICHED AND CASES AND
THIS IS GOING TO BE
STATISTICALLY SIGNIFICANT AND
WILL ALLOW THE RESEARCHER TO
NAÏVELY CONCLUDE THAT THAT
SPECIFIC STATISTICALLY
SIGNIFICANT SIGNAL COULD BE
EXPLOITING THE DISEASE. BUT
REALLY THAT SIGNAL IS
ORIGINATING FROM GEOGRAPHICAL
BARRIERS AND DIFFERENT
ANCESTRAL INFORMATION. THIS
HAS A HUGE CONSEQUENCE IF YOU
DO NOT KEEP YOUR POPULATION
HOMOGENEOUS. [INDISTINCT]
>>: WE JUST LOST YOU.
>>: OH SORRY, CAN'T HEAR
HEAR ME NOW.
>>: YES WE CAN.
>>: SO THERE ARE
UNFORTUNATELY, NOT COMMENTS
ALS IS HAPPENS ACROSS ALL
DISEASES. WE ARE ABLE TO
LEARN DIFFERENT GROUPS THAT
HAVE BEEN REALLY WORKING TO
FIX THIS ISSUE. THIS
PSYCHIATRIC GENOMICS
ASSOCIATION FOR EXAMPLE HAS
REALLY GOOD ESTABLISHMENTS
FROM EAST ASIA, SOUTH AMERICA,
SOUTH AFRICA AND EAST AFRICA
THEY'VE BEEN ABLE TO PUT BEST
PRACTICES IN PLACE HERE.
TYPICALLY WHAT YOU CAN DO IS
CREATE SMALLER SUBSETS OF
MATCHING ANCESTRIES SO THAT
YOU CAN EITHER DO A COMBINED
META-ANALYSIS OF THE EVERYBODY
IS INCLUDED AND YOU ARE
ACCOUNTING FOR THESE
STATISTICAL FALSE
ASSOCIATIONS, OR YOU COULD
CREATE A BETTER SOFTWARE
PROGRAMS THAT ARE ABLE TO
ACCOUNT FOR THESE VERY COMMON
STATISTICAL ARTIFACTS AS WELL.
BOTH EFFORTS ARE HAPPENING,
IT'S IMPORTANT NOT BECAUSE YOU
WANT TO FEEL GOOD ABOUT
OURSELVES THAT WE WANT TO BE
INCLUSIVE, BUT THIS HAS ACTUAL
REAL IMPLICATIONS. THE EFFECT
SIZE OF A SPECIFIC REEL THAT
MIGHT BE ASSOCIATED WITH
DISEASE COULD BE A LOT
DIFFERENT IN A CERTAIN
ETHNICITY THAN IT IS IN YOUR
PLANS FOR EXAMPLE. WE HAVE
EVIDENCE OF THAT WIND
CONDITIONS ADMINISTER UP. OH
AND THE UPPERCUT RIGHT THERE
WAS MEDICATION. IF YOU GIVE
THE WRONG DOSE THAT COULD HAVE
TREMENDOUS IMPLICATIONS FOR
THE PATIENTS THEMSELVES. THIS
IS AN ONGOING EFFORT AND I
WENT TO RECOGNIZE A GENETICIST
HERE WHO IS WORKING ON THIS.
HIS NAME IS [INDISTINCT] IS A
COLLEAGUE OF MINE AND WORKS
CLOSELY OF COURSE AND HE IS AT
KINGS COLLEGE AND HATS OFF TO
HIM FOR REALLY BRINGING IN
UNDERREPRESENTED THESE
COMMUNITIES AND HE HIMSELF IS
THE RESEARCHER AND HAS BROUGHT
IN GROUPS FROM TURKEY,
ETHIOPIA, INDIA, FROM ISRAEL,
OTHER PARTS OF THE MIDDLE EAST
AS WELL AND HIS GOAL IS TO
MAKE HIMSELF, AND ALL OF US
AVAILABLE IN ADVANCING ALS
GENETICS RESEARCH ACROSS
DIFFERENT COUNTRIES THAT ARE
NOT REPRESENTED AS WELL. THIS
IS AN ONGOING EFFORT AND THIS
HAS VERY CLEAR IMPLICATIONS
AND STAY TUNED AS OUR DATA
BECOMES MORE DIVERSE AND WE
LEARN ABOUT THE EFFECTS THAT
WE CAN SEE IN THE EUROPEAN
POPULATION AS WELL AS NEW ONES
THAT WE HAVE UNVEILED AS WELL.
>>: THANK YOU VERY MUCH.
OUR FIRST PRIORITY IS TO
ATTACK SPORADIC ALS AND WE CAN
ALL RECOGNIZE THIS IS AN AREA
WHERE WE ALL KNOW VERY LITTLE
AND ONE REASON FOR THAT IS
BECAUSE OF THE CHALLENGES IN
MODERATING IT AND MAYBE GLENN
AND SAMMY IF YOU COULD COMMENT
ON THAT.
>>: SURE. I'M HAPPY TO
TALK A LITTLE BIT ABOUT SOME
OF THE NEWER APPROACHES FOR
MODERATING MONITORING SPORADIC
ALS. I THINK IN DOING SO IT'S
IMPORTANT TO THINK ABOUT WHAT
SPORADIC DISEASE IS AND TO
RECOGNIZE OUR LIMITATIONS. IF
WE WANT TO REPRODUCE SOMETHING
WE NEED TO KNOW WHAT TO
REPRODUCE AND I THINK THAT'S
ONE OF THE BIGGEST CHALLENGES
AND SPORADIC SEES. THERE'S
TWO WAYS OF GOING ABOUT THIS.
WE CAN SAY I DON'T KNOW WHAT
THIS IS BUT I CAN STILL GET
CELLS FROM INDIVIDUALS WITH
SPORADIC ALS AND THOSE CAN BE
REPROGRAMMED INTO STEM CELLS
AND THOSE CAN BE MADE INTO
NEURONS IN THE CELL TYPE IS
AFFECTED AND THEN WE CAN STUDY
THAT IN ADDITION WE CAN TEST
OUT THERAPIES AND TRY TO
DETERMINE DISEASE MECHANISMS.
AND THAT IS PROVING FRUITFUL
IN A NUMBER OF RESPECTS BUT,
THE ALTERNATIVE WAY IS TO
ACTUALLY TRY TO IDENTIFY THE
UNDERLYING REASONS FOR
SPORADIC ALS AND I THINK A LOT
OF THE GENETIC STUDIES ARE
MAKING QUITE A BIT OF PROGRESS
THERE. THERE'S ALSO A LOT OF
INTEREST IN THE ENVIRONMENTAL
EXPOSURES THAT MAY CHANGE ONCE
RISK OF DEVELOPING ALS OVER
TIME. THIS IS NOT LIMITED TO
ALS. THIS IS SOMETHING THAT
WE RUN INTO A LOT WITH MANY
AGE-RELATED DISORDERS OF THE
PROBABLY EXPOSURES OVER THE
COURSE OF OUR LIFETIME THAT
AFFECT RISK, MAYBE NOT
IMMEDIATELY, BUT TEN-YEARS
DOWN THE LINE. AND IT BE VERY
CHALLENGING TO PARCEL THOSE
OUT. THIS IS AN AREA OF FOCUS
FOR THE NIH. IT IS ACTUALLY
ONE OF THE TOPICS THAT WAS
AWARDED A TRANSFORMATIVE
RESEARCH APPLICATION OR AWARD
FOR A GROUP HERE TO LOOK AT
ENVIRONMENTAL EXPOSURES AND
ACTUALLY THE CONNECTION WITH
GENETICALLY INHERITED FACTORS.
SO SOME SORT OF PREDISPOSITION
THAT YOU GET WHEN YOU'RE BORN
IN THE INTERACTION WITH THE
ENVIRONMENT I THINK ONE OF THE
QUESTIONS THAT CAME UP IN THE
QUESTION AND ANSWER BOX ASKED
ABOUT THE QUESTION AND ANSWER
AND TO THE GENES AND THE RISK
OF DEVELOPING THAT OVER THE
COURSE OF A LIFETIME. IT'S
EXACTLY THE QUESTION THAT
RESEARCHERS ARE TRYING TO
ANSWER THROUGH THIS
TRANSFORMATIVE AWARD AND THEY
HAVE DEVELOPED APOLOGETIC RISK
THIS POTENTIALLY COULD EXPLAIN
SOME OF THAT RISK AND THE
QUESTION NOW IS HOW IT
INTERACTS WITH THE
ENVIRONMENT. ONE BIG PROBLEM
IS THAT ALL OF HER INFORMATION
NOW IS RETROSPECTIVE. PEOPLE
WITH ALS AND WE TRIED TO GO
BACK IN TIME TO FIGURE OUT
WHAT THEY MAY BE EXPOSED TO.
ONE PRIORITY WILL BE TO OBTAIN
INFORMATION AND EVEN MATERIALS
FROM PEOPLE AND TO SEE WHAT
HAPPENS TO THEM OVER TIME.
THIS WILL TRY TO DETERMINE
WHAT ARE THE FACTORS THAT WE
CAN MEASURE LATER ON AND
DETERMINE THEIR PROBABILITY OF
HELPING ALS. I THINK THAT IS
AN AREA THAT CAN CHANGE A LOT
IN THE NEXT SEVERAL YEARS. IT
WILL HELP US MODEL THE DISEASE
WAS WE IDENTIFY THOSE FACTORS.
>>: THANK YOU.
>>: I COULD SIMPLY ADD
THAT I THINK THAT WE CAN
RESPOND TO PROGRESS OVER THE
LAST COUPLE OF YEARS HAVING
ACCESS TO DATA SETS. IT WAS
MENTIONED ABOUT WORK AND
SUPPORT FOR THE NY DC. THAT
CERTAINLY HAS FACILITATED, NOT
ONLY IDENTIFY DISEASE CAUSING
MUTATIONS BUT ALSO GENETIC
MODIFIERS AND MARKERS.
THERE'S SUCH EXAMPLES AND I
THINK HAVE VERY IMPORTANT
IMPLICATIONS FOR THE DISEASE
PROCESS. AT THE END OF THE
DAY IT'S JUST AN INCREDIBLY
COMPLEX SPORADIC ALS DISEASE.
THERE'S MANY UNDERLINING
PATHOLOGIES, T DP 43 FOR
EXAMPLE, YOUR POST WITH THE
LOSS OF FUNCTION AS WELL AS
THE TOXIC GAIN OF FUNCTION AND
THAT UNDERSTANDING THOSE
EVENTS AND THEN TRYING TO
MODEL IT. WHETHER IT'S AN ISP
CULTURES ARE LOW MOUSE MODELS.
THIS ALSO PRESENTS SOME
LIMITATIONS BECAUSE OF THE
FACT THAT THERE IS SPECIES
DIFFERENCES IN TERMS OF HOW
THESE BIOLOGICAL PROCESSES AND
EVENTS AND SPLICING OCCUR FOR
EXAMPLE. IT'S A COMBINATION
OF UNDERSTANDING THE
COMPLEXITY OF THE DISEASE AND
THEN DEVELOPING THE
APPROPRIATE TOOLS AND PUBLICLY
AVAILABLE DATA SETS FOR US TO
MODEL THE SYSTEMS BETTER.
>>: THANK YOU SO MUCH.
THE SECOND CLARITY IS TO THEN
FOCUS ON A BETTER
UNDERSTANDING OF WHAT THIS
MICROORGANISM THAT TENDS TO
ANALYZE THE CLINICAL
[INDISTINCT] AND IN
PARTICULAR, WHY SOME NEURONS
ARE DYING FOR PEOPLE THAT LIVE
WITH ALS IN THIS NEURONS HAVE
DIED. AND THAT HAPPENS
SOMETIMES WITH THE SAME
MUTATION FOR EXAMPLE. SO
MICHAEL YOU HAVE EXPERIENCE IN
BOTH OF THESE AND CAN MAYBE
DESCRIBE WHAT WE KNOW ABOUT
THIS AND MECHANISMS BETWEEN
THESE DISEASES?
>>: YES, THIS IS A REALLY
IMPORTANT TOPIC THAT THE
WORKING GROUP FELT THAT WE
SHOULD ADDRESS SYSTEMATICALLY.
SO AS BOB BROWN AND MARK VERY
NICELY STATED IN THEIR
INTRODUCTIONS, FTD AND ALS IS
A SPECTRUM OF BURROW DISORDERS
AND THE PATIENT CAN OF FTD,
ALS AND CIGNA BOTH TOGETHER,
IT CAN HAVE A ONE FOR THE
OTHER ONE AFTER THE OTHER WORK
TOGETHER. WE UNDERSTAND THAT
THESE DISORDERS ARE RELATED
BOTH CLINICALLY BUT ALSO
GENETICALLY WITH A LOT OF
OVERLAPS OF CAUSAL GENES AND
FAMILIES. UNFORTUNATELY SOME
GENES ONLY CAUSE ALS OR ONLY
COST FTD. IT IS A RELATED THE
AGGREGATION AND CIVILIZATION
OF THIS COMMONALITY ACROSS
MANY TYPES OF FTD ANIMALS ALL
OF ALS. WHAT WE REALLY DON'T
UNDERSTAND IS WHY SOME PEOPLE
DEVELOP FTD AND OTHER PEOPLE
DEVELOP ALS? AND SOMETIMES AS
MENTIONED, IN A SINGLE FAMILY.
THIS IS GOING TO TELL US A LOT
ABOUT WHETHER THE TERM IS
SELECTIVE VULNERABILITY AND
TWICE A CERTAIN TYPE OF NEURON
DEGENERATES IN FROM THE CORTEX
OR THE TEMP ORAL LOBE AND THAT
ANOTHER TYPE OF NEURON
DEGENERATES AND ALS ONTO THE
MOTOR CORTEX WERE OFF TO THE
SPINAL CORD. SO, WHAT IS
DRIVING THAT EVEN WITHIN A
SINGLE FAMILY? ARE THESE
ADDITIONAL GENETIC RISK
FACTORS ARE PROTECTED GENES?
ARE THESE ENVIRONMENTAL RISK
THAT SOMEBODY WITHIN THE
FAMILY HAS BEEN EXPOSED TO TO
MAKE THEM FORM FTD IN ADDITION
TO ALS? THESE ARE REALLY
UNKNOWNS IN ONE OF THE BIG
CHALLENGES IS THAT GENETICS
BENEFITS FROM LARGE SAMPLE
POPULATIONS. BUT THIS IS
RELATIVELY RARE DISORDER SO
WERE GOING TO HAVE TO REALLY
HARNESS THE POWER OF
COLLABORATIVE EFFORTS
WORLDWIDE TO START TO DEVELOP
DATABASES THAT ARE SHARED AND
MINED ACROSS TO RESEARCHERS
AND IDENTIFYING THESE
CONTRIBUTE FACTORS THAT CAUSE
ONE TO DEVELOP FTD, ALS, OR
BOTH. I THINK IT'S GOING TO
BE CRUCIAL IN HIS HYPOTHESIS
GENERATE APPROACH TO THEN COME
BACK TO BASIC SCIENCE AND THEN
TO BE MODELED AND WITH ANIMAL
MODELS DETERMINE IF THOSE
FACTORS ARE THERE THAT MIGHT
BE CAUSAL OR ACTUALLY HAVING
AN IMPACT ON THE TYPE OF
NEURON THAT IS VULNERABLE AND
POTENTIALLY THE TYPE OF
PATHOLOGY THAT DEVELOPS.
>>: THANK YOU. SO,
ANOTHER THING THAT WE HAVE
DISCUSSED A LOT AND WHY SOME
INDIVIDUALS WOULD BE RESISTANT
TO ALS? AS THEY ARE CARRYING
THAT MUTATION. AND RELATED TO
THIS EQUATION IS WHY IS THE
AGE OF ONSET OF ALS CAN BE SO
WIDELY DIFFERENT. SAMMY COULD
YOU PLEASE EXPLAIN SOME OF THE
DEFINING FACTORS UNDERLINING
THIS RESILIENCE AND WHY IT
MIGHT PROVIDE CRUCIAL
INFORMATION.
>>: I THINK YOU'RE RIGHT
THIS IS A REALLY IMPORTANT
QUESTION THAT I'M NOT SURE IF
WE REALLY PAY ENOUGH ATTENTION
TO A LOT OF TIMES. WERE VERY
FOCUSED ON THE CAUSES OF
DISEASE BUT WERE NOT ALWAYS
THINKING ABOUT WHAT TO PREVENT
DISEASE. WHILE THERE'S MANY
PEOPLE WHO GET ALS THERE'S
MANY PEOPLE WHO DO NOT. IS
THERE SOMETHING RATHER THAN
SOMETHING BEING PRESENT IN
PEOPLE WITH ALS OR IS IT
RATHER THAT THEY ARE MISSING A
FACTOR THAT'S IMPORTANT FOR
RESILIENCE? IT'S GOOD THAT WE
TALK ABOUT THIS NOW RIGHT
AFTER MICHAEL SPOKE ABOUT THE
FACT THAT SOME CELL TYPES ARE
SUSCEPTIBLE OR VULNERABLE ANTS
WERE THINKING ABOUT SOMETHING
THAT CAUSES DEAF IN THOSE
CELLS. BUT MAYBE THEY'RE
MISSING SOMETHING THAT MAKES
ALL OF THE REST OF THE SALES
RESISTANCE. IT'S THE WAY THAT
MANY OF OUR STUDIES ARE
CURRENTLY DESIGNED IS TO PICK
OUT THOSE RISK FACTORS BUT
THERE ARE METHODS AND
APPROACHES THAT WE CAN USE TO
LOOK AT THE OTHER SIDE OF THE
COIN TO FIND OUT IF THERE'S
OTHER FACTORS THAT PROMOTE
RESILIENCE THAT WE MAY NOT
HAVE NECESSARILY IDENTIFIED
BEFORE. THERE'S LOTS OF
LESSONS TO BE LEARNED HERE
FROM OTHER CONDITIONS AND
OTHER NEURODEGENERATIVE
DISORDERS, INCLUDING
ALZHEIMER'S DISEASE. THEY'VE
BEEN ABLE TO TAKE ADVANTAGE OF
POPULATIONS THAT HAVE GENETIC
PREDISPOSITIONS TO DISEASE AND
DIFFERENT ON SENSE OF AGES AND
FIND OUT WHAT FACTORS ARE
IMPORTANT FOR THE ONSET OF
AGING AND CAN FIND SOME SORT
OF FACTOR THAT DELAYS ONSET.
THIS IS OFTEN DONE IN GENETIC
STUDIES IN HUMANS BUT WITH
VERY LARGE ANIMAL STUDIES THAT
A SIMILAR APPROACH CAN BE
TAKEN TO IDENTIFY RESILIENCE
FACTORS. I THINK THERE'S A
LOT TO BE GAINED BY FOCUSING
ON THIS PARTICULAR ASPECT.
>>: THANK YOU. THE NEXT
THING I WOULD LIKE TO MENTION
AND I THINK IT'S ALREADY BEEN
INVOLVED BEFORE AND IT'S GREAT
TO COME BACK AND SIT DOWN AND
SEE THAT THERE IS A NEED TO
HAVE THIS AND TO UNDERSTAND
AND PREDICT WHAT OTHER EVENTS
CAN LEAD TO CONFESSION FROM
PRESENTING SYMPTOMATIC STAGES
OF ALS. WITH THE INDIVIDUAL
CARRIERS HEARING THIS
MUTATION. COOPER MAYBE YOU
CAN TELL US WHAT YOU THINK
ABOUT THIS AND THEN I THINK
THAT IF YOU CAN CONTRADICT
THAT DISCUSSION.
>>: AS YOU SAID I THINK
THIS IS GOING TO COME UP A
LOT. THIS IS CRITICALLY
IMPORTANT AND I THINK
UNDERSTUDIED TRADITIONALLY
ANYWAY. IN MY MIND THERE'S
REALLY TWO FUNDAMENTAL REASONS
WHY WE HAVE TO UNDERSTAND THIS
PROCESS. AS A MORAL AND THEN
THERE'S A PRACTICAL REASON.
MORALLY SPEAKING, AS A GENE
CARRIER DAYS FROM I HAVE NASTY
THE CIRCULATION TO MY ARM I
WANT TO BE ABLE TO READ
LITERATURE THAT CAN TELL ME
WHAT'S GOING ON AND WHAT I CAN
POTENTIALLY TAKE AND WHAT I
EXPECT FOR MY FUTURE. I THINK
A LOT OF FOLKS FEEL THAT WAY
TOO. AND THEN PRACTICALLY
SPEAKING, WE KNOW THIS DISEASE
THIS HAS BEEN STATED, IT
STARTS PROBABLY DECADES BEFORE
SYMPTOM ONSETS AND THE
COMPLEXITY OF THE BIOLOGICAL
PHENOMENON AT PLAY ONCE THE
DISEASE STARTS EXPANDS
EXPONENTIALLY. IT BECOMES
MUCH HARDER TO KNOW WHAT'S
GOING ON WE ARE LOOKING AT
INDIVIDUALS WHO PROBABLY HAVE
A LOT OF DIFFERENT
PATHOLOGIES. SO, IN ORDER TO
MEANINGFULLY DETER THIS
DISEASE AND TO MEANINGFULLY
UNDERSTAND WHAT'S GOING ON WE
NEED TO BEGIN SEARCHING MUCH
EARLIER. IN MOUSE MODELS, AND
I SEE DERIVED NEURAL LINES AND
YES. WITHIN THIS IS IMPORTANT
THAT WE INCLUDED THIS IN OUR
SUGGESTIONS AND THAT PEOPLE
BEGAN TO THINK IN A MORE
HOLISTIC TERM ABOUT WHEN THIS
DISEASE BEGINS AND ENDS. WE
MET I LIKE TO ADD HOW WE GO
ABOUT DOING THAT IS TO FOLLOW
INDIVIDUALS THAT HAVE DISEASE
CAUSING MUTATIONS SEE NINE FOR
EXAMPLE WOULD BE AN OBVIOUS
EXAMPLE OF WHERE YOU TRY TO
UNDERSTAND THE UNDERLYING
BIOLOGICAL MECHANISMS AND THEN
DEVELOP STRATEGIES. WHETHER
IT BE A BIOMARKER FOR A
BIOMARKER WOULD BE A CLEAR
EXAMPLE OF TRYING TO DETERMINE
WHETHER OR NOT IN
PRESYMPTOMATIC CARRIERS THERE
MIGHT BE AN INDICATION OF FINO
CONVERSION OR ESTATE OF
PROGNOSIS FOR THE INDIVIDUAL
WHO ONLY I BELIEVE, TO FEEL
THAT THAT TRANSLATES INTO
SPORADIC ALS AND THE WORK THAT
WE'RE DOING FROM A SPECIFIC
GENE CAUSING MUTATION WOULD
HAVE IMPLICATIONS FOR
OBVIOUSLY A MUCH LARGER GROUP
AND THIS WOULD BE A SPORADIC
DISEASE. I THINK MANY LABS
ARE PURSUING THAT AND I THINK
THAT I AM QUITE OPTIMISTIC
THAT IN THIS SPACE
UNDERSTANDING SPECIFIC DISEASE
CAUSING MUTATIONS IN THE
BROADER IMPLICATIONS FOR
SPORADIC ALS AND WITH WHAT
COOPER HAD JUST MENTIONED.
>>: THANK YOU. I THINK
THAT IS A VERY IMPORTANT ONE
WHICH IS REALLY HIGHLIGHTING
HOW WE MEET AND DEVELOP THESE
TECHNOLOGIES AND SUPPLIES
THESE TECHNOLOGIES TO UPDATE
MECHANISMS AND ALWAYS
QUANTIFIED IN THE SPECIFIC
TARGET. SO MICHAEL AND SAMMY
YOU CAN DESCRIBE WHITE IS THE
SO PARTICULAR IN ONE AND WITH
APOLOGIES?
>>: I THINK THAT A S ALS
FILLED HAS BEEN FANTASTIC AT
ABDUCTOR ANSWERS THE MISSED
OPPORTUNITIES OF THIS GROUP
HAS IDENTIFIED MY WIFE IS IN
THE ONCOLOGY ALWAYS REALIZE
THAT WE ARE ABOUT THE CANCER
FIELD AND TIME DURATIONS
CANCER AND A LOT OF WHAT MY
TEAM IS UNSUCCESSFUL HE HAS
COME FROM THE CANCER FIELD.
SOME OF THAT IT COMES FROM
SCREENING AND IDENTIFY
RESILIENCE FACTORS THAT SAMMY
MENTIONED THAT'S BEEN DONE BY
THE CANCER FIELD FOR A LONG
TIME AND WE NEED TO DO MORE OF
THAT HERE. SOME OF THOSE
OTHER USES FACIAL TRANSCRIPT
TONE EXCEPT MALL COLEY
MENTIONED. IT'S ONLY BEING
APPLIED ALS FIELD. SOMETHING
THAT WE DO WELL IN THIS FIELD
IS BEEN AN EARLY ADOPTION OF
HUMAN STEM CELL MODELS AND I
THINK THAT THERE'S MANY
INVESTIGATORS ON THIS PANEL
THAT USE THESE AND THINK ABOUT
THE FOREFRONT OF USING THESE
TWO MODEL FAMILIAL FORMS OF
THIS DISEASE AND THIS HAS NOW
GENERATED THE LARGEST
GENETICALLY LAUNCH ANY
DISEASE. I THINK IN SOME
RESPECTS WE ARE TAKING A
LEADERSHIP ROLE HERE. THIS
BEHOOVES US TO IDENTIFY OR
ADOPT SOME OF THESE NEW
TECHNOLOGIES THAT CAN BE
TRANSFORMATIVE IN OTHER FIELDS
AND THEN ALSO TO ENTICE SOME
OF THOSE INVESTIGATORS WHO ARE
LEADERS IN THEIR FIELDS TO
COME AND JOIN US IN THE ALS
FIELD AND WORK WITH US. WHO
MAYBE HAVE NEVER WORKED IN
THIS FIELD BEFORE BUT BRING A
LOT TO THE TABLE.
>>: I COMPLETELY AGREE
AND I KEEP THINKING ABOUT THIS
SAYING WHEN SOMEBODY TOLD ME
WHEN I FIRST STARTED AND OLD
QUESTIONS WITH NEW TECHNOLOGY
AND YOU CAN USE THAT THERE'S
SO MUCH NEW TECHNOLOGY OUT
THERE THAT MICHAEL ALLUDED TO
PEOPLE HAVE ALLUDED TO AND
HAVE PUT TOGETHER TO ANSWER
SPECIFIC QUESTIONS OUTSIDE THE
REALM OF ALS AND NEVERTHELESS
CAN STILL BE APPLIED TO THE
SAME QUESTIONS THAT WE HAVE
BEEN TRYING TO ANSWER FOR A
LONG TIME. ONE AREA THAT
COMES TO MIND IS TO THIS AND SMY
WITH SPATIAL TRANSFER SCHOOL
MAKES BUT IT GOES BEYOND THAT
TO LOOK BACK SPECIALIZED SORT
OF METHODS FOR CAPTURING
CHANGES TO DNA AND ART AND A
AND ONE OF THE STRUCTURE OF
RNA AND CHANGES THAT ARE
ANYTHING THAT AFFECTED DNA OR
RNA AND NOT AN ACTUAL CODE BUT
STILL CHANGES IN GENE
EXPRESSION DISPLACING AND
ACTIVITY IN TRANSLATION
TRANSCRIPTIONAL ACTIVITY IN
ANY NUMBER OF VERY SPECIFIC
APPROACHES THAT HAVE YET TO BE
APPLIED TO SOME OF THE MODELS
AND QUESTIONS ABOUT ALS. THIS
IS AN AREA THAT I AM SUPER
EXCITED ABOUT THIS CHANGES BY
THE MINUTE AND THAT IS PART OF
THE GOOD THING IN THAT CASE.
>>: THAT'S WHY THIS
CHANGES BY THE MINUTES AND
THAT IS BY IMPLEMENTING NEW
TECHNOLOGY IS VERY IMPORTANT
BECAUSE IT'S GOT CHALLENGES
INCLUDING, TO BE RECRUITS THIS
BUT ALSO TO RETRAIN THESE GENE
TRANSMITTALS AND MY LAST
QUESTION THIS DISCUSSION IS IF
YOU WANT TO ADDRESS THIS AND
HOW DO WE DO WITH THAT?
>>: I AM HAPPY TO DO SO.
FIRST I AM VERY HAPPY TO AGAIN
BE A PART OF THIS AND BE A
PART OF THIS ON THE CO-
PANELIST ENTERING YOUR PAPERS
AS I WAS A GRAD STUDENTS
ALREADY WERE WALKING THE WALK
WHEN WE SAY WERE TRAINING THE
NEXT GENERATION OF SCIENTISTS.
THANK YOU TO ALL FOR LAYING
THE GROUNDWORK FOR US NEW
SCIENTIST AS WELL. I THINK
WHAT I COULD DO IS WHEN WE SEE
SOMEBODY EXCITED TO JOIN THE
ALS WHO HAS A DIFFERENT
PERSPECTIVE IS TO INVITE THEM.
THIS CAN HAPPEN ACROSS ALL
FIELDS IS NOT UNIQUE TO ALS.
RESEARCH HAS CHANGED AND
PREPRINTS ARE OUT AND PEOPLE
ARE MORE COMFORTABLE SHARING
DATA AND WE ARE SEEING VERY
EXCITED PEOPLE THAT ARE COMING
IN FROM DIFFERENT FIELDS, LIKE
COMPUTER SCIENCE. AS MICHAEL
AND SAM WERE ALLUDING TO, THEY
ARE APPLYING NEW TECHNOLOGIES
AND NEW APPROACHES TO THE
FIELD AND THEY SHOULD BE
WELCOMED. I THINK WE SHOULD
ALL TRY TO BE THE BEST
VERSIONS OF OURSELVES AS WE
TRY TO MENTOR THE NEXT
GENERATION. MANY OF THESE
PEOPLE HERE ARE EXTREMELY
APPROACHABLE AND NICE TO WORK
WITH AND I'VE HAD THE
OPPORTUNITY TO WORK WITH THEM
AS WELL. I THINK WE CAN
CONTINUE TO DO THAT. WOULD WE
SEE A NEW SCIENTIST
APPROACHING US WITH NEW IDEAS,
LET'S SHARE DATA AND TO BE
OPEN. IF THEY HAVE NEW IDEAS
WE SHOULD WELCOME THEM AS
WELL. ACADEMIA AND THE WAY IT
IS SET UP, PUBLICATIONS ARE A
LITTLE BIT DIFFERENT. PEOPLE
CAN BE TERRITORIAL OF
AUTHORSHIP ET CETERA. BUT THE
MODEL IS CHANGING. I THINK
WERE NOW BEING MORE OPEN
BECAUSE THE DISEASES THAT WE
WORK WITH AFFECTED PATIENTS.
IT'S NOT JUST ABOUT OUR CAREER
GROWTH AS WELL. I THINK ALL
OF US AT DIFFERENT LEVELS IF
WE CAN ENCOURAGE NEW
SCIENTISTS. THE OLDER
SCIENTIST PERHAPS TO JUST
SHARE DATA OPENLY AND APPLYING
NEW METHODS AND AGAIN, BE THE
BEST VERSION OF OURSELVES AS
WE TRAINED GENERATION OF
SCIENTISTS I THINK WE COULD
TACKLE THIS DISEASE AND WE
COULD BE GOOD STEWARDESS AND
GOOD SCIENTISTS AS WELL.
EMILY YOU CERTAINLY HAVE A LOT
MORE EXPERIENCE THAN I DO SO I
WELCOME YOUR COMMENTS.
>>: THERE'S A WELCOMING
NEW PEOPLE INTO THE FIELDS AND
THERE'S ACTIVELY GOING OUT
INTO TESTING THEIR ARMS AND
STRONGLY URGING THEM TO CHANGE
THE GROUP AND THEN
FACILITATING THE ADOPTION OF
NEW TECHNOLOGIES REQUIRES
TRAINING AND DISSEMINATION.
SOMETIMES IT REQUIRES HANDS ON
TRAINING AND WORKSHOPS AND
SOMETIMES IT REQUIRES
DIFFERENT INCENTIVES FOR
EXPERTS, SUCH AS EXPERTS IN
THOSE METHODS TO JOIN THE
FIELDS AND ALL OF THESE
EFFORTS ARE UNDERWAY. CAN SEE
IT IN THE CHANGES IN FUNDING
OPPORTUNITY ANNOUNCEMENTS FROM
THE NIH, FROM PUBLIC AND
PRIVATE PARTNERSHIPS. THE
FOCUSES MORE ON COLLABORATION
AND ON BRINGING IN NEW
TECHNOLOGIES TO THE FIELD AND
INCENTIVIZING THIS THROUGH AN
EMPHASIS ON INTERDISCIPLINARY
TEAM SCIENCE AND ON THE
DEVELOPMENT OF COURSES AND
BOOKSHOPS THAT TEACH PEOPLE
HOW TO DO THIS AND ON
PUBLISHING VIDEOS THAT SHOW
PEOPLE IMPLEMENTING THESE
METHODS. SO, IT'S NOT GOING
TO BE ONE SOLUTION. IT'S
GOING TO BE A COMBINATION OF
SOLUTIONS TAILORED TO HAVE THE
MOST STRATEGICALLY TAILORED TO
HAVE THE MOST IMPACT.
>>: THANK YOU SAMMY AND
EVERYONE. THIS IS THE END OF
THIS DISCUSSION AND WE ARE NOW
GOING TO SPEND OUR REMAINING
TIME TO ANSWER AS MANY
QUESTIONS AS POSSIBLE ABOUT
THE PRIORITIES IDENTIFIED IN
THIS WORKING GROUP. FOR
EVERYONE FEEL FREE TO CONTINUE
TO ENTER QUESTIONS USING THE
ZOOM QUEUE AND A BOX. ALL OF
THE QUESTION AND COMMENTS WILL
BE ON THE WEBSITE. WE MAY NOT
HAVE TIME TO ANSWER ALL
QUESTIONS THAT WE ARE
COLLECTING THEM AND WE WILL
CONSIDER THEM. WE MAY COMBINE
SOME QUESTIONS AND WE WILL
SYNTHESIZE QUESTIONS AND
ANSWERS ON THE MEETING
WEBSITES AFTER THIS EVENT. WE
HAVE RECEIVED A FEW QUESTIONS
AND WE WILL READ THEM AND
MEMBERS OF THE PANEL WILL
ANSWER THEM AS MANY QUESTIONS
AS WE CAN. YOU WANT TO START?
>>: THANK YOU. BUT I AM
AFRAID THAT YOU GET THEM BOTH
TO QUESTIONS, BOTH OF YOU.
THE FIRST ONE IS, HOW ARE WE
MAKING FORMS OF ALS AND
GENETIC CAUSES OF ALS THAT
OCCUR IN LOW AND MIDDLE INCOME
COUNTRIES A PRIORITY? QUITE
OBVIOUSLY BIOLOGY AND MENTAL
FACTORS ARE SIGNIFICANTLY
DIFFERENT IN THESE COUNTRIES
AND FOR THESE POPULATIONS
COMPARED TO THE GLOBAL NORTH.
EQUITY DICTATES IT WOULD MAKE
A CONCERTED EFFORT TO INCLUDE
RESEARCH IS RELEVANT FOR THESE
POPULATIONS. COVER THIS A
LITTLE BIT WOULD YOU LIKE TO
START?
>>: I DID COVER AND I DO
WANT TO RECOGNIZE THE EFFORTS
WHO ARE WORKING HARD ON THIS
AS WELL. SOMETIME THE CALLS
ARE AT 6:00 A.M. SO I MISS
THEM BUT HE IS GRACIOUS ENOUGH
TO SEND EVERYBODY THE MINUTE
SO THAT'S WONDERFUL. WHAT WE
NEED OUR SAMPLE SIZES FROM
THESE COUNTRIES. WE NEED TO
SUPPORT OBTAINING GRANTS,
WEATHERS NIH GRANTS ARE LOCAL
GRANTS AS WELL. I KNOW THIS
DISCUSSIONS AT THESE MEETINGS
ABOUT LOCAL GRANTS THAT GROUPS
CAN GET AS WELL. SO WHAT ARE
THE END OF SENDING DATA TO
GROUPS THAT ARE SET UP TO
PROCESS DATA, IT WOULD BE
PREFERABLE FOR THEM TO HAVE
FULL AUTONOMY OVER THEIR DATA.
THEY ARE THE ONES ANALYZING
THEIR DATA. THERE IS AN
EFFORT AND THERE NEEDS TO BE A
BIGGER EFFORT AND WE DO SEE
THAT IN THE PSYCHIATRIC GENOME
CONSORTIUM GROUP. ALSO VERY
LUCKY TO HAVE AN AMAZING
STATISTICAL GENETICIST IN
AUSTRALIA, NAOMI RAY OF
COURSE. I WENT TO REQUEST ALL
OF HER BECAUSE SHE DOES A LOT
OF WORK FOR OUTSIDE OF THE
PRIMARY EUROPEAN COHORT AS
WELL. BUT WE NEED ARE SAMPLE
SIZES. I THINK DOCTOR MICHAEL
WARD ALSO ILLUSTRATED THIS AS
WELL. WE ALL HAVE A DIFFERENT
GENETIC RISK, IS THE GENETIC
RISK FROM A DIFFERENT
POPULATION PROTECTIVE? OR IS
IT ACTUALLY COMBINED WITH
SEPARATE SYSTEM? SO, THE
EFFORTS ARE THERE AND THEY
NEED TO BE AMPLIFIED AND
AGAIN, THIS WAS ONE OF THE
MAIN PRIORITIES LISTED BY OUR
GROUP. LET'S SEE HOW THINGS
GO IN THE FUTURE. BUT SAMPLE
SIZES FROM THESE GEOGRAPHICAL
AREAS THAT ARE MISSED IN THE
CURRENT STUDIES IS WHAT IS
ABSOLUTELY NEEDED TODAY.
>>: THANK YOU.
>>: SOMETIMES WE ARE
LIMITED BY RESEARCH
INFRASTRUCTURE IN THESE
LOCATIONS AND THAT'S WHY
COLLECTING LARGE NUMBERS CAN
BE CHALLENGING. BUT AS A
MULTI, MODEL DATA SETS GROW
AND AS WE LEARN HOW SOME
ASPECTS OF WHAT YOU CAN STUDY
ADDITIONALLY TO GENOTYPE AND
ENVIRONMENTS, PERHAPS WE CAN
BRIDGE SOME OF THESE GAPS BY
STUDYING SAMPLES THAT ARE
RELATIVELY MORE FEASIBLE TO
CORRECT ON THESE POPULATIONS
AND LINKING STUDIES IN THOSE
TYPES OF SAMPLES AND LEARNING
FROM THE LARGER DATA SETS THAT
WE HAVE ALREADY COLLECTED.
THAT ALSO EMPHASIZES THE
IMPORTANCE OF MAXIMIZING
INFORMATION THAT YOU CAN
COLLECT FROM COHORTS THAT IT
IS POSSIBLE FOR YOU TO STUDY
AT SCALE. ASPECTS OF THESE
CAN INFORM MORE FOCUSED
STUDIES WHERE FEASIBLE.
>>: INFRASTRUCTURE KEY IS
THAT HE IS IN IT AND BEING
ACTIVE IS VERY IMPORTANT. BUT
MAKING SURE THAT WE DO ENGAGE
THE RESEARCHERS IN LOCAL
COMMUNITIES. THE SECOND
QUESTION IS AGAIN FOR BOTH OF
YOU, GEOCODE INCLUDE PEOPLE
WITH C9 EXPANSION IN YOUR
STUDIES? I AM IN FRANCE AND
WE ARE MANY AND ALL OVER THE
WORLD. HOW ABOUT YOU START
US.
>>: WE ABSOLUTELY DO AND
IF THEY ARE IN FRANCE, THEN
THEY ARE ALREADY PART OF A
PROJECT OF MINE. THIS IS THE
LARGEST AIRLESS GENOME
SEQUENCING STUDY AND
MULTIMODAL CITY IN THE WORLD.
WE MAKE A CONCERTED EFFORT TO
INCLUDE EVERYBODY HE WANTS TO
PARTICIPATE, THAT'S THE WHOLE
POINT OF HIS LARGE,
MULTINATIONAL STUDIES.
>>: I JUST WANT TO
CLARIFY, BECAUSE I UNDERSTAND
WHY THIS QUESTION EVEN AROSE.
IT ALSO DEPENDS ON YOUR
RESEARCH QUESTION. FOR
EXAMPLE, AND TRADITIONAL
ASSOCIATION STUDIES PEOPLE
WANT TO FIND A NEW GENETIC
SIGNATURE. A LOT OF THE TIME
ACTUALLY INDIVIDUALS THAT ARE
POSITIVE FOR KNOWN CAUSAL
MUTATIONS, LIKE C9 ARE 72 ARE
EXCLUDED IN THAT THEY MAY OR
THEY ARE GOING TO GIVE A
SIGNAL OF SOMETHING WE ALREADY
KNOW, THAT BEING SAID DESPITE
EFFORTS TO EXCLUDE AND THEN
FINDING SOMETHING NOVEL, THE
TOP HIT IS ALWAYS SOD ONE.
THAT MEANS THAT WERE DOING THE
SIGNS CORRECTLY. IT'S NOT
THAT WE ARE EXCLUDING THEM TO
EXCLUDE, IT FOLLOWS THE
RESEARCH QUESTION.
ALTERNATIVELY, I THINK IT WAS
BOTH TWO OF OUR PANELISTS
MENTIONED THIS AS WELL. THERE
IS A FAMILIAR WORLD BUILDING
AS WELL AS INTERNAL
VARIABILITY AND C9 IS A
CLASSIC EXAMPLE OF THAT AS
WELL. SOME INDIVIDUALS
PRESENT WITH ALS, SOME WITH
FTD, AND SOME COMBINED. IS
THERE ANOTHER GENETIC HIT OR
IS OR ANYTHING ELSE HAPPENING.
THAT QUESTION SPECIFICALLY
TARGETS INDIVIDUALS AND
INCLUDE INDIVIDUALS WITH SEAT
NINE OR SEVEN TO EXPANSION.
IT DEPENDS ON THE RESEARCH
QUESTION AS WELL. BUT OF
COURSE, EVERYBODY IS WELCOME
AS WAS JUST MENTIONED.
>>: ACTUALLY SOME
QUESTIONS THAT YOU ARE
MENTIONED, SOME QUESTIONS CAN
ONLY BE ANSWERED BY TAKING A
PEOPLE ONLY WITH C9 OR OTHER
EXPANSION.
>>: WOULD BE GRATEFUL IF
YOU COULD TRY TO ANSWER A
DIFFICULT BUT IMPORTANT
QUESTION. WHICH IS, WHAT IS
THE BEST EFFORT FOR
IDENTIFYING AND VALIDATING NEW
SURVEY TARGETS?
>>: I THINK THIS IS
REALLY CHALLENGING BECAUSE
IT'S INCREDIBLY EXPANSIVE.
MAYBE SOME EXAMPLES WOULD
HELP. IN MY OPINION MOST OF
OUR PROMISING TARGETS HAVE
COME EITHER FROM GENETICS OR
FROM HUMAN PATHOLOGY FROM
PEOPLE WHO UNFORTUNATELY DIED
OF ALS. A GREAT EXAMPLE IS
SOD ONE DISCOVERED BY BOB
BROWN WHICH EXPERIENCED
SEVERAL DECADES AND AFTER MUCH
RESEARCH INTO THE MECHANISMS
OF HOW THOSE MUTATIONS CAN'T
NEURON DEAF, WE NOW HAVE A
VERY PROMISING PHASE THREE
THERAPY THAT WAS DEVELOPED.
AND THEN OF COURSE, FOR NON-
FAMILIAL CAUSES, THE DISCOVERY
OF TB 343 GLOBALIZATION WAS
FOUND IN 97% OF PATIENTS WITH
ALS. THIS REALLY PROVIDES A
MECHANISM INTO STUDYING
SPORADIC ALS FOR PATIENTS WE
DON'T HAVE FAMILIAL GENES TO
ASSOCIATE WITH THIS DISEASE.
IN MUCH WORK SINCE DISCOVERED
IN 2006 HAS LED TO AN
UNDERSTANDING OF MECHANISMS OF
ACTION. WHEN HE GETS LOST
FROM A NUCLEAR IS THAT BAD
THINGS HAPPEN THE SPLICING OF
GENES AND ONE OF THE MAJOR
DISCOVERERS OF SOME OF THE
GENES THAT BECOME SPLICE CAN
BE SEEN IN BOTH CELLULAR
MODELS AND PATIENTS WITH
DISEASE. AND NOW THERE'S A
NUMBER OF DRUG COMPANIES TO
DEVELOP EFFORTS TO TARGET THAT
SPLICING BIOLOGY THAT IS GOING
ON. I THINK THOSE HAVE BEEN
EARLY LEADS FROM STRONG GENES
THAT CAUSE FAMILIAR FORMS OF
DISEASE AND PATHOLOGY THAT'S
OBVIOUS. THE NEXT CHALLENGES
ARE GOING TO BE TO IDENTIFY
THOSE OTHER CAUSES OF SPORADIC
PROVIDERS AND WE'VE BEEN
DISCUSSING THIS DURING THE
SESSION AND HOW TO MODEL THOSE
IN CELLULAR OR ANIMAL MODELS.
FIGURE OUT INTERVENING
PATHWAYS IF THEY IMPROVE THOSE
MODELS AND THEN ULTIMATELY
WORKING WITH COMPANIES TO
DEVELOP THERAPIES AND THEN
TESTING THOSE HYPOTHESES IN
TRIALS.
>>: I THINK AN IMPORTANT
POINT IS WE TALKED ABOUT
QUANTITY EMERGING TECHNOLOGIES
AND I FELT LIKE I DID IN THE
PAST MAYBE TEN-YEARS AGO OR
SO. WE WERE WORKING UNDER
SOME ASSUMPTIONS. BUT IF YOU
CAN LOOK AT ADVANCES IN CRYO
EM TECHNOLOGIES IN MASS -BASED
APPROACHES, THIS APPROACH IS
ARE NOW TURNING US INTO MUCH
SMARTER SCIENTIST BECAUSE FOR
UNDERSTANDING THE STRUCTURES
OF HIS DISEASE-RELATED
PROTEINS WHICH NORMALLY
ACCUMULATE. THE POTENTIAL
PROTEIN POST- TRANSLATIONAL
MODIFICATIONS THAT ARE
ASSOCIATED FOR EXAMPLE WITH T
DP FOUR THREE, HOW DOES
PHOSPHOR RELATIONAL OR
SEDATION INFLUENCE THAT
SHUTTLING BETWEEN THE NUCLEAR
AND CYTOPLASMIC COMPARTMENTS?
THAT WAS CERTAINLY A THING
THAT WAS ECHOED WITHIN THIS
WORK GROUP IS HOW EMERGING
TECHNOLOGIES ARE IMPACTING,
AND ONLY DNA AND RNA
CAPABILITIES, BUT CERTAINLY
PROTEIN STRUCTURES AS WELL.
>>: DO YOU WANT TO ASK
THE NEXT ONE?
>>: THANK YOU. THIS
QUESTION IS GOING TO PEER AND
SCOOPER. OUR LARGE FAMILY OF
FAMILIAL ALS AND DEVASTATED AS
WE CONTINUALLY LOSE FAMILY
MEMBERS FROM THIS HORRIFIC
DISEASE. THE ALS GENE HAS
BEEN IDENTIFIED BUT IS NOT AS
COMMON AS SOME OF THE OTHER
ALS GENES. OUR QUESTION TO
YOU IS WHAT IT ALL MAKES SENSE
TO START INCREASING GENE
CARRIERS ON MEDICATION AS SOON
AS POSSIBLE? THIS MAY ALLOW
FOR A SLOWER PROGRESSION OF
THE DISEASE AND MAY EVEN HOLD
THE DISEASE. OUR FAMILY HAS
SADLY WITNESSED TOO MANY
MEMBERS WHO BARELY LAST WHEN
YOU'RE WITH THIS DISEASE.
SINCE HER SUIT FEW SUCH
OPTIONS IT WOULD MAKE NO SENSE
TO STOP THESE APPRECIATIVE
OCCASIONS TO IMPROVE THESE
GENE CARRIERS. AS A
GRANDMOTHER WITH A HUSBAND TO
HAVE THE DISEASE I'VE SEEN MY
CHILDREN AND MY GRANDCHILDREN
PASS FROM ALS, EACH AND EVERY
DAY OF MY LIFE I'M REMINDED OF
THE LOVE ONCE I HAVE LOST AND
I WILL CONTINUALLY FIGHT FOR
THE TREATMENT OF THE DISEASE
UNTIL MY DYING DAY. COOPER
PERHAPS YOU WOULD LIKE TO
START.
>>: MAYBE I CAN START
COOPER. I WENT TO THINK YOU
FOR THIS IMPORTANT QUESTION
AND IT'S A VERY MOVING
QUESTION. I WILL SAY THAT WE
ARE ORGANIZE AND TO RECOGNIZE
HOW IMPORTANT IT IS TO TAKE
PATIENTS EARLY AND AGAIN, I
WILL SAY BETWEEN THEORY AND
PRINCIPLE YES. IT WOULD MAKE
SENSE TO START TREATMENT EARLY
ON AND REGARDLESS OF SYMPTOM.
BUT I THINK IN REALITY THE
SITUATION IS A LITTLE BIT MORE
COMPLICATED THAN THAT BECAUSE
EACH OF THE DRUGS THAT ARE
APPROVED THAT HAVE POTENTIAL
SIDE EFFECTS AND WE KNOW WHAT
THE POTENTIAL SIDE EFFECTS OF
LENO AND THEREFORE, WHEN WE
ARE DOING THIS AND AS A
PHYSICIAN IN THE ABSENCE OF
DISEASE IT IS REALLY HARD TO
JUSTIFY GIVING THE PATIENT A
DRUG THAT HAS OR MAY HAVE
SERIOUS SIDE EFFECTS. NOT TO
MENTION THE FACT, IN TODAY'S
DAY GENETIC COUNSELORS TELL
PACERS AND TELL US THAT EVEN
THE FAMILIAL PATIENT THAT GENE
CARRIERS MAY NOT NECESSARILY
DEVELOP THIS DISEASE. I WOULD
LIKE TO REASSURE HER THAT
AGAIN, AS WE DISCUSSED EARLIER
TODAY THAT EFFORTS THAT WE ARE
UNDERGOING NOW AND EVERYBODY
UNDERSTANDS THE IMPORTANCE
DIAGNOSED EARLY AND TO START
TREATMENT EARLY, EVEN UP
RECENT EMETIC PHASES. THERE
ARE STUDIES UNDERGOING NOW AND
A DOCTOR IN MIAMI FLORIDA FOR
INSTANCE IN DOCTORS AT
MASSACHUSETTS GENERAL HOSPITAL
REALLY FOLLOW REFLECTIVE
CARRIERS AND WIDE VARIETY OF
GENE MUTATION KNOWN TO CAUSE
ALS. THIS IS REALLY A
LONGITUDINAL AND NATIONAL
BIOMARKER PEOPLE WHO ARE
FAMILY MEMBERS THAT WE KNOW
ARE DEVELOPING ALS AND
RECOGNIZING THAT ALS SYMPTOMS
CAN BEGIN AT ANY AGE. THE
CRITICAL OBSTACLES THAT WE DO
NOT HAVE A BIOMARKER. IN
TERMS OF THAT STUDY I THINK
THAT BY LOOKING AT SYMPTOMATIC
PATIENTS CARING FOR GENE
MUTATION RESEARCHERS HAVE
FOUND FILAMENT LEVELS AND THEY
RISE IN THE SIX-12 MONTHS
PRIOR TO THE CLINICAL DISEASE.
NOW THIS NARROW FILAMENT I
BELIEVE HAS KEY BECAUSE WE MAY
NOW BE ABLE TO USE INCREASING
BLOOD FILAMENT LEVELS TO
IDENTIFIED INDIVIDUALS WITH
ANY GENE MUTATIONS, AND EVEN
PERHAPS CONVERT THIS TRANSFER
WITH SPORADIC PATIENTS WHO ARE
THE GREATEST SHORT-TERM RISK
OF DEVELOPING ALS. THEREFORE,
WE MAY ENROLL AN INCREASING
AMOUNT OF TRIALS AND EVEN
START TREATMENT WITH THE
APPROVED DRUGS. THE GOALS FOR
THIS BIOMARKER HAVE BEEN
SYMPTOMATIC TRIALS HAVE LED
THE FOUNDATION FOR DELAYING
THE ONSET PERHAPS IN
PREVENTING THE DISEASE BY
STARTING TRIALS EARLY AND BY
STARTING DRUGS OF THE
PRESYMPTOMATIC WERE SMALL
SYMPTOMATIC LEVELS. I'M SURE,
CLARITY ITSELF I THINK THAT
COOPER WILL HAVE A MEANINGFUL
ANSWER TO THIS QUESTION.
>>: THIS IS A VERY
IMPORTANT QUESTION LIKE THAT
WAS SET AT THE BEGINNING. I
APPRECIATE YOU BEING SO
VULNERABLE IN SHARING YOUR
FAMILY STORY. I HAVE A
SIMILAR SITUATION AND IS VERY
HEARTBREAKING AND SCARY. YOU
WANT TO ASK, I FEEL THAT WAY
ALL OF THE TIME. YOU WANT TO
ACT, TAKE SOMETHING, AND DO
SOMETHING. THERE'S NOT A
REALLY GREAT TO REASON, IN MY
OPINION FOR THIS. AS IT WAS
SAID A LOT OF IT COMES DOWN TO
THAT PREVIOUSLY WE DIDN'T HAVE
GREAT BIOMARKER SINCE IT WAS
REALLY HARD TO RUN THESE
STUDIES. HIS [INDISTINCT]
THERE IS VARIABLE PENETRANCE
WHICH IS TO SAY WHICH WAS
STATED BEFORE THAT THIS
DISEASE SHOWS UP IN DIFFERENT
WAYS AT DIFFERENT TIMES AND IT
BECOMES REALLY CHALLENGING TO
RUN A STUDY. NOW WE HAVE
BETTER TOOLS AND PEOPLE
RECOGNIZE THIS IS AN IMPORTANT
UNDERTAKING AND THEY ARE DOING
IT. I HOPE WE HAVE SOME
RESULTS FOR YOU SOON AND AS I
SAID PREVIOUSLY, I THINK THIS
IS A MORAL ISSUE, WE SHOULD BE
TAKING DRUGS AND COMPANIES AND
RESEARCHERS ARE RECOGNIZING IN
THE FUNCTIONAL ISSUE TOO. AT
THE END OF THE DAY YOU MAY NOT
GET GOOD RESULTS IF YOU'RE
WAITING TOO LONG. IT MAY BE
REALLY IMPORTANT TO DETER
DISEASE AT EARLY STAGES, JUST
SCIENTIFICALLY WE NEEDED TO
UNDERSTANDS. THANK YOU FOR
YOUR QUESTION.
>>: THANK YOU COOPER.
I'M GOING TO TAKE ONE OF THE
COMMENTS OF THE CHAT AS WELL
AND HIGHLIGHTED AS WELL. SO
JEAN WHO ALSO SITS ON ONE OF
THE PANELS HAS SAID, AVERAGE
LIFE EXPECTANCY OF A SEAT 90
CARRIERS 65, ACCOUNTING FOR
THE 90% PENETRANCE.
HIV-POSITIVE PEOPLE WERE PUT
ON DRUGS WITH NOTE WITH SIDE
EFFECTS OF THOSE SIGNS EVIDENT
DISEASE ACTIVITY TO GREAT
EFFECT. I SUPPOSE AT THAT
TIME THERE MIGHT'VE BEEN A
BIOMARKER OF HIV INFECTION OF
COURSE, BUT NECESSARILY A
BIOMARKER OF TRANSFORMATION
INTO AIDS.
>>: NEXT QUESTION FOR
SAMMY AND IT IS ASKED IN A
PROGRESSIVE USING THE REPEAT
[INDISTINCT]
>>: I LIVED IN THESE
QUESTIONS EACH OF THEM CAN BE
45 MINUTES TO ONE HOUR.
>>: YES, TIME IS GOING.
>>: I WILL TRY TO
SUMMARIZE. FIRST I WANT TO
PREFACE BY SAYING, CHRISTOPHER
IS A REALLY POWERFUL
TECHNOLOGY, THERE STILL SOME
QUESTIONS REGARDING HIS
SPECIFICITY. IF YOU TARGET OR
USE THIS TO REACH THE GENOME
YOU CAN EXCISE THAT REGION OF
THE GENOME AND IN THIS CASE,
THIS MAY BE A GOOD THING BUT
THAT IS A LIFELONG CHANGE. IF
IT'S 100% SPECIFIC AND YOU DO
WHAT YOU INTEND TO DO THAT IS
GREAT BUT THERE'S ALWAYS THE
QUESTION OF WHETHER OR NOT
IT'S DOING SOMETHING SOMEWHERE
ELSE AND THAT HAS BEEN
SOMETHING THAT, I'M NOT SURE
IF WE HAVE A GREAT ANSWER TO.
IT'S COME UP IN SOME RESPECTS
IN CHINA, FOR INSTANCE, WERE
THERE HAVE BEEN SOME STUDIES
DONE ON PEOPLE WHO MAY NOT
UNDERSTAND THE IMPLICATIONS OF
THESE ADVANCES. GETTING BACK
TO THE SPECIFIC QUESTION,
THERE'S BEEN A LOT OF
ATTENTION AND SOME VERY
EXCITING DATA ON USING CRISPER
TO EXCISE THE REPEAT. JUST TO
MENTION A FEW. CLAIRE AND I
THINK, CLEAR: AT ANOTHER
INSTITUTE HAS DEVELOPED A
GREAT MEANS OF EXCISING THE
REPEAT FROM HUMAN STEM CELL
DIRECT NEURONS AND LOOKING AT
THE IMPLICATIONS IT'S
INCREDIBLY INTERESTING BECAUSE
DEPENDING ON HOW YOU DO IT AND
WHAT EXCISE YOU GET DIFFERENT
RESULTS, SOME OF WHICH ARE
UNANTICIPATED WHICH IS WHY WE
NEED THIS WORK. JUST A FEW
DAYS AGO I THINK THERE WAS A
STUDY OUT FOR CHRISTIAN
MUELLER'S GROUP AT THE
UNIVERSITY OF MASSACHUSETTS
LOOKING AT THIS AND SEE NINE
REPEAT IN MODEL SYSTEMS,
INCLUDING TRANSGENIC MICE AND
HUMAN STEM CELL DIRECT
NEURONS. THIS INVOLVES MANY
PEOPLE ON THIS CALL TODAY. I
THINK THIS IS MOVING QUICKLY,
AND EVEN IF WE DO NOT USE
CRISPER TO EXCISE REPEATS. I
THINK OTHER SCIENTISTS HAVE
USE CRISPER TO TARGET THE
EXPANDED REPEATS OF RNA THAT
IS MADE FROM THE EXPANDED C9
LOCUST AND THAT HAS SHOWED
SOME PROMISING RESULTS TOO.
THIS IS AN AREA OF ACTIVE
RESEARCH AND HOPEFULLY WE WILL
SEE SOON.
>>: SAMMY THERE'S A FEW
OF THE QUESTIONS IN A BEACON
ANSWER BECAUSE OF YOUR
AUTHORITY IS RELATED TO THAT.
IT'S TOO ELABORATES ON
APPROACHES TO STUDY DARK
MATTER [INDISTINCT] IS A
GENERAL SET OF APPROACHES? I
KNOW THEY HAVE THAT STUDY SO
MAYBE QUICKLY IF YOU CAN.
>>: I CAN TOUCH ON IT A
LITTLE BIT BECAUSE I THINK
PRIMARILY RIGHT NOW WE ARE IN
A PHASE THAT'S FOCUSED ON
EPIDEMIOLOGY. IT'S REALLY
USING DATA THAT'S AVAILABLE TO
US TO IDENTIFY THOSE EXPOSURES
THAT ARE MOST CLOSELY EXPOSURE
THE RISK OF DEVELOPING ALS. I
GUESS HERE IN MICHIGAN WE HAVE
THE DUBIOUS DISTINCTION OF
HAVING ONE OF THE HIGHEST
RATES OF ALS IN THE COUNTRY.
MAYBE THAT'S BECAUSE OF THE
SUPERFUND STATES SO A LOT OF
TOXINS AND TRASH HAS BEEN
DUMPED HERE AND PESTICIDES.
GREAT PLACE TO LIVE, IT IS
VERY BEAUTIFUL BUT THERE'S A
SLIGHTLY HIGH RISK OF
DEVELOPING ALS. TRYING TO
TURN AROUND AND USE AS AN
ADVANTAGE TO IDENTIFY THE
SPECIFIC EXPOSURE THAT ARE
ASSOCIATED WITH ALS. THAT IN
TURN NEEDS TO MOVE BACK INTO
THE AND OUTCOMES. LIKE I
SAID, THAT IS ONE OF THE
PURPOSES OF THE TRANSFORMATIVE
AWARD.
>>: THANK YOU SAMMY.
>>: THANK YOU. SO THIS
IS A QUESTION FOR LYNN AND
MICHAEL. HUGH IS RESPONSIBLE
FOR CONFIRMATORY STUDIES AND
ON BIOMARKERS? MANY PAPERS
HAVE BEEN ALTERED IN THE PAST
DECADE ALL ENDING WITH
CONFIRMATION NEEDED AND
SEEMINGLY NOTHING HAPPENS AND
NO CONSENSUS ON BIOMARKERS HAS
BEEN MADE. LIKELY IT'S NOT
TESTING OR TRUSTING ANY
BIOMARKER. IN SO TO ENTER
THIS GOPHERS?
>>: SURE. I THINK IT
LARGELY DEPENDS ON THE
BIOMARKER IN AND OF ITSELF.
WE ALREADY HEARD ON NARROW
FILAMENT LIGHT WHICH IS A WELL
ACCEPTED MARKER FOR NEURAL
ACCIDENTAL INJURY. IT HAS
BEEN HIGHLY WORKED UP AN ALS
PATIENT COHORTS. BOTH
SPORADIC AS WELL AS
GENETICALLY DEFINED ALS GROUPS
C9 AND SOD ONE. THERE I THINK
THAT GIVEN THE PLATFORM, SINCE
THIS IS A WIDELY AND IS A
COMMERCIALLY AVAILABLE KIDS IT
IS WELL VALIDATED THAT THOSE
RESULTS, EVEN THOUGH THEY
MIGHT BE PRODUCED BY
INDEPENDENT GROUPS AT VARIOUS
INSTITUTIONS IN BOTH ACADEMIA
AS WELL AS AN INDUSTRY. YOU
HAVE HIGH CONFIDENCE THAT FOR
THE SET BIOMARKER IT REALLY
HAS EMERGED AND IS WELL
VALIDATED. IN ADDITION, SOME
CLINICAL SITES INCLUDING MAYO
CLINIC FOR EXAMPLE NOW ARE
OFFERING THAT TO PATIENTS AS
THEY GET THEIR ALS WORK UP.
IT'S NOT NEEDED OBVIOUSLY FOR
THE DIAGNOSIS FOR ALS BUT I
THINK NOW SOME CLINICIANS AND
NEUROMUSCULAR AS WELL AS
BEHAVIORAL NEUROLOGY INCLUDING
THAT AS A MEANS TO FOLLOW NFL
LEVELS DURING PROGRESSION.
NOT ONLY FOR CLINICAL BUT
PERHAPS FOR RESEARCH AND
POINT. I THINK WERE THINGS
GET A LITTLE BIT, AND THIS MAY
BE BECAUSE YOUR QUESTION IS
FOR NEWER TARGETS, SOME
TARGETS ARE DEVELOPED BY
COMPANIES FOR EXAMPLE FOR
TARGETING ENGAGEMENTS. IS
THERE A DRUG GETTING INTO THE
BRAIN AND HAVING A THERAPEUTIC
EFFECT? FOR THOSE TYPES OF
BIOMARKERS THEY MIGHT BE
DEVELOPED BY A SPECIFIC GROUP
AND THOSE FREE AGENTS WOULD BE
SPECIFIC TO THAT LABORATORY OR
INSTITUTIONS. THERE COMES A
LITTLE BIT MORE CHALLENGING.
BY IN LARGE, FOUR NOVEL
BIOMARKERS IT COMES THROUGH
THAT THE COOPERATIVE EFFORTS
IN THOSE FREE AGENTS ARE
SHARED AND WE HAVE HAD GREAT
TRACK RECORD AS A GROUP FOR
THIS. ONE WOULD BE THE
DEVELOPMENT OF A POLY GDP FOR
C9 AND HOW PATIENTS, AS WELL
AS THE BIO FLUIDS OF THAT WE
ARE SHARED TO DEVELOP
MEANINGFUL COHORTS INVALIDATED
COHORTS. THIS WAS ACHIEVED SO
I THINK FOR NEWER BIOMARKERS
TO SPECIFICALLY ANSWER YOUR
QUESTION, I THINK IT'S
CHALLENGING BECAUSE THEY ARE
NOT A COMMERCIALLY AVAILABLE
KIT. IT WOULD REQUIRE FURTHER
OPTIMIZATIONS OF THOSE AND
VALIDATION OF OTHER
INDEPENDENT COHORTS TO REALLY
INCREASE YOUR CONFIDENCE THAT
WHAT YOU'RE SEEING WITH THIS
MARKER IS IN FACT MEANINGFUL.
MICHAEL.
>>: TO ADD ON TO WHAT WAS
SAID, I THINK NARROW FILAMENT
HAS BEEN AN UNBELIEVABLY
USEFUL BIOMARKER. I THINK ANY
SERIOUS STUDY INCLUDES THIS AS
A COMMON READOUTS. ONE OF THE
CHALLENGES HOWEVER IS THAT A,
IT'S NOT SPECIFIC. AS SEEN IN
ALS AS WELL AS A RANGE OF ORAL
GENERATIVE DISORDERS BECAUSE
ITS RELEASE AS THEY DO THIS.
THAT'S A RELATIVELY LATE
BIOMARKER BUT IS STILL REALLY
USEFUL. ONE CAN SEE FROM
TRIALS THAT THE NEURAL
FILAMENT LEVELS CHANGE IN
THOSE RETREATED VERSUS
UNTREATED. IT IS VERY CLEAR
EVEN BEFORE CLINICAL DATA CAME
BACK TO THIS DRUG WAS WORKING.
I THINK THAT'S AN ILLUSTRATION
OF HOW THAT BIOMARKER HAS
ALREADY PROVEN ITS WORTH. BUT
WE NEED TO MOVE FURTHER
UPSTREAM AND WE NEED TO START
MOVING TOWARDS MOLECULAR
TARGETS AS IT WAS SAID. BUT I
ALSO THINK THERE'S A LOT OF
EXCITEMENT AND ONGOING EFFORTS
TO DEVELOP BIOMARKERS, THAT'S
A PROTEIN THAT IS LOCALIZED IN
90% OF ALS. THERE'S BEEN A
NUMBER OF ATTEMPTS TO MAKE
BIOMARKERS TO EITHER MONITOR
THE AGGREGATION STATUS PROTEIN
BUT INCREASINGLY TO LOOK AT
WHAT HAPPENS WHEN IT'S NOT
FUNCTIONAL. OUR TEAM HAS BEEN
DEVELOPING THIS IN EARLY DAYS
BUT I THINK, FINALLY BECAUSE
OF THE EFFORTS OF OTHER GROUPS
WE KNOW HOW TO DESIGN HIS
BIOMARKERS. I THINK THE
FUTURE IS BRIGHT FOR FTD ALS
BIOMARKERS, BUT I THINK IT'S
EARLY DAYS.
>>: THANK YOU MICHAEL AND
WHILE YOU'RE ANSWERING, THERE
IS A QUESTION IN THE CHAT I
WONDER IF YOU COULD ADDRESSES
IS, IT IS GREAT TO FIND NEW
PATHWAYS AND DRUG TOPICS BUT
HOW WILL HE BALANCE RESEARCH
FOR NEW PATHWAYS IF WE ARE
TURNING TO PATHWAYS OF PURITY
FOUND IN TREATMENTS? WE
CLEARLY HAVE TO DO BOTH AT THE
SAME TIME TO WHAT IS THE RIGHT
BALANCE? DUE TO A SHORTAGE OF
RIGHT NOW?
>>: THIS IS A GREAT
QUESTION AND A HARD QUESTION
IS NUMBER OF APPROACHES. IF
YOU LOOK AT SOD ONE DISCOVERED
IN 1990 THREE, AND IN 2022,
NEARLY THREE DECADES LATER, IT
SEEMS WE HAVE AN EFFECTIVE
THERAPY. I THINK THE PATH
TOWARDS DRUG DEVELOPMENT IS
SHORTENING * SHORTENING AS WE
GET BETTER MODELS LIKE STEM
CELL MODELS. BUT IT'S STILL
NOT GOING TO HAPPEN OVERNIGHT.
WE NEED TO IDENTIFY THOSE
TARGETS IN A MEAN TO ENGAGE
PHARMA. ACADEMIC IS NOT GOOD
AT DEVELOPING DRUGS, WE NEEDED
THEM ON BOARD. THEY GET
EXCITED WHEN THEY SEE
MECHANISTIC DATA THAT IS
COMPELLING TO WHAT THEY WANT
TO INVEST HUNDREDS AND
MILLIONS OR BILLIONS OF
DOLLARS INTO THERAPY. I THINK
THAT SOMETHING THAT WE NEED TO
DO TO CONVINCE AND COMPEL THEM
TO BE PARTNERS. THAT'S GOING
TO HELP WITH TARGETS THAT HAVE
BEEN IDENTIFIED BUT IT IS
ACADEMIA AND IT IS THE MOST
BASIC OF SCIENCES THAT
IDENTIFY THOSE NEW TARGETS IS
ABSOLUTELY CRITICAL TO DO
THAT. IT'S ONLY BEEN SEVERAL
YEARS WE KNOW THAT TV FOR
THREE MISS SPLICING IS A
CORNERSTONE OF ALS
PATHOGENESIS. THAT IS A
BRAND-NEW TARGET THAT WE NEED
TO CONTINUE TO PURSUE. I
THINK ANY OF US WOULD BE NAÏVE
TO CONTINUE TO THEIR SUDDENLY
BIG SURPRISES IN THE ALS FIELD
WITH THINGS AND IT BEING VERY
IMPORTANT, VERY UPSTREAM, AND
VERY TARGETABLE. I THINK WE
NEED TO DO BOTH WITH THE WAY
THAT WE DO THAT AS WE CONTINUE
TO GET MORE FUNDING, BRINGING
PEOPLE FROM THE OUTSIDE TO GET
MORE RESEARCHERS, WE INVOLVE
PHARMA TO BROADEN THE NUMBER
OF GROUPS ARE INVESTED AND
ENGAGED. TAKE YOU VERY MUCH
DOCTOR MICHAEL.
>>: YES, HAVE A QUESTION
WHICH IS, WHO IS RESPONSIBLE
FOR SOME ACQUISITION OF GENE
TESTING? EACH LAB TEST
DIFFERENT SETS OF GENES.
>>: IS AN EXCELLENT
QUESTION BECAUSE I'M GLAD IT'S
BEING ASKED BECAUSE THERE IS A
VERY SPECIFIC EFFORT
HAPPENING. ACTUALLY BY THE
NIH ECONOMY OF THIS CLINICAL
GENE GNOME INTERNSHIP. THAT
IS FOR ALS BUT FOR MANY
DISEASES. AS A FORMATION OF
EXPERT PANEL, THERE IS IN ALS
EXPERTS PANEL AND WE ARE LED
BY OUR FEARLESS LEADER, MATT
HARMS, ALSO FROM COLUMBIA. HE
HAS INVITED A DIVERSE GROUP OF
EXPERTS ACROSS THE GLOBE AND
WE MEET TWICE A MONTH AND WE
GO OVER EVERY SINGLE GENE THAT
WAS PROPOSED TO BE ASSOCIATED
WITH ALS. AND I SAY PROPOSED
BECAUSE SOME OF IT IS NOT REAL
ASSOCIATIONS, THE SAMPLE SIZES
ARE SMALL DESPITE IT BEING
PUBLISHED. WE GO THROUGH
EVERY GENE AND WE AS A
COMMUNITY DECIDE IS THIS GENE,
SHOULD WE RECOMMEND TESTING OF
THIS GENE? WE HOPE THAT OUR
EFFORTS WOULD THEN BE DIGESTED
BY COMMERCIAL COMPANIES AS
WELL AS ACADEMIC LABS TO
MODIFY THEIR GENE PANELS.
THAT WAY IT IS STANDARDIZED.
AND ACTUALLY GOING TO POST AND
I WILL FIND A WAY TO POST THE
LINK TO OUR EFFORTS SO FAR.
WE HAVE BEEN MEETING SINCE
2020 AND WE HAVE A LIST. FOR
EVERY GENUS BEEN PROPOSED TO
BE ASSOCIATED WITH ALS, AS
THEIR DEFINITIVE EVIDENCE, AND
WE USED A VERY STRICT
CRITERIA, SOMETHING LIKE SOD
ONE. WE'VE ALL AGREED THAT IT
IS A BONA FIDE ALS GENE AND
THIS SHOULD BE ON EVERY SINGLE
PANEL AS WELL AS C9 AND MANY
OTHERS. THERE'S OTHER ALS
GENES THAT FAILED THESE VERY
RIGOROUS AND AGREED-UPON
CRITERIA. THOSE GENES SHOULD
NOT BE TESTED IN ANY PATIENTS,
PRESYMPTOMATIC OR NOT. OUR
RECOMMENDATION IS FOR THEM TO
BE REMOVED FROM PANELS.
AGAIN, WE CANNOT FORCE
COMPANIES TO REMOVE GENES.
BUT WHAT WERE TRYING TO DO IS
ENSURE THAT THEIR PANELS ARE
COMPREHENSIVE. THIS DOES NOT
MEAN BIG, THIS MEANS THAT
YOU'RE TESTING THE CORRECT
TARGETS. THERE WAS ANOTHER
QUESTION THE CHECK TO THAT WAS
RELATED IF YOU DON'T MIND,
SOMEBODY ASKED WHY DON'T WE DO
GENETIC TESTING FOR
PRESYMPTOMATIC INDIVIDUALS?
WE CAN. I'M ALSO A CLINICAL
MOLECULAR GENETICIST AND AS
PART OF THE RECOMMENDATIONS
FROM A COLLEGE IS THAT
INDIVIDUALS THAT HAVE A FAMILY
HISTORY, THEY THEMSELVES WE
DON'T KNOW IF THEY CARRY THE
GENETIC MUTATION OR NOT. FOR
THEM TO BE ELIGIBLE FOR THIS
ADULT ONSET DISORDER, THEY
HAVE TO BE GREATER THAN 18
YEARS OF AGE, THAT'S WHAT OUR
COLLEGE RECOMMENDS AND THEY
ALSO HAVE TO GO THROUGH A
GENETIC, PRESYMPTOMATIC
PROGRAM. THEY CAN'T JUST BE
IN A ROOM NEUROLOGIST FOR
EXAMPLE. ALTHOUGH MANY OF THE
NEUROLOGIST HAVE VERY
EXTENSIVE GENETIC BACKGROUND
OF COURSE AND I WENT TO
RECOGNIZE THAT. BUT THE
INDIVIDUAL THAT'S ABOUT TWO
AND WHO IS CURRENTLY
PRESYMPTOMATIC AND IS ABOUT TO
BE PRETESTED FOR THE
PRESENTATION THEY RECOMMEND
THEY TALK TO A GENETICIST AND
UNDERSTAND WHAT THIS MEANS.
UNDERSTAND WHAT POSSESSION OF
THIS VARIANCE THAT COULD LEAD
TO THEIR DISEASE MEANS. WERE
NOT DEALING WITH CYSTIC
FIBROSIS OR SOME OF THESE
HIGHLY PENETRANT MONOTONIC
DISORDERS. WHILE DEALING WITH
THE DISORDER, DEPENDING ON
YOUR SPECIFIC MUTATION THAT
YOU MAY CARRY, YOUR PHENOTYPE
MAY DIFFER. SO, THAT IS
ACTUALLY IN PLACE. WE CANNOT
OFFER THAT TO THE GENERAL
PUBLIC BECAUSE THE NATURE OF
THE DISEASE IS THE FACT THAT
WE NEED MORE CLINICAL
INFORMATION, WE NEED FAMILY
HISTORY AT TIMES SO FOR
INDIVIDUALS WITHOUT ANY FAMILY
HISTORY, BUT THEY THEMSELVES
HAVE THE DISEASE WERE ABLE TO
INTERPRET THAT GENETIC
VARIANTS CLEARLY AND FOR
INDIVIDUALS THAT HAVE A FAMILY
HISTORY AND WE KNOW EXACTLY
WHAT WERE LOOKING FOR, TESTING
FOR THOSE PRESYMPTOMATIC
INDIVIDUALS AS STRAIGHTFORWARD
AS WELL. THAT IS THE NATURE
OF GENETICS AND WHAT WE KNOW
ABOUT PENETRANCE AND WHAT WE
KNOW ABOUT THESE GENES THAT
HAVE BEEN STATED AS WELL.
>>: IS A HIGHLIGHTED
QUESTION AND THIS IS FOR THIS
AND AS YOU SHOW THERE HAS BEEN
GREAT PROGRESS WITH GENE
IDENTIFICATION AND THERE'S A
LARGE PROPORTION OF PATIENTS
WITH NO NONENERGY NOTE TYPES.
HOW MANY MARGINS HAVE YET TO
BE FOUND AND WHEN DO WE REACH
A POINT OF DIMINISHING
SYMPTOMS?
>>: SELL YOU ANSWER IF
YOU LIKE.
>>: OKAY, I GET ASKED
THIS QUESTION ALL THE TIME AND
I WANT TO COME BACK TO THE
COMMENTS THAT MICHAEL MADE
ABOUT HIS WIFE BEING IN
ONCOLOGISTS. ALSO AS A
CLINICAL MOLECULAR GENESIS,
PRENATAL AND CANCER ARE
BREAD-AND-BUTTER WE HAVE TO
KNOW THEM REGARDLESS OF OUR
SPECIALTY. IN CANCER IF YOU
HAVE A SPECIFIC MUTATION RIGHT
AWAY YOU'RE GIVING A MEDICINE
IF IT FITS YOUR PROFILE.
ROUTE RIGHT AWAY YOU'RE GIVING
ELIGIBILITY TOWARDS A CLINICAL
TRIAL IF YOU HAVE A SPECIFIC
GENETIC PROFILE. THAT'S JUST
BECAUSE WE HAVEN'T LOOKED AT
THESE AND SIMPLE REPEATS IN
CANCER, WE'VE LOOKED AT LOTS
OF OTHER THINGS, COPY NUMBER
VARIATIONS AND LOTS OF OTHER
THINGS THAT CAN DISRUPT THE
GENOME IN INDIVIDUALS WITH
CANCER. WE HAVE NOT LOOKED AT
EVERY ROCK OR UNDER EVERY ROCK
FOR ALS. IT MAY BE CERTAIN
THINGS ARE ABSOLUTELY NOT
ASSOCIATED WITH ALS THAT WERE
NOT THERE YET. SO, THERE IS A
POINT OF DIMINISHING RETURNS.
ABSOLUTELY, SOME NEW MUTATIONS
ARE SOME GENES THAT WE FIND
ARE QUITE RARE. BUT, IT WOULD
BE WORTHWHILE AGAIN TO COME
BACK TO THE IDEA USING THE
TECHNOLOGIES THAT'S FAIR AND
USING THE DATA THAT'S THERE
ALREADY AND APPLYING A NEW
PROPOSED IS TO DATA AND CF
COPY NUMBER VARIATIONS ARE
ENRICHED IN ALS. AT THE
DIFFERENT TYPES OF MUTATIONS
THAT WE SEE IN CANCER ARE THEY
ENDED AND RICH IN ALS SO WE
COULD MOVE ON AND WE CAN KIND
OF KNOW EXACTLY WHAT WERE
LOOKING FOR SO THAT WAY
CONTINUE TO INVEST IN
DIMINISHING RETURNS. I WOULD
LOVE TO HEAR HEAR YOUR AS
WELL.
>>: I LIKE WHAT YOU SAID
A LOT AND I WOULD ALSO LIKE TO
SEE THIS CONVERSE VIEW WHICH
IS THAT FOR THE RARE VARIANCE,
USUALLY VARIANCE OF A LARGE
EFFECT. THIS ALSO
CONTRIBUTION FROM THE VERY
SMALL EFFECT VARIANCE AND
PROBABLY EVERYBODY HAS LOTS
AND LOTS OF SMALL EFFECT
VARIANCE THAT TO MOVE THE
PERSON TOWARDS DEVELOPING ALS
BUT THAT OTHER FACTORS GO OVER
THE THRESHOLD. SO HOW MANY OF
THOSE GENES ARE YET TO BE
FOUND? WE DON'T KNOW. WE DID
A LARGE ENOUGH ASSOCIATIONS
STUDY HOW MANY WOULD YOU FIND?
PROBABLY HUNDREDS MORE. WE
SEE THAT AND OTHER DISEASES ET
CETERA, THE LARGER THE STUDY
THE MORE THE SMALL EFFECTS
THAT YOU FIND. THE QUESTION
BECOMES HOW IMPORTANT IS THAT
THERAPEUTICALLY? I THINK THEY
MIGHT BE SURPRISINGLY
IMPORTANT AND THERAPEUTICALLY.
IF YOU LOOK AT SOMETHING LIKE
HYPERCHOLESTEROLEMIA, SOME OF
THE EXAMPLE THAT THEY HAVE AN
EFFECT ON A VARIANCE THAT
REALLY ARE A SMALL EFFECTS BUT
YET THEY CAN LOWER YOUR
CHOLESTEROL MORE EFFICIENTLY
TO BE THERAPEUTIC. IT MAY BE
THAT EVEN THOSE COMMON
VARIANCE IF THERE ANY CRUCIAL
PART OF THE PATHWAY THEY MIGHT
BE WORTH INTERVENING
THERAPEUTICALLY. SO, I HOPE I
CAN TAKE THIS OPPORTUNITY TO
ASK THIS QUESTION ON THE LIST,
IS THAT OKAY? ELLEN PHILLIPS
HAS SAID THAT SHE WOULD LIKE
TO ANSWER THIS QUESTION LIVE.
THIS QUESTION IS FROM HADLEY.
DEAR FRIENDS, IN MY OPINION,
ONE OF THE LIMITATIONS THAT WE
FACE TODAY IS DUE TO OUR
INABILITY TO INCLUDE THE
BREAKING POINT OF ALS TO THE
BIG PICTURE. WE USUALLY LEAVE
THE UPPER NEURONS OF THIS
DISCUSSION WHAT DO YOU THINK
WE SHOULD DO TO CHANGE THIS?
>>: NOT REALLY I DON'T
KNOW HOW THAT HAPPENED.
>>: I WAS WONDERING TOO.
ANYBODY HERE ON THE PANEL
WOULD LIKE TO REFLECT ON THE
ROLE OF MULTI- NEURONS AND THE
FACT THAT WE DON'T STUDY THEM
AS MUCH AS WE HAVE DONE.
>>: OTHERWISE. THINK
THINK ABOUT AND GIVE A WRITTEN
RESPONSE.
>>: I COULD SAY THIS IS A
QUESTION BUT THIS HAS BEEN
IMPORTANT TO LOOK AT THIS
ACTUALLY QUITE CHALLENGING AND
I THINK IT'S INDEED A PLACE
AND A LOT OF THE MODELS THAT
WE HAVE NOT HAD NOT BEEN
EXPLORED AND I THINK IT'S A
POINT HERE THAT IS BEEN MADE.
>>: MICHAEL ARE YOU GOING
TO ANSWER?
>>: I WAS GOING TO THINK
OF EFFORTS TO BETTER
UNDERSTAND WHAT THE CORTEX IS
INVOLVED IN THE FRONTAL
TEMPORAL WALL WHICH WILL BE
ILLUMINATING. THERE'S MANY
EFFORTS IN THE STEM CELL FIELD
TO BE ABLE TO MODEL THESE
DIFFERENT NEURAL SUBTYPES,
WHICH INCLUDES UPPER MOTOR
NEURONS. WE DO NOT HAVE GOOD
CELLULAR MODELS AS OPPOSED TO
LOWER ONES. THAT IS AN AREA
OF A GAP IN OUR KNOWLEDGE.
>>: IF I CAN EDIT
SOMETHING IT'S IMPORTANT THAT
IT'S BEEN SAID AND IT WAS SAID
BEAUTIFULLY. IT WAS REALLY
PIONEERING THESE CHALLENGES
AND THEY ARE STUDYING MOTOR
NEURONS BUT I THINK THEY CAN
ABOUT NEW TECHNOLOGIES WE HAVE
TO TAKE ADVANTAGE REALLY OF
IMAGING AND IN PATIENTS TO
REALLY LOOK AT THE UPPER MOTOR
NEURON AND IN THIS PANEL AND
THEN OFTEN IN RESEARCH WE
DON'T REALLY THINK ABOUT
STUDIES AND THESE NEW
TECHNOLOGIES THAT GO BEYOND
THE BASIC SCIENCE. THAT IS
PERHAPS AN AREA WHERE WE COULD
REALLY INVEST MORE AND LOOK AT
THE PROCESSES OF UNDERGOING
[INDISTINCT]
>>: I THINK A LOT OF
ASPECTS OF POORLY MENTIONED
CLINICALLY THINGS AS WELL. WE
DON'T HAVE THE SAME DETAIL
CLINICALLY FOR THIS. SO I
THINK WERE VERY CLOSE TO THE
FINISH TIME. YOU PROBABLY
WILL HAVE TIME FOR THE LAST
QUESTION. I'M GOING TO DIRECT
IT TO A CLOSE THEY ARE. ALL
OF THE OTHER QUESTIONS WILL BE
ANSWERED AND WILL TAKE THEM
INTO ACCOUNT THIS IS ALL WE
HAVE TIME FOR THE SESSION.
THANK YOU VERY MUCH OUR
WORKING GROUP. IT'S BEEN
WONDERFUL WORKING WITH YOU ALL
AND IT'S BEEN PRACTICALLY
PLEASURABLE WORKING WITH SUCH
LOVELY PEOPLE. THANK YOU TO
THE ATTENDEES FOR SUCH GREAT
QUESTIONS TO GET TO MY COCHAIR
FOR BEING AMAZING TO WORK WITH
AS WELL. WE WILL CONTINUE TO
COLLECT QUESTIONS THROUGH THE
ENGAGEMENT FORM ON THE MEETING
WEBSITE AND LOOK FORWARD TO
SHAPING THE ALS STRATEGIC PLAN
AS YOUR PLAN IT IS SHARE
STRATEGIC LIGHT AND ONE OF THE
IMPORTANT OPPORTUNITIES TO
ADVANCE RESEARCH. THANK YOU
ALL AGAIN.
>>: THANK YOU SO MUCH
EVERYONE.
>>: BREAKDOWN.
>>: THANK YOU TO THIS
WORKING GROUP. THIS HAS BEEN
AN INCREDIBLY SIMILAR TO A
CONVERSATION WE HAD. THANK
YOU FOR ALL OF THE
PARTICIPANTS TO ASK THESE
WONDERFUL QUESTIONS AND
CHALLENGING QUESTIONS AS YOU
CAN SEE WE DON'T HAVE ANSWERS
FOR ALL OF THESE QUESTIONS.
WE NEED TO HEAR THESE
CHALLENGING QUESTIONS THAT WE
THINK REALLY ARE FORWARD AND
WHERE DO WE NEED TO FOCUS ON
NEXT
>>THANK YOU I'M PLEASED TO BE
PART OF THIS GROUP WITH STACY.
I'D LIKE TO BEGIN BY INTRODUCING
MYSELF AND THE MEMBERS AND I'LL
ASK THEM TO INDUCE THEMSELVES IN
TURN.
I'M NEIL SCHNEIDER.
THE DIRECTOR OF THE LOU GHERIG
CENTER AT COLUMBIA AND HEAD OF
MOTOR DISORDERS HERE AND I AM A
NEUROLOGIST I FOCUS ON THE
PRACTICE OF ALS SCIENTISTS AND
MY LABORATORY FOCUSES ON
UNDERSTANDING MECHANISMS OF
NEURODEGENERATION AND ALS AND
FRONTAL TEMPORAL DEMENTIA AND
INVOLVED IN THE DEVELOPMENT OF
NOVEL THERAPEUTICS LARGELY FOR
THE RARE GENETIC FORMS OF THE
DISEASE.
BEFORE I TURN TO STACIE, I WANT
TO SAY UNFORTUNATELY FRANK
BENNETTE AND THOMAS IS UNABLE TO
JOIN US.
THOMAS IS A PROMISING YOUNG
SCIENTIST AT THE UNIVERSITY OF
ILLINOIS CHAMPAGNE.
THEY'VE CONTRIBUTED EXTENSIVELY
TO OUR STIMULATING DISCUSS AND
UNFORTUNATELY UNABLE TO JOIN US
THIS AFTERNOON.
STACIE.
>>STACE WIE WENINGER AND Ph.D.
NEUROSCIENTIST AND RUN A PROGRAM
CALLED FBRI WHERE WE FOCUS ON
INVESTING AT NEURODEGENERATIVE
DISEASES IN ACADEMIA AND IN
THERAPEUTICS AND COMPANIES AND
RUN A WEBSITE PRIMARILY FOCUSSED
ON ALZHEIMER'S DISEASE AND
COVERS MORE NEURODEGENERATIVE
DISEASES.
IT'S A WEBSITE FOR RESEARCHERS
BUT FOR ANYBODY INTERESTED IN
NEURODEGENERATIVE DISEASES AND
LEARN THE LATEST THERE.
WE'LL TURN IT TO INTRODUCE THE
REST OF OUR MEMBERS.
JOE, DO YOU WANT TO INTRODUCE
YOURSELF?
>>HI, I'M CHIEF SCIENTIFIC
OFFICER AT A COMPANY WHERE
UNIFORMLY FOCUSSED ON COMBATTING
NEURODEGENERATIVE DISEASE.
I'VE BEEN DOING DRUG DISCOVERY
AND ALS SPECIFICALLY CLOSE TO 20
YEARS AND HAVE BEEN LUCKY TO
BRING THREE DIFFERENT DRUGS TO
CLINICAL TRIALS FOR ALS.
GREAT TO BE PART OF THE
INITIATIVE AND THANKS FOR
INCLUDING ME.
STEFFEN.
>>I'M THE VICE PRESIDENT AND
HEAD OF NEUROSCIENCE AT A
PRIVATELY HELD THERAPEUTIC
COMPANY IN BOSTON FOCUSSING ON
CNS DISORDER.
I'VE BEEN AT DRUG DISCOVERY AT
LARGE PHARMA AND ADJUNCT
PROFESSOR OF BRAIN SCIENCE AT
BROWN UNIVERSITY.
>>AND NADIA I'M HEARING FROM
SOME PEOPLE THEY CAN'T SEE OTHER
PANELISTS.
>>I'M NADIA SETHI I LANDED HERE
BECAUSE I LOST MY HUSBAND TO AN
AGGRESSIVE FORM OF ALS IN 2020.
I'M A DENTIST BY TRAINING AND
VERY INTERESTED IN ALS RESEARCH
AND BACK IN SCHOOL LEARNING MORE
ABOUT THE GENETICS OF ALS AND
I'VE BEEN INVOLVED IN A LOT OF
ADVOCACY INITIATIVES OVER THE
LAST THREE YEARS AROUND STRONG
SCIENCE FOR ALS.
>>HAPPY TO BE HERE AND WORKING
WITH THE COMMITTEE ON WHAT WE'LL
PRESENT TODAY.
I'M BEEN AT PENN OVER 30 YEARS
AND RUN THE GENE THERAPY PROGRAM
IN THE ORGAN DISEASE CENTER.
>>AND HENRIK.
>>I'M HENRIK ZETTERBERG AT THE
UNIVERSITY OF LONDON AND I
ENJOYED AND GOTH ENBURG AND MY
RESEARCH IS FOCUSSED ON FLUID
BIOMARKERS FROM
NEURODEGENERATIVE DISEASES AND
HAVE BEEN WORKING ON ALZHEIMER'S
AND FRONTAL LOBE DEMENTIAS AND
LOOKING FORWARD TO THE SESSION.
THANKS.
>>I'LL TAKE THE NEXT SLIDE.
>>STACIE WILL BE DESCRIBING IN
MORE DETAIL THE PRIORITIES WE
LAID OUT IN THE DRAFT DOCUMENT.
I THOUGHT I'D BEGIN BY OFFERING
INTRODUCTORY COMMENTS AND OUR
PAN DATE WAS TO TALK ABOUT AND
MEASURE MANDATE WAS TO MAKE
SUGGESTIONS AND PRIORITIES TO
THE NIH ABOUT HOW TO TRANSLATE
THE ACCELERATION OF FUNDAMENTAL
RESEARCH INTO EFFECTIVE ALS
THERAPEUTICS.
WHAT IS TRANSLATIONAL RESEARCH.
AS DEPICTED HERE IT SITS IN
BETWEEN AT THE INTERFACE BETWEEN
BASIC AND CLINICAL RESEARCH.
THERE'S A LOT OF OVERLAP AND
THAT'S REFLECTED IN THE DRAFT
DOCUMENT.
AS WE HEARD FROM OUR BASIC
SCIENCE COLLEAGUES THIS MORNING,
BASIC RESEARCH REALLY IS
FOCUSSED ON UNDERSTANDING
MECHANISMS OF DISEASE,
UNDERSTANDING PATHWAYS THAT ARE
ACTIVE IN THE NEURODEGENERATIVE
PROCESS AND THERAPEUTIC TARGETS
TO GO AFTER IN OUR DRUG
DEVELOPMENT.
TRANSLATIONAL RESEARCH IS MORE
FOCUSSED ON TRANSLATING OR
TAKING ADVANTAGE OF THOSE
CONVENIENCES AND DOING WHAT IS
NECESSARY AND THERE'S TARGET
VALIDATION AND INVOLVES
BIOMARKER DEVELOPMENT AND THESE
ARE BIOMARKERS OF PREDICTOR
PURPOSES TO TRY TO AND YOU HEARD
ALS IS A VERY HETEROGENEOUS
DISORDER AND ONE QUESTION IS
WHETHER THERE'S BIOMARKERS THAT
CAN IDENTIFY SUB TYPES THAT MAY
RESPOND TO ONE THSHT APPROACH
VERSUS ANOTHER.
ALL THIS WOULD HAPPEN WITHIN AN
IT VO
INVOLVES THE THERAPEUTIC FOR THE
BENEFIT OF OUR PATIENTS AND
FAMILIES.
AND HOW COULD IT BE WE
UNDERSTAND TO LITTLE ABOUT ALS.
THE TRUTH IS AND AS WE HEARD
THIS MORNING, WE UNDERSTAND A
LOT ABOUT ALS.
MUCH MORE THAN WE DID CERTAINLY
80 YEARS AGO AND EVEN 10, 20
YEARS AGO.
I THINK MUCH OF THE RESEARCH
ADVANCES WE HEARD THIS MORNING
COMES FROM STUDY OF THE RARE
GENETIC FORMS OF THE DISEASE.
A BETTER UNDERSTANDING OF THE
GENETIC LANDSCAPE OF ALS.
THIS HAS PROVIDED IMPORTANT
INSIGHT INTO DISEASE MECHANISMS
AND LOOK AT CELLULAR MODELS OF
DISEASE AND USED FOR FURTHER
McN
MECHANISTIC OF THE DISEASE AND
WHAT ABOUT THE OTHER 85%, 90% OF
PATIENTS THE GENETIC STUDIES
IGNORE SOME PEOPLE.
I ARGUE THAT'S NOT THE CASE AND
THE INSIGHTS GAINED ABOUT THE
BIOLOGY OF ALS THROUGH GENETIC
FORMS OF DISEASE IS HIGHLY
RELEVANT TO THE SPORADIC FORMS
OF THE DISEASE AND WE CAN APPLY
THE LESSONS LEARNED FROM THE
RARE GENETIC FORMS TO UNDERSTAND
SPORADIC DISEASE AND WILL DEPEND
ON THE EFFORT THAT EXISTS FOR
THE NEED OF GROWTH.
SO TRANSLATIONAL RESEARCH REALLY
INVOLVES THE MOST RELEVANT OF
MODELS FOR ALS, THE HUMAN MODEL.
WHAT WE NEED TO DO THROUGH OUR
TRANSLATIONAL EFFORTS IS TO
CHARACTERIZE OUR PATIENTS
THROUGH CLINICAL,
ELECTROPHYSIOLOGICAL MARKERS AND
STUDY ALL THE VARIETIES.
WE NEED TO DO THAT THROUGH
SAMPLE COLLECTION, STORAGE,
SHARING, USE OF BIOFLUIDS AND
CELL LINES YOU HEARD DISCUSSED
THIS MORNING AND SKIN CELLS AND
FIB
FIBROBLASTS AND PLURIPOTENT STEM
CELLS AND STUDY OF THE HUMAN
MODEL.
AND INFRASTRUCTURE IS NEEDED FOR
BIOMARKER AND DISCOVERIES AS
DISCUSSED AND ALL THE EFFORT
GENERATES A LOT OF DATA.
DATA THAT NEEDS TO BE CURATED,
HARMONIZED, STORED, MANAGED AND
IMPORTANTLY SHARED.
SAMPLES AND DATA NEED TO BE
SHARED BROADLY AND YOU'LL HEAR
THEMES MENTIONED THROUGHOUT OUR
DISCUSSION TODAY AND IN THE
DOCUMENT WE SUBMITTED TO THE
NIH.
THOSE THEMES INCLUDING TO
ACCELERATE TRANSLATION OF
FUNDAMENTAL RESEARCH INTO
EFFECTIVE THERAPIES, WHAT WE
NEED IS SUSTAINED LONG-TERM
INVESTMENT BY THE NIH IN
DEVELOPING AND MAINTAINING A
TRANSLATIONAL RESEARCH
INFRASTRUCTURE TO ENSURE
RESOURCES AND INFORMATION ARE
RETAINED AT SCALE AND ENABLE
MULTIPLE STAKEHOLDERS
REPRESENTED I THINK BEAUTIFULLY
IB -- IN OUR COMMITTEE TO
SUCCEED IN THIS SPACE.
IN THINK ABOUT THE CHALLENGES
THERE'S NO NEED TO REINVENT THE
WHEEL.
THERE'S MANY EXCELLENT
TRANSLATIONAL EFFORTS SPONSORED
BY NIH THE DOD AS DR. KOROSHETZ
MENTIONED THIS MORNING, IN
RELATED DISORDER LIKE
ALZHEIMER'S AND PARKINSON'S
DISEASE AND FRONTAL TEMPORAL
DEMENTIA.
WE DON'T NEED TO REINVENT THE
WHEEL.
WE NEED TO BUILD ON THE MODELS
AND ON ALS AND INCORPORATE
EXISTING EFFORTS ONGOING WITHIN
THE ALS RESEARCH COMMUNITY SOME
OF THAT YOU HEARD ABOUT THIS
MORNING AND TARGETED ALS AND
PROJECT ALS.
THERE'S MANY GROUPS SUPPORTING
INITIATIVES AND WE NEED THE
STRUCTURE TO DO THIS BIGGER AND
BETTER.
WE NEED TO WORK ACROSS DISEASES
TO INTEGRATE DATA FROM MULTIPLE
DISORDER AND TO BREAK DOWN THE
SILOS THAT EXIST BETWEEN THE
DISORDERS IMPEDING OUR PROGRESS
IN ALS.
KEY TO OUR SUCCESS IS
PUBLIC-PRIVATE PARTNERSHIPS TO
BENEFIT OUR PATIENTS.
THE NIH HAS AN IMPORTANT ROLE TO
PLAY IN FACILITATING THIS
BETWEEN INDUSTRY AND ACADEMIA
AND ENCOURAGING PUBLIC RESOURCES
AND INDUSTRY NEEDS TO SHARE DATA
FROM TRIALS TO THE BROAD ALS
RESEARCH COMMUNITY TO ADVANCE
OUR COMMON GOALS.
SO WITH THAT, I'D LIKE TO TURN
IT OVER TO STACIE TO REVIEW OUR
SPECIFIC PRIORITY
RECOMMENDATIONS.
>>THANK YOU.
I'LL TRY TO KEEP THIS BRIEF TO
HAVE MORE TIME FOR QUESTIONS AND
DISCUSSIONS.
WE'LL BUILD ON THESE IN A LITTLE
BIT OF DETAIL BUT WAYS THE NIH
CAN CONTRIBUTE TO THE GREATER
EFFORTS OF TRYING TO TRANSLATE
THE RESEARCH FOR THESE DISEASE
AND TO ESTABLISH A NETWORK OF
ALS CENTERS OF EXCELLENCE TO
SUPPORT ALS TRANSLATIONAL
RESEARCH.
AND THE DESIGN IS NOT TO FOCUS
ON THE CARE BUT THE GOAL IS TO
HELP US UNDERSTAND THE DISEASE
BETTER AND SUPPORT
INFRASTRUCTURE SO THAT WE CAN
DEVELOP THERAPEUTICS AND DEVELOP
BETTER STANDARDS OF CARE THAT
CAN THEN BE SHARED ACROSS THE
GREATER COMMUNITY TO HOSPITALS
AND PHYSICIANS EVERYWHERE.
BUT BY FOCUSSING ON THE CENTERS
OF EXCELLENCE WE'RE GOING TO BE
ABLE TO LEVERAGE A LOT OF THE
GREAT RESEARCH BEING DONE ACROSS
DIFFERENT DISEASE AREAS TO LEARN
FROM THOSE AND TO BE ABLE TO
REALLY TAKE BASIC SCIENCE
DISCOVERIES AND BE ABLE TO
SUPPORT MORE BASIC SCIENCE
RESEARCH THROUGH THE LARGE DATA
REPOSITORIES THAT BY DEFINITION
NEED TO BE CONCENTRATED FOR
EFFICIENCY AND CONSISTENCY IN
HOW SAMPLES ARE COLLECTED AND
STORED AND USED.
AND IN SHARING THAT DATA BROADLY
WITH THE ENTIRE COMMUNITY OF
RESEARCHERS SO THAT WE CAN
TRANSLATE FINDINGS OUT OF THE
CENTERS OF EXCELLENCE INTO
BETTER CARE AND BETTER
THERAPEUTICS.
SO WITHIN THESE CENTERS OF
EXCELLENCE WE'RE PROPOSING A
PROGRAM PROJECT CORE THAT REALLY
IS FOCUSSED ON STUDYING THE
BASIC MECHANISMS OF ALS AND
TRYING TO IDENTIFY NEW
THERAPEUTIC TARGETS.
THERE'LL BE A CLINICAL CORE TO
OVERSEE BIO FLUID COLLECTION AND
DEEP PHENOTYPING AND THAT'S
INCREDIBLY IMPORTANT AND A WANT
TO EMPHASIZE JUST COLLECTING BIO
FLUIDS AND SAMPLES FROM PATIENTS
AND JUST CATEGORIZING AS ALS IS
NOT ENOUGH WE NEED DEEP
PHENOTYPING AND UNDERSTANDING
THAT GOES BEHIND EACH SAMPLE
WHICH IS HOW FAST DOES THE
DISEASE PROGRESS.
WHAT'S THE GENETIC BEHIND THE
DISEASE?
HOW DO WE PAIR THE DIFFERENT
BIOMARKERS WE SEE WITH THE
CLINICAL PICTURE?
BECAUSE I THINK WE UNDERSTAND
THAT ALS CONSISTS OF A GROUP OF
DISEASES THAT CAN ACTUALLY BE
CAUSED BY MUTATIONS IN DIFFERENT
GENES OR DIFFERENT RISK FACTORS
AND BEING ABLE TO UNDERSTAND
IT'S NOT ALS IS ALS IS ALS JUST
LIKE YOU DON'T SAY SOMEONE WITH
CANCER IS ALL THE SAME WE HAVE
TO UNDERSTAND THE GENETICS
DERIVING THAT FORM OF CANCER TO
PAIR IT WITH THE RIGHT
THERAPEUTIC SO WE NEED DEEP
CLINICAL PHENOTYPING TO
UNDERSTAND WHAT AN INDIVIDUAL
ALS LOOKS LIKE TO UNDERSTAND THE
DIFFERENCES BETWEEN PATIENTS SO
EVENTUALLY WE'LL BE ABLE TO PAIR
THE RIGHT PATIENTS TO THE RIGHT
TYPES OF THERAPEUTICS.
WE PROVIDE CHARACTERIZATION OF
ALL PARTICIPANTS TO UNDERSTAND
THE GENETICS TO GO WITH THE
CLINICAL PHENOTYPING TO BE ABLE
TO SUBDIVIDE PATIENTS TO
UNDERSTAND THE DISEASE
PROGRESSION AND HOW IT'S
DIFFERENT ACROSS GENETIC
DRIVERS.
AND WE NEED AN ADMINISTRATIVE
CORE TO PROVIDE ASSISTANCE
THROUGHOUT THE PROGRAM.
SO BUILDING ON THE IMPORTANCE OF
THE BIO SAMPLES AND DATA
INFRASTRUCTURE, IDENTIFICATION
OF MARKERS AND MECHANISMS THAT
DISTINGUISH THE SUBTYPES OF ALS
IS SO IMPORTANT.
AGAIN, I THINK WE NEED TO
UNDERSTAND WHAT AN INDIVIDUAL'S
ALS IS BEING DRIVEN BY
BIOLOGICALLY TO PAIR WITH THE
RIGHT TREATMENT.
TO DO THAT REQUIRES LOOKING AT A
LOT OF PATIENTS WITH ALS HAVING
BEEN DEEPLY PHENOTYPED AND
STUDIED TO LOOK FOR BIOMARKERS
OF DISEASE.
WE HEARD ABOUT THE IMPORTANCE OF
BIOMARKERS.
WE'LL HEAR MORE IN THIS SECTION,
BIOMARKERS, BIOMARKERS,
BIOMARKERS NOT BE EMPHASIZED
ENOUGH.
WE ALL UNDERSTAND THAT TO TREAT
ANY NEURODEGENERATIVE DISEASE,
ALS INCLUDED, AS EARLY AS
POSSIBLE WE'LL WANT TO TREAT
BEFORE SOMEONE IS SHOWING
SYMPTOMS OR AT LEAST AS EARLY AS
IS POSSIBLE.
HOW WILL THAT BE ACHIEVED?
BIOMARKERS.
WE NEED TO UNDERSTAND WHEN THE
BIOMARKERS START TO MUTATE AND
USE THEM TO SUPPORT CLINICAL
TRIALS.
I CAN'T OVERSTATE THE IMPORTANCE
OF BIOMARKERS.
TO BE SUCCESSFUL WE'LL NEED A
LARGE SCALE STANDARDIZED
REPOSITORY AND HENRIK WILL SPEAK
MORE TO THE IMPORTANCE OF HOW
WE'RE COLLECTING THE BIOMARKERS
KEPT IN THE FOREFRONT OF
STANDARDIZATION AND WE NEED TO
COLLECT THEM IN THE SAME WAY AND
BEING TREATED IN THE SAME WAY SO
WE CAN COMPARE ACROSS STUDIES.
IT IS ALSO INCREDIBLY IMPORTANT
THE SAMPLES BE BROADLY AVAILABLE
TO THOSE SCIENTISTS IN ACADEMIA
AS WELL AS INDUSTRY.
WHEN WE'RE TALKING ABOUT
DEVELOPING NEW THERAPEUTICS
THAT'S GOING TO COME FROM NOVEL
DISCOVERIES IN ACADEMIA AND
TRANSLATION OF DISCOVERY AND
INDUSTRY THAT REQUIRES US TO
BOTH SUPPORT THE INDUSTRIAL
SCIENTISTS TRYING TO DEVELOP THE
THERAPEUTICS.
AGAIN, WE DON'T NEED TO REINVENT
THE WHEEL AND FINALLY A
SIGNIFICANT PRIORITY AND THERE'S
A NOVEL APPROACH WHETHER
KNOCKING DOWN A DREAM AND AWAY
HEARD ABOUT CRISPR AND GENE
EDITING.
THERE'S INCREDIBLE NEW
TECHNOLOGIES AT OUR FINGER TIPS
BUT THERE'S STILL A LOT OF
DEVELOPMENT TO GO INTO ACTUALLY
HAVING THESE READY FOR USE IN
THESE POPULATIONS.
SO HAVING FEDERAL SUPPORT TO
VALIDATE THE NOVEL TARGETS AS
WELL NOVEL TECHNOLOGIES IS GOING
TO BE INCREDIBLY IMPORTANT AND A
WILLINGNESS.
THERE'S RISK INVOLVED HERE TO
BRING THE NOVEL TECHNOLOGIES
FORWARD AND WE NEED TO
UNDERSTAND THAT AND WAYS TO DO
EXPLORATORY TRIALS.
WE ALSO ENCOURAGE MORE
PUBLIC-PRIVATE PARTNERSHIP AND
ACADEMIA AND INDUSTRY BECAUSE IT
WILL TAKE THE COLLABORATION TO
TAKE THESE TO THERAPEUTICS.
WE ALSO THINK HAVING THE SUPPORT
THROUGH THE ALS CENTERS OF
EXCELLENCE AND THROUGH THE CORPS
WE TALK ABOUT TO ENABLE CLINICAL
TRIALS WHETHER THAT THE BE
PERFORMED BEEN THE CENTERS OF
EXCELLENCE OR CLINICAL END
POINTS OR DEVELOPED IN
COLLABORATION IN THE BIOMARKER
CORE, ALL THAT WILL BE IMPORTANT
TO ENABLE EFFICIENT TRIALS BASED
ON BIOMARKERS AND ENROLL THE
RIGHT PATIENTS AT THE RIGHT TIME
AND QUICKLY SEE IF WE'RE HAVING
AN EFFECT ON THESE.
AND WITH THAT I'LL PASS IT OVER
TO YOU, JOE, TO TALK MORE.
THANK YOU, STACIE AND NEIL
OUTLINING THE PRIORITIES OUR
TEAM HAS COME UP WITH.
I'LL TRY TO DO LEVEL SETTING
REGARDING WHAT'S INVOLVED IN THE
DRUG DISCOVERY PROCESS AND THEN
OUTLINE HOW THE PRIORITIES THAT
WERE GENERATED BY OUR TEAM CAN
IMPACT THIS DRUG DISCOVERY
PROCESS IN A POSITIVE WAY.
AND TO START AND DRUG DISCOVERY
CANDIDATES DEFINITELY APPLY AND
AS I THINK MOST FOLKS ON THE
CALL ARE AWARE IN ALS THE
CHALLENGES ARE EVEN GREATER THAN
I WOULD SAY ON AVERAGE FOR ANY
DRUG DEVELOPMENT CANDIDATE.
SO JUST TO POINT OUT A FEW
THINGS IN THIS FUNNEL CHART ON
THE LEFT, I THINK MOST PEOPLE
AND EARLY STAGE CLINICAL TRIALS
ARE GOING THROUGH PHASE 3 TRIALS
AND WHAT IS PERHAPS LESS
FAMILIAR ARE ALL THE STEPS THAT
LEAD UP TO THOSE CLINICAL
TRIALS.
THEY INVOLVE SCREENING A LARGE
NUMBER OF POTENTIAL THERAPEUTICS
CANDIDATES IN ORDER TO IDENTIFY
WHAT ARE A SMALL NUMBER OF
COMPOUNDS THAT ARE SUFFICIENTLY
ACTIVE AND SAFE TO ENTER
CLINICAL TRIALS.
AND I THINK THIS HIGHLIGHTS THE
NUMBERS INVOLVED AS WELL AS THE
TIME AND COST AND ALSO KNOWING
THERE'S MANY FAILURES AS STACIE
MENTIONED AND IF WE WANT A HIGH
LEVEL OF SUCCESS WE NEED A HIGH
LEVEL OF INVESTMENT.
AND ON AVERAGE AND SO I THINK
THIS HIGHLIGHTS THEN SOME OF THE
IDEAS THAT OUR WORK GROUP CAME
UP WITH THE TIME AND NUMBERS
INVOLVED HOW DO YOU OPTIMIZE HOW
THE FUNNEL WORKS AND GIVE DRUG
CANDIDATES THE BEST CHANCE OF
SUCCESS.
AND THE ONE I'LL HIGHLIGHT IS
ONE STACIE MENTIONED IN PRIORITY
3 AROUND THE TRANSLATION BETWEEN
YOUR INITIATIVE DISCOVERY AND
THE DRUG DISCOVERY PROCESS.
INITIATING THE CANDIDATE
THERAPEUTIC SPACE ON THAT IDEA.
AND THE FIRST BAR TENDS TO BE
BEST DONE BUT NOT ALWAYS IN
ACADEMIA AND THE BAR'S AFTER IT
ARE MOST OFTEN DONE IN INDUSTRY.
SO ANYTHING WE CAN DO TO LOWER
THE BAR AND MAKE THAT MORE
EFFECTIVE IS GOING TO HAVE A
HUGE IMPACT ON OVER ALL SUCCESS.
AND THE WAY I LIKE TO THINK
ABOUT IT IS AND GARBAGE IN,
GARBAGE OUT, IF YOU START THE
FUNNEL WITH NOT THE BEST IDEAS
YOU'LL END WITH NOT THE BEST
IDEAS.
THAT'S A PRETTY DISAPPOINTING
PLACE TO BE OVER A DECADE OF
WORK.
IT'S CRITICALLY IMPORTANT TO
MAKE SURE THE BEST SCIENTIFIC
IDEAS ARE MOVING FORWARD INTO
DRUG DISCOVERY EFFORTS.
AND THE SECOND POINT STACIE AND
NEIL HIGHLIGHTED AROUND BIO
SAMPLES AND THE USE OF
BIOMARKERS.
AND MAKING SURE WE TAKE THE BEST
IDEAS FORWARD IN DRUG DISCOVERY.
THE BOTTOM LINE IS OUR
UNDERSTANDING AND IT'S WHAT THE
USE OF OUR SAMPLES AT THE EARLY
STAGE CAN DO IS TO MAKE SURE
WE'RE PURSUING NOT JUST ALS AND
WE'VE BEEN ABLE TO DO THAT MANY
TIMES AND IT JUST DOESN'T HAVE
THE SAME IMPACT.
AND IN TERMS OF IDENTIFYING THE
RIGHT PATIENTS TO BE INVOLVED IN
TRIALS AND HOW TO MEASURE EARLY
EFFECTIVENESS OF COMPOUNDS
WITHIN CLINICAL TRIALS IS
ANOTHER KEY POINT WHERE BIO
SAMPLES HAVE PLAYED A KEY ROLE
AND WILL CONTINUE TO DO SO AND
HAVING LARGE EASILY ACCESSIBLE
REPOSITORIES OF THE SAMPLES TO
BE LEVERAGED BY AC DIM --
ACADEMICS AND INDUSTRY ALIKE
WILL BE NECESSARY TO BE
EFFECTIVE AND ONCOLOGY IS AN
AREA THAT'S HAD MORE SUCCESS AND
THE BOTTOM LINE OR A BIG PART OF
THE REASON WHY IS BECAUSE YOU
DON'T JUST TREAT CANCER ANYMORE,
YOU TREAT A SPECIFIC SUBTYPE OF
CANCER IDENTIFIED THROUGH THE
SAME TYPE OF BIOMARKERS WHICH IS
SOMETHING THAT IS REALLY GOING
TO BE CRITICAL TO TRANSLATE INTO
ALS.
AND A GREAT EXAMPLE MENTIONED
EARLIER TODAY WE LEARNED A LOT
FROM SPECIFIC GENETICALLY
DEFINED SUB POPULATIONS OF ALS
PATIENTS AND BIOMARKER WILL BE
KEY TO EXTENDING THOSE
DISCOVERIES AND UNDERSTANDING
WHICH OF THOSE PATHWAYS MAY BE
RELEVANT IN THE BROADER ALS
POPULATION.
THAT'S A VERY CONCRETE EXAMPLE
OF HOW THESE CAN BE USED TO
EXTEND THE POTENTIAL OF
THERAPIES IN ALS.
I'LL STOP THERE AND HAND IT OVER
TO HENRIK WHO WILL TALK A LITTLE
BIT MORE IN DETAIL ABOUT THE ALS
BIOMARKERS.
>>THANK YOU.
THIS IS A SIMPLE SLIDE
EXPLAINING A LITTLE BIT ON HOW
WE WORK WITH THE FLUID
BIOMARKERS.
IT'S BEEN AN EXCITING TIME TO
WORK IN THIS FIELD.
ESPECIALLY DURING RECENT YEARS.
BASICALLY THE SLIDE YOU SEE THE
CHARACTERISTIC OF THE UNDERLYING
CAUSE RELEASES FILAMENT PROTEINS
HIGHLY COMMON IN ALS AND
THROUGHOUT THE YEARS THE BASIC
IDEA FROM THE BIOMARKERS HAVE
BEEN ALLUDED TO IN SEVERAL TALKS
AND YOU SEE THE TIP OF THE
ICEBERG BUT THE SYMPTOMS ARE
CAUSED BY FACTORS THAT RESULT IN
BIO CHEMICAL CHANGES.
SO AND YOU SEE A NUMBER OF THESE
BIOMARKERS THAT HAVE BEEN
DEVELOPED IN RELATION TO ALS.
YOU SEE SERUM LEVELS THAT START
TO INCREASE YEARS BEFORE
CLINICAL ONSET OF ALS AND SEE
THE LEVELS ARE RELATIVELY
STABLE.
AND YOU CAN SEE THE MUTATIONS
AND THEN IN THE LOWER RIGHT YOU
SEE VERY EXCITING MARKER WITH A
MEASUREMENT IN URINE.
IN ALS WE HAVE MULTIPLE
BIOMARKERS AT HAND BUT NEED TO
DEVELOP NEW BIOMARKERS AND SINCE
THERE'S BEEN SUBFORMS OF ALS WE
NEED TO DISCOVER BIOMARKERS TO
REFLECT THE SPECIFIC AND THIS IS
MY FAVORITE SLIDE AND I OFTEN
RETURN TO THIS WHEN I THINK
ABOUT NEURODEGENERATIVE DISEASE
AND THIS IS AN EXAMPLE OF A
SUCCESSFUL TREATMENT OF A
NEURODEGENERATIVE AND SPINAL
MUSCULAR ATROPHY AND YOU HAVE A
PROTEIN THAT AFFECTS THE
SURVIVAL OF MOTOR NEURONS AND
YOU CAN STABILIZE THE PROTEIN BY
INJECTING OR GIVING A NUCLEOTIDE
YOU CAN RESTORE EXPRESSION OF
THE PROTEIN AND THE KIDS YOU SEE
HOW YOUNG THEY ARE IN THIS CASE,
THE KIDS YOU CAN SE THE LEVELS
DROP RAPIDLY.
AND OF COURSE THIS IS WHAT WE'RE
KNOWN FOR SEEING IN ALS.
AND WE'RE STARTING TO SEE THIS
APPEAR IN THE ALZHEIMER'S
DISEASE AND YOU SEE
DOSE-DEPENDENT LURING OF
FILAM
FILAMENT.
IT STARTS TO LOOK PROMISING.
THIS IS WHY THIS IS A HIGH
PRIORITY.
THEN I I'LL HAND IT OVER TO
STEVE.
>>THANK YOU.
I'LL GIVE A QUICK OVERVIEW OF A
RICH SUBJECT, HOW ONE WOULD FIND
THE MOLECULAR INVENTION OF
DISEASE ONCE WE HAVE THE
RESOURCES IN THE INDUSTRY AND
THE WORLD.
ULTIMATELY YOU WANT TO MIMIC THE
DISEASE SOMEHOW.
SOME MAY DO DISEASE IN A DISH
MODELS TAKING CELLS FROM AN
ANIMAL MODEL OF DISEASE OR CELLS
DIRECTLY FROM A HUMAN PATIENT
AND TRY TO PERTURB THE GENES AND
THE CHALLENGE IS HOW DOES IT
RELATE TO HUMAN DISEASE?
SIMILARLY, ANIMAL MODELS OF
DISEASE WE CAN PUT HUMAN-DISEASE
CAUSES CELLS INTO MICE AND FLIES
AND MANIPULATE THESE
PHARMACOLOGICALLY OR WITH TEST
THERAPEUTICS.
KEY QUESTION, HOW'S IT RELATE TO
HUMAN DISEASE?
WHAT'S BEEN VERY FRUITFUL IS
LOOKING AT HUMAN GENETICS AND
GENOMICS AMONG HEREDITARY CASES
AS YOU SEE WITH CHROMOSOME 9 AND
CAN YOU ZERO INTO THE MOLECULAR
CAUSE AND THEN HAVE YOU
SOMETHING TO WORK ON AND THERE'S
A CAVEAT YOU CANNOT DO ANYTHING
OBSERVATIONAL AND CAN'T
MANIPULATE OR INTERVENE.
ARE ONES YOU HAVE IDEAS FOR A
THERAPEUTIC HYPOTHESIS IT'S
BEWILDERING AND ASPIRIN PEPTIDES
AND EVER INCREASINGLY NUCLEIC
ASSETS AND WHEN SHOWN IS A SHORT
INTERFERING RNA OLIGOSACCHARIDES
AND GENE EDITING AND GENE
THERAPIES WHERE ONE WOULD
MANUFACTURE CELLS TO REGROW
TISSUE.
ONE HAS PLUSES AND MINUS.
THE IDEAL DRUG WILL BE ABLE TO
BE TAKEN INFREQUENTLY, TAKEN IN
A PILL, DIFFUSED THROUGHOUT THE
BRAIN AND HAVE SPECIFICITY TO
THE TARGET AND MANUFACTURING.
EACH HAVE PLUSES AND MINUSES AND
IT'S A WONDERFUL MESH THAT'S
NEEDED BETWEEN TARGET HYPOTHESES
AND INDUSTRY WHO WILL TAKE WHAT
IS THE BEST ONE AND TRY TO MATCH
IT WITH THE APPROPRIATE
ENGINEERING.
THESE THEN WILL BUILD IN TO
WHERE WE HAVE EXACTLY WHAT
ALREADY EXISTS INTO WHAT WE'RE
PROPOSING AND ONCE YOU HAVE A
TARGET AND IT WILL ENABLE
BIOMARKERS.
THIS WILL ENABLE US TO SELECT
THE PATIENTS AND MONITOR PATIENT
PROGRESSION PERHAPS EVEN SELECT
PATIENTS PRESYMPTOMATICALLY AND
APPRECIATION ORGANIZATIONS,
INDUSTRY AND OF COURSE THE FDA
AND APPROPRIATE REGULATORY
COMMANDS.
I'LL PASS IT ON.
>>I'M JIM WILSON AND HAVE BEEN
ASKED TO COMMENT AND WE HEARD
IMPORTANT PRINCIPLES
HISTORICALLY ABOUT HOW ABOUT THE
TRANSLATION AND AN CLINICAL
RESEARCH AND WE HEARDS THE
DEPRESSING OR REALISTIC VIEW OF
HOW HOW LONG IT TAKES AND HOW
MUCH IT COSTS AND WE'RE IN AN
ERA NOW ABOUT A KNEW MODALITY OF
GENETIC MEDICINES AND YOU CAN
LEVERAGE FACTORS AND IT TURNS
OUT THE ACADEMY IS POSITIONED
THAN BEFORE TO TAKE GENETIC
MEDICINES AND TAKE GENETIC
MEDICINES INTO THE CLINIC.
AND WHAT THIS ENABLED US TO DO
NOT ONLY US BUT THE WHOLE ECO
SYSTEM IS THAT WE'VE BEEN ABLE
TO DERISK THE STRATEGIES MAKING
IT MORE ATTRACTIVE.
AND WE AGGRESSIVELY MORE THAN
ANYONE FIND WAYS TO TARGET WITH
INDUSTRY IN OUR TRANSLATIONAL
RESEARCH BUT THERE ARE TIMES I
WOULD ARGUE THE COMMUNITY MAY
NEED TO MOVE THE BAR FURTHER
INTO FIRST IN HUMAN STUDIES BY
OURSELVES WITH INFRASTRUCTURE
THAT HAS BEEN DESCRIBED OR THAT
EXISTS SO THAT WE CAN THEN
DETERMINE WHETHER THE CONCEPTS
ARE VALID OR NOT IT'S BEEN OUR
EXPERIENCE AT PENN WHEN WE DO
THAT WE GET INVESTING FROM.
NADIA.
>>I'M HERE TO PROVIDE THE
COMMUNITY PERSPECTIVE ON WHAT IS
PROPOSED.
WE DON'T HAVE TIME ON OUR SIDE
IN THIS DISEASE.
THERE'S A MEDIAN SURVIVAL OF 30
MONTHS FROM FIRST SYMPTOM.
THERE'S A LOT OF URGENCY.
AND SO MANY OTHERS EMPHASIZED
THERE'S A 30% GENETIC COMPONENT
AND WE'RE ONLY ON THE VERGE OF
TREATMENT AND WE HAVE SOME IN
THE PIPELINE BUT NOTHING
DEFINITE.
FOR EVERYONE ELSE THAT HAS A
SPORADIC FORM OF THE DISEASE WE
NEED A BETTER APPROACH TO ALS.
IT'S DIFFERENT IN HOW IT STARTS
AND PROGRESSES AND UNDERLYING
CAUSES FROM PERSON TO PERSON.
THAT'S THE HETEROGENEITY PROBLEM
IN ALS.
WE HAVE ABOUT 100 INTERVENTIONAL
TRIALS AND THERE'S PROMISE IF
YOU TALK TO ANYBODY THEY'LL TELL
YOU THAT'S MORE CLINICAL TRIALS
THAN WE'VE HAD INVEST PAST AND
HAVE BETTER SCIENCE IN THE
TRIALS AND THOSE CLOSEST TO
BEING ACCESSIBLE TO COMMUNITY
AND TO HAVE SCIENCE EXCEL BEHIND
IT THAT'S WHERE THE
TRANSLATIONAL RESEARCH COMES IN
TO MAKE A DIFFERENCE.
THE PURPOSE OF THIS WORKING
GROUP WAS TO PROPOSE WAYS TO
TRANSLATE EARLY RESEARCH
FINDINGS INTO BETTER TRIALS AND
TREATMENTS.
HOW DO WE PUSH THE ALS TREATMENT
PIPELINE FOR EVERYONE LEAVING
WITH ALS.
HOW DO WE OVERCOME HETEROGENEITY
AND THE VARIABILITY IN THE
PROGRESSION AND ONSET.
THE PURPOSE OF THE GROUP IS TO
OUTLINE MORE TARGETED TREATMENTS
FOR ALL TYPES OF ALS.
TRANSLATIONAL RESEARCH IS THE
BRIDGE BETWEEN EARLY SCIENCE AND
TREATMENTS.
SO HOW CAN WE USE TRANSLATIONAL
RESEARCH TO OVERCOME THE
HETEROGENEITY OF ALS.
CONCERTED DATA AND BIO SAMPLE
COLLECTION FROM PEOPLE LIVING
WITH ALS THE MORE THE BETTER AND
SHARING THE INFORMATION AND
SAMPLES OPENLY AND BROADLY WITH
THE RESEARCH COMMUNITY AND
INDUSTRY TO FIND MORE BIOMARKERS
AND SOMETHING MEASURABLE TO TELL
US WHAT'S HAPPENING WITH AN
INDIVIDUAL AND WHEN AND THE
OUTLINES BY THE WORKING GROUP
INCLUDED CREATING A NETWORK OF
ALS CENTERS OF EXCELLENCE, BIO
SAMPLE AND FOR NIH TO SUPPORT
THERAPEUTICS FROM THE CLEAR
STRATEGY AND PROCESS.
THIS WILL BE THE MOST EFFICIENT
WAY TO UNDERSTAND ALS BETTER
WHICH WILL THEN LEAD TO BETTER
TREATMENTS WITH STRONGER
RATIONALE AND GUIDE US TO THE
PATH OF MATCHING THE RIGHT
TREATMENT TO A PARTICULAR PERSON
WITH ALS NOT JUST BASED ON
GENETIC SUBTYPES.
IT'S ALSO THE PATH TO FASTER
DIAGNOSIS AND MEASURING
PROGRESSION AND THE EXPERIMENTS
WILL AMEND OUR EXPERIMENTAL
PIPELINE WITH THE ALS COMMUNITY.
THANK YOU, EVERYBODY.
>>THANK YOU.
WE'RE NOW GOING TO TURN IT OVER
TO QUESTIONS AND POST ANY
QUESTIONS HAVE YOU IN THE Q&A
AREA OF ZOOM AND WE'LL GET TO AS
MANY AS WE CAN NOW.
I'LL START WITH A QUESTION THAT
CAME IN AHEAD OF TIME WHICH I'LL
DIRECT TO NEIL.
THE QUESTION READS, WHY AREN'T
DRUGS BEING TESTED AND SHOULDN'T
WE TREAT AT EARLIER PROGRESSION
PLEASE LOOK TOWARDS THOSE
WITHOUT DISEASE.
>>THANK YOU.
THIS IS A GREAT QUESTION
IMPORTANT QUESTION AND ONE THAT
IS ING AND MY ANSWER WILL
PROVIDE HOPE TO THOSE WHO ARE IN
THIS POSITION.
THERE'S NO QUESTION TREATING AS
EARLY IN THE PROCESS WILL LEAD
TO THE MOST POSITIVE THERAPEUTIC
OUTCOMES.
IDEALLY WE WANT TO TREAT
PATIENTS BEFORE THEY DEVELOP
SIGNS AND SYMPTOMS OF DISEASE.
WE DON'T HAVE THE BIOMARKERS NOW
TO DO THIS IN THE STRATA
POPULATION BUT WE CAN IN RARE
GENETIC FORMS OF THE DISEASE.
THE FIRST STEP IN TREATING THE
PATIENTS IS IDENTIFYING THEM AND
FOLLOWING THEM IN THAT
PRE-SYMPTOMATIC PHASE TO
IDENTIFY MARKERS THAT ARE
HARBINGERS OF DISEASE ONSET AND
FIGURING OUT WHEN TO INTERVENE
TO PREVENT OR DELAY OR PREVENT
DISEASE ONSET.
THIS IS HAPPENING AND TOOK PLACE
IN THE DISCUSSION THIS MORNING.
THERE'S EFFORTS IN THE UNITED
STATES TO IDENTIFY AND
CHARACTERIZE PRESYMPTOMATIC
CAREERS ARE OF THE MUTATIONS AND
ONE WAS LED BY MICHAEL BENNATAR
EFFORTS AND IT'S ACTIVE IN
COLUMBIA.
WE RUN A PROGRAM CALLED THE ALS
FAMILIES PROJECT AND WE'RE
WORKING NOW CLOSELY TO PERFORM
THE ENTITY INITIATIVE CALLED
PREVENT ALS TO COMBINE AND
HARMONIZE OUR EFFORTS AND OUR
EFFORTS TO MORE CENTERS TO
INVOLVE MORE PATIENTS OF DIVERSE
BACKGROUNDS, GENETIC AND
OTHERWISE.
WE'RE FOLLOWING THE PATIENTS TO
COLLECT SAMPLES AND DO BIOMARKER
STUDIES AND IDENTIFY INDIVIDUALS
WHO WOULD BENEFIT FROM AN EARLY
INTERVENTION.
THIS IS HAPPENING ALREADY.
THERE'S A TRIAL AND THE ATLAS
TRIAL STARTED ON THE
LONGITUDINAL STUDY OF
PRESYMPTOMATIC CARRIES OF THE
MUTATION AND BASED ON THE BASIS
OF THAT INFORMATION OF THE TRIAL
DESIGN WAS BIASED.
IN MY OWN TRIALS WE'RE WORKING
ON A TRIAL AND WE BEGAN TO
EXPAND ACCESS TO THE PROGRAM AND
AS MENTIONED BY OUR GROUP
EARLIER WE WERE ABLE TO SPONSOR
THE TRIAL.
BUT IN OUR EXPANDED ACCESS STUDY
WE TREATED FIRST SYMPTOMATIC
INDIVIDUALS BUT MOVED
PROGRESSIVELY BACK TO EARLIER
STAGE PEOPLE AND THE
PRESYMPTOMATIC INDIVIDUAL OF THE
DISEASE.
THIS NEEDS TO HAPPEN AT GREATER
SCALE AND WITH THE FOUNDATION WE
AT COLUMBIA LAUNCHED AN EFFORT
CALLED SILENCE ALS TAKING ON THE
INDIVIDUAL RARE CASES DEVELOPING
THERAPEUTICS EVEN AS SMALL AS A
CASE WITH A THERAPEUTIC THAT
SEEMS TO WORK IN SYMPTOMATIC
CHALLENGE IS TO GO BACK TO
COHORT ARE AT RISK WITH
PRESYMPTOMATIC SYMPTOMS.
THE NEXT QUESTION, STACIE, I'LL
DIRECT TO YOU, WHY DO YOU SAY
YOU ARE RESEARCHING THERAPIES
AND NOT POTENTIAL CURE LIKE IN
CANCER?
SHOULDN'T THE RESEARCH FOCUS BE
ON FINDING THE CURE?
>>ULTIMATELY ABSOLUTELY BUT I
THINK THAT WE ARE AWARE THEY
MOVE FORWARD IN A STEPWISE
FASHION.
CANCER HAS BEEN EXTENDED BY A
QUALITY OF LIFE IT'S ONLY A
SMALL NUMBER OF CANCERS THAT WE
CURE.
AND THERE'S SIGNIFICANT BENEFIT
TO INCREASING QUALITY OF LIFE,
INCREASING LIFE SPAN AND QUALITY
OF LIFE.
ULTIMATELY PREVENT HOW I THINK
WE'LL GET TO THE CURE TO TREAT
EARLY.
BUT THE TIME SOMEONE IS SHOWING
SYMPTOMS, THERE'S ALREADY ALL
RIGHT DAMAGE THAT'S BEEN DONE IN
THE BRAIN.
I THINK THE FIRST STEP OF WHAT
WE'RE TRYING TO DO IS STOP THE
PROGRESSION OF EARLY STAGE
DISEASE THAT WOULD BE INCREDIBLY
SIGNIFICANT.
I THINK THAT'S WHAT WE'RE
STRIVING FOR.
YOU'LL HAVE TO GET IT RIGHT AND
WE HAVE TO LEARN A LOT HERE.
SO I THINK EACH STEP WE MAKE
EVEN IF PERHAPS OUR FIRST
THERAPEUTICS ARE SLOWING THE
PROGRESSION OR STOPPING THE
PROGRESSION AND WALK IT BACK
WE'LL HAVE A MORE SIGNIFICANT.
THERE'S ABSOLUTELY A GOAL
EVENTUALLY THAT WE WILL HAVE A
QUOTE, CURE.
ANYTHING TO INCREASE QUALITY OF
LIFE IN THE INTERIM HELPS.
I'M GOING READ THE NEXT
QUESTION.
THIS CAME UP IN THE EARLIER
SESSION AS WELL.
SO THE QUESTION IS READS, I'M A
BIG BELIEVER IN CRISPR PLATFORM
FOR RESOLVING ISSUES.
HAS THERE BEEN PROGRESS IN
CRISPR TO EXTEND WHAT THE
MUTATIONS HAVE?
I'M GOING TO MAYBE STEPHAN, DO
YOU WANT TO TALK A BIT ABOUT
THIS?
YOU'VE BEEN INVOLVED WITH
COMPANIES.
>>NO QUESTION, CRISPR IS A VERY
PROMISING MODALITY ACROSS MANY
DISEASES.
AND IT'S STARTING TO SHOW REALAL
PROMISE.
IN PRINCIPLE, YES, GOING BACK TO
MATCH THE MODALITY TO THE
DISEASE.
THE BRAIN IS TENDS TO BE ONE OF
THE LAST THINGS PEOPLE WANT TO
GET INTO.
IT'S HARD TO GET DRUGS INTO IT
AND YOU DON'T KNOW HOW THE BRAIN
RESPONDS WITH NUCLEIC ACIDS IN
IT AND PEOPLE ARE LOOKING AT IN.
IN ADDITION TO CRISPR THERE MAY
BE SMALL MOLECULE APPROACH AND
RNA INTERFERENCE APPROACHES AND
WHAT HAS BEEN IN THE CLINIC ARE
MANY APPROACH.
IT'S ON THE WAY.
IF CRISPR CAN BE ENGINEERED TO
C972 PEOPLE WILL TRY IT.
RIGHT NOW CRISPR IS AT A LITTLE
BIT MORE ACCESSIBLE DISEASES.
>>THANK YOU.
STEFAN.
>>ULTIMATELY THERE'S DELIVERY
TO THE RIGHT CELL.
IT TURNS OUT THAT AT LEAST A
SUBSET OF CELLS THAT MAY BE
NECESSARY TO TREAT FOR ALS,
SPINAL MOTOR NEURONS ARE EASILY
TARGETED.
SOME OF THE EASIEST CELLS TO
TARGET WITH VIRAL VECTORS.
THAT'S A HUGE ADVANTAGE AND USE
OF A VECTOR TO TREAT MOTOR
NEURONS AND THE MOST SPECTACULAR
RESULT IN THE HISTORY OF GENE
THERAPY.
SO ONE QUESTION IS DO WE NEED
SPECIFICITY OF THE VIRAL VECTOR
IT DEPENDS ON WHAT YOU'RE TRYING
TO EXPRESS BUT WE HAVE ALSO
SHOWN ANOTHER CELL THAT IS
HIGHLY TARGETED IS THE SENSORY
NEURON IN THE GANGAL ROOT AND WE
CAN LIMIT THE EXPRESSION IN THE
DORSAL ROOT GANGLIA AND
OTHERWISE THE SPECIFICITY IS
DEVELOPED NOT BY TARGETING THE
THE CELLS AND THERE'S WAYS TO
ACHIEVE SUCH SPECIFICITY.
I WOULD SAY IT'S NOT THE RATE
BUT IDENTIFYING THE RIGHT PART
OF THE GENE WHICH SPEAKS TO THE
FIRST QUESTION AND FOR VIRAL
VECTOR IN ACHIEVING STABLE
EXPRESSION WE MAY HAVE CRACKED
THAT NUT.
I THINK WHAT'S NOW LIMITING ARE
A MODEL SYSTEM WE CAN CRANK
THROUGH OUR CANDIDATES WITH
VIRAL VECTOR IN ORDER TO
DETERMINE WHAT WOULD LOOK THE
MOST PROMISING AND THERE'S
ANIMAL MODELS WHERE CERTAIN
FORMS OF ALS THAT ARE NOT GREAT
AND NOT ROBUST ENOUGH TO GO INTO
HIGH THROUGHPUT SCREENING THAT
COULD BE ACHIEVED TO ADDRESS
THIS POTENTIAL AVENUE OF
RESEARCH.
>>THE NEXT QUESTION FOR CRATING
AN INFRASTRUCTURE FOR BIO SAMPLE
QUESTION REPOSITORYIES TO
UNDERSTANDING THE DISEASE AND
IT'S GOOD TO HAVE MEDICAL BIO
REPOSITORIES.
>>YES, IT'S SOMETHING WE
DISCUSSED IN THE GROUP.
WE HAVE NOT MADE A FIRM DECISION
ON THIS YET IN REGARDS TO
RECOMMENDATIONS BECAUSE WE WANT
INPUT FROM YOU ALL ALSO.
BUT WHERE THERE'S CENTERS ARE
SUBMITTING SAMPLES AND GET
ANALYZED TO THE BEST AVAILABLE
BIO MARKERS USING CENTRALIZED
ASSAYS LEADING TO VARIATION AND
THE BIO REPOSITORY WILL BE
POPULATED WITH DATA AND FILA
FILAMENTS AND OTHER BIOMARKERS
PROMISING FOR ALS AND RELATE
THEM TO ACHIEVE PROGRESS AND
COORDINATE FOR THE USE OF THE
SAMPLING SO FROM MY POINT OF
VIEW, BOTH ALTERNATIVES ARE
REALLY GREAT.
WE'RE FIRMLY RECOMMENDING
ESTABLISHING THE BIO
REPOSITORIES AND HAVING THEM
AVAILABLE.
I THINK WE SHOULD DISCUSS THIS A
LITTLE BIT.
>>THANK YOU.
NEXT QUESTION, DID YOU BELIEVE
THERE'S OLD FDA APPROVED DRUGS
THAT MAY HAVE THERAPEUTIC EFFECT
ON ALS THAT ARE NOT BEING
RECOGNIZED AND THE REPURPOSING
TECHNIQUE ON ALS MAY BE
EFFECTIVE?
THERE'S PROS AND CONS TO THAT
TYPE OF APPROACH.
I THINK THE POSITIVES ARE I
SHOWED THIS LONG DEVELOPMENT
TIME LINE AND USING FDA APPROVED
DRUGS ALLOW YOU TO SKIP A LOT OF
STEPS THERE.
THE SAFETY HAS BEEN DEMONSTRATED
TO YOU CAN MOVE TO LATER STAGES
SO THAT'S AN EXCITING APPROACH
AND IF WE CAN UNDERSTAND THE
MECHANISMS OF DISEASE AND SHOW
THESE DRUGS IMPACT THEM, OFTEN
THAT CAN BE A BIG ADVANTAGE.
THE DOWN SIDE TO BE REALISTIC
ABOUT IT, AS MENTIONED EARLIER I
THINK BY STEFAN THAT ONE OF THE
BIGGEST CHALLENGES IS DELIVERING
DRUGS TO THE BRAIN.
THEY MAY MIND AN INTERESTING
COMPOUND BUT THEN CORNERS ARE
OFTEN CUT BECAUSE THE COMPOUND
HAS CERTAIN QUALITIES YOU WANT.
YOU PUSH IT FORWARD MAYBE IF
IT'S NOT PERFECT FOR TREATING
THE DISEASE YOU'RE INTERESTED
IN.
THAT'S SOMETHING WE NEED TO BE
CAREFUL OF OF BRYNING --
BRINGING THE COMPOUND FORWARD
AND WHETHER THEY'RE USED
DIRECTLY OR USED AS TOOLS FOR
NEXT GENERATION OF MEDICINES, I
THINK IT CAN BE AN EFFECTIVE
STRATEGY.
>>GREAT, THANKS.
HENRIK, WE HAVE ANOTHER
BIOMARKER QUESTION FOR YOU,
WHICH IS WHAT KIND OF NUMBERS IN
TERMS PATIENT PARTICIPATION WILL
BE NEEDED TO ADDRESS YOUR
PRIORITIES AND IN PARTICULAR TO
VALIDATE A BIOMARKER OF DISEASE
PROGRESSION.
WE'VE TALKED ABOUT THAT A LOT.
IT WOULD BE PRESUMABLE TO THE
FDA OPPOSED TO A NICE
PEER-REVIEWED PAPER PUBLICATION.
I THINK TALKING A LITTLE BIT
ABOUT WHAT NUMBERS DO WE NEED
AND AS WE'RE TALKING ABOUT
DIFFERENT SUB TYPES OF PATIENTS
WHAT NUMBERS DO WE NEED TO START
TO PLOT MEANINGFUL THINGS?
>>THERE'S PROCESSES AT PLAY.
IT DEPENDS ON HOW STRONGLY THE
AND IT'S THE EFFECT SIZE OF THE
BIOMARKER THAT WILL SHOW THIS
AND YOU CAN SEE AND THERE'S
DYNAMICS IN IT.
AND THEY ALSO SEE WE DON'T NEED
HIGH NUMBERS BUT WE NEED HIGH
NUMBERS IF WE'RE TO STUDY
APPROACHES AND THE CHANGES NEED
TO BE SMALLER.
THIS COULD BE A GLOBAL
COORDINATION TO INCREASE THE
NUMBERS SINCE THERE'S MANY TYPES
OF ALS AND THE NUMBERS THE MORE
THE BETTER.
IT'S IMPORTANT WE COLLABORATE
AND SHARE THE RESOURCES.
I'M PRETTY SURE WE'LL SEE
INTERESTING THINGS COMING UP AND
LOOK AT CHEMICAL BIOMARKERS.
IF THEY WANT PROSPECTUS STUDIES
THAT'S IMPORTANT AND YOU CAN
TOGETHER DESIGN A PROSPECTUS
STUDY TO EVALUATE HOW WELL A
BIOMARKER WORKS TO TRY DISEASE
OR PREDICT DISEASE PROGRESSION
AND WE MAY GET TO KNOW EACH
OTHER AND WE COULD DESCRIBE THE
BIOMARKER AND I WOULD LIKE TO
VALIDATE THE STUDY
>>PLEASE COMMENT ON POTENTIAL
NEED TO DEVELOP ALS APPROACHES
TO TARGET THE ALLELE
SPECIFICALLY.
IS IT ADVERSE TO SUPPRESS THE
MUTANT AND NON-MUTANT ALLELE.
THIS IS AN IMPORTANT QUESTION.
I THINK IT RAISES A POINT THAT
WAS MADE EARLIER BY JIM THAT THE
ALS INVESTIGATORS CLINICIANS AND
SCIENTISTS, HAVE THE OPPORTUNITY
NOW GIVEN EXISTING TECHNOLOGIES
TO DEVELOP GENE-BASED
THERAPEUTICS AND INTRODUCE THEM
WITH LITTLE OR NO INDUSTRY
SUPPORT.
IN SOME CASES AND SOME ASOs
TARGET ALL TRANSCRIPTS OF THE
GENES AND THE THINKING IS YOU
CAN DO IT SAFELY.
THERE'S OTHER WHERE DEFICIENCY
STATES CANNOT BE TOLERATED AND
IT WOULD BE DANGEROUS TO KNOCK
DOWN A GENE IRRESPECTIVE OF THE
MUTATION OR NOT.
IN THOSE CASES YOU'LL NEED TO GO
AFTER THE MUTANT ALLELE AND COPY
IN A SPECIFIC WAY.
AND DR. BROWN AT U-MASS IS DOING
THAT AND WE'RE DOING THAT
THROUGH THE SCIENCE ALS
INITIATIVE AND THESE WILL BE
RARE CASES.
AND THIS IS GOING TO NEED TO
HAPPEN IN THE NON-PROFIT SPACE
AND HERE'S WHERE I THINK NIH AND
PUBLIC SUPPORT GENERALLY WILL BE
NEEDED TO MOVE THE THERAPEUTICS
THROUGH IN SOME CASES IN AN
INDIVIDUAL WAY OR IN SMALL
POPULATIONS AND THAT IS EXCITING
OPPORTUNITY I THINK FOR US.
>>IT'S WELL STATED.
THE OVER ALL ISSUE IS IT'S AN
ELEGANT CONCEPTUAL APPROACH AND
SPARING THE NON-DISEASE COPY OF
THE ALLELE AND IF THE GENE IS
CRUCIAL, YES, ABSOLUTELY.
IF IT'S NOT CRUCIAL, NO, YOU
DON'T NEED TO.
MOST FALL IN BETWEEN THE GRAY
MATTER WHERE WE DON'T KNOW
ENOUGH AND HAVE TO TRY TO INFER
FROM MODEL AND ANIMAL
INFORMATION AND WHAT'S THE
RETURN FOR WHAT CAN BE A STEEP
ENGINEERING CHALLENGE.
>>THIS IS SOMETHING SOME CARE
TREMENDOUSLY IN THE FIELD ABOUT
WHO GETS PRIORITIZED FOR TRIALS.
AND THOSE THAT ARE P
PRESYMPTOMATIC TRIALS.
IT'S A CRITICAL QUESTION.
>>WE NEED TO UNDERSTAND WHEN
THE ALS PATHOLOGY STARTS AND WHY
IT STARTS IN SOME PEOPLE AND NOT
IN OTHERS.
ALL THOSE THINGS WILL BE BETTER
UNDERSTOOD IF MORE PARTICIPATE
IN THE GENE THERAPY STUDIES.
IN ACCESSING TREATMENT EARLIER,
YES, TREATMENTS SHOULD BE
ACCESSED EARLY WHEN WE KNOW THAT
THOSE TREATMENTS ARE NOT GOING
TIP SOMEBODY OVER TO THE DISEASE
PROCESS WHEN THERE ARE NOT A LOT
OF SIDE EFFECTS TO DEAL WITH.
SO CURRENTLY APPROVED TREATMENTS
DO NOT HAVE A LOT OF SIDE
EFFECTS SO I SEE WHY SOMEONE WHO
IS PRESYMPTOMATIC WOULD WANT TO
TRI THESE.
THAT NEEDS TO BE STUDIED IN
PEOPLE WHO ARE PRESYMPTOMATIC
INDIVIDUALS AND WHAT'S THE
TREATMENT?
IT'S KNOWING WHEN IS THE RIGHT
TIME TO START DOSING SOMEBODY.
WHEN YOU SEE ALS LOOMING IN YOUR
FUTURE, YOU WANT TO TRY
ANYTHING.
YOU WANT TO TRY ANYTHING TO MAKE
THAT STOP.
PEOPLE SAY THEY'RE NOT WORRIED
ABOUT SIDE EFFECTS BUT THERE'S A
REAL CAUTION WE HAVE TO HAVE AND
APPROACH THIS CAREFULLY BECAUSE
WE DON'T WANT TO TIP SOMEBODY
OVER INTO THE DISEASE EARLIER.
THERE IS NOTHING WORSE THAN
HAVING TO MANAGE MORE SERIOUS
SIDE EFFECTS ON TOP OF THE
WORRIES OF ALS.
I JUST THINK IT NEEDS A CAREFUL
APPROACH AND BIOMARKERS WILL BE
THE WAY TO GET THERE.
I WELCOME ANY OTHER RESPONSES
FROM PEOPLE ON THIS TEAM.
AND PEOPLE WHO ARE GENE CARE REZ
HAVE A HIGHER THAN NORMAL RISK
TOLERANCE BUT IT'S NOT THE SAME.
AND WHAT ARE THE POTENTIAL
CONSEQUENCES OF LONG-TERM
TREATMENT WITH SAY AN EXAMPLE A
THERAPEUTIC.
WE DON'T KNOW.
AND THERE'S REASONS TO BE MORE
CAUTIOUS AS NADIA IS POINTING
OUT.
AND IF YOU'RE TEAM GOT
EVERYTHING YOU IDENTIFIED AS
CRITICAL FOR IMPROVING, HOW
WOULD AFFECT THE 15-YEAR TIME
LINE FOR DRUG DEVELOPMENT AND
LESS THAN 5% SUCCESS RATE
>>I SAW THE QUESTION COME
THROUGH THE Q&A DURING THE
SESSION AND IS PARTICULARLY
IMPORTANT.
I SHARED THE REALITY IN TERMS OF
PIPELINE AND POTENTIAL FOR
SUCCESS.
I THINK THIS IS A CORE QUESTION
OF HOW MUCH IS THIS GOING TO
IMPACT THINGS IN A POSITIVE
DIRECTION.
AND THE IMPACT OF THESE TYPES OF
EFFORTS CAN BE SUBSTANTIAL BOTH
IN TERMS OF TIME LINES AND
POTENTIAL FOR SUCCESS AND I'D
LOVE TO HEAR COMMENTS FROM
OTHERS ON THE PANEL AS WELL.
BUT IN TERMS OF TIME LINES, I
THINK JIM HIGHLIGHTED NEW
THERAPEUTIC APPROACHES THAT ARE
TARGETED AND HAVE SHORTER TIME
LINES.
THOSE ARE STILL NOT APPLICABLE
TO THE MAJORITY OF ALSES BASED
ON WHAT WE KNOW ABOUT DISEASE.
SOME OF THE THINGS WE'RE TRYING
TO ESTABLISH ARE TO GENERATE
THAT UNDERSTANDING.
AND THEN IN TERMS OF POTENTIAL
FOR SUCCESS, I THINK THE IMPACT
IS PERHAPS EVEN MORE TANGIBLE
WHERE BETTER UNDERSTANDING
DISEASE TO MATCH THE RIGHT
PATIENTS WITH THE RIGHT DRUGS I
THINK CAN HAVE AN ORDER OF
MAGNITUDE LEAP IN TERMS OF OUR
SUCCESS BRINGING DRUGS FORWARD.
THUS FAR I THINK THE SUCCESS HAS
BEEN VERY LIMITED AND REALLY TO
GET CLOSER TO THE CURE TO HAVE A
BIG IMPACT WE NEED TO
FUNDAMENTALLY IMPROVE THAT
UNDERSTANDING AND MAKING SURE
WE'RE MATCHING DRUGS WITH
PATIENTS.
SO I'D LOVE TO IT UP TO OTHERS
FOR COMMENTS BECAUSE I THINK
THAT'S THE REASON WE'RE ALL HERE
TODAY TO SOME DEGREE.
>>YEAH.
IT DEPENDS ON WHAT WE FIND.
THE BEST CASE SCENARIO WE FIND
AS LDL IS TO HEART DISEASE, X IS
TO ALS.
WE WON'T KNOW UNTIL WE HAVE A
GOOD LOOK AT IT.
>>WE STARTED OFF WITH
BIOMARKERS BEING FUNDAMENTAL.
I'LL THANK EVERYBODY AND THANK
MY FELLOW MEMBERS OF THIS
WORKING GROUP AND THE AUDIENCE
FOR TERRIFIC QUESTIONS.
IT'S BEEN A GREAT PROCESS IN
THINKING THROUGH HOW CAN WE HELP
MAKE A DIFFERENCE IN THE FIELD.
NEIL, ANYTHING TO ADD?
>>I WANT TO ADD MY THANKS TO
THE GROUP.
WORKING WITH THESE WONDERFULLY
THOUGHTFUL PEOPLE CAN'T HELP BUT
LEAVE ME OPTIMISTIC WE'LL MAKE
REAL ADVANCES IN THE YEARS TO
COME AND THANKS TO DR. KOROSHETZ
AND THE NIH LEADERSHIP FOR THIS
REALLY IMPORTANT INITIATIVE AND
FOR THE STEERING COMMITTEE AND A
SPECIAL THANKS TO EMILY WHO LED
US THROUGHOUT THIS.
THANK YOU, EMILY.
>>THANK YOU, EVERYONE.
NOW WE'RE READY TO GO TO BREAK
AGAIN, IS THAT RIGHT?
RITA?
>>THANK YOU, EVERYBODY.
THANK YOU, NEIL AND STACIE AND
THE REST OF THE WORKING GROUP
MEMBERS.
THIS WAS A TERRIFIC SESSION.
WONDERFUL QUESTIONS FROM THE
AUDIENCE.
WE'RE EXCITED WE HAVE SUCH A
GREAT COMMUNICATION AND
PARTICIPATION IN THIS.
WE'LL TAKE A 15-MINUTE BREAK SO
WE'LL BE BACK AT 2:30 EASTERN
WHATEVER TIME THAT IS IN YOUR
OWN TIME ZONE AND WE'LL CONTINUE
FROM THERE WITH OUR LAST WORKING
GROUP DISCUSSION.
THANKS, EVERYBODY AND I'LL SEE
YOU IN 15 MINUTES
>>WELCOME BACK EVERYONE.
I'M DELIGHTED TO TURN THE
PROGRAM TO THE CO-CHAIRS, MERIT
CUDKOWICZ AND TIMOTHY MILLER
MANAGING THE DISCUSSION ON
OPTIMIZING ALS CLINICAL
RESEARCH.
>>WE WANT TO WELCOME THE OTHER
MEMBERS OF THE WORKING GROUP TO
TURN ON THEIR CAMERAS AND IF YOU
HAVEN'T, TURN IT ON NOW.
WE'LL INTRODUCE OURSELVES AND
START WITH A SHORT PRESENTATION
AND I THINK HAVE LOTS OF TIME
FOR QUESTIONS.
I'LL START WITH INTRODUCING
MYSELF.
I'M TILL MILLER A NEUROSCIENTIST
AT WASHINGTON UNIVERSITY AND
UNDERSTANDING AT DEVELOPING
NOVEL THERAPEUTIC APPROACHES AND
UNDERSTANDING MECHANISMS.
BOB.
>>BOB BOWSER AT THE BARO
NEUROLOGICAL INSTITUTE IN
PHOENIX, ARIZONA.
I WORK ON BIOMARKERS IN THE
DISEASE AND MOLECULAR MECHANISMS
AND TRANSLATIONAL NEUROSCIENCE.
>>I'M CHRISTIE FOURNIER AND
NEUROLOGIST AND CLINICAL
RESEARCHER WITH AN INTEREST IN
IMPROVING OUTCOME MEASURES FOR
ALS.
>>I'M CHIADDI ONYLKE A NEURO
PSYCHOLOGIST AT JOHNS HOPKINS
AND UNDERSTANDING THE OVERLAP
WITH ALS AND TREATMENT AND
DEVELOPMENT AND CLINICAL TRIALS.
>>I'M GWEN PETERSEN OF.
I WAS DIAGNOSED WITH ALS IN 2018
THANKS FOR HAVING ME.
>>HELLO, MELANIE QUINTANA AT
BERRY CONSULTANTS WHERE WE
DESIGN INNOVATIVE AND CLINICAL
TRIALS TRIALS ACROSS A WIDE
RANGE OF THERAPEUTIC AREAS IN
PARTICULAR INTERESTED IN
DEVELOPING DISEASE PROGRESSION
MODELS IN SEVERAL DISEASES.
>>I'M JEREMY SCHEFNER FROM THE
BARO NEUROLOGICAL INSTITUTE IN
PHOENIX AND CLINIC NEUROLOGIST
AND INTERESTED IN DESIGNING
CLINICAL TRIALS FOR ALS MANY
YEARS AND HAVE SPECIFIC INTEREST
IN DEVELOPING OUTCOME MEASURES.
I KNOW STEVEN GOUTMAN IS NOT
ABLE TO JOIN US THE PROFESSOR OF
NEUROLOGY AT THE UNIVERSITY OF
MICHIGAN AND NOT SURE IF ALBERTO
IS ON NORT.
-- ON OR NOT.
ALBERTO ASCHERIO AT HARVARD
SCHOOL OF PUBLIC HEALTH.
>>HE'S NOT HERE AT THE MOMENT.
>>OKAY.
VERY GOOD.
I'M DELIGHTED TO BE HERE AND TO
BE WORKING WITH THIS GROUP.
THIS WAS A LOT OF FUN TO GO
THROUGH THE PROCESS I'LL NOW
HAND IT OVER TO MERIT TO KICK US
OFF.
>>I'M MERIT CUDKOWICZ CHAIR OF
NEUROLOGY AT HARVARD MEDICAL
SCHOOL AND WITH JEREMY IN 1995
WAS HONORED TO START THE ALS
CONSORTIUM AND HAVE FOCUSSED ON
IMPROVING CLINICAL TRIALS AND
RESEARCH IN THE FIELD AND
EXCITED TO HAVE WORKED WITH TIM
AND OTHERS ON THIS WORKING GROUP
SESSION.
OUR GROUP MET SEVERAL TIMES AND
OUR PRIORITIES ARE VERY
INTRAREINT
INTRARELATE AND THINKING OF GAPS
IN CLINICAL TRIAL WE COULD SOLVE
WOULD SPEED UP DEVELOPMENT.
WE HEARD IN THE PREVIOUS MORNING
AND EARLY AFTERNOON ABOUT SOME
OF THE GREAT EXCITEMENT COMING
FROM SCIENCE AND TRANSLATION AND
THE GAPS THERE.
AND PREFACE BY SAYING THE MORE
WE UNDERSTAND WITH THE SCIENCE
THE BETTER OUR TREATMENTS AND
TARGETS ARE GOING TO BE FOR
BRINGING THEM TO PATIENTS BUT
THERE'S GENETIC SPORADIC
CLINICAL TRIALS AND RESEARCH
NOW.
ONE OF THE GOALS WE PUT TOGETHER
WAS THE IMPORTANCE OF LEARNING
FROM EVERYBODY WITH ILLNESS
WHETHER IT'S SOMEBODY WHO
CARRIES THE GENE, AT RISK OR AND
ESPECIALLY IN THE RARE DISEASE
AND WE CAN SPEED THE PROGRESS.
WE KNOW FROM OTHER FIELDS THAT
WHEN A FIELD DEVELOPS
UNDERSTANDING WITH CLINICAL
TOOLS TO UNDERSTAND DIFFERENT
BIOLOGY IN PEOPLE OR TO DEVELOP
BETTER OUTCOMES MEASURES TO
FOLLOW THE ILLNESS AND TELL US
IF THE DRUG WORKS OR BETTER
FLUID OR DIGITAL BIOMARKERS TO
SUBSET PEOPLE THE THERAPY
DEVELOPMENT JUST GETS SPED UP
TREMENDOUSLY.
IN PARTICULAR DEVELOPING THINGS
LIKE SURROGATE MARKERS WHERE IF
YOUR DRUG CAN CHANGE A MARKER IN
THREE MONTHS AND PREDICT
LONG-TERM OR CLINICAL AFFECTS
YOU CAN SEE THE DRUG DEVELOPMENT
TREMENDOUSLY.
WE HAVE AN ILLNESS VERY HETRO
GENEIC BETWEEN PEOPLE AND WE
DON'T HAVE SHORT TERM MARKERS TO
PREDICT LONG-TERM CLINICAL
AFFECT AND WE DON'T KNOW HOW TO
INTERVENE EARLY YET.
SO OUR GROUP REALLY FOCUSSED ON
WHAT COULD WE DO TO SOLVE THE
FUNDAMENTAL QUESTIONS.
IT CAME DOWN TO THE IMPORTANCE
OF WELL-DONE NATURAL HISTORY
STUDIES.
YOU CAN LEARN A LOT FROM A
NATURAL HISTORY STUDY AND WE
WERE BLESSED TO HAVE
EPIDEMIOLOGISTS ON THE COMMITTEE
TO GIVE US INPUT ON THAT.
WHAT WE CAN LEARN FROM A NATURAL
HISTORY STUDY ARE SEVERAL FOLD
AND WELL GO THROUGH THESE IN
MORE DETAILS.
ONE IS UNDERSTANDING THE
HETEROGENEITY BETWEEN PEOPLE AND
UNDERSTANDING THE COURSE OF THE
ILLNESS THAT CAN PROVIDE DATA TO
PEOPLE LIKE DR. QUINTANA AND
ANOTHER STATISTICIANS TO COME UP
WITH TO DO EARLY TRIAL DESIGN.
WE CAN DEVELOP BETTER WAYS TO
ASSESS WHETHER A DRUG WORKS OR
NOT AND LOOKING WHETHER EARLY
SCIENCE CAN INTERVENE EARLY.
THOSE ARE SOME THINGS WE CAN
LEARN AND KEY PRINCIPLES THAT
CAN DEVELOP IN THE FIELD OF
ROBUST NATURAL HISTORY STUDY
APPROACH.
AND WE KNOW THERE ARE NATURAL
HISTORIES GOING ON FOR PEOPLE AT
RISK FOR THE ILLNESS BUT NOWHERE
NEAR THE SIZE AND NEED TO HAVE A
HUGE IMPACT.
THERE ARE NATURAL HISTORY
STUDIES FUNDED BY THE FDA IN
PEOPLE WITH SYMPTOMATIC STUDIES
AND HAVE TO BE LARGER FOR IMPACT
AND GET DATA REFLECTED THROUGH
MEDICAL RECORDS OR INSURANCE
COMPANIES.
THERE'S CREATIVE WAYS TO ANSWER
KEY QUESTIONS AND GAPS IN
KNOWLEDGE.
SO OUR PRIMARY AND WAS THE
ESTABLISHMENT OF A ROBUST
NATURAL HISTORY STUDY THAT WOULD
ENROLL PEOPLE AT RISK FOR THE
ILLNESS, PEOPLE PRE-SYMPTOMATIC
AND ASYMPTOMATIC AND PROVIDE
INFORMATION CRITICAL FOR
SPEEDING UP THERAPY DEVELOPMENT
FOR ALS AND WITH THAT I'LL PASS
IT TO TIM TO TALK ABOUT PRIORITY
2.
>>PRIORITIES 2 AND 3 DERIVED
FROM THE LARGE NATURAL HISTORY
STUDY AND THE GOAL ESTABLISHING
THAT TO THEN ENABLE SOME OF THE
OTHER THINGS.
SO ENABLE BETTER OUTCOME
MEASURES AND BIOMARKERS IN
INDIVIDUALS WITH DISEASE AND
THOSE AT RISK.
TO HAVE MORE DETAIL BEHIND THAT,
I THINK DEVELOPING BETTER TRIAL
METHODOLOGY AND ONE OF THE KEY
IDEAS IS THE MOST EFFICIENT USE
OF RESOURCES FOR CLINICAL TRIALS
RESPECTING THE PARTICIPANT'S
TIME AND ENERGY THAT GOES INTO
THAT AND OTHER RESOURCES THAT GO
INTO THAT AS WELL.
THINKING ABOUT NOVEL CLINICAL
TRIAL DESIGNS.
ONE WOULD BE THE PLATFORM TRIAL.
I THINK YOU ALL KNOW OTHERS HAVE
PIONEERED AND THERE MAY BE OTHER
TRIAL DESIGNS AND WAYS TO RUN
TRIALS.
I THINK ALSO NOVEL WAYS TO SHARE
AND ENHANCE THE GATHERING OF
DATA.
WAYS WE CAN SHARE DATA FOR
PLACEBO TREATMENTS AND WAYS TO
ENHANCE CLINICAL TRIAL BY
SHARING DATA AND I THINK ALSO
WITHIN THAT MORE BROADLY
INCLUSIVE THERE WAS A QUESTION
THAT CAME IN ABOUT ENROLLING
PEOPLE IN RURAL AREAS.
OUR AIM IS TO BE MORE INCLUSIVE
OF MORE GROUPS IN CLINICAL
TRIALS.
THE OTHER IS DEVELOPING OUTCOME
MEASURES.
I THINK WE ALL RECOGNIZE THAT
THERE IS ROOM FOR IMPROVEMENT OF
A FUNCTIONAL OUTCOME MEASURE.
I THINK WE ALSO ALL RECOGNIZE
THAT WE NEED A FUNCTIONAL
OUTCOME MEASURE.
SO WE HAVE ONE, THE ALS SCALE
AND CAN THAT BE IMPROVED OR DO
WE NEED TO DEVELOP SOMETHING
ELSE.
SO FUNCTIONAL OUTCOME MEASURE
AND NOVEL OUTCOME MEASURES AND
THERE'S A WHOLE VARIETY OF THESE
PROPOSED THAT WE CAN USE AND
SOME BEING EXPLORE AND HAVEN'T
IN THE SETTING OF ALS AND MAYBE
WE CAN BRING THESE IN FROM OTHER
FIELDS WHETHER IT'S FROM CANCER
OR OTHER NEURODEGENERATIVE
DISEASES AND ONE IS DIGITAL
HEALTH AND THOSE ARE JUST NOW
BEING TAPPED INTO THAT MAY
INCLUDE SOME AT-HOME MEASURES AS
WELL.
AGAIN, NOVEL MEASURES.
AND BIOMARKERS.
THERE'S BEEN A LOT OF DISCUSSION
ABOUT BIOMARKERS ALREADY.
RECOGNIZING THE POWER OF THIS
LARGE STUDY TO HELP DEVELOP
MARKERS.
ALSO WANT TO THINK ABOUT
PHARMACO DYNAMIC STUDIES SO WE
KNOW WHETHER THE DRUG HIT ITS
TARGET AND MAY MEAN BROAD
DEVELOPMENT ACROSS STUDIES.
AND ONE WE'RE MOST INTERESTED IN
IS MARKERS OF SUCCESS AT THE
EARLIEST TIME POINT.
IN MY OWN OPINION I THINK IF
NEURAL FILAMENT IS A GOOD SIGN
AND AN EARLY MARKER OF SUCCESS
BUT IS THAT THE ONLY MARKER AND
HAU COULD WE DEVELOP MARKERS
THAT WOULD BE ABLE TO SEE EACH
OF THE DIFFERENT AREAS THAT
MIGHT BE TREATED BY A DRUG THAT
WAS HELPFUL FOR ALS.
AND THEN LASTLY WE'VE INCLUDED
THIS DISEASE THOSE WITH DISEASE
AND AT RISK.
THIS IS A MAJOR PART OF OUR
THINKING.
H
HERE WE NEED TO INCLUDE THOSE AT
RISK AND THIS HAS COME UP
SEVERAL TIMES TODAY BUT
INCLUDING THOSE AT RISK AND
THERE ARE A NUMBER OF SMALL
STUDIES AND NEIL SCHNEIDER
HIGHLIGHTED THOSE AND WE NEED TO
EXPAND THOSE AND GROW THOSE AND
MAKE THOSE MORE PROMINENT.
PRIORITY NUMBER 3, TO FACILITATE
EARLIER INVENTION AND IMPROVE
DIAGNOSIS AND DISCOVER THE
EARLIEST MANIFESTATIONS OF ALS
AND THE NON-GENETIC ALS CAN WE
DIAGNOSE THAT SOONER AND THERE'S
WAYS PEOPLE WHO THOUGHT ABOUT
HOW TO MAKE THE DIAGNOSES
SOONER, ONE IS GETTING SOMEONE
TO AN ALS CENTER AND GETTING
SOMEONE TO A GROUP THAT'S GOING
TO RECOGNIZE THE DISEASE.
THAT WOULD BE HELPFUL IN
UNDERSTANDING WHETHER IT'S
ASSOCIATED WITH ALS OR THE
MECHANICS OF REFERRALS OR
GETTING PEOPLE TO THE RIGHT
PLACE.
AND THEN EARLIER INVENTION.
I THINK IT'S OBVIOUS WHEN STATED
THAT MOST OF US WOULD AGREE --
MAYBE NOT EVERYONE BUT I THINK
ALL OF US WOULD AGREE IF SOMEONE
IS ASYMPTOMATIC STARTING SOMEONE
EARLIER AND GETTING DIAGNOSIS
EARLIER AND SOONER IS ALMOST
ALWAYS BETTER AND STUDYING THE
EARLIEST MANIFESTATIONS FROM ALS
AND WE WANT TO STUDY EARLY ALS
OR THE BEGINS BOTH IN THE
NON-GENETIC FORM AND IN THE
GENETIC FORM.
BUT WHEN WE LOOK AT SOMEONE WHO
IS SYMPTOMATIC WITH ALS THE
WORLD OF MOTOR NEURONS IS
ALREADY ON FIRE.
COOPER PENNER SAID EXPANDING
EXPONEN
EXPONENTIALLY.
THE OPPORTUNITY BY MOVING THIS
AS EARLY AS POSSIBLE TO SEE WHAT
STARTED THE FIRE AND MAYBE WE
CAN PUT OUT THE FIRE AND DISEASE
BEFORE IT GROWS INTO THE AWFUL
DISEASE THAT IS SYMPTOMATIC ALS.
AND WITH THAT I'M GOING TURN IT
BACK TO MERIT.
>>THANK YOU.
OUR GROUP ALSO DISCUSSED WAYS TO
KEEP LEARNING ABOUT THE ILLNESS
AND ACCELERATE HOW WE GO THROUGH
WHAT NOW A RICH PIPELINE OF
THERAPEUTIC IDEAS IN THE FIELD.
AND I KNOW MANY KNOW ABOUT THE
PLATFORM TRIALS AND THIS IS ONE
WAY OF BEING MORE EFFICIENT IN
HOW WE TEST TREATMENTS IN PEOPLE
WITH ALS PROVIDING MORE ACCESS
TO PEOPLE AND CONTINUING TO
LEARN ABOUT THE ILLNESS THROUGH
CLINICAL TRIALS AND THIS
COMPLEMENTS NATURAL HISTORY
STUDIES.
AND YOU SHARE DATA AND NO MATTER
THE OUTCOME OF THE MEASURES AND
YOU'RE LEARNING ABOUT THE
ILLNESS AND BIOLOGY AND
DEVELOPING NEW BIOMARKERS.
WE KNOW FOR EXAMPLE FROM
PLATFORM TRIALS AND ONCOLOGY
THAT NOT ONLY DID THEY GET DRUGS
TO MARKET THROUGH THAT WAY AND A
MUCH FASTER WAY AND LOWER COST
BUT ALSO DEVELOPED THOSE
SURROGATE BIOMARKERS.
SO THE FIRST STUDIES MAY HAVE
BEEN LONGER BUT DEVELOPED
SHORT-TERM MEASURES OF SUCCESS
AND EXCITING ADVANCE IN ALS IS
THERE'S NOW THREE DIFFERENT
APPROACHES OF THIS GOING ON
THROUGHOUT THE WORLD.
AND THE GROUPS DOING THESE TYPES
OF INNOVATIVE TRIALS ARE TALKING
TO EACH OTHER AND SHARING AND
LEARNING BEST PRACTICES TO
CONTINUE TO TEST THE MOST
EXCITING THINGS THAT COME FROM
BASIC SCIENCE LABS AND
TRANSLATION GROUPS.
WITH THAT WE'D LIKE TO SPEND OUR
REMAINING TIME ANSWERING AS MANY
QUESTIONS AS POSSIBLE ABOUT THE
PRIORITIES IDENTIFIED BY OUR
WORKING GROUP.
PLEASE FEEL FREE TO CONTINUE TO
ENTER QUESTIONS USING THE ZOOM
Q&A BOX OR IN THE QUESTIONS AND
COMMENTS FORM AVAILABLE ON THE
MEETING WEBSITE.
I HOPE WE'LL HAVE TIME TO ANSWER
ALL THE QUESTIONS.
BUT WE'RE GOING PLEASE KNOW
WE'RE COLLECTING ALL QUESTIONS
TO IN OUR WORK GROG FORWARD.
-- GOING FORWARD.
WE COMBINED QUESTION ARE SIMILAR
BUT AGAIN WILL TRY TO ANSWER ALL
OF THEM.
>>AND WITH THAT BEING SAID
THANK YOU, I'M GOING JUMP TO THE
FIRST QUESTION SUBMITTED IN
ADVANCE AND IT'S FOR JEREMY.
JEREMY, WHAT IS YOUR
RECOMMENDATION OR YOUR PLAN,
TIMETABLE FOR A ROBUST ALS
NATURAL HISTORY STUDY?
I DON'T KNOW I HAVE A SPECIFIC
TIMETABLE AND ONE HAS BEEN
APPROACHED BY THE ALS COMMUNITY
ALREADY LOOKING AT GENE CARRIERS
AND FOLLOWING PEOPLE THEY'RE
SYMPTOMATIC WITH ALS.
THOSE STUDIES EXIST.
BECAUSE OF THE RARITY OF EACH
INDIVIDUAL GENETIC CAUSE OF ALS
WITH THE POTENTIAL EXCEPTION OF
C9, THEY HAVE TO BE VERY
BROAD-BASED BECAUSE THERE'S NOT
HAVE MANY PATIENTS TO ACCUMULATE
TO THOSE STUDIES.
IN THE QUESTIONS THAT CAN BE
ASKED OF THE STUDIES IS WELL,
WHEN ONE IS PRE-SYMPTOMATIC HOW
INTENSE SHOULD THE EVALUATION BE
AND WHAT SHOULD WE KNOW ABOUT
SYMPTOMS THAT OCCUR THAT GIVE US
THE INFORMATION ABOUT WHEN THE
FIRE'S ABOUT TO START?
BUT I THINK THE TIMETABLE FOR
THAT IS NOW.
THERE'S NEEDS TO BE
AMPLIFICATION IN TERMS OF SIZE
AND IN TERMS OF THE
INTENSIVENESS WITH WHICH
PARTICIPANTS ARE EVALUATED PRIOR
TO THIS.
THAT ONLY COVERS 10% OR MORE OF
PEOPLE WITH ALS AND IS IT MORE
COMPLICATED FOR THOSE WHOM WE
CAN'T IDENTIFY EASILY IN A
PRE-SYMPTOMATIC WAY.
THERE'S ONLY TWO OPTIONS I
PERCEIVE AND WOULD BE GREAT TO
UNDERSTAND MORE AND ONE IS TO
LOOK AT A GENERAL POPULATION
THIS IS DONE IN COHORT STUDIES
IN GENEALOGY AND FOR ALS WOULD
HAVE TO BE LARGE.
IF YOU THINK OF INSTITUTES A
COHORT TO LOOK PRIMARILY AT
EARLY ONSET ALS WHAT'S THE
SAMPLE SIZE?
YOU THINK PERHAPS IF YOU ENROLL
A MILLION PEOPLE ABOUT 60 MAY
HAVE ALS AND MAYBE THE SAME
AMOUNT MAY BE PRE-SYMPTOMATIC.
THAT MAY BE ENOUGH.
YOU MAY NEED A COUPLE MILLION OR
10 MILLION.
IN ORDER TO DO THAT I THINK THE
ALS COMMUNITY HAS TO PARTNER
WITH OTHER GROUPS INTERESTED IN
PRE-SYMPTOMATIC ONSET OF
DISEASE.
MAYBE A NEURODEGENERATIVE
DISEASE RESEARCH CONSORTIUM TO
TRY TO WORK HARD TO ISOLATE AND
IDENTIFY PRE-SYMPTOMATIC, EARLY
SYMPTOMATIC FOLKS IN A VARIETY
OF DISEASES TO COMMAND THE SIZE
OF THE CONSORTIUM AND HAVE TO
DECIDE WHAT'S A MINIMALLY
CRITICAL SET OF EVALUATIONS TO
APPLY TO THESE PEOPLE OVER TIME
RECOGNIZING IT'S MILLIONS OF
PEOPLE.
AND I KNOW THERE'S MORE EXPERT
IN DESIGN BUT IT'S A DIRECTION
WE HAVE TO GO.
AND GO BACK AND IDENTIFY THROUGH
BLOOD SAMPLES AND GO BACK TO SEE
WHAT LIFE WAS LIKE PRIOR TO
SYMPTOMS.
THAT'S A MORE LIMITED APPROACH
BUT MAY BE MORE FEASIBLE.
THOSE ARE THE OPTIONS I SEE.
>>MAY I MAKE A QUICK FOLLOW-UP
BREAKING ALL THE RULES RIGHT
NOW.
CAN NEURODE GENE RATION BORROW
THE -- NEURODEGENERATION BORROW
THE MODEL FROM OTHER DISEASES
AND DOES THAT EXIST ANYWHERE?
>>IF YOU LOOK AT PAST LARGE
COHORTS THEY WEREN'T DESIGNED TO
LOOK AT SPECIFIC DISEASE STATES.
THERE'S THE NURSES HEALTH STUDY
WHERE A LARGE GROUP OF PEOPLE
VOLUNTEERED TO BE PERIODICALLY
FOLLOWED AND WE'VE HAD SUCCESSES
WITH RESPECT TO ALS WITH COHORTS
AND THERE WAS A LARGE
CARDIOVASCULAR COHORT THAT
IDENTIFIED PEOPLE WITH THE EARLY
1800s AND PEOPLE WITH
PARTICIPATION DURING THAT TIME
OF SERVICE HAD AN INCREASED RISK
OF ALS AND IT WAS IN A LARGE
MULTIPLE COHORT PRIMARILY
DIRECTED TOWARDS CARDIOVASCULAR
DISEASE AND OTHER DISEASE
ENCOUNTERS AS WELL.
THAT'S THE BEST I CAN DO.
>>MY NEXT QUESTION IS FOR TIM.
WILL ALS RESEARCH BE OPTIMIZED
TO LOOK AT MULTIPLE CURES IN
PARALLEL RATHER THAN A SLOW AND
SEQUENTIAL APPROACH?
>>THERE ARE MULTIPLE TRIALS AND
MULTIPLE COMPANIES RUNNING
TRIALS AND AND A BUNCH MORE
TRIALS COMING THROUGH AND I WANT
TO ACKNOWLEDGE THE PLATFORM
TRIAL MANY OF YOU KNOW ABOUT AND
LAUNCH A PLATFORM TRIAL AND I
THINK IT'S AC SELT RATING OUR
ABILITY TO GET DRUGS IN THE
TRIAL.
MAYBE YOU CAN SPEAK TO THAT MORE
THAN I WOULD.
WHETHER IT REACHED THE
ACCELERATION WE THOUGHT IT WOULD
TO GET MORE DRUGS IN AND TEST
MORE DRUGS.
I THINK THEY'RE HAPPENING
QUICKLY.
I THINK THEY'RE HAPPENING IN
PARALLEL RATHER THAN MULTIPLE
EFFORTS GOING ON ALL AT ONCE.
>>THE NEXT QUESTION IS ALSO FOR
TIM, THERE'S A FEW DIFFERENT
PARTS TIM, MULTIPLE PEOPLE
SUBMITTED QUESTIONS ABOUT
CLINICAL TRIALS FOR PREVENTING
ALS IN PEOPLE WHO HAVE GENE
MUTATIONS BUT DON'T YET HAVE
SYMPTOMS.
SO FIRST PART OF THIS, WHY ARE
THERE NO TRIALS TESTING WHETHER
CURRENT ALS THERAPIES PREVENT
DISEASE IN PEOPLE WHO WERE AT
HIGH RISK OF DEVELOPING ALS?
>>
>>AND I PUT IN THE LINK TO THE
ACCESS TRIAL THAT DESCRIBES THE
TRIAL IN MORE DETAIL.
THERE'S A TRIAL BY THE ACADEMIC
INVESTIGATOR LOOKING AT PEOPLE
WHO HAVE MUTATIONS AND LOOKING
WHETHER THEY HAVE A BIOMARKERS
RISE IN FILAMENT TO GET FIRST ON
TO A DRUG TO FOCUS ON PROTEIN
AND THERE'S A NEW TRIAL FOR US
IN THE ALS WORLD.
THERE MAY BE OTHERS COMING
THROUGH AS WE DEVELOP OTHER
GENETIC FOCUSSED THERAPIES.
THERE'S AN INTERESTING TRIAL
DESIGN AND CHALLENGING TO RUN
WE'LL GET TO IN A SECOND, I
THINK.
>>WHAT ARE THE CHALLENGES FOR
CONDUCTING PREVENTION TRIALS?
>>IN SOME DISEASE WHEN YOU GET
SICK SEEMS TO BE CLOSELY LINKED
TO WHEN OTHER PEOPLE IN YOUR
FAMILY GET SICK.
FOR EXAMPLE, PLUS OR MINUS FIVE
YEARS AND YOU CAN USE THAT
INFORMATION TO MAKE PREDICTIONS
AND MAYBE GET SOMEBODY ON A
THERAPY CLOSE TO THE TIME WHEN
YOUR FAMILY TENDS TO GET
DISEASE.
IN ALS THERE'S A WIDE RANGE.
IT COULD BE 40 YEARS DIFFERENCE
AND DOESN'T MAKE SENSE TO
INTEREST PEOPLE ON A DRUG FOR 40
YEARS.
WHAT WAS BROUGHT UP BEFORE IS
WHEN IS SOMEONE CONVERTING OR
HOW DO WE KNOW SOMEONE'S ABOUT
TO CONVERT TO SYMPTOMATIC ALS?
AND NEURO FILAMENT MAY BE THE
MARKER.
IT'S NOT CLEAR FOR OTHER FORMS
OF DISEASE AND MAYBE WE NEED
OTHER MARKERS COMING THROUGH AND
IT WILL COME FROM THE NATURAL
HISTORIES STUDIES AND UNDERSTAND
POPULATION AND TESTING MULTIPLE
MARKERS.
THE MAIN CHALLENGE IS HOW DO WE
KNOW THEY'RE ABOUT TO CONVERT
BECAUSE IT DOESN'T MAKE SENSE TO
KEEP THEM ON DRUG FOR LONG
PERIOD OF TIME, DECADES.
I THINK YOU TOUCHED ON THIS IN
THE STUDIES.
>>STEP 1 IS GENETIC
COUNSELLING.
TO PEOPLE AT RISK FOR CARRYING A
GENE BUT DON'T YET KNOW WHETHER
THEY HAVE A GENE SHOULD GO
THROUGH A FORMALIZED FOR
CAREFUL, THOUGHTFUL PROCESS
ABOUT IDENTIFYING WHETHER OR NOT
THEY CARRY THE GENE.
THAT COULD BE DONE CLINICALLY
AND DONE IN RESEARCH STUDIES AND
THE OTHER WAY TO GET PEOPLE IN
IS A NUMBER OF RESEARCH STUDIES
AND UNIVERSITY OF MIAMI AND
WASH-U WITH JAMES BERRY AND
MYSELF.
AND I'D ANYTHING THE GENE
THROUGH GENETIC STUDIES OR
COUNSEL SELL -- COUNSELLING.
>>HOW CAN MORE BE DONE TO FIND
OUT AT WHAT STAGE AND HOW EARLY
MODIFYING TREATMENTS SHOULD
BEGIN?
>>GOOD QUESTION.
RIGHT NOW WE'RE TREATING PEOPLE
WHEN THEY HAVE CLINICALLY
OBVIOUS ALS BUT AS EARLY AS
POSSIBLE UNDERSTANDING A LOT ARE
AIMED AT SLOWING PROGRESSION AND
IT'S BEEN TOUCHED ON WE THINK IF
WE'RE ABLE TO IDENTIFY PEOPLE
EARLIER THERE COULD BE A BENEFIT
TO TREATING EARLIER.
A LOT OF WHAT'S BEEN DISCUSSED
IDENTIFYING EIGHT RISK PEOPLE
AND EXPEDITING DIAGNOSIS AND
TIME TO REFERRAL TO A TERTIARY
CENTER ARE CRITICAL TO FIND
PEOPLE EARLIER WHERE THEY MIGHT
BENEFIT MORE FROM SOME OF THE
TREATMENTS BEING TESTED.
ALSO WE KNOW THEY'RE GOOD AT
MEASURING CHANGE IN THE MIDDLE
RANGE AND DEVELOPING THINGS MORE
RESPONSIVE TO CHANGE EARLY IN
DISEASE AND EVEN BEFORE WE'RE
CURRENTLY DIAGNOSING PATIENTS IS
CRITICAL AND WE HEARD FROM
PATIENT ADVOCATES PATIENTS
EXCLUDED INTEREST TRIALS AND
CONSIDERED ADVANCED STAGES WANT
ACCESS TO TREATMENT TOO AND IS A
GROUP TO CONSIDER IN THIS AND
NOT LEAVE OUT IN RESEARCH
EFFORTS.
I DON'T THINK THERE'S AN ANSWER
AND MAY BE DRUG SPECIFIC.
>>DO YOU THINK WE NEED IT
CHANGE OUR DIAGNOSTIC CRITERIA
AND THE REASON I ASK IS I AM
SEEING PEOPLE EARLIER IN THE
ILLNESS.
THEY DON'T QUITE MEET THE
CRITERIA.
I'M WONDERING WHETHER WE COULD
WORK ON REVISED CRITERIA FOR
EARLIER DIAGNOSIS.
>>I SHARE THE CONCERN ABOUT
USING THE SCORE OF CRITERIA TO
MAKE THE DIAGNOSIS.
IT DOES INCLUDE EXCLUDE PEOPLE
WITH EARLY ALS WHICH DON'T HAVE
ENOUGH REGIONAL SPREAD BUT HAVE
ALS.
WE'D LIKE A TEST TO DETERMINE
ALS BUT WE STILL RELY ON CLINIC
EXAM AND IT DOES MAKE THINGS
TRICKY.
IN THE FUTURE HOPEFULLY WE'LL
HAVE MORE OBJECTIVE MARKERS BUT
RELYING ON THIS CRITERIA ALONE
IS NOT WISE BECAUSE WE'LL BE
EXCLUDING PATIENTS WHO CLEARLY
HAVE ALS BUT DON'T HAVE ENOUGH
REGIONAL SPREAD YET AND I DON'T
THINK THERE'S A BENEFIT TO THAT.
>>THANK YOU.
THE NEXT QUESTION IS FOR MERIT.
WHAT IS THE STATUS OF RESEARCH
AND TRIALS ON THE C9 MUTATION.
>>I'M VERY EXCITED ABOUT THE
RESEARCH GOING ON WITH C9.
MANY THINGS FROM AT-RISK AND
NATURAL HISTORY STUDIES AND
THERAPEUTIC STUDIES.
ALMOST CALLING OUT FOR OUR
PLATFORM C9.
I'M NOT VOLUNTEERING TO PUT THAT
TOGETHER BUT OFFERING TO HELP
OTHERS.
THERE'S A COUPLE GENE THERAPY
TRIALS IN C9.
WE DID KNOW THE BIO GEN ONE HAS
STOPPED AND SOME ARE BEING
ENROLLED IN THE TRIAL AND
THERE'S SMALL MOLECULE STUDIES
GOING ON IN C9 AND ONE IS ON
A.I. THERAPEUTICS.
THOSE ARE ALL ACTIVELY ENROLLING
THERAPEUTICS BUT MANY ARE
WORKING ON C9 SPECIFIC
TREATMENTS.
I THINK IT'S IMPORTANT FOR
PEOPLE TO KNOW AND WITH THE
COUNSELLING IF THEY CARRY THE
GENE AND FIND OUT ABOUT THE
TRIALS AND FOR THERE TO BE AN
EASY WAY TO LEARN ABOUT STUDIES.
AND ONE OF THE CHALLENGES WE'RE
FINDING IS WE'RE STARTING TO
DOUGH -- DO THE TRIALS OF C9 IS
WE DON'T HAVE ALL THE OUTCOME
MEASURES TO CAPTURE ALL THE
COMPLEXITY OF C9.
IT'S BEEN BRINGING TOGETHER THE
WORLDS OF ALS AND DEVELOPING
WAYS FOR COMMUNITIES TO COME
TOGETHER AND MANY TRIALS OF
ENROLLING THOSE WITH C9 AND ALS
AND THOSE WHO HAVE FRONTAL
DISRUPTION OR BOTH WE NEED TO
TELL SUCCESS UPON ALL THE
POPULATIONS.
>>THE NEXT QUESTION IS FOR BOB.
ARE THERE COLLABORATIONS FOR
CLINICAL RESEARCH TO FIND A CURE
AND IF THERE ARE, ARE THERE WAYS
TO IMPROVE THE COLLABORATION
BETWEEN COUNTRIES?
>>I THINK WE'RE DOING A GOOD
JOB BUT SO MUCH MORE WE CAN DO
BETTER.
WITH COLLABORATIONS ACROSS THE
BOUNDARIES OF BORDERS AND
BETWEEN NATIONS THERE'S A NUMBER
OF STUDIES ONGOING AND FUNDED
WITHIN THE UNITED STATES OR FROM
OTHER COUNTRIES THAT INVOLVE
U.S. INVESTIGATORS AND CLINICAL
CLINICIANS AND RESEARCHERS AND
THERE'S A LARGE NUMBER, TOO MANY
TO TRY TO LIST.
GIVEN THAT, THERE'S MORE THAT
CAN BE DONE WITH THE SENSE OF
SHARING DATA AND INFORMATION AND
SHARING RESOURCES AND TOOLS THAT
CAN GO ACROSS THE BORDERS.
WE'RE GETTING BETTER AND BETTER
AT INFORMATION AND RESOURCES AND
THERE'S EXAMPLES ON THE RESOURCE
SIDE AND THAT'S BIO FLUIDS AND
SAMPLES SHARED DURING CLINICAL
TRIALS AND THE ANSWER CONSORTIUM
SHARING LINES FROM -- AND
TARGETED ALS ANOTHER NATURAL
HISTORIES STUDY AND SHARING THE
SAMPLES AND SHARING POST MORTEM
INFORMATION AND ONE CHALLENGE
THAT REMAINS AS WE GENERATE MORE
AND MORE INFORMATION AROUND THE
DATA IS HOWE TO SHARE THE DATA
RESULTS.
THAT TAKES EFFORTS ONGOING FROM
A LARGE NUMBER OF INDIVIDUALS TO
PUT THEM ON PLATFORM THAT'S
SHARABLE BUT THE CHALLENGE
BECOMES THAT IF WE LOOK AT
DIFFERENT MEASURES IF PEOPLE
AREN'T DOING THEM IN A
STANDARDIZED APPROACH AND METHOD
IT'S HARD TO SHARE THE
INFORMATION.
IT'S CREATING STANDARD OPERATING
PROCEDURES AND KEEPING THEM
INCORPORATED INTO OUR RESEARCH
STUDIES THAT WILL ENABLE FURTHER
EVOLUTION OF THE TYPES OF DATA
THAT IS SHARED AND THE RESOURCES
THAT ARE GENERATED AND THE DOWN
STREAM ABILITY WITH THE CLINICAL
COURSE OF DISEASE PROGRESSION.
WE'RE DOING A LOT BUT I THINK
THERE ARE AVENUES WE CAN ENHANCE
TO BETTER FACILITATE THE SHARING
AND INTERNATIONAL COLLABORATION.
>>I FOUND IT COOL EARLIER WHEN
WALTER WAS TALKING ABOUT CREATE
CONSORTIUM IS LOOKING AT DIVERSE
POPULATION AND GOING TO SOUTH
AFRICA AND CREATE IS LOOKING AT
THE GENETIC UNDER PINNINGS OF
THOSE WITH ALS.
THAT WAS NEAT TO HEAR.
>>I'M GOING BREAK RULES AND
RESPOND TO WHAT YOU JUST SAID.
I THINK AS WE GO FORWARD THERE
ARE WAYS AND MEANS AND GROUPS
THAT ARE VERY INTERESTED IN EVEN
WITH OUR ONGOING AND UPCOMING
NATURAL HISTORY STUDIES TO BE
MORE INCLUSIVE AND DIFFERENT
WAYS TO REACH OUT WITHIN BOTH
THE DIVERSE POPULATIONS BOTH
WITHIN THIS COUNTRY AND AS YOU
JUST MENTIONED INCLUDING OTHER
NATIONS.
OTHER COUNTRIES, OTHER REGIONS
OF THE WORLD INTO THE TYPES OF
STUDIES SO WE GAIN GREATER
INSIDE INTO THE DIVERSITY OF ALS
ACROSS PATIENT POPULATIONS.
>>THIS IS FOR TIM AND MERIT.
WHAT IS THE DIFFERENCE BETWEEN A
THERAPY AND A CURE?
>>WELL, IT'S INTERESTING IN THE
SECOND PART OF THAT IS HELPING
THINK ABOUT CURE.
I LOVE THIS QUESTION.
IT'S A GREAT REMINDER TO ALL OF
US TO GO FOR CURES AND THAT'S
WHY WE'RE WORKING ON IT AND WE
TALK TO COLLEAGUES AROUND THE
NATION THAT WORK ON ALS, THAT'S
WHAT THEY'RE THINKING ABOUT,
THEY'RE THINKING ABOUT CURES.
THE DIFFERENCE BETWEEN A
TREATMENT AND CURE IS A
TREATMENT IS PARTIALLY SLOWING
THINGS DOWN AND A CURE STOPS THE
DISEASE IN ITS TRACKS.
I'LL COMMENT IN A NUMBER OF
OTHER DISORDERS THERE'S
TREATMENT ONE WAS OKAY,
TREATMENT TWO ADDED IN AND MADE
IT BETTER AND TREATMENT ONCE YOU
GET THREE AND SOMETIMES FOUR
SOMETIMES IT TAKES MORE THAN ONE
TREATMENT AND IF YOU GET TO
THREE, FOUR, REALLY GOOD
TREATMENTS, YOU MIGHT END UP
WITH A CURE.
AND SO I THINK THAT WE'RE MOVING
THAT WAY.
AND YOU WILL OF US ARE REALISTIC
ABOUT HOW MUCH CAN WE MOVE THE
BAR IN THE CLINICAL RESEARCH AND
IN THIS TOUGH DISEASE THAT'S
BEEN RESISTANT TO A HOST OF
CLINICAL TRIALS.
I THINK WE NEED TO BE REALISTIC
BOTH AIM FOR CURES, ACCEPT
TREATMENTS AND HOPEFULLY PUT THE
TREATMENTS TOGETHER THAT WILL
END UP AS A SECURE.
I'LL PASS IT TO MERIT.
>>COMPLETELY.
WE'RE LOOKING TO FIND TREATMENT
THAT WILL STOP PROGRESSION AND
BRING BACK FUNCTION AND TO STOP
THEM FROM STARTING.
ALL IS THIS COMPLEX AND WE'LL
PROBABLY FOR NOW TAKE MANY
THERAPIES TO GET US THERE BUT
THERE COULD BE A DAY WHERE WE
UNDERSTAND ENOUGH ABOUT THE
SCIENCE WHERE IT WILL BE
SIMPLER.
AGAIN, CANCER IS A GREAT MODEL
WHERE FOR SOME CANCERS ARE
TREATABLE NOW IT STARTED OUT
WITH DRUGS THAT MAY BE HAD A
TWO-MONTH AFFECT AND ANOTHER
ADDED ON AND NOW YOU'RE UP TO
FIVE MONTHS AND KEEP ADDING
UNTIL IT'S CURED AND ALS I THINK
IS A MISPRESCRIBED ILLNESS RIGHT
NOW AND GOING DOWN THE SAME
PATH.
>>LOOKING AT BIOLOGICAL
SIGNATURES CAN WE LEARN FROM
HAVING A BROADER HETROGENEIC
SUBGROUPS.
>>WE SHOULD NEVER BE LIMITED BY
OUR DESIGN OR BY POWER.
WE SHOULD NEVER HAVE TO HAVE TO
MAKE IT HARDER TO ASK QUESTIONS
YOU WANT TO ASK AND THERE'S WAY
TO ASK SMARTLY AND SHARE
INFORMATION ACROSS THE GROUPS
BUT LOOK AT THE HETEROGENEITY
ACROSS THEM AND IT BOILS DOWN TO
WHAT TIM MENTIONED IN OUR
PRIORITIES WHICH IS USING ALL OF
THE INFORMATION THAT WE HAVE AND
ALSO BUILDING SMARTER CLINICAL
TRIALS AND MORE POWERFUL
ANALYSIS METHODS AND BETTER
OUTCOME MEASURES, PUTTING ALL
THAT TOGETHER SO WE AREN'T
LIMITED BY THE THINGS AND WE CAN
DESIGN VERY POWERFUL TRIALS THAT
ENROLL A HOMOGENOUS SUBSET.
>>THANK YOU.
>>THE NEXT ONE IS FOR MERIT,
SHOULD A HORRIFYING FATAL
DISEASE LIKE ALS WITH NO CURE BE
GIVEN PRIORITY?
>>FIRST, I'LL CONFESS IN
CLINICAL BIAS I HAVE AND
EVERYBODY ON THE CALL HAS.
>>I WANTED TO ANSWER THIS ONE,
MERIT.
SAME REASON.
>>ABSOLUTELY.
I THINK NOT JUST AT THE NIH BUT
ALSO AT THE FDA AND I THINK
WE'RE SEEING THAT AND HEARING
THAT FROM THE FDA THAT THEY
UNDERSTAND THE SERIOUSNESS OF
THE ILLNESS AND THE FLEXIBILITY
NEEDED AND HOW TO PRIORITIZE AND
BY HAVING THE MEANING AND WE'RE
SEEING THAT FROM NIH AS WELL I
THINK THERE ARE A LOT OF
ILLNESSES NEUROLOGICAL ILLNESSES
THAT HAVE UNMET NEEDS BUT THIS
IS ONE OF THE MOST RAPID AND I'M
EXCITED ABOUT THE AMOUNT OF
SCIENCE HAPPENING.
IT DEFINITELY NEEDS TO BE
PRIORITIZED.
>>DOES ANYBODY FROM THE
COMMITTEE WANT TO WEIGH IN.
>>WE'LL ALL AGREE WITH THE IDEA
IT SHOULD BE A PRIORITY FOR LOTS
OF REASONS.
>>TO WEIGH IN ON HOW STRINGENT
CRITERIA NEED TO BE AND GET USE
OF SOMETHING AND THE QUESTION
ABOUT DO WE HAVE MODELS IN OTHER
DISEASES AND THIS IS A PLACE
WHERE WE DO.
IN GENERAL PEOPLE WITH CANCER AT
VIRTUALLY ALL PHASES CAN FIND A
PROTOCOL AND IMPORTANT CRUCIAL
INFORMATION CAN BE LEARNED BY
THEIR PARTICIPATION IN TRIALS
ALL THE WAY THROUGH THE GAMUT OF
THE DISEASE.
I THINK WE SHOULD BE VERY
EXPLICIT ABOUT OUR DESIRE FOR
ALS TRIALS IN THE FUTURE SHOULD
BE ANYBODY WHO WANTS TO BE IN
THE TRIAL SHOULD BE IN ONE AND I
DON'T REALLY MEAN EXPANDED
ACCESS NECESSARILY.
A TRIAL BY WHICH WE LEARN
SOMETHING THAT TAKES THE FIELD
FORWARD.
>>NEXT QUESTION MAYBE FOR THREE
OF OUR PANELISTS, JEREMY,
CHRISTINA AND COMBINING TWO
QUESTIONS AND ONE IS HOW CAN NIH
ENCOURAGE THE DEVELOPMENT OF
BETTER CLINICAL OUTCOME MEASURES
WITH HIGH REPRODUCIBILITY?
AND HOW DO WE ENCOURAGE MORE
DEVELOPMENT OF THE BIOMARKERS
AND THE LAST PART I'LL ADD IN IS
SOMETHING THAT CAME FROM THE Q&A
SHOULD WE BE MANDATING EVERY
TRIAL HAS THE GSF BIOMARKERS?
MAYBE JEREMY, IF YOU WANT TO GO
FIRST AND THEN CHRISTINA AND
THEN BOB.
>>WELL, I'LL DEFER ON THE FLUID
BIOMARKERS TO BOB AND JUST TALK
ABOUT ALS OUTCOME MEASURES MORE
BROADLY.
THERE IS A PERCEPTION THAT
CLINICAL TRIAL DEVELOPMENT IS
LIMITED BY THE QUALITY OF OUR
BIOMARKERS.
AND I'M REALLY NOT CONVINCED
THAT THE CLINICAL TRIALS THAT
WE'RE PERFORMING TODAY ARE SO
LIMITED.
I THINK WE HAVE A SCALE THAT'S
SHOWN TO BE SENSITIVE TO VERY
MODEST MODIFICATIONS BY A DRUG.
AND IT CLEAR METRIC DIFFICULTIES
AND CHRISTINA HAS DEVELOPED A
SCALE THAT MAY ACTUALLY ADDRESS
A GOOD NUMBER OF THESE
WEAKNESSES BUT NONETHELESS IT
DOES A GOOD JOB OF SHOWING
MODEST AFFECTS AND WHEN IT DOES
SHOW AN EFFECT, IT SHOWS AN
AFFECT THAT IS MIRRORED BY
EVERYTHING ELSE WE DO INCLUDING
EVALUATIONS OF STRENGTH,
EVALUATION MUCH BREEDING --
BREATHING AND QUALITY OF LIFE.
MY VIEW OF WHAT NEEDS TO BE DONE
IN THE FUTURE INCLUDES NOT ONLY
MAKING A FUNCTIONAL RATING SCALE
BETTER BUT TO THINK ABOUT WHAT
PARTS OF ALS DON'T WE ADDRESS?
AND THERE ARE A NUMBER OF THEM.
ALS IS A DISEASE OF CENTRAL AND
PERIPHERAL MOTOR NEURONS.
WE EVALUATE THEM PRETTY POORLY
AND THAT MAY NOT DIRECTLY HELP
OUR CLINICAL TRIAL INVESTIGATION
BUT HELP LEARN ABOUT THE DISEASE
IF WE CAN INVESTIGATE THAT
BETTER.
THERE IS A CLEAR OVERLAP BETWEEN
FRONTAL TEMPORAL DEMENTIA AND WE
EVALUATE COGNITIVE DEFICIENCIES
POORLY AND WE TREAT THEM BETTER
WHEN WE CAN MEASURE THEM BETTER.
THAT'S THE DIRECTION THAT I
WOULD LIKE TO SEE US GO AS TO
FOCUS ON WHAT WE KNOW WE'RE NOT
MEASURING IN ALS AND FOCUS ON
WHY THAT'S IMPORTANT AND WHAT WE
CAN DO BETTER AND HOW DO WE
MEASURE THAT IMPROVEMENT AND WE
KCAN DO THAT.
>>THERE'S AN OPPORTUNITY TO
TACK ON TO EXISTING TRIALS AND
EXISTING NATURAL HISTORY EFFORTS
AND NOVEL THINGS TO ADVANCE THEM
QUICKER.
NIH CAN SUPPORT ADJUNCT MEASURES
TO LEARN MORE ABOUT BIOMARKERS
AND NOVEL OUTCOMES EVEN IF THE
STUDY IS NEGATIVE APPROACHING
EACH STUDY MAKING SURE WE LEARN
SOMETHING WHETHER IT'S HOW TO
BETTER MEASURE DISEASE OR
SOMETHING NEW TO MAKE SURE EVERY
STUDY CONTRIBUTE TO MOVING
FORWARD EVEN IF IT'S NOT A
POSITIVE DRUG.
THIS IS ONE PLACE WHERE ACADEMIC
AND INDUSTRY PARTNERSHIPS ARE
CRITICAL AND NIH PARTNERSHIPS TO
LEVERAGE WHAT WE'RE ALREADY
DOING TO LEARN MORE AND ADVANCE
OUR OUTCOMES.
>>THERE WAS A TALK OF ABOUT
LUMBAR TAPS INCLUSION IN THE
TRIALS AND THINK WE NEED MORE
THAN ONE AND SHOULD BE.
IN SOME OF THE RATIONALE
INVOLVES A QUESTION AROUND
PHARMACO DYNAMIC BIOMARKERS.
IF YOU WANT TO GET THE FEEL IF
THE DRUG IS HITTING THE TARGET
IN THE CENTRAL NERVOUS SYSTEM
YOU NEED TO ADD LUMBAR PUNCTURES
AT THE BEGINNING, BASELINE AND
TOWARDS THE END OF THE TREATMENT
IN ORDER TO DEMONSTRATE THAT BUT
THE MORE THE BETTER IF YOU ASK
ME.
ANOTHER QUESTION WAS AROUND
REPRODUCIBILITY AND RELIABILITY
AND MEASUREMENTS, ETCETERA.
ONE AREA I THINK NIH COULD
REALLY PARTICIPATE AND TAKE A
LEAD IN SPONSORING IS SOME OF
THE APPROACHES THAT HAVE BEEN
INCLUDED IN THE FEW BUT HAVE
BEEN MAINLY OUT OF OR WITH OUR
EUROPEAN COLLEAGUES AND THAT IS
REALLY DOING MORE ASSAY
VALIDATION FOR WHATEVER A
PARTICULAR BIOMARKER IS.
SO YOU LOOK AT THEM AND SAY LIKE
ROUND ROBIN TYPES OF STUDIES
HARD TO GET FUNDING TO DO.
NO ONE WANTS TO FUND IT.
AND SO IT'S A CHALLENGE.
IF YOU HAVE A BIOMARKER OF
INTEREST AND DEVELOP A
PARTICULAR ASSAY FOR IT, BEING
ABLE TO INCLUDE A NUMBER OF
SITES THAT ALL RUN THE SAME
SAMPLES AND ASSAY AND
REPRODUCING THE RELIABILITY OF
THE SIGNAL IS CRITICAL TO MOVING
ANY BIOMARKER FORWARD.
WE'RE AT A POINT WHERE WE HAVE A
HOST OF BIOMARKERS THAT LOOK
INTERESTING.
SOME FOR SPECIFIC FORMS OF ALS
AND SOME FOR THE MORE SPORADIC
POPULATION AND ONE AREA NIH CAN
HELP MOVE THE NEEDLE IS TO FUND
THE STUDIES THAT DEMONSTRATE
BIOMARKER VALIDATION.
>>THANK YOU.
THIS NEXT ONE IS FOR CHIADI SO
QUESTION IS I WOULD LOVE TO SEE
ONE OF THESE TALENTED GROUPS
STUDY PATIENTS WHO ARE DOING
UNEXPECTEDLY WELL WITH THE
DISEASE, FOR EXAMPLE, THOSE WITH
SLOW PROGRESSION, LONG PLATEAUS
OR EVEN APPARENT RECOVERY FROM A
DISEASE.
STUDYING PATIENTS WHO ARE DONE
EXPECTEDLY WELL WITH OTHER
DISEASES HAS LED TO BETTER
TREATMENTS.
IE, HIV CONTROLLERS.
>>THE CHALLENGE IS IDENTIFYING
THE SPECIFIC NUMBER TO DO THIS.
FOR EXAMPLE IN THE FRONTAL
DEMENTIA FIELD THEY LOOK LIKE
THEY HAVE THE VARIANT BUT NOT
DECLINING AND OFTEN DO NOT HAVE
THE MRI FROM THE
NEUROPSYCHOLOGICAL PROFILES YOU
EXPECT FROM THE CLASSICALLY
DESCRIBED CONDITIONS BUT WITH
THE ADVENT AND DISCOVERY AND
GENETICS WE WERE THEN ABLE TO
SHOW SOME ARE MUTATION CARRIERS
AND MADE IT CLEAR WHAT WAS
VIEWED AS THE TERM PHENOCOPY
SUGGESTS THEY'RE MIMICS OPPOSED
TO THE ACTUAL THING.
BY BEING ABLE TO DEMONSTRATE
SOME OF THE LIMITATION CARRIERS
AND DEMONSTRATE AT LEAST IN
THOSE WHO PASSED EARLY THEY HAVE
CORRESPONDING PATHOLOGY WE WERE
ABLE TO IDENTIFY ESSENTIALLY
THAT THERE ARE MORE THAN ONE
TRAJECTORY OF PROGRESSION.
SO THEY'RE VERY SLOW
PROGRESSERS.
WHAT IS NEXT NEEDED IS
UNDERSTAND WHAT GOVERNS
HETEROGENEITY OF EXPRESSION.
FOR EXAMPLE, IF WE GO BACK TO
FTD AND ALS, WHY DO SOME PEOPLE
DEVELOP ALS AND SOME DEVELOP FTD
OR BOTH?
THERE'S A NUMBER OF QUESTIONS A
NUMBER OF QUESTIONS HOW AND WHEN
DISEASE IS EXPRESSED AND WE
COULD PROVIDE AN AVENUE FOR CURE
IF WE HAVE MORE INFORMATION.
>>THE NEXT QUESTION I THINK
ALSO, CHIADI AND MELANIE ALSO,
THERE'S A QUESTION BY WHETHER
EXERCISE IN DIET MAY CONTRIBUTE
TO ALS PROGRESSION WE KNOW MAKES
A HUGE DIFFERENCE IN AGING AND
IN OTHER NEURODEGENERATIVE
DISEASES HAVE SHOWN TO GET
BETTER WITH EXERCISE.
ARE THERE WAYS TO STUDY THIS
WHETHER IT'S TRIALS OR OTHER
APPROACHES WHETHER EXERCISE AND
DIET CAN MAKE A DIFFERENCE?
>>IT'S A PRIORITY TO UNDERSTAND
WA THE SOCIAL CULTURAL FACTORS
ARE THAT AFFECT DISEASE
PROGRESSION AND GOES BEYOND
EXERCISE AND DIET TO OTHER
SOCIAL PRACTICES, SOCIALIZATION
IN GENERAL, FOR EXAMPLE.
IT SEEMS CLEAR THAT DIET IN
PARTICULAR, NUTRITIONAL STATUS
AFFECTS ALS OUTCOMES AND WHAT
MAYBE IS LESS CLEAR IS TO WHAT
EXTENT DIET MAY DETERMINE ALS IN
THE FIRST PLACE AND THEN OF
COURSE YOU WANT TO KNOW TO WHAT
EXTENT IT'S MODIFIABLE.
NATURAL HISTORY STUDIES DEVELOP
ANSWERS TO THE QUESTIONS.
>>MELANIE, I DIDN'T KNOW IF YOU
HAD ANYTHING TO ADD OF WAYS TO
INCORPORATE IT INTO TRIALS.
>>WE DO A LOT OF TRIALS THAT
HAVE MULTIPLE DOMAINS IN WHICH
WE LOOK AT DIFFERENT TYPES OF
THINGS.
AND LOOKING AT THE PLATFORM
TRIAL IN WHICH WE'RE STUDYING
DIFFERENT THERAPEUTICS
INTERVENT
INTERVENTIONS LOOKING AT DIET
DOMAINS OR EXERCISE DOMAINS TO
UNDERSTAND WHICH INTERACTION OF
ALL THE THINGS LEADS TO THE BEST
POSSIBLE OUTCOME.
AND THERE'S A LOT THAT'S BEEN
DONE IN TERMS OF COVID IN
PLATFORM TRIALS.
AND THERE'S ROOM TO ADD THOSE
INTO TRIALS.
>>DO WE HAVE TIME FOR ONE MORE
QUESTION?
>>I THINK SO, YEAH.
I THOUGHT WE HAD UNTIL 3:44.
>>WE HAVE GOT TIME.
SO THIS ONE'S FOR BOB.
MY PERSON WITH ALS IS NEWLY
DIAGNOSED IN THE REGISTRY.
SO FAR IT SEEMS THE ONUS IS ON
THE PATIENT TO REACH OUT AND
SEARCH FOR STUDIES.
I CAN RELATE.
ARE THERE TRIAL-MATCHING TOOLS
UNDER DEVELOPMENT TO CONNECT
WITH POTENTIAL STUDIES AND/OR
BIO SAMPLE COLLECTION.
I'LL STOP THERE.
>>WOW, THAT'S A GREAT QUESTION.
I'M ACTUALLY NOT SURE IF THERE
ARE TOOLS BEING DEVELOPED TO GO
THE OPPOSITE DIRECTION OF WHAT
YOU JUST SAID, GWEN, TRYING TO
TAKE AND IDENTIFY INDIVIDUALS
FROM EITHER LISTINGS OR OTHER
AREAS IN ORDER TO IDENTIFY THOSE
THAT MIGHT BE BEST ENROLLED IN A
PARTICULAR STUDY OR TRIAL.
I KNOW THERE ARE A FEW GROUPS
THAT ARE QUITE GOOD AT LISTING
ALL THE VARIOUS TRIALS AND
RESEARCH STUDIES THAT ARE
AVAILABLE.
BUT AGAIN I'M NOT REALLY -- I'M
NOT KNOWLEDGEABLE ABOUT ANY
KNOWN ILLNESS OR ALGORITHM THAT
WOULD TAKE INFORMATION AROUND AN
INDIVIDUAL PATIENT AND IDENTIFY
WHAT ARE THE BEST OR OPPORTUNE
STUDIES OR TRIALS AVAILABLE FOR
THAT INDIVIDUAL.
I'M THROW IT TO THE OTHER
PANELISTS IF ANYONE'S AWARE OF
SUCH A TOOL.
>>I'M GOING TO JUMP IN ABOUT
THE CDC AND MAYBE PASS ITS -- IT
TO MERIT.
THE CDC WILL ADVERTISE FOR
TRIALS.
SO THEY DO AND WE CAN HELP WITH
CONNECTING PEOPLE AND THERE'S
INCUMBENT ON THE PERSON
CONTACTED TO REACH OUT TO THE
TRIAL.
>>
>>IT'S A GOOD IDEA.
AND THERE'S A CLINICAL TRIAL
MATCH MAKING TOOL.
THE NEED IS THERE AND THERE'S
ENOUGH TRIALS TO DO THIS.
THANK YOU.
>>NEIL'S WEBSITE HAS
INFORMATION ABOUT TRIALS AND
THREES A TRIAL NAVIGATOR PEOPLE
CAN CONTACT AS A PERSON THAT
WILL HELP THEM NAVIGATE AND FIND
TRIALS.
THOSE PEOPLE EXIST AND THERE'S
WAYS TO MAKE THE MATCH EASIER
AND ALGORITHM MAY BE BETTER BUT
ALSO MAYBE PROBLEMATIC.
>>THERE'S PATIENT INVOLVEMENT
AND TRYING TO GET THE NAVIGATION
AND INFORMATION THAT WILL BEST
HELP THEM DECIDE WHAT TRIAL THEY
WISH TO GET INTO.
>>DO WE HAVE ENOUGH SCIENTISTS
TO DO THE WORK?
IF NOT WHAT RECOMMENDATIONS DO
YOU HAVE TO ENSURE WE DO?
I HAVE THOUGHTS ON IT TOO BUT
OTHER COMMITTEE MEMBERS GO
FIRST.
>>I CAN START IF YOU'D LIKE.
>>SOMETIMES I THINK YES AND
SOMETIMES NO AND WE NEED MORE
PEOPLE COMING THROUGH WITH THE
SKILL SETS AND HAVE PLACES
PEOPLE CAN GET TRAINED.
THE FIX FOR THAT IS TO ENABLE A
TRAINING PROGRAM FOCUSSED ON ALS
OR MAYBE CLINICAL SCIENTIST
TRAINING MORE BROADLY.
I THINK THERE IS A NEED AS
HIGHLIGHTED BY THE QUESTION.
>>DO OTHER PEOPLE WANT TO WEIGH
IN ON THE QUESTION?
>>I'LL THROW IT THE OPPOSITE
DIRECTION.
SO I THINK AS YOU JUST SAID,
TIM, I THINK THERE'S A NEED FOR
MORE ALS NEUROMUSCULAR FOCUS
CLINICIAN SCIENTISTS.
YOU CAN ALSO GO THE OTHER
DIRECTION AND THAT IS HAVE A
Ph.D. LEVEL NEUROSCIENTIST THAT
WORKS OUT WITH CLINICAL
COLLEAGUES AT ACADEMIC
INSTITUTIONS OR OTHER SITES THAT
HELP DRIVE AND PUSH THE
GENERATION OF NEW STUDIES.
SO I THINK WE CAN WORK BETTER AT
PROVIDING OPPORTUNITIES FOR THE
Ph.D. NEURO SCIENTISTS TO
INTERACT WITH COLLEAGUES TO HELP
FACILITATE THE GENERATION OF NEW
RESEARCH STUDIES IN THE AREA OF
ALS.
>>IF I MAY WEIGH IN AS WELL.
THERE'S OPPORTUNITIES TO
COLLABORATE WITH PEOPLE IN
SCHOOLS OF PUBLIC HEALTH WHETHER
THEY'RE ACCUSTOMED TO DOING
LARGE-SCALE CLINICAL TRIALS.
IN THE EARLY DAYS OF DEMENTIA
CLINICAL TRIALS IT WAS A COMMON
PRACTICE TO HAVE WHAT I CALL
COORDINATING UNDER THES USUALLY
BASED IN SCHOOLS IN EPIDEMIOLOGY
AND STATISTICS AND THE PEOPLE IN
THE ALS FIELD COULD PARTNER IN
THE IMPLEMENTATION OF CLINICAL
TRIALS TO GET MORE DONE EVEN
WITHOUT HAVING TO TRAIN UP THAT
MANY PEOPLE.
>>AND FOR THE RECOVERING
NEUROLOGY CHAIR, IT'S A
MULTI-FACTORIAL PROBLEM AND
ACROSS THE C STATE IT'S HARD TO
FIT THIS INTO EITHER AN ACADEMIC
OR PRIVATE PRACTICE CAREER.
ON THE ACADEMIC SIDE, IN
GENERAL, IT'S NOT AS HIGHLY
THOUGHT OF WHEN YOU'RE GOING UP
FOR PROMOTION.
AS IT ALSO NOT AS EASY TO
SUPPORT AN ONGOING PROGRAM.
AND SO IT'S LESS ATTRACTIVE THAN
POTENTIALLY OTHER FIELDS.
THE MONETARY PART AND PEOPLE ARE
STARTING TO RECOGNIZE THIS IN
THE ALS ASSOCIATION JUST HAD A
GRANT FUNDING CALL TO FUND A
MEMBER OF CLINICAL TRIALS SITES
TO IMPROVE THEIR INFRASTRUCTURE
AND I THINK THAT'S A REALLY GOOD
EFFORT BUT I DON'T THINK IT
ADDRESS THE PANOPLY OF
CHALLENGES PEOPLE HAVE AND I
THINK CHIADI MENTIONED THE OTHER
IMPORTANT PART WHICH IS EVEN IT
THERE'S INFRASTRUCTURE AND
INCENTIVE, THERE IS A BOOK OF
KNOWLEDGE REQUIRED TO DO A GOOD
JOB ON THIS AND TO EVOLVE FROM
BEING A SITE INVESTIGATOR TO A
STUDY INVESTIGATOR TO DEVELOPING
YOUR OWN STUDIES.
I THINK WE DON'T HAVE ANYWHERE
NEAR THE INSTITUTIONAL
INFRASTRUCTURE TO DEVELOP THAT
AT THE PACE WE NEED.
>>WE HAVE A SHORTAGE.
WE TRAIN ALS TRIALISTS AND THEY
GET HIRED AWAY IMMEDIATELY FOR
INDUSTRY AND THAT'S GREAT FOR
INDUSTRY BUT WE DON'T HAVE THE
STAFFING TO ENROLL PEOPLE
EVERYDAY IN TRIALS AND GIVEN THE
NUMBER OF TRIALS OUT THERE.
I LOVE SOME OF THE IDEAS WE
HEARD FROM PANEL MEMBERS
INCREASE THE NUMBER OF CLINICAL
RESEARCHERS.
>>AND I WANT TO ASK THE
QUESTION FOR ANYONE.
CAN WE ENSURE EVERY CLINICAL
TRIAL SETS A TARGET ENROLLMENT
GOALS FOR PEOPLE OF COLOR AND
REPORT THEIR SUCCESS AT REACHING
THOSE GOALS TO THE COMMUNITY?
HOW CAN WE ASK FDA TO APPROVE
DRUGS BASED ON SUBSTANTIAL
EVIDENCE IF IT'S ONLY EVIDENCE
IN A WHITE POPULATION?
>>TIM, I KNOW YOU'RE INVOLVED
IN THE TAMBOURINE INITIATIVE.
>>I THINK IT'S RECOGNIZED THAT
ALS CLINICAL TRIALS AND CLINICS
AND WE'RE BEGINNING TO GATHER
DATA THROUGH THE NORTHEAST
CONSORTIUM FUNDED BY A GROUP
CALLED TAMBOURINE LOOK AT THE
MEDICARE DATABASES AND TABLE 1
OFTEN REPORTS THE INFORMATION
FOR CLINICAL TRIALS.
MY POINT IS IN CLINICAL TRIALS
AND IN CLINICS, THERE'S A LACK
OF REPRESENTATION OF DIFFERENT
ETHNIC GROUPS AND MINORITIES AND
PEOPLE IN RURAL POPULATIONS.
WHAT KIND OF DIFFERENCE WE STILL
WRAP OUR HEAD AROUND THAT BUT
IT'S STILL LOW.
I THINK IT IS A CHALLENGE IN
TERMS OF RECRUITING PEOPLE TO
CLINICS AND ALSO TO CLINICAL
TRIALS FOR A WHOLE VARIETY OF
REASONS THAT WE'RE JUST
BEGINNING TO WRAP OUR HEAD
AROUND AND IT'S IMPORTANT TO DO.
SO WE'RE TRYING TO PUSH THAT --
WE DON'T HAVE ANY SOLUTIONS YET.
THAT'S STEP ONE TO ANSWERING THE
QUESTION ABOUT AND MAKING SURE
THE APPROVED DRUGS WORK IN ALL
POPULATIONS.
>>THAT'S A HUGE SETTING FOR
RECRUITING DIVERSITY AND MEETING
THE CRITERIA.
I DON'T MEAN THIS TO BE A PASS
THE BUCK ANSWER BUT IT'S AT
LEAST PARTIALLY A REFLECTION OF
OUR HEALTH CARE SYSTEM WHICH
DOESN'T PROVIDE THE SAME ACCESS
TO CARE ACROSS THE DIVERSE
COMMUNITY OF PEOPLE WHO LIVE IN
THE UNITED STATES.
IN ARIZONA WHERE I LIVE, THE
BIGGEST CHALLENGE IS
UNDOCUMENTED IMGRAMIGRANTS WHICS
A HUGE PART OF OUR POPULATION.
THERE'S FEAR THAT PREVENTS THEM
TO COME TO OUR CLINIC AND
RESOURCES THAT PREVENT THEM AND
I DON'T KNOW WE CAN COMPLETELY
SOLVE THIS BY IMPROVING THE
CLINICAL TRIAL INFRASTRUCTURE
THOUGH WE CERTAINLY SHOULD.
I THINK IT'S A BIGGER PROBLEM.
>>MANDATES HAVE NOT BEEN
SUCCESSFUL.
THAT'S WHY WE STILL TALK ABOUT
THIS PROBLEM.
ESSENTIALLY WHAT THE
CONVERSATION IS ABOUT IS THE
MAKING THE RESEARCH EERS
DEMONSTRATE INCLUSIVENESS OR
ELSE AND WHAT WORKS IS NOTE
SETTING MANDATES FOR THE
INVESTIGATORS BUT SUPPORTING
COMMUNITY ENGAGEMENT.
IT'S COMMUNITY ENGAGEMENT HAS
BEEN SHOWN OVER AND OVER AGAIN
THE WAY TO DRIVE PARTICIPATION
IN DISADVANTAGED COMMUNITIES.
WE OUGHT TO HAVE A REORIENTATION
TO DEMANDING MANDATES TO
IMPORTING AND INCENTIVIZING
COMMUNITY-ENGAGEMENT EFFORTS.
I THINK WE'LL GETTING BETTER
RESULTS IF WE ENCOURAGE
COMMUNITY ENGAGEMENT AND THE
OTHER ADVANTAGE IS IT PROVIDES
OPPORTUNITIES FOR THE COMMUNITY
TO HAVE SOME OWNERSHIP IN THE
RESEARCH AND BE ABLE TO DRIVER
SOME RESEARCH QUESTIONS
OTHERWISE YOU HAVE AN
INVESTIGATOR THAT'S COME UP WITH
AN IDEA IN THEIR WEB A.R. AND
COMING TO A COMMUNITY AND SAYING
COME DO WHAT I WANT TO YOU DO IN
THE RESEARCH AND YOU WANT A
PROJECT THAT RESONATES WITH THE
COMMUNITY BECAUSE IT'S ANSWERING
QUESTIONS THAT THEY WOULD LIKE
TO HAVE ANSWERED AND YOU ONLY
KNOW THE QUESTIONS THEY WOULD
LIKE TO HAVE ANSWERED IF YOU ARE
ENGAGED IN A CONVERSATION.
I THINK COMMUNITY ENGAGEMENT IS
CRUCIAL.
IT SHOULD BE AN INVESTMENT.
>>SO WELL SAID, CHIADI.
>>DIAGNOSTIC DELAY IS WORSE IN
PEOPLE OF COLOR.
I THINK YOU HAVE TO TAKE IT A
STEP BACK THAT THAT IS GOING TO
TRICKLE DOWN INTO TRIALS AND WHO
IS ELIGIBLE AND I THINK WE NEED
TO TAKE A FIRST STEP IN
ADDRESSING THIS.
>>I WANT TO SEE IF PANELISTS
SEE A ROLE FOR NON-TRADITIONAL
SITES TO BRING CLINICAL
PARTICIPATION TO A LARGER
PERCENTAGE OF THE POPULATION
PERHAPS WITH EXPANDED ACCESS OR
A BIOMARKER OR A STUDY WITH
LOWER BURDEN.
>>ONE MINUTE REMAINING.
I'LL OPEN IT TO ANYONE IN THE
PANEL.
>>YES.
>>YES, AND WE SHOULD THINK OF A
TOOLBOX TO DEVELOP TO HELP
ENGAGE AND MAKE IT EASIER TO DO
STARTING FROM SCRATCH IS
DIFFICULT FOR A HARD-RESOURCED
AREA AND WE NEED A TOOL TO MAKE
IT EASIER TO JUMP IN.
>>AND NOT BECOME SOMETHING THAT
COMPETES WITH THE FIRST PRIORITY
WHICH IS TO PROVIDE THE CARE.
>>AGREED.
>>MAYBE TERTIARY SITES CAN
UTILIZE MONITORING TO SUPPORT
SITES.
>>I THINK THIS WILL CONCLUDE
THE CLINICAL RESEARCH PANEL.
THANK YOU.
>>THANK YOU.
THANKS TO EVERYONE.
THANKS FOR THE QUESTION.
>>THANKS FOR THE EXCELLENT
MODERATION.
>>YOU'RE WELCOME.
>>THANK YOU VERY MUCH.
THAT WAS AN EXCELLENT SESSION
AND WONDERFUL TO SEE THAT MUCH
GIVE AND TAKE.
GREAT NUMBER OF GOOD QUESTIONS.
THANK YOU FOR THAT.
WE'LL GO TO THE CONCLUDING
ASPECT OF WHICH IS A SERIES OF
COMMENTARIES THAT HAVE BEEN
SUBMITTED.
THE PROCEDURE HERE IS THAT THESE
ARE OPEN FOR PUBLIC COMMENT AND
IF YOU WANT TO MAKE A COMMENT,
PLEASE TYPE IT IN THE QUESTION
AND ANSWER BOX.
FIRST, TYPE ALLOWED IF YOU WOULD
LIKE TO READ YOUR COMMENT
YOURSELF OR READ IF YOU'D LIKE
IT READ FOR YOU.
WE'LL IDENTIFY YOU WITH YOUR
NAME IN ZOOM UNLESS YOU ADD
ANONYMOUS.
THEN WE WILL HAVE YOU TYPE THE
REST OF THE COMMENT AND WE'LL
READ COMMENTS THAT WERE SHARED
IN ADVANCE.
THE FIRST COMMENT SAID THOSE OF
US BATTLING ALS ARE LOOKING FOR
RESOLUTIONS WITH LIFE
EXPECTATIONS SHORT TWO YEARS
EVERY MINUTE IS APPRECIATION
AND -- PRECIOUS AND WE DON'T
HAVE THE LUXURY OF TIME FOR
SOLUTIONS BUT HOPE YOU SOLVE
THIS PLAGUE RIGHT NOW IF NOT IN
MY LIMITED LIFE TIME AT LEAST IN
THE NEAR TERM.
THANK YOU AND SEMPER FIDELIS.
>>I HAVE AN ANONYMOUS QUESTION
FOR ALS CARRIERS IS OF THE
UTMOST IMPORTANCE AS IS COULD
GREATLY DELAY HALT DISEASE
PROGRESSION.
WE HAVE FAMILIAL ALS IN OUR
FAMILY AND WATCHING IT RIP
THROUGH OUR LOVED ONES IS HARDER
THAN ANYONE CAN IMAGINE.
USE THE TREATMENT OPTIONS BEFORE
THE DISEASE STARTS AND GENE AREA
CARRIERS.
THIS IDEA MUST BE CONSIDERED.
IF THE ONLY OPTION IS TO DO
NOTHING, WHAT WOULD YOU CHOOSE?
THANK YOU.
>>OUR NEXT COMMENT IS FROM
CASSANDRA HADAD.
>>THANK YOU.
I WANT TO START BY THANK YOU ALL
FOR YOUR HARD WORK AND
DEDICATION TO THE ALS COMMUNITY.
AS I READ THROUGH THE STRATEGIC
PLAN I SEE YOUR HOPE SHOWING
THROUGH AND THANK YOU FOR
INTEGRATING THE COMMUNITY AND
WHY PEOPLE SPEAKING TO YOU
TODAY.
AUGUST 30 OF THIS YEAR MY MOTHER
DIED OF ALS.
SHE WAS AT LEAST THE 33rd PERSON
IN OUR FAMILY.
WE HAVE RAPIDLY AGGRESSIVE
SOD1A5B SO OUR FAMILY DIES
QUICKLY.
BECAUSE OF ADVOCACY AND TRIALS
AND EXPANDED ACCESS, MY MOTHER
LIVED 25 MONTHS FROM SYSTEM
ONSET.
THE LONGEST IN OUR FAMILY.
THOSE EXTRA FEW MONTHS MEANT
EVERYTHING TO MY FAMILY AND WITH
YOUNG CHILDREN IT GAVE MOM MORE
OPPORTUNITIES TO MAKE MEMORIES
BECAUSE OF RESEARCH AND ADVOCACY
BECAUSE OF PEOPLE LIKE EVERYONE
HERE TODAY.
THE ONLY REASON SHE GOT INTO
TRIALS AND EXPANDED ACCESS WAS
THROUGH MY FAMILY FIGHTING EVERY
STEP OF THE WAY FOR HER AND
DR. QUIN A TRUE ALS HERO GETTING
MEDICATION FOR MY MOM.
THERE NEEDS TO BE MORE RESOURCES
TO GUIDE PATIENTS THROUGH THIS
PART OF THE JOURNEY.
THANK YOU FOR RECOGNIZING THE
SIGNIFICANT MENTAL AND FINANCIAL
IMPACT CARING FOR A LOVED ONE
WITH ALS BRINGS AND THERE'S A
SIGNIFICANT FINANCIAL IMPACT FOR
THOSE PARTICIPATING IN GENETIC
RESEARCH AS CARRIERS.
THIS MUST BE ADDRESSED.
I KNOW IF I MY GENE TURNS ON AND
GET DIAGNOSED WITH ALS I WILL
DIE BECAUSE OF NOW THERE'S NO
HOPE.
IF I'M LUCKY I MAY GET TWO EXTRA
YEARS WITH MY TWINS AND I
IMPLORE YOU TO ADD AN AGGRESSIVE
TIME LINE TO THE STRATEGIC PLAN.
IT'S PACKED FULL OF GREAT IDEAS
AND WONDERFUL INTENTIONS BUT THE
RIGHT TRAJECTORY BUT MYSELF AND
MY CHILDREN ARE COUNTING ON A
CURE.
THE CLOCK IS TICKING AND MUST
MOVE FORWARD TO INTERVENE AND
IDENTIFY WHEN TO ACT IN THE
ASYMPTOMATIC POPULATION TO
PREVENT ALS AND LOOK AT THE
AMOUNT PEOPLE ARE WILLING TO
TAKE WITH THE GEN PENETRANTS
RATE OF MORE THAN 90% AND
RESEARCH THAT CAN CHANGE MY
CHILDREN'S LIVES I WILL
LITERALLY TRY EVERYTHING.
I'M INVOLVED IN COLUMBIA AND
MASS GENERAL'S OBSERVATIONAL
TRIALS AND BIOGEN'S ATLAS.
I'M DOING EVERYTHING ON MY PART
TO HELP BUT DOESN'T SEEM LIKE
ENOUGH.
THE COMMUNITY IS WILLING TO
SERVE AS BOOTS ON THE GROUND.
THANK YOU FOR TAKING THE TIME TO
HEAR MY COMMENTS.
IF YOU REMEMBER ONE THING ABOUT
ME AND MY ALS FAMILY REMEMBER WE
NEED TO YOU FIND THE OPTIMUM
TIME TO INTERVENE BEFORE IT'S
TOO LATE.
I KNOW TOGETHER WE CAN END ALS.
>>I AM MINDY ERRLAB BY A GROUP
OF VOLUNTEERS IMPACTED BY
GENETIC ALS AND GENETIC FTD.
WE WANT TO THANK THE NIH FOR
RECOGNIZING THE HUNDREDS OF
AMERICANS AT RISK AS STAKEH
STAKEHOLDERS AND THANK THE
MEMBERS WHO CREATED THE
DOCUMENT.
WE'RE PLEASED OUR COMMUNITY IS
CONSIDERED A PRIORITY.
WE'RE GRATEFUL THE COMMON SENSE
CALL TO INVESTIGATE POTENTIAL
THERAPIES AT ALL STAGES OF
DISEASE WAS INCLUDED.
WE WANTED TO POINT OUT ONE
WEAKNESS.
ALS HAS THREE MODIFYING DRUGS
THE FIRST APPROVED IN 1995.
IT'S INCOMPREHENSIBLE WHEN TO
INITIATE THE THERAPIES HAS NEVER
BEEN ASKED.
HOW MANY MORE THERAPIES FOR ALS
WILL BE APPROVED WITH NO
INVESTIGATION INTO WHETHER THEY
CAN FORESTALL STABILITY AND
DEATH MORE EFFECTIVELY WITH
EARLIER ADMINISTRATION?
OUR PRE-SYMPTOMATIC COMMUNITY'S
HEALTH MATTERS.
THANK YOU FOR YOUR
CONSIDERATION.
>>ARE YOU GOING TO JOIN US,
ELLEN?
>>I'M HERE.
I'VE UNMUTED.
KAREN ROBERTS STATES LOTS OF
TREATMENT IN DEVELOPMENT COULD
BE TRIED EARLIER TO PREVENT THE
DISEASE EVER STARTING.
SEEMS LUDICROUS TO ONLY FOCUS ON
TREATMENTS AFTER SYMPTOMS HAVE
STARTED.
PLEASE FOCUS ON PREVENTING ALS
FROM THE DEVELOPING AN AT-RISK
GENE CARRIERS.
PLEASE RESEARCH PREVENTIVE
TREATMENTS FOR THOSE WITH
RELEVANT GENE DEFECTS WHO ARE
NOT SHOWING DISEASE.
>>THE NEXT COMMENT IS ANONYMOUS
BUT FOLLOWS FROM THE PREVIOUS
CLINICAL TRIALS ARE NEEDED FOR
PRY-SYMPTOMATIC GENE CARRIERS TO
FOCUS ON PREVENTION.
>>THE NEXT COMMENT IS FROM
NEIL.
POLICE UNMUTE YOURSELF.
AND WE NEED TO FOCUS ON TIME TO
HUMAN IMPACT, TIME TO REAL
CHANGE IN THE LIVES OF PEOPLE
WITH ALS AND CONSIDER THE
SPECIFIC MILESTONE TO GET US
THERE.
I DIDN'T SEE TIME LINES IN THE
PLAN AND I THINK IT NEEDS IT.
I WOULD ALSO LIKE TO YOU THINK
OF THE BALANCE OF RESEARCH AND
INVESTMENTS ACROSS THE PLAN IN
TERMS OF TIME AND RESOURCES.
THESE RESEARCH EFFORTS ARE
WORKING ON DIFFERENT TIME
SCALES.
PLEASE BE SPECIFIC ABOUT WHAT
THE TIME SCALES ARE SO THE
COMMUNITY CAN MORE FULLY
UNDERSTAND THE PLAN AND ITS
POTENTIAL.
OUR EXISTING RESEARCH CAPACITY
ARE PEOPLE AND INSTITUTIONS ARE
ALSO NOT EVENLY DISTRIBUTED
AROUND THE COUNTRY.
WITHOUT CAREFUL PLANNING WE'LL
NOT GIVE THE RESEARCH AND
RESULTS WE NEED WE'LL END UP IN
THE SAME PLACE WE ARE TODAY AND
JUST GET MORE APPLICATIONS FROM
THE STATEMENT PLACES AND
SPECIFICALLY AND IMPORTANTLY WE
NEED TO CONSIDER TRIAL CAPACITY.
THERE'S AN EMPHASIS IN THE DRAFT
AND PERHAPS A RISK TO FURTHER
CENTRALIZE RESEARCH CAPACITY AND
THAT MIGHT BE THE RIGHT STRATEGY
FOR FUTURE OF WORK AND FOR HUMAN
RESEARCH IT MIGHT BE COUNTER
PRODUCTIVE.
WE NEED TO RUN CLINICAL TRIALS
WHERE PEOPLE WITH ALS LIVE NOT
WHERE ALS SCIENTISTS ARE
CURRENTLY LIVING.
SO WE NEED TO WORK ON THAT
PROBLEM.
AND WE NEED TO JUST GET
TREATMENTS AND CURES INTO PUB
MED.
>>THANK YOU, NEIL.
OUR NEXT COMMENT IS FROM MIKE.
PLEASE UNMUTE YOURSELF.
>>THANK YOU.
I WANT TO APPLAUD THE GROUP ON A
VERY BROAD AND WELL THOUGHT.
OUT STRATEGY OF RESEARCH MY
CONCERN IS IS IT BEING
ACTIONABLE AND NOT BECAUSE THE
RESEARCH ISN'T SOLID AND
ACHIEVABLE BUT TOO MUCH AND I
FIND IT TOO BROAD.
I FEEL WE NEED TO TURN THE
STRATEGY INTO A PLAN AND NEEDS
TO HAVE DISCOVERY MILESTONES AND
RATHER THAN TO ATTACK THE
DISEASE MECHANISM, ETCETERA.
ALL AT ONE TIME.
THANK YOU.
>>THANK YOU, MIKE.
NOW BACK TO RITA.
>>I'M GOING READ A COMMENT.
I'M A C9 CARRIER AND DIAGNOSED
IN APRIL OF THIS YEAR.
I DETECTED DIFFICULTIES WITH MY
SPEECH STARTLING IN DECEMBER
2021 SO CONSIDERED MYSELF
FORTUNATE TO BE TREATED SO SOON
AFTER MY SYMPTOMS BEGAN.
HOWEVER MUCH TO MY DISMAY MY
NEUROLOGIST INDICATED THE
SYMPTOMS STARTED A YEAR PRIOR
DETECTING ANYTHING.
I THINK I COULD HAVE STARTED
TREATMENT EARLIER.
TO THINK I WOULD HAVE HAD MORE
FUNCTION NOW THAN 10 MONTHS INTO
THE DISEASE.
RECENTLY RESEARCH HAS BEEN
PUBLISHED DOCUMENTING THE
PRESENCE OF TD43 A HALLMARK OF
ALS IN MULTIPLE TISSUES AND
ORGANS GOING BACK 14 YEARS AND
THIS IS SHATTERING AND DEMANDS
WHEN TO THINK TO START TREATMENT
AND I HAVE THREE CHILDREN THAT
MAY OR MAY INTO THE CARRY THE
CARRIER AND I SHUTTER TO THINK
ABOUT THE YEAR-LONG PROCESS OF
NEURODEGENERATION TO THINK THEY
HAVE TO WAIT UNTIL THEY INTEREST
TROUBLE BEFORE GETTING
TREATMENT.
THIS WAIT SEEMS CRUEL AND UNJUST
AT THIS JUNCTURE.
I URGE THIS ESTEEMED GROUP TO
TREAT THOSE WITH BIOMARKERS OR
MUTATIONS SOONER AS A TOP
OBJECTIVE IN THE ALS STRATEGIC
PLAN.
THIS HAS TO BE FIRST AND
FOREMOST IN MY VIEW DRIVING
EVERYTHING ELSE WITHIN THE PLAN.
THANK YOU, DEBORAH.
>>THE MONTH OF MAY IS ALS
AWARENESS MONTH ALS AND FOX
DON'T HAVE ANY NEWS ABOUT THE
ALS AWARENESS MONTH.
THE ORGANIZATIONS NEED TO MAKE
AN EFFORT IN GETTING THE WORD
OUT AND THE WRONG PEOPLE ARE
BEING TARGETED AND PEARL WITH
ALS ALREADY KNOW ABOUT ALS.
IT'S THE NON-ALS COMMUNITY THAT
NEEDS THE MESSAGE TENT TO THEM.
>>THE DOCUMENTED SUB GROUPS
SUGGEST THE RESEARCH IS CREATING
AN INEFFICIENT INFRASTRUCTURE TO
GATHER PATIENT DATA SUCH AS BIO
FLUIDS AND CLINICAL OBSERVATIONS
INTO THE LOOKING AT THE COURSE
OF THE DISEASE.
I HOPE AND PLEAD WITH NINDS THAT
THIS IS IS LOOKED AT IN THE
POPULATION EVERY FIVE YEARS.
RIGHT NOW IT SEEMS THE STRATEGIC
PLAN AND THE NEXT GENERATION OF
PATIENTS AND THE GOVERNMENT
ALTER IN FAVOR OF A LINEAR
PROFESSOR.
AND CONSIDERING NEEDS TO BE
GIVEN TO THE ALS CLOCK.
>>THIS IS FROM BARBARA KITT.
I'M A RETIRED BUSINESS EXECUTIVE
AND ETHICS OFFICER ADVOCATING
FOR ADVANCES IN ALS RESEARCH AND
TREATMENTS WITH THE ALS PROBLEM
SOLVERS FOR THE PAST TWO YEARS.
AS IT RELATES TO THE STRATEGIC
PLAN FOR RESEARCH, WE COMMEND
THE NIH FOR UNDERTAKING THE
EFFORT WE BELIEVE THE STRATEGIC
PRIORITIES ARE ALL IMPORTANT AND
GENERALLY MAP TO THE FIVE
COGS/SOLUTIONS PRESENTED AND
DISCUSSED WITH NINDS STAFF FIRST
IN OCTOBER 2021 AND SUBSEQUENT
MEETINGS IN 2022.
THANK YOU FOR DOING THIS.
IN YOUR DRAFT STRATEGIC PLAN WE
SEE AN ADMIRABLE LIST OF 15
PRIORITIES.
THEY'RE LIKE 15 FEATURES.
THERE'S OVERLAPS BETWEEN WE
BELIEVE SOME WORK STREAMS ARE
TOO MANY TO BE CONSIDERED
PRIORITIES.
THESE NOW NEED TO BE WOVEN INTO
A COHESIVE STRATEGIC PLAN IN THE
SAME WAY A SKILLED ARCHITECT
DESIGNS A HOME AND WE NEED A
FAST TRACKED TIME LINE THAT
RECOGNIZE THE ALS CLOCK.
WE CAN'T AFFORD DISPARATE
PRIORITIES THAT ARE NOT
IMPLEMENTED EFFICIENTLY AND THAT
WILL TAKE THE EXPERTISE AND
LEADERSHIP OF NINDS.
WE CAN'T AFFORD TO BUILD IT AND
THEY WILL COME APPROACH TO
INFRASTRUCTURE COMPONENTS.
A STRATEGIC PLAN NEEDS TO
CONSIDER THE IMPRACTICALITIES AN
ARCHITECT DEALS WITH IN DRAWING
UP SCHEMATICS FOR THEIR ENTIRE
MOMENT.
-- HOME.
>>THE NEXT COMMENT IS
ANONYMOUS.
I THINK THE ALS STRATEGIC PLAN
IS STILL IN ITS INFANCY TAKING
SMALL STEPS BUT NOT ENOUGH SINCE
ALS KILLS FASTER THAN A BABY CAN
BECOME AN ADULT.
IT SHOULD BE ON A WIDER GLOBAL
SCALE.
CELEBRITIES, SINGERS, SPORTS
PERSONS CAN BE THE FACE OF ALS.
THE COMBINATION OF DIFFERENT
THERAPEUTICS SHOULD BE TRIED
LIKE AMEX 0035 AND THE EXAMPLE
BEING AIDS THERAPY.
THANK YOU FOR THAT.
>>I HAVE JUST RETIRED FROM
PFIZER AFTER 35 YEARS IN R&D AND
MOST RECENTLY AS CHIEF
DEVELOPMENT OFFICER RESPONSIBLE
FOR ALL CLINICAL DEVELOPMENT AND
REGULATORY AFFAIRS.
I NOW VOLUNTEER AS THE ALS
PROBLEM SOLVERS.
I'VE BEEN INVOLVED IN THE ALS
PROBLEM SOLVER DISCUSSIONS THIS
YEAR AND I'M HAPPY TO SEE MUCH
OF THE FIVE COGS WE RECOMMENDED
ARE CENTRAL TO THE DRAFT
STRATEGY AND THEY DOES AN
EXCELLENT JOB OF EXPLAINING THE
NATURAL HISTORY STUDY FOR THEIR
WORK AND SAW THE NEED FOR SUCH
LONGITUDINAL INTEROPERABLE DATA.
A NATURAL HISTORY STUDY WAS
SPECIFICALLY MENTIONED NINE
TIMES AND REFERENCES TO THE DATA
AND IT IS CLEAR THAT THEREFORE
THE NATURAL HISTORY STUDY IS
FOUNDATIONAL TO MULTIPLE
PRIORITIES IN THE DRAFT STRATEGY
DOCUMENT AND SHOULD BE
IMPLEMENTED IN A MANNER TO
PROVIDE BROAD ACCESS TO A
REPRESENTATIVE POPULATION OF
PEOPLE LIVING WITH ALS.
IT'S CRITICAL DESIGN CRITERIA
ARE FINALIZED AND THE STUDY
STARTED AS SOON AS POSSIBLE AND
SHOULD BE OPERATIONAL AND
QUALITY AND SPEED SHOULD DEFINE
THE TIME LINE NOT PROCESS AND
EVERY MINUTE MATTERS.
>>THE NEXT ITEM IS AN ANONYMOUS
COMMENT ORIGINALLY IN FRENCH AND
TRANSLATE.
WE'RE A DOUBLE GLOBAL C9
COMMUNITY AND YOU KNOW OUR
STARTS AND NOTHING IS DONE AND
WILLING TO BE VOLUNTEERS.
WHY DON'T WE TEST EXISTING DRUGS
THAT DON'T WORK ONCE THE DISEASE
BUT TEST THEM BEFORE THE DISEASE
WHETHER FTD OR ALS DEVELOPS
THANK YOU FOR THE QUESTION.
>>THE COMMENT IS FROM AN A
WOMAN WHO'S SPOUSE PASSED AND
I'VE BEEN INVOLVED IN ADVOCACY
FOR 17 YEARS.
MOSTLY AS PART OF THE ALS
PROBLEM SOLVERS.
WE SALUTE NINDS FOR THOSE
SUPPORTING PATIENTS AND
CAREGIVERS ON THE STRATEGIC
PLANNING AND WE EXPECT THE
REPRESENTATION TO CONTINUE AS A
PLAN IS IMPLEMENTED.
I NOTICED PAGE 29 SAYS, AND I
QUOTE, FORMATION OF A COMMITTEE
THAT INCLUDES REPRESENTATION
FROM ACADEMIA AND NONPROFIT AND
GOVERNMENT FUNDING AGENCIES WITH
A FOCUS ON THE GOALS AND
RESOURCES FROM DIVERSE
CATEGORIES ALONG WITH PROTOCOLS
AND METHODOLOGIES FOR THE
GENERATIONAL USE.
END QUOTE.
I WOULD IMPLORE THAT PEOPLE
PEOPLE LIVING WITH ALS BE
REPRESENTATI
REPRESENTED IN THE COMMUNITY AND
THEY'RE THE EXPERTS AS THEY'RE
LIVING ON THE ALS CAR.
THANK YOU FOR THIS CHANCE TO
COMMENT.
WE THINK THE ALS PROBLEM SOLVERS
AND PEOPLE LIVING WITH ALS HAVE
SHOWN HOW HARD THEY'LL WORK TO
DELIVER ON THE MISSION.
AND PROVIDE AN A COMMUNITY OF
OUTREACH AND EDUCATION.
PUT US TO WORK WITH YOU.
WE CAN AND WILL HELP.
THANK YOU, JIM.
>>THIS IS FROM SOMEONE WHO'S
PARTNER PASSED FROM ALS.
76 DAYS AFTER DIAGNOSIS.
THANK YOU FOR PUTTING THE
STRATEGIC PLAN TOGETHER AND
THERE WAS NO TIME TO PLAN WITH
ME AS HER ONLY CAREGIVER WE
MOVED FORWARD WITH NO EQUIPMENT,
NO SKILLED NURSING CARE AND NO
REAL KNOWLEDGE AT HOW TO MANAGE
THE MEDICAL SYSTEM.
THIS STRATEGIC PLAN FOR
IMPLEMENTATION OF THE PLAN WITH
IMPLEMENTATION TO BEGIN IN LATE
2024 IS NOT AGGRESSIVE ENOUGH.
IT DOES NOT REFLECT THE ALS
CLOCK.
FOR US THE CLOCK WAS LESS THAN
THREE MONTHS.
IT WILL BE OVER TWO YEARS FROM
THE TIME THE STRATEGIC PLANNING
EFFORT WAS ANNOUNCED TO
BEBEGINNING -- BEGINNING OF THE
IMPLEMENTATION AND DURING THAT
TIME OVER 12,000 PEOPLE LIVING
WITH ALS WILL DIE AND MANY WILL
LOSE THEIR ABILITY TO WALK,
TALK, FEED AND PERFORM BASIC
DAILY LIFE FUNCTIONS.
NIH SHOULD AGGRESSIVELY ACC
ACCELERATE THE TIME LINE, WHAT
CAN I DO TO SUPPORT NIH IN
ACCELERATING THIS PLAN?
WHAT CAN WE THE ALS COMMUNITY DO
TO SUPPORT NIH IN ACCELERATING
THIS.
WHAT CAN NIH DO TO ACCELERATE
THE IMPLEMENTATION OF THE K
COHESIVE PLAN.
THANK YOU.
>>AND GIVEN THE STUDY OF
DECLINE AND JAPAN AND INDONESIA
AND GUAM AND POST-WORLD WAR II
AND THE DISTINCT GENETIC GROUPS
NONE OF THOSE WITH A GENETIC
PHENOTYPE AND IT'S THOUGHT
EXOGENOUS FACTORS CAN PLAY AN
EXCLUSIVE ET YO LODGE --
ETIOLOGIC ROLE AND THERE'S A HOT
SPOT IN THE FRENCH ALPS WHERE
FUNGI CONTAINING CHEMICALS
COMPARED WITH THOSE IN THE
WESTERN PACIFIC ALS.
THE DISCOVERY OF THIS CAN LEAD
TO PRIMARY ALS PREVENTION
UNDERSTANDING CAUSE-ASSOCIATED
MECHANISMS CAN LEAD TO BIOMARKER
DISCOVERY AND THERAPEUTIC
DEVELOPMENT.
THANK YOU, PETER.
>>THE NEXT COMMENT.
I GOT INVOLVED IN ADVOCACY WHEN
MY FRIEND WAS DIAGNOSED WITH THE
DISEASE IN EARLY 2021.
SADLY, SHE PASSED NINE MONTHS
LATER AND THE ALS CLOCK MOVES
FAST.
I'M HAPPY NIH IS PUTTING
TOGETHER A STRATEGY PLAN TO
ADVANCE RESEARCH, THERAPIES AND
CURE FOR ALS.
I WONDER HOW QUICKLY ELEMENTS OF
THE PLAN WILL TAKE AND THE
OVERLAP OF SOME ACTIVITIES
ESPECIALLY RELATED TO NATURAL
HISTORY AND THE NEED FOR
LONGITUDINAL DATA.
A
ARE THERE FUNDS AT NIH TO BEGIN
EFFORTS IMMEDIATELY OR WILL YOU
HAVE TO WAIT UNTIL 2024 WHEN
CONGRESS CAN APPROPRIATE FUNDS?
MANY MUCH THE FRIENDS WITH ALS
DON'T HAVE TIME TO WAIT UNTIL
2024 TO SEE ACTION.
WE NEED TO WORK WITH SPEED AND
URGENCY.
LIVES DEPEND ON IT.
>>THERE'S BEEN TIME AND EFFORT
BY THE FIVE WORKING GROUPS TO
THANK YOU TO EACH MEMBER.
ONE COMMON THEME THROUGHOUT THE
DRAFT IS DATA COLLECTION.
DESCRIBED IN WORKING GROUP THREE
AS A NATURAL HISTORY STUDY.
OTHERS PRESCRIBE DATA COLLECTION
OF BIO SAMPLES AND THIS
LONGITUDINAL NATURAL HISTORY
STUDY SHOULD BE THE TOP PRIORITY
OF THE STRATEGIC PLAN BECAUSE IT
REPRESENT THE LARGEST POPULATION
OF PEOPLE LIVING WITH ALS.
AND A LARGE NUMBER OF WORKING
GROUP PRIORITIES NATURALLY FIT
AND PROCEED FROM IT.
ONE AREA I THINK THE STRATEGIC
PLAN RECOGNIZES BUT FAILS TO
PROVIDE AN ADEQUATE SOLUTION FOR
IS THAT OF DIVERSITY, EQUITY AND
INCLUSION.
THE AREAS PEOPLE ARE BEING LEFT
OUT ARE RURAL AND INTERCITY AND
SOCIO ECONOMICALLY ADVANTAGED
GROUPS.
ACROSS THE U.S., WE HAVE A BROAD
NETWORK OF MULTI-DISCIPLINARY
CLINICS AND THOSE LEFT BEHIND
AREN'T ABLE TO ACCESS THE
EXISTING RESOURCES.
PROPOSING TO USE THE EXISTING
NETWORK OR DESIGNATE SOME OF
THEM AS RESEARCH CENTERS OF
EXCELLENCE DOESN'T SOLVE THE
PROBLEM.
I WOULD SUGGEST REACHING OUT TO
INDIVIDUAL SINGLE PRACTICE
NEUROLOGISTS WHO TREAT ALS
PATIENTS AS WELL AS INCORPORATE
BEING ENVIRONMENT CLINICAL
RESOURCES THAT ANYONE DIAGNOSED
WITH OR THINK MAY HAVE ALS CAN
ACCESS.
ADDING NEW CLINICS WILL HELP.
THE GOAL IS TO BROADEN THE
PATIENT POPULATION SO ALL CAN
RECEIVE CARE AND PARTICIPATE IN
THE LANDMARK NATURAL HISTORY
STUDY AND CLINICAL TRIALS AND
MORE SPECIALIZED STUDIES
INVOLVING DATA COLLECTION OF BIO
SAMPLES AND OTHER USEFUL DATA TO
LEARN AS MUCH AS WE CAN ABOUT
ALS AND ITS CAUSES AND A CURE.
THANK YOU VERY MUCH, GLEN.
>>AND THIS ONE SAYS I WAS
DIAGNOSED IN AUGUST OF 2018.
I'M AN ADVOCATE FOR A MORE
INCLUSIVE CLINICAL TRIALS IN
ALS.
THE CENTERS OF EXCELLENCE
PROGRAM AND ALS RESEARCH AS
DESCRIBED AND AND THERE'S WELL
ESTABLISHED MULTI-DISCIPLINARY
ALS FUND IING AND IT'S COUNTER
PRODUCTIVE WHEN IT COMES
DIVERSITY EQUITY AND INCLUSION
AND MAY MAYBE IT HARDER, NOT
EASIER, TO STUDY THE NATURAL
HISTORY OF ALS AS IS ONLY LOOKED
AT A SUBSET OF THE POPULATION
AND THE CENTERS OF EXCELLENCE
COULD BE GEOGRAPHICALLY OR
SOCIALLY ECONOMICALLY
EXCLUSIONARY.
THE DEI PROBLEM IS DESCRIBED BUT
NO TANGIBLE SOLUTIONS WERE
OFFERED.
PERHAPS A PROGRAM COULD INCLUDE
HBCUs AND MEDICAL SCHOOLS AND
HOW DO WE EXPAND THIS IN THE
U.S.?
WE NEED TO DO MORE THAN THE DEI
PROBLEM.
WE NEED AND THOSE NOT TREATED IN
ESTABLISHED CLINICS OR BY
PROMINENT CLINICIANS NEED TO BE
REACHED AND INCLUDED.
AND WE MUST HAVE DECENTRALIZED
CLINICAL TRIALS THAT CAN BE USED
TO OVERCOME THE BARRIERS.
THANK YOU.
>>THE COMMENT IS FROM
JEAN-PIERRE.
AS SOMEONE WHO HAD TWO PEOPLE IN
ALS IN MY FAMILY I THINK
RESEARCH SHOULD ADOPT A TOOL
FAMOUS TO THE HALLMARKS OF
CANCER.
A TENTATIVE CHECKLIST WOULD BE
TO ASK, 1, DOES IT OFFER A
COMPELLING EXPLANATION MUSCLE
WASTING BASED ON METABOLISM AND
NOT PROLONGED INACTIVITY OF
UPPER NEURONS.
2, DOES IT EXPLAIN WHY SYMPTOMS
OFTEN START IN A SPECIFIC AREA?
3, DOES IT EXTEND WHY SYMPTOMS
EXTEND PROGRESSIVELY?
4, DOES IT EXPLAIN WHY IT
STRIKES THE ELDERLY.
5, DOES IT EXPLAIN WHY SOME
SURVIVE 10 TO 20 YEARS AND SOME
SIX MONTHS?
6, DOES IT EXPLAIN WHY ONLY
SKELETAL MUSCLES ARE IMPACTED?
7, DOES IT EXPLAIN WHY ONLY
HIGHER PRIMATES SEEM TO HAVE
ALS-LIKE DISEASES?
ANOTHER THOUGHT IS THAT RESEARCH
ABOUT MANAGING THE DISEASE IS
LACKING, FOR EXAMPLE, I THINK
ALS SCIENTISTS HAS A LOT TO
LEARN FROM STROKE AND FINAL
INJURY SCIENTISTS AND FINALLY IT
WOULD BE DESIRABLE TO FUND
SCIENTISTS WITH BACKGROUNDS IN
HUMAN PHYSIOLOGY AND ALS
METABOLISM AND THE CORTICOBULBO
TRACK RATHER THAN SPECIALISTS IN
MOLECULAR BIOLOGY WHICH SEEM
UNABLE TO HELP PROGRESS BEYOND
LOW-HANGING FRUITS.
THANK YOU.
>>MUCH DISEASE FOCUSSED
RESEARCH AIMS TO JUNG TO THE
CURES WITHOUT RESTING ON
NEUROSCIENCE UNDERSTANDING OF
MOTOR NEURO BIOLOGY AND
FUNCTION.
I BELIEVE WE MUST MAKE IT CLEAR
THE LACK OF TREATMENT FOR ALS
ARE INHERENTLY LIMITED BY A POOR
UNDERSTANDING OF MOTOR NEURON
GENE REGULATION AND FEATURES OF
NEUROBIOLOGY AND ASPECTS OF RNA
REGULATION.
A NEW VISION FOR AN ALS
TREATMENT PIPELINE MUST CLEARLY
EMPHASIS BASIC NEUROSCIENCE
GOALS AND UNANSWERED QUESTIONS.
I DO NOT SEE SUCH A VISION IN
THE CURRENT FORM OF THE
STRATEGIC PLAN.
WHERE IS THE DISCUSSION OF THE
BASIC NEUROSCIENCE OBJECTIVES
THAT WOULD ADD TO THE NEEDS OF
THE BROADER ALS COMMUNITY?
THANK YOU, NEIL.
>>MOM DIED FROM ALS 25 YEARS
AGO.
I'VE BEEN INVOLVED IN ALS
ADVOCACY WORK SINCE.
I'M A MEMBER OF THE ALS PROBLEM
SOLVERS.
AS A GROUP WE FIRST MET WITH
NINDS LAST OCTOBER.
WE'RE VERY HAPPY NINDS HAS
UNDERTAKEN THE STRATEGIC PLAN
FOR ALS.
THERE'S ONLY ONE REFERENCE TO
EXPANDED ACCESS IN THE DRAFT.
EXPANDED ACCESS FOR ALS
RESOURCES SHOULD NOT LIVE IN A
SILO.
IF WE PUT PEOPLE LIVING WITH ALS
AT THE CENTER OF THE STRATEGIC
PLAN THEY SHOULD HAVE A ROLE IN
MOVING THE SCIENCE FORWARD AND
FOR THOSE WHO DO NOT QUALIFY FOR
TRIALS, THE EXPANDED ACCESS PATH
SHOULD BE AVAILABLE AND USED TO
ITS BEST SCIENTIFIC PURPOSE.
I HOPE THIS MAY BE HELPFUL TO
THE TRANSLATIONAL GROUP AND
CLINICAL TRIAL TRIALS GROUP AND
THE GROUP ADDRESSING QUALITY OF
LIFE ISSUES.
THANK YOU, MARY.
>>THE NEXT COMMENT IS FROM
ASHLEY LEE.
THE CURRENT EFFORTS AND WORK
PERTAIN TO ALS AND THE RESULTING
COLLABORATION IS INCREDIBLE.
I KNOW WE STILL HAVE A LONG WAY
TO GO BUT COMPARED TO THE
EXTREMELY MINIMAL AMOUNTS OF
RESEARCH AND ADVOCACY EFFORTS I
EXPERIENCED IN , WHEN WE BEGAN
THE JOURNEY, THIS IS TRULY
INSPIRING AND ENCOURAGING.
THANK YOU.
>>THINK THIS IS THE LAST
PRE-SUBMITTED COMMENT AND IT
COMES FROM I HOPE I'M
PRONOUNCING THIS RIGHT, NEIL
RESNICK.
I LIVED FOR 10 YEARS WITH MY
HUSBAND'S ALS PARALYZED WITH A
RESPIRATOR AND WE RECEIVED VERY
LITTLE FINANCIAL SUPPORT AND HAD
TO FUND RAISE TO AFFORD TO PAY
CAREGIVERS AND LOANS FOR FOOD.
FOR THOSE WHO SURVIVE WHAT IS
IMPOSED BY RESEARCH NEEDS TO GO
BACK TO ALS RESEARCH.
IF WE WANT TO SURVIVE LONG TERM
UNTIL RESEARCH DISCOVERS A CURE
WE NEED MAJOR FUNDING FOR THE
CARE, SUPPORT OF THE FAMILY
CAREGIVERS THEMSELVES.
>>THERE'S A COUPLE COMMENTS
THROUGH THE Q&A BOX.
THIS IS AN INCREDIBLE INITIATIVE
BY EVERYONE.
THERE IS -- EVERYONE IN THE ALS
STRATEGIC PLANNING COMMITTEE.
MY HEARTFELT GRATITUDE TO BRING
HOPE IN THE COMMUNITY.
DAY BY DAY WE ARE REACHING
TOWARDS DECODING THIS INCURRABLE
AND DEVASTATING DISEASE.
ONE DAY WE WILL SUCCEED.
THERE WAS ANOTHER ONE BUT IT
DISAPPEARED FROM MY BOX.
>>I THINK WE READ ALL THE
COMMENTS WE RECEIVED.
WE'RE GRATEFUL FOR ALL OF THE
COMMENTS THAT EVERYONE POSTED.
THIS WAS VERY INSPIRING AND
WE'LL CERTAINLY TAKE THESE
COMMENTS INTO CONSIDERATION WHEN
WE REVISIT OUR DRAFT PROPOSAL
YOU WERE ALL ABLE TO LOOK OVER
AND ADDRESS.
I THINK THIS WAS AN INCREDIBLY
SUCCESSFUL DAY.
THANK YOU FOR EVERYBODY FOR
PARTICIPATING.
THANK YOU TO ALL OF OUR WORKING
GROUPS AND THEIR MEMBERS FOR
PUTTING TOGETHER THIS WONDERFUL
SUMMARY OF HOW THEY PRIORITIZED
WHERE WE SHOULD GO NEXT AND I
THINK IT BECAME CLEAR THAT TIME
IS ONE OF THE THINGS THAT
ESPECIALLY IN THE COMMENTS
BECAME OBVIOUS THAT THE ALS
CLOCK IS AN IMPORTANT ISSUE FOR
MOST OF THE ALS CAREGIVERS AND
WE SHOULD KEEP IN MIND MOVING
FORWARD AND WE'LL DO SO IT'S
GOOD TO BE REMINDED OF THIS AT
ALL TIMES AND AN IMPORTANT ISSUE
THAT'S RELEVANT FOR THE ALS
COMMUNITY.
WE APPRECIATE THE HONESTY AND
COMMENTS IN REGARDS TO MAKING IT
IMPORTANT FOR US THAT THIS IS
SOMETHING THAT WE SHOULD ALWAYS
KEEP IN MIND AS WE MOVE FORWARD.
BOB, DO YOU WANT A FEW MORE
COMMENTS BEFORE WE CLOSE UP?
>>NOT REALLY.
I THINK IT'S BEEN A MOTIVATING
AND ALL-IMPORTANT DAY.
WE SUFFER HISTORICALLY BECAUSE
ALS IS SAID TO BE AN ORPHAN
DISEASE AND IF WE LOOK AT THE
STATISTICS, MORE THAN 500,000
PEOPLE ALIVE IN THE UNITED
STATES TODAY WILL DIE OF ALS.
THAT'S LOOKING AGAIN AND AGAIN
AT DEATH CERTIFICATES ACROSS THE
U.S. AND WESTERN EUROPE.
IT'S NOT AN ORPHAN DISEASE FROM
THE PERSPECTIVE OF A TOTAL
BURDEN OF THE MEDICAL CHALLENGE
AND OF THE TRAGEDY THIS
REPRESENTS.
WHILE I'M DEEPLY GRATEFUL TO THE
NINDS FOR ALL YOU'RE DOING AND
LOOK FORWARD TO TOMORROW IN
CONTINUING THE MOTIVATING
DISCUSSION.
THANK YOU VERY MUCH.
>>ALSO, I ECHO WHAT YOU SAID,
BOB.
I LOOK FORWARD TO TOMORROW AND
AS YOU CAN SEE THE COMMUNITY
INVESTED IN ALS IS WE VOE BUST
AND INNOVATIVE AND NATION AT AND
WILLING TO ROLL UP THEIR
SLEEVES.
WE'RE ON THE SAME TEAM HERE.
I WANTED TO ADDRESS ONE THING
THAT'S ABOUT THE TIME FRAMES.
THE ACTIONS THAT ARE COMING OUT
OF THE PLAN CAN INFLUENCE
RESEARCH STARTING TOMORROW.
IT'S NOT -- NO ONE HAS TO WAIT.
THERE'LL BE THINGS THAT COME
ALONG AT DIFFERENT TIMES BUT THE
IMPACT SHOULD BE IMMEDIATE.
WITH THAT I'D LIKE TO THANK
EVERYONE ONCE AGAIN AND WE'LL
SEE YOU TOMORROW.
>>THANK YOU, EVERYBODY.
SEE YOU TOMORROW.