>> WE'RE HERE TO KICK OFF DAY
THREE AND I THINK IT'S FITTING
THE SESSION FOLLOWS THE LAST ONE
WHERE THERE WAS TALK ABOUT THE
BIOMARKERS.
WE'RE GOING TO TALK ABOUT THE
FLUID DIGITAL AND OCULAR ONES.
TO GET US STARTED THOUGH I WANT
TO START BY TALKING ABOUT THE
ARGENTINE ANT WHO I THINK OF AS
THE ULTIMATE TEAM PLAYER BECAUSE
IF YOU TAKE IT FROM ITS COLONY
AND WANDERS INTO ANOTHER COLONY
OF DIFFERENT ANTS IT WILL PICK
UP WHAT THE TEAM IS DOING AND
CONTRIBUTE IN ANY WAY THAT IT
CAN.
IT TURNS OUT IF YOU TAKE ANY OF
THESE ARGENTINE ANTS AND HAVE
THEM MOVE TO ANY PART OF THE
WORLD, THEY WILL CONTRIBUTE TO
THAT TEAM WHICH THEN CONTRIBUTES
TO A MUCH LARGER ECO SYSTEM THAT
IS CUSTOMIZED TO DIFFERENT
REGIONS.
AND I REALLY THINK THIS SETS A
GREAT CONTEXT FOR WHAT WE'RE
TRYING TO DO AS WELL.
SO LET'S START WITH FLUID
BIOMARKERS.
WE'LL HEAR TODAY ABOUT ALL THE
DIFFERENT WAYS IN WHICH FLUID
BIOMARKERS ARE NOW STARTING TO
REALLY CHANGE THE LANDSCAPE OF
HOW WE DO OUR RESEARCH.
MORE AND MORE, WE'RE TALKING
ABOUT NOW DIGITAL BIOMARKERS.
I WAS REALLY EXCITED EVERY DAY
SOMEONE MENTIONED DIGITAL.
THIS IS NO LONGER SOMETHING IN
THE BACKGROUND BUT MOVING TO THE
FOREGROUND.
AND THEN THE OTHER YOUR PEOPLE
ARE TALKING A LOT ABOUT ARE
THESE OCULAR BIOMARKERS WE'LL
HEAR ABOUT AS WELL.
I THINK IN COMBINATION WHAT WE
NEED TO THINK ABOUT IS HOW ALL
THESE DIFFERENT TYPES OF
BIOMARKERS ARE GOING TO COME
TOGETHER ALL ACROSS THE WORLD IN
UNIQUE COMBINATIONS IN ORDER TO
ACTUALLY FACILITATE REALLY NEW
SCIENCE IN DIFFERENT DIRECTIONS
AND WAYS WE NEVER THOUGHT OF
BEFORE.
SO WITH THIS WE'RE GOING TO GET
STARTED WITH OUR PANEL.
I AM GOING TO UP FRONT TELL YOU
THAT DONNA AND I ARE GOING TO BE
THE TIME NAZIS AND WE'RE GOING
TO KEEP EVERYBODY ON TIME.
SO WITH THAT, I'D LIKE OUR FIRST
SPEAKER, DONNA WILL GO AHEAD AND
INTRODUCE EACH ONE.
THANK YOU.
>> ABOUT MORNING, EVERYBODY.
OUR FIRST SPEAKER OF THE DAY IS
SUDHIR SRIVASTAVA FROM THE
NATIONAL CANCER INSTITUTE.
>> GOOD MORNING.
CAN YOU LOAD MY SLIDES, PLEASE.
I JUST WANT IT SAY HOW FAST
NATING THE OPENING REMARK --
FASCINATING TE OPENING REMOOSHG
AND IN WE SAY IT TAKES A VILLAGE
AND THIS TAKES A GLOBAL EFFORT.
I CANNOT SEE MY SLIDES.
THE TOPIC IS FROM FIVE YEARS AT
NCI.
IT TAKES A VILLAGE.
WE JUST HAD A FASCINATING
INTRODUCTION AND I DON'T THINK I
CAN CAPTURE THOSE BUT I WANT TO
GIVE A SNIPPET.
SO AS YOU KNOW OVER THE YEARS WE
HAVE A MADE PROGRESS AND
THEREFORE WE HAVE BEEN TRYING TO
PROTECT CANCER.
IN OUR EFFORTS FOR BIOMARKERS
AND TO JUSTIFY THE BIOMARKERS IF
YOU DETECT CANCER AT THE EARLY
STABLE THE FIVE-YEAR SURVIVAL IS
MUCH BETTER FOR EPITHELIAL
TUMORS AND PROSTATE AND LUNG
CANCER AND SO ON.
THIS IS ALL ABOUT THE
BIOMARKERS.
THEY HAVE DEVELOPED A NUMBER OF
BIOMARKERS AND THE RADIOMICS AND
THERE'S DISTAL BIOMARKERS AND IN
IMAGING AND ALWAYS KIND IMAGING
WITH BIOMARKERS AND WHAT WE CALL
DIAGNOSTIC ODYSSEY BECAUSE WE
NEED TO CONFORM AND YOU CAN SEE
VERY IMPRESSIVE GAIN IN TERMS OF
FIVE-YEAR SURVIVAL DATE.
SO OVER THE YEARS WE HAVE BEEN
DEVELOPING BIOMARKERS AND
THERE'S SPECIFICITY BUT THERE'S
FEW IN THE PROCESS AND ON THE
RIGHT HAND I SHOW THERE'S MODEST
FIVE BIOMARKERS PER YEAR FOR
EARLY DETECTION AND DIAGNOSIS.
EVEN THE SLIDE IS OLDER FROM
2013 BUT THE FINDINGS ARE STILL
VALID.
A
AND THIS IS VERY CHALLENGING FOR
US AND I HAVE NOT SERVED US VERY
WELL THE REASON MOST STUDIES
HAVE BEEN DEVELOPED OVER THE
YEARS AND FOR STUDY DESIGN
THERE'S INCOMPLETE PROTOCOL AND
REPORTING.
IN A BASIC SCIENCE SETTING
PROTOCOL IS LIKE HAVING A PAPER
DESCRIBING DESIGN.
THAT'S NOT THE CASE IN THE
CLINICAL SETTING WHEN YOU HAVE
BIOMARKERS.
ALSO SOMETIMES BIOMARKERS ARE
PUBLISHED BY INVESTIGATORS IN
WHAT WE CALL SELECTIVE REPORTING
AND NOT REPORTING NEGATIVE SIDE
AND THERE'S A CHALLENGE IN THE
BIOMARKER FIELD BECAUSE MOST THE
BIOMARKERS ARE DEVELOPED IN A
SINGLE LAB AND THEN VALIDATED.
HOWEVER, AS YOU KNOW ONE CANNOT
BE PROSECUTOR AND JUDGE AT THE
SAME TIME.
IF YOU'RE A DISCOVERER OF THE
BIOMARKER YOU NEED TO HAND IT
OVER TO A LAB FOR VERIFICATION
AND THAT'S THE BASIC CANNON OF
THE NETWORK AT NCI.
AND IN TERMS OF BIOMARKER
DISCOVERY YOU NEED TO
COLLABORATE WITH THE PEOPLE
EXPERT IN DESIGNING TRIALS OR
VALIDATING THE BIOMARKERS.
THEREFORE WE NEED TO GET TO THE
SPACE.
THIS HAS BEEN THE BASIC TENET
BEHIND THE EDI AND WE NEED TO
HAVE TO BE IN THE BUSINESS OF
DISCOVERY AND NEED EXPERTS TO
VALIDATE THE ASSAY.
BIOMARKER DISCOVERY WITHOUT
CONSIDERING THE CONTENT IS NOT
HELPFUL BECAUSE WE NEED TO THINK
OF THE PERSON IN MIND BEFORE WE
EMBARK ON THE BIOMARKER.
STATISTICIANS PLAY IMPORTANT
ROLES AND WE SEE APPLICATION IN
THE BIOMARKERS.
WE FIND THE DETAILS ABOUT STUDY
DESIGN ARE MISSING.
THIS IS BECAUSE YOU NEED TO
MANAGE DATA AND PROVIDER QUALITY
AND IN A NUTSHELL EDRN.
THEY'RE OPTIMIZED IN THE
FOLLOWING STRUCTURE.
THERE'S A BIOMARKER
DEVELOPMENTAL LAB AND THE
DISCOVERY IS MADE AND GOES TO
THE REFERENCE LAB AND THEN
DISCOVERY LAB AND THE VALIDATION
CENTER WHERE THE STUDY DESIGN IS
CONDUCTED TO VALIDATE THE
BIOMARKERS.
IF YOU FAIL IT'S BACK TO THE
DRAWING BOARD TO LOOK TO THE
REGION.
EVEN THE FAILURE IN THIS CASE
ARE HELPFUL FOR WHAT WENT WRONG
AND HOW IT CAN BE BETTER.
SO THE OBJECTIVE ARE TO SUPPORT
RESEARCH FOR THE DEVELOPMENT AND
VALIDATION OF BIOMARKERS
PROGRESSION, COOPERATION BETWEEN
ACADEMIC AND INDUSTRIAL LEADERS.
ESTABLISH AND APPLY STANDARDIZED
BIOMARKERS CRITERIA AND MOST
IMPORTANTLY WHAT TO FACILITATE
THE PROCESS TO BRING BIOMARKERS
INTO CLINICAL USE.
AND THE PROGRAM ON BIOMARKER
DISCOVERY AND EARLY VALIDATION
FOR EARLY DETECTION OF CANCER.
IT HAS DEVELOPED MORE THAN EIGHT
BIOMARKERS TO BE APPROVED AND 22
THAT ARE WAITING TO BE APPROVED.
SO, THEY DON'T FOLLOW THE
BIOMARKER SIGN.
WE DEVELOPED GUIDELINE FOR
DISCOVERY AND DEVELOPMENT.
THIS IS ONE OF THE MOST CITED
PAPERS IF YOU'RE LOOKING FOR
THIS.
THERE'S BIOMARKER VALIDATION
INCLUDING CRITERIA PHASE 1, 2,
3, 4 AND 5 AND BASED ON
STATISTICAL RIGOR.
THE PHASE 1 IS PROGRAM OF
PROMISING DIRECTION IDENTIFIED
AND THEN PHASE 2, THE CLINICAL
ASSAY DETECTS THE ESTABLISHED
DISEASE AND THEN PHASE 3 IS
SCREEN POSITIVE AND MOST ARE IN
PHASE 1 WAS THEY CANNOT MAKE IT
TO PHASE 2.
NEITHER DEVELOPMENT OF THE
CLINICAL ASSAY OR --
>> YOU NEED TO WRAP UP PRETTY
SOON YOU HAVE LESS THAN A
MINUTE.
>> OKAY.
NEXT, PLEASE.
WE DEVELOPED WHAT IS USED TO
TREAT OUR BIOMARKERS FROM GOOD
TO BAD BIOMARKERS AND THESE ARE
STORED AT NCI FREDERICK AND THEY
CAN LOOK AT THE CANCER TARGET.
OUR SYSTEM ALLOWS NOVEL
MECHANISM.
I JUST WANTED TO SHOW YOU THE
LIST FACILITATED.
>> WE NEED TO WRAP UP NOW TO GET
TO THE NEXT SPEAKER.
>> I'LL STOP HERE.
>> THANK YOU SO MUCH FOR THAT.
OUR NEXT SPEAKER IS DR. MICHAEL
SNYDER FROM STANFORD UNIVERSITY.
MICHAEL.
>> OKAY.
IT'S A GREAT PLEASURE TO BE
HERE.
IF WE CAN GO BACK TO THE FIRST
SLIDE THAT WOULD BE GREAT.
THESE ARE THE PEOPLE THAT DID
THE WORK.
SO, OUR LAB GENERATES DEEP DATA
WITH THE IDEA OF TRYING PROFILE
THEM BASED ON THE PREMISE WE
THINK WE PRACTICE SICK CARE
THESE DAYS RATHER THAN HEALTH
CARE.
WHAT OUR LAB HAS BEEN TRYING TO
DO IS CHANGE THE PARADIGM ON
THIS.
SPECIFICALLY WHEN WE PRACTICE
HEALTH CARE YOU'LL TYPICALLY GET
IN A CAR, ALWAYS AT A TIME AND
TRAVEL TO A PHYSICIANS OFFICE
WHERE THEY'LL STICK A NEEDLE AND
TAKE LOTS OF BLOOD AND THEY ARE
DON'T MAKE VERY MANY
MEASUREMENTS AND FROM THAT
THEY'LL MAKE DECISIONS ABOUT
YOUR HEALTH BASED ON POPULATION
AGGREGATES SO THIS IS WHAT I
WANT TO TALK ABOUT TODAY.
A NUMBER OF YEARS AGO ROUGHLY 14
AND A HALF WE SET UP CRYSTAL
OMICS PROFILING.
THE IDEA IS TAKE BLOOD, URINE
AND STOOL AND SEQUENCE GENOME
AND MEASURE TRANSCRIPTOME,
PROTEOME AND OTHER THINGS AS
WELL AND OUT OF THE PLASMA
MEASURE CYTOKINES AND BIOMARKER
AND WEARABLES.
THE IDEA IS TO TAKE DEEP DATA ON
PEOPLE AND THE OTHER ASPECT IS
OVER TIME.
ROUGHLY EVERY THREE MONTHS WHILE
THEY'RE HEALTHY.
SO WE'RE TAKING SAMPLES WHILE
HEALTHY AND IN AN ADVERSE EVENT
LIKE A VIRAL INFECTION WE'LL
TAKE ADDITIONAL SAMPLES.
WE'RE TRYING TO UNDERSTAND WHAT
A HEALTHY PROFILE LOOK LIKE AND
HOW DOES IT CHANGE OVER TIME,
WHAT HAPPENS AT THE EARLIEST
TIME OF ILLNESS AND CAN YOU USE
GENOME SEQUENCING TO BETTER
MANAGER HEALTH WHICH WAS
CONTROVERSIAL WHEN WE LAUNCHED.
WITH REGARD TO THE LAST POINT
THE FIRST THREE AND A HALF YEARS
OF PROFILING FROM A SMALL GROUP
OF 109 PEOPLE NEARLY HALF
LEARNED SOMETHING PRETTY
IMPORTANT ABOUT THEIR HEALTH AND
HEART ISSUES AND WE HAVE EARLY
LYMPHOMA, TWO PRECANCERS ALL
FOUND PRESYMPTOMATICALLY AND YOU
CAN SEE WHAT'S GOING ON IN
ADVANCE OF SYMPTOMS.
EVERYTHING I'M TELLING YOU IS
CONFLICTED HERE.
AND THE OTHER THING YOU CAN GET
AS YOU PROFILE DEEPLY YOU CAN
SEE HOW THEY CHANGE OVER TIME WE
INTERPRET AS AGING.
FROM THE HEALTHY TIME POINTS YOU
CAN SEE EVERYBODY'S AGING
DIFFERENTLY.
THE AMERICAN IN THE MIDDLE,
PERSON 2 HAVE SIGNALLING PATHWAY
THAT CHANGES AND THE ONE ON THE
LEFT IS A TYPICAL AGER, THEIR
IMMUNE SYSTEM, METABOLIC AND
OTHER PATHWAYS SHIFT OVER TIME.
WE THINK FROM AS FEW AS FIVE
TIME POINTS OVER TWO YEARS WE
CAN SEE HOW PEOPLE ARE AGING
THOUGH YOU CAN DO IT MUCH
RAPIDLY AS WELL AND CALL THESE
AGING PATTERNS AGOTYPES.
YOU SEE FOUR TYPES OF FOUR
PEOPLE AND THEY'LL HAVE
DIFFERENT AGEOTYPES AND THERE'S
MARKERS YOU CAN ACT UPON.
IF YOU LOOK AT THE GROUP AS A
WHOLE YOU CAN SAY SOMETIMES
DURING THESE YEARS WHERE THERE
MIGHT BE MORE CHANGES THAN
OTHERS AND RECENTLY PUBLISHED
AND AGING IS NOT MANY OR YOU
DON'T JUST GRADUALLY GET OLDER.
KNOW YOUR IMMUNE CHANGES AND YOU
GET VACCINATED AND THERE'S A
BURST THERE WE SEE OTHER CHANGES
AS WELL BECAUSE WE'RE PROFILING
SO DEEPLY.
IT SHOULD SAY 135,000 MARKERS.
THERE'S ALSO A BIG SHIFT AROUND
THE 40s.
YOU'RE EITHER ON WERE WAY TO
THIS IN YOUR 40s OR 50s AND 60s
AND THERE'S MARKERS ASSOCIATED
ONCE AGAIN.
YOU CAN TAKE ACTION ON THE
INFORMATION.
THE OTHER THING WE'RE PUSHING
HARD IS THE IDEA ABOUT DOING
REMOTE HEALTH MONITORING WHICH I
THINK IS RELEVANT FOR RUNNING
STUDIES IN THE MENTAL HEALTH
SPACE BECAUSE MOST PEOPLE DON'T
WANT TO COME IN TO GET MEASURED
AND MEASUREMENTS IN A CLINIC ARE
NOT REFLECTING WHAT'S GOING ON
AT HOME.
WE'VE BEEN PUSHING TWO FRONTS.
ONE IS THE WEARABLES.
ANOTHER IS CALLED HOME MICRO
SAMPLING AND WE DO DEEP
MEASUREMENTS THERE'S DEVICES OUT
THERE IN THE FORM OF SMART
WATCHES.
I MYSELF USUALLY HAVE FOUR
WATCHES, ONE BROKE AND HEARING
AIDS ARE USEFUL FOR INFORMATION
AND I LOST MINE ON THE AIRPLANE.
THEY'RE MEASURING YOU 24/7.
I WON'T TALK ABOUT THIS TODAY
BUT WE SHOWED YOU CAN PICK UP
WHEN PEOPLE ARE GETTING
INFECTIONS, LYME DISEASE AS WELL
AS VIRAL INFECTIONS IN ADVANCE
OF SYMPTOMS BECAUSE YOUR RESTING
HEART RATE GOES UP.
IT'S MORE SENSITIVE THAN
TEMPERATURE WHICH IS WHAT WE DO
TODAY.
THAT'S A 300-YEAR-OLD CONCEPT
WHICH DOESN'T WORK WELL FOR
COVID AND RESTING PICK UP OTHER
THINGS IN TERM OF MENTAL HEALTH
STRESS.
WE'RE RUNNING DIGITAL STUDIES
WITH THE WEARABLES FOR MENTAL
HEALTH CONDITIONS.
SPECIFICALLY TRYING TO FOLLOW
THINGS LIKE DEPRESSION.
WE'RE RUNNING A STUDY MEASURED
FOR WELLNESS MARKERS IF YOU WILL
AS WELL AS RUNNING THROUGH AN
INTERVENTION AND THIS IS FAIRLY
PRELIMINARY AND WHAT WE
DISCOVERED IS THAT YOU ACTUALLY
CAN START MAKING CORRELATIONS
BETWEEN MEASUREMENTS ON A DEVICE
AND MENTAL HEALTH STATE,
WELLNESS STATES.
THIS IS AGAIN SOMEWHAT
PRELIMINARY BUT SHOWS DATA.
THERE'S VO2 MAX AND THIS IS
HAPPINESS OF ALL THINGS AND DOES
PAY TO SEGREGATE MALES AND
FEMALES BECAUSE THE BASELINE ARE
VERY DIFFERENT.
YOU CAN PICK UP SIGNIFICANT
SIGNALS BETWEEN THOSE HAPPY
VERSUS NOT IN TERMS OF VO2 MAX
AMONG MALES AND FEMALES
BREATHING RATE DIFFERS AND YOU
GET MARKERS AND WE ARE TRYING TO
BRING MARKERS FOR COGNITION AND
DEMENTIA WHICH CAN BE USEFUL AND
THE POWER IS YOU'RE COLLECTING
ALL PASSIVELY AND WE THINK IT'S
QUITE VALUABLE.
THE OTHER AREA IS GLUCOSE
MONITORING I MYSELF AM A TYPE II
DIABETIC.
IT'S PERFECT FOR MENTAL HEALTH
BECAUSE DIABETES IS VERY
HETEROGENEOUS.
WE LUMP IT ALL TOGETHER AND THE
WAY WE TREAT IT SHOULDN'T BE BY
LUMPING IT BECAUSE THERE'S
DIFFERENT TREATMENTS FOR
DIFFERENT CONDITIONS.
WE DISCOVERED THE CONTINUOUS
GLUCOSE MONITORING MEASURE EVERY
FIVE MINUTES AND PUT THEM ON
NORMAL AND PRE-DIABETICS AND
HAVE GONE ON TO SHOW DIFFERENT
PEOPLE SPIKE TO DIFFERENT FOODS.
55 PEOPLE RUNNING THROUGH THE
EXACT SAME AMOUNT OF CARBS AND
DIFFERENT PEOPLE SPIKE TO
DIFFERENT FOODS.
THIS PERSON'S A BREAD SPIKER,
THIS IS A GRAPE SPIKER AND MOST
PEOPLE ARE WHITE RICE SPIKERS
AND THINK OF THIS FROM AN
ALZHEIMER'S STANDPOINT.
CAN YOU SUB TYPE.
WHICH FOODS WILL RESPOND TO
WHICH SUBTYPES.
IT TURNS OUT IF YOU'RE INSULIN
RESISTANT YOU'RE ON AVERAGE
GOING TO BE A POTATO AND PASTA
SPIKER AND IT'S DIFFERENT IF YOU
HAVE DIFFERENT SUBTYPES.
YOUR LIFESTYLE WE'VE WRITTEN
ALGORITHMS TO MATCH LIFESTYLES
WITH PEOPLE'S RESPONSE AND
USEFUL HEALTH THINGS.
THE LAST THING IS THE IDEA OF
HOME MICROSAMPLING.
HERE'S HOW IT WORKS.
YOU TAKE LITTLE DROPS OF BLOOD,
MAIL TO US AND WE'LL DO DEEP
PROFILES AND DIFFERENT OMICS AND
MEASURE ABOUT 7,000 MARKERS IN A
FAIRLY QUANTITATIVE FASHION.
THESE ARE FAIRLY STABLE.
WE'VE DONE A LOT OF WORK AND
HAVE SEVERAL METHOD FOR
COLLECTIONS.
LIPIDS ARE A MIXED BAG AND IF
YOU DRINK AN ENSURE SHAKE SOME
PEOPLE IT WILL BE
PRO-INFLAMMATORY FOR OTHERS
ANTI-INFLAMMATORY.
VERY DIFFERENT RESPONSE.
THIS IS ONE PERSON WHO GOT A
MICROSAMPLE EVERY HOUR FOR SEVEN
STRAIGHT DAYS DURING WAKING
HOURS WHILE WEARING A CGN AND
SMART WATCH MEASURING FLEW COSE
AND ACTIVITY AND -- GLUCOSE AND
ACTIVITY AND WE'RE TRYING TO
MATCH THEIR PHYSIOLOGY WITH
LIFESTYLE AND STEPS AND OTHER
THINGS THEY DO AND YOU CAN GET
THOUSANDS OF CORRELATIONS.
WE CAN MAKE CORRELATIONS BETWEEN
ACTIVITY AND OTHER CYTOKINES AND
LIPIDS.
YOU CAN SEE THE PEPTIDES AND
GLUCOSE AND YOU MEASURE
PRECISELY FOR THIS PERSON AND
TURNS OUT YOUR BLOOD IS BOUNCING
AROUND.
IT'S TOTAL BLOOD AND WE THINK
IT'S FOLLOWING A PATTERN THAT'S
SIMILAR TO STRESS.
SO WE CAN MEASURE THE BLOOD.
IT'S CONTROVERSIAL.
THAT'S IT.
HERE'S A SUMMARY.
DEEP DATA LINK IS POWERFUL AND
LONGITUDINAL MONITORING IS VERY
POWERFUL AND HERE'S THE PEOPLE
WHO DID THE WORK.
THANKS.
>> NOW RHODA AU FROM BOSTON
UNIVERSITY.
>> ONE THING I HOPE YOU TAKE
AWAY IS DIGITAL BIOMARKERS AND
PHENOTYPING HAVE NOT THE SAME
THING AND WE HOPE TO GET TO
BIOMARKERS.
JUST TO GIVE YOU A LITTLE BIT OF
CONTEXT WHERE DIGITAL NOW
STANDS, SINCE THE LAST SUM IT
WE'VE BEEN VERY PRODUCTIVE AS WE
HEARD IN THE LAST COUPLE DAYS
AND WILL FOR THE REMAINDER OF
TODAY.
WE'VE BEEN GENERATING LOTS OF
SCIENCE IN THE ALZHEIMER'S
DISEASE SPACE OVER THE LAST FEW
YEARS.
WHERE DOES DIGITAL FIT IN?
THERE'S A FAIR NUMBER OF GROWING
PUBLICATION INTERESTS IN THE
AREA OF DIGITAL.
IF YOU LOOK AT SPECIFICALLY AT
THE CONCEPT OF DIGITAL
BIOMARKERS YOU'LL FIND THAT'S A
SMALLER SUBSET BUT ONE OF THE
THINGS THAT'S VERY IMPORTANT TO
REALIZE ABOUT THE LITERATURE
TODAY IS THE ACTUAL NUMBER OF
STUDIES DOING WORK RELATED TO
DISCOVERY VALIDATION OF A
DIGITAL BIOMARKER IS EVEN A
SMALLER SUBSET.
THE TAKE HOME MESSAGE IS IT'S
NOW OF GREAT INTEREST.
IT'S NO LONGER EMERGING.
IT'S MOVING INTO THE MAINSTREAM
BUT WE HAVE MANY MANY THINGS
STILL LEFT TO DO.
THE FDA TAKEN AN INTEREST IN THE
CONCEPT OF DIGITAL BIOMARKERS
AND STARTED TO PROVIDE SOME
DEFINITION.
I THINK THE MOST IMPORTANT THING
IS WHEN WE'RE GOING TO DIGITAL,
WE'RE TRYING TO CREATE OBJECTIVE
MEASURES.
IN THAT SENSE IT'S NO DIFFERENT
FROM BIOMARKERS AND THE DIGITAL
ERA IS HERE NOW.
AS WE JUST HEARD THERE'S LOTS
AND LOTS OF DEVICES,
APPLICATIONS IN HOME SENSORS,
ETCETERA.
THIS IS GOING TO CONTINUE TO
GROW.
SO WE REALLY NEED TO THINK ABOUT
HOW WE'RE GOING TO HARNESS THIS
EXTRAORDINARY RESOURCE THAT
WE'RE GENERATING ON A CONTINUOUS
BASIS.
SO IF WE THINK ABOUT DIGITAL
BIOMARKERS TODAY WE'RE REALLY
LOOKING AT ONES OBVIOUSLY
DIAGNOSTIC AND THEN THE ONES
THAT ARE REACTIVE TO TREATMENTS
WHICH IS WHAT CLINICAL TRIALS IS
INTERESTED IN AND THE CONCEPT OF
ONGOING MONITORING FOR CHANGES
RELATED TO THE DISEASE OF
INTEREST WHICH IN THIS CASE IS
ALZHEIMER'S DISEASE.
SO IF WE THINK ABOUT ALL THE
DIFFERENT WAYS IN WHICH WE CAN
COLLECT DIGITAL DATA WHICH
MICHAEL JUST TALKED ABOUT, I
THINK THE IMPORTANT THING TO
REMEMBER TODAY RIGHT NOW MUCH OF
WHAT WE DO IS REALLY FALLING IN
THE REALM OF DIGITAL
PHENOTYPING.
WE'RE MEASURING LOTS AND LOTS OF
THINGS.
THE GOAL HERE IS HOW DO WE GET
FROM WHAT I SAY IS MOSTLY
DERIVED MEASURES FROM DIGITAL
DEVICES.
THESE ARE DIGITAL MEASURES OF
BEHAVIORS OF INTEREST.
AND I THINK THE REAL GOAL IS HOW
DO WE GET TO THIS NEW REALITY OF
WHAT A DIGITAL BIOMARKER IS
LIKELY TO BE.
BECAUSE OF THE WAY IN WHICH
WE'RE COLLECTING THE DATA
THROUGH ALL THESE DIFFERENT
TYPES OF APPLICATIONS, DEVICES,
SENSORS, ETCETERA, I THINK WHAT
WE HAVE TO RETHINK IS WHAT DOES
THE BIOMARKER SIGNAL REALLY LOOK
LIKE?
I THINK IT'S GOING TO BE VERY
DYNAMIC, FLOWING, CHANGING
REFLECTING THE HETEROGENEITY IN
ALL THESE BEHAVIORS OF INTEREST.
SO I THINK THAT'S THE REAL
CHALLENGE.
I'M GOING TO JUST SHIFT A LITTLE
BIT AND TALK ABOUT SOME OF THE
WORK THAT MY COLLEAGUES HAVE
DONE IN LOOKING AT SOME OF THE
VOICE RECORDINGS THROUGH THE
FRAMINGHAM HEART STUDY.
WHAT'S IMPORTANT ABOUT WHAT THE
PAPER HAS DONE IS USING
AUTOMATED PROCESSING.
IT'S COMPLETELY DATA SCIENCE
A.I.-DRIVEN, HANDS FREE.
THERE'S NO MANUAL INTERVENTION.
THEY TOOK RECORDINGS WE HAVE
BEEN COLLECTING SINCE 2005 IN
THE COHORT AND FOLLOWED THEM
LONGITUDINALLY FOR INCIDENT
CHANGES IN MCI AND 2 DEMENTIA.
THE TEAM TOOK ALL THOSE
RECORDINGS, PROCESSED THEM,
EXTRACTED AUTOMATED
TRANSCRIPTIONS AND ANALYZED
THAT.
IN LOOKING AT THE ABILITY OF
PREDICTION OF LATER ONSET
DEMENTIA THEY FOUND IT'S THE
SPEECH RELATED MEASURES THAT
WERE MOST PREDICTIVE COMPARED TO
SOME OTHER MEASURES OF INTEREST
THAT ARE TYPICALLY USED TO
EVALUATE DEMENTIA.
AND I THINK WHAT'S IMPORTANT IS
THAT THE SPEECH ALONE WAS ABLE
TO PREDICT WITH ALMOST AS GREAT
AS SENSITIVITY IF YOU COMBINE
THEM.
YOU DON'T GET A LOT OF ADDED
VALUE BY ADDING IN ADDITIONAL
INFORMATION AND THIS HIGHLIGHTS
HOW MUCH SPEECH AS A POTENTIAL
MEASURE OF COGNITION AND AS A
MEASURE PREDICTIVE OF LATER
POTENTIAL ONSET OF DEMENTIA CAN
BE VERY POWERFUL.
AND THE REASON I LIKE TO
HIGHLIGHT DIGITAL VOICE IS
BECAUSE IT'S SO EASY TO COLLECT.
IN ADDITION TO THE FRAMINGHAM
HEART STUDY SINCE 2005 THE
ALZHEIMER'S RESEARCH CENTERS ARE
ABOUT TO LAUNCH AND START
COLLECTING DIGITAL VOICE AS WELL
AS PART OF THEIR UDS4.0 AND WE
HAVE ADNI.
WHAT'S HAPPENING IS BECAUSE IT'S
SO EASY TO COMPLEX AND SPEAKING
IS A COGNITIVELY COMPLEX TASK
IT'S ABLE TO PUSH FORWARD AT A
SCALABLE LEVEL QUICKLY.
IF WE THINK WHERE WE ARE TODAY,
WE'VE BEEN COLLECTING LOTS OF
DATA AND NOW WE'RE STARTING TO
COLLECT DIGITAL DATA.
HERE'S THE PROBLEM, THE
INTEROPERABILITY PLATFORMS
ACTUALLY CAN'T STORE ALL THIS
DIGITAL DATA AND THEREFORE WE
HAVE A DISCONNECT AS A RESULT
WHAT'S HAPPENING IS WE HAVE ALL
THIS GREAT CLINICAL AND
BIOMARKER DATA AND GREAT DIGITAL
DATA YET WE'RE NOT ABLE TO DO
THE SCIENCE OF COMBINING THEM
TOGETHER.
SO AS WE THINK ABOUT HOW TO GO
FORWARD, BLOOD CONTINUES TO LEAD
THE CHANGE AND IT'S ALSO EASY TO
COLLECT, STORE AND THEN ANALYZE
AND WE HAVE.
WE'VE ANALYZED IT FROM A NUMBER
OF NOW EMERGING BIOMARKERS AS
WELL GENETIC, GENOMICS,
ETCETERA.
I LIKE TO THINK ABOUT DIGITAL IN
THE SAME WAY.
THERE'S LOTS AND LOTS OF DEVICES
NOW THAT CAN COLLECT DIGITAL
DATA.
YOU CAN ACTUALLY STORE THE DATA
LIKE YOU WOULD BLOOD AND THEN
YOU CAN PUSH THIS DATA OUT AND
SHARE IT IN THIS KAY START TO
MOVE TO THE DIGITAL BIOMARKER
REALITY I PRESENTED EARLIER AND
I'D LIKE TO THINK ABOUT DIGITAL
THEN AS BEING THE NEW BLOOD.
SO AS WE SORT OF MOVE INTO THIS
REALM WHERE WE NEED TO NOW
COMBINE ALL THESE DIFFERENT
BIOMARKERS OF INTEREST TOGETHER
I THINK WHAT WE WANT TO TAKE
TAKEAWAY FROM US IS WE'RE AT A
POINT WHERE WE KNOW LONGER HAVE
TO BE PATIENT WAITING FOR THIS
TO HAPPEN BECAUSE IT'S NOW READY
TO HAPPEN TODAY.
WITH THAT I ENDED EARLY.
>> THANK YOU SO MUCH, DR. AU.
THE NEXT SPEAKER IS LEE
GOLDSTEIN ALSO FROM BOSTON
UNIVERSITY.
WELCOME.
>> THANK YOU.
I'VE BEEN ASKED TO TALK ABOUT
OCULAR BIOMARKERS WITH THE FOCUS
ON THE LENS.
MY DISCLOSURES ARE LISTED BELOW.
TO REMIND YOU FROM JUNIOR HIGH
SCHOOL OR HIGH SCHOOL BIOLOGY
THE LENS IS PART OF THE EYE.
IT'S NOT A PIECE OF GLASS IN
YOUR HEAD IT'S A LIVING TISSUE
IN THE EYE AND WILL REMAIN A
LIVING TISSUE LONGER THAN YOU'LL
BE ALIVE.
OFTEN BY AS MANY AS DAYS TO
WEEKS.
IT'S IN THE ANTERIOR COMPARTMENT
BEHIND THE CORNEA AND AQUEOUS
FLUID AND RECITES HERE.
IT GROWS THROUGHOUT LIFE
ACTUALLY BEFORE LIFE AND
CONTINUES AFTER LIFE, BELIEVE IT
OR NOT.
YOU HAVE THE OLDEST PROTEIN IN
THE BODY ONE OF THE FEW PLACES
WHERE YOU HAVE PROTEIN FROM
BEFORE BIRTH AND WE USE THIS FOR
ANOTHER TYPE OF TECHNOLOGY TO
LOOK AT MOLECULAR AGING.
WE HAVE SOME PUBLICATIONS ON
THAT I WON'T GET INTO HERE.
THESE ARE POTENTIALLY RELATED
STEM CELLS THAT RESIDE THROUGH
LIFE AND DIFFERENTIATE INTO
FIBER CELLS AND GROWS LIKE A
TREE WITH GROWTH RINGS AND THE
PATHOLOGY IS UNDER THE IRIS AT
THE POSTERIOR REGION WHICH IS
NOT LONG THE OPTICAL AXIS.
THE DOESN'T IMPAIR VISION AND
THE CELLS ARE VERY MUCH ALIVE
AND THE ONES IN THE CENTER ARE
OLDER THAN YOU ARE AND THE
DIFFERENTIATION PROCESS OCCURS
WHERE I'LL SHOW YOU THE
PATHOLOGY.
THERE'S RELATIONSHIP WITH
NEURONS AT THE TERMINAL DE RIFF
TIFS FROM STEM CELLS AND
POST-MITOTIC AND THE MACHINERY
FOR REGENERATING BETA PATHOLOGY
IS PRESENT.
BACK IN 2003 WE REPORTED IN THE
LANCET THIS USUAL FINDING TOO
UNUSUAL FOR PSYCHIATRISTS
REPORTING OPHTHALMALGIC FINDINGS
AND IT TURNS OUT WE HAVE BETA
AMYLOID AND IT'S EQUIVALENT TO
LATE PLAQUE.
THE MOLECULAR PATHOLOGY BEFORE
THIS IS THE KEY.
WE WON'T LOOK FOR THE CATARACT.
THIS IS A SIGNATURE TIME PART.
THESE ARE VARIOUS PAPERS RELATED
TO THIS.
WE COLLECTED A BUNCH OF LENSES
FROM ANATOMIC DONORS WHO DONATED
EYES AND BRAIN.
ALL THESE WERE A.D. PATHOLOGY
CONTROLLED CASES AND HERE'S THE
CATARACT AND IT'S ABETA.
THIS IS AMYLOID PANELOLOGY IN
THE LENS OF THE EYE.
HERE'S AN AGE RELATED NUCLEAR
CATARACT THAT HAS NOTHING TO DO
WITH ALZHEIMER'S DISEASE.
COMORBID IN THE SAME LENS.
YOU SEE DIFFERENT POLYMORPHIC
EXPRESSION AND IT'S AGE
DEPENDENT.
WE DON'T SEE THIS IN ANY OTHER
NON-A.D. DEMENTING DISORDER BY
VIRAL PENETRANT AND ANATOMICALLY
DISTINCT AND PATHOPHYSIOLIGIALLY
AND LOOK AT CATARACTS AND THE
PHENOTYPE IS IDENTICAL TO WHAT
WE SEE IN A.D. AND IS SHOWING
FROM THE BRAIN IN THIS DISORDER.
I DRAW YOUR ATTENTION TO THIS
ONE RIGHT HERE.
THIS IS FROM AN 18 MONTH OLD
WITHOUT ANY EVIDENCE OF THE
SIGNATURE SUPER NUCLEAR CATARACT
AND SEE THE AGE DEPENDENCE HERE.
YOU'LL SEE RIGHT HERE, THIS IS
AN EARLIER SLIDE, THE SAME CASE
RIGHT HERE.
WHEN WE LOOK AT THE A BETA IN
THAT REGION OF THE LENS, THIS IS
MORE ABETA THEN WHAT WE SEE IN A
LENS FROM AN INSTATE FAD CASE
FROM A 57 AND 59-YEAR-OLD.
EXTRAORDINARY AMOUNTS OF A BETA.
WE SEE IT IN DOWN SYNDROME EARLY
BEFORE YOU SEE ELEVATED A BETA
IN THE DOWN SYNDROME BRAIN.
MOREOVER IT PRECEDES THE SUPER
NUCLEAR PHENOTYPE.
SO THIS IS EXTRAORDINARY LEVELS
OF A BETA WE CAN DETECT.
WE TO THE THERE'S A
CO-LOCALIZATION OF THE PATHOLOGY
AND WE KNOW WHAT CAUSES THE
CATARACT ITSELF, LIGHT
SCATTERING FROM THE A BETA AND
ALPHA B CRYSTALLIN.
WE LEARNED SOMETHING ABOUT THE
BRAIN FROM LOOKING IN THE LENS.
WE CAN SEE THE INTERACTION
BETWEEN ALPHA B CRYSTALLIN AND
HAVE A PAPER COMING OUT SOON AND
KNOW IT'S A BETA BY CHEMICAL AND
MASS SPECTOMETRY METHODS.
THIS LED TO OUR INITIAL
DEVELOPMENT WORK STARTED WITH
THE AMERICAN HEALTH ASSISTANCE
ACROSS TOWN AND COMMERCIALIZED
THROUGH A COMPANY I STARTED AND
DISCLOSED, BY THE WAY, TO PICK
UP NOT THE CATARACT BUT THE
MOLECULAR PATHOLOGY.
THIS IS BASED ON A FLUORESCENT A
BETA BINDING AND IT'S BEEN
COMPOUNDED ON ATOM CAL
APPLICATION AND COMBINES ABETA.
WE CAN APPLY THIS TO THE EYE
DIRECTLY AND DETECTING USING
FLUORESCENCE LIFE TIME DECAY
SPECTROSCOPY.
WE WANT TO PICK UP THE MOLECULAR
SIGNATURES AND HAVE LATER
VERSIONS OF THIS AND WE HAVE
EARLY CLINICAL DATA THE COMPANY
CONDUCTED SHOWING IT'S
EFFICACIOUS.
THIS IS A DRUG DEVICE PRODUCT
AND IT'S RECEIVED FDA
BREAKTHROUGH DESIGNATION STATUS.
IN SUMMARY WE SHOWED THE A BETA
PHENOTYPE SPECIFIC TO LATE ONSET
ALZHEIMER'S DISEASE.
WE SEE THE SAME PHENOTYPE IN
DOWN SYNDROME.
AND WE WORKED THIS OUT IN THE
TG2 TRANSGENIC MOUSE A COUPLE
YEARS AGO.
WE SHOWED THERE'S AN AGE
DEPENDENCE TO THIS EXPRESSION.
I MENTIONED EARLIER ABOUT THE
AQUEOUS HUMOR EQUIVALENT TO ACF
AND WERE THE FIRST TO REPORT A
BETA HERE AND IT TURNS OUT THE A
BETA 40 TO 42 THE CONCENTRATION
IS SIMILAR TO CSF.
USING THE TECHNOLOGY I JUST
SHOWED YOU THERE'S POTENTIAL TO
USE THIS OPTICAL PERISENTISIS
AND LOOK AT A BETA GENERATION
USING THE TECHNOLOGY.
THAT'S IN THE FUTURE BUT HAS
POSSIBILITY.
I MENTIONED WHY WE GET THE
CATARACT THE FOCAL SCATTER IN
WHICH THE A BETA ACCUMULATES AND
RECEIVED FDA BREAKTHROUGH DEVICE
DESIGNATION AND AS MENTIONED
YESTERDAY THIS TAKES A HECK OF A
LONG TIME IN THE LIFE SPAN OF
ONE LAB, ONE GROUP TO DEVELOP
THESE TECHNOLOGIES FROM THE
FLOOR UP TO INITIAL DISCOVERY
AND THANKFUL FOR NIH SUPPORT TO
TRY TO DO THE VALIDATION STUDIES
AND COLLABORATIONS AS WE MOVE TO
THE CLINIC.
THANK YOU VERY MUCH.
>> THANK YOU.
NEXT SPEAKER IS DR. MATTHIAS
ARNOLD FROM HELMHOLTZ
UNIVERSITY.
WELCOME.
>> THANK YOU VERY MUCH.
SO I'VE BEEN INSTRUCTED BY NIH
TO NOT WASTE MY TIME WITH
ACKNOWLEDGE MANIES.
-- ACKNOWLEDGEMENTS AND THE
WORK IS THE WORK OF MANY IN THE
METABOLISM CONSORTIUM AND
WITHOUT THE PARTICIPANTS OF THE
STUDIES AND I'LL TALK ABOUT HOW
METABOLOMIC CAN HELP BROADEN THE
PORTFOLIO OF BIOMARKERS WE HAVE
FOR ALZHEIMER'S DISEASE.
METABOLOMICS IS THE STUDY OF THE
HUMAN METABOLOME.
AND TO GIVE YOU AN IDEA OF WHAT
WE'RE WORKING WITH AND WE PUT
THE CONTENT MUCH A PLATFORM THAT
WE'RE REGULARLY USING ON THE TOP
LEFT OF THE SLIDE.
WHAT YOU SEE IS METABOLOMICS NOT
ONLY COVERS THE BUILDING BLOCKS
OF NUCLEOTIDES OR AMINO ACIDS
FOR PROTEINS BUT COVERS AND
COVER LIPIDS.
WHAT IS ALSO IMPORTANT AND ARE
BY FUNCTION AND CLASS BEHIND BY
ENZYMATIC REACTIONS AND IT'S
HIGHLY DYNAMIC.
THERE ARE SIGNIFICANT CHANGES.
SAME IS TRUE IF YOU TAKE IN
FOOD, YOU EXERCISE OR ANYTHING
ELSE AND IT REACHES A STEADY
STATE AFTER.
AND THERE'S INTAKE OF DRUGS OR
SUPPLEMENTS AND ALSO THE GUT
BIOMEDICAL COMPOSITION.
THOSE ARE ONLY A FEW EXAMPLES
AND SHOW THE DYNAMIC READ OF
HUMAN PHYSIOLOGY.
AND THERE'S DIFFERENT PHENOTYPES
AND WE SEE A FEW METABOLITES ARE
DISEASE SPECIFIC ALONE WHEREAS
MANY METABOLITES HAVE MANY
DIFFERENT DISEASES AND THIS
STAND TO REASON BECAUSE THEY
COME WITH CHRONIC INFLAMMATION.
WE'LL SEE INFLAMMATORY MARKERS
POPPING UP FOR EACH AND EVERY
ONE OF THEM.
WHAT IS ALSO IMPORTANT IS MANY
OF THE CHRONIC CONDITIONS THAT
ARE OBSERVED IN PATIENTS WITH
COGNITIVE IMPAIRMENT YOU HAVE
CARDIOVASCULAR DISEASE AND
HYPERTENSION.
THE MISSION OF OUR CONSORTIUM
WAS TO MAP OUT THE ALZHEIMER'S
DISEASE METABOLOME.
WHAT WE HAVE DONE IN THE LAST
DECADE OR SO WAS TO GENERATE
MORE THAN 60,000 METABOLOMIC
PROFILES UP ALZHEIMER'S DISEASE
STUDY IN BLOOD BRAIN AND MOUSE
MODELS WITH ALZHEIMER'S DISEASE
AND WE HAVE BEEN USING DIFFERENT
TECHNOLOGIES THERE TO IDENTIFY
THOSE PATHWAYS THAT ARE RELEVANT
TO ALZHEIMER'S DISEASE.
IN ADDITION TO JUST GENERATING
THE DATA AND MAKING IT AVAILABLE
WE HAVE INVESTED A LOT OF EFFORT
INTO TECHNOLOGY STANDARDIZATION
INCLUDING QUALITY CONTROL
PROCEDURES AND WE ALSO DID
CROSS-PLATFORM COMPARISONS TO
IDENTIFY THOSE THAT GIVE THE
MOST ROBUST DATA AND HAVE
DESCRIBED ALL OF THIS IN
ADDITION TO MAKING THE METHODS
AVAILABLE AND OUR METHOD KEEP
EVOLVING AS WE LEARN MORE SO WE
CONTINUE TO CALL FOR PROCESSING
ANALYSIS UP STUDY WE PUBLISH.
NOW, IF WE LOOK AT THE
METABOLITE ASSOCIATIONS WE SEE
FOR ALZHEIMER'S DISEASE IN BLOOD
AND BRAIN ON A PATHWAY WE SEE
INFLAMMATION, OXIDATIVE STRESS,
CHOLESTEROL METABOLISM AND
COMPLEX LIPID METABOLISM AND
LOOKING AT THE SINGLE METABOLITE
LEVER SHOWN IN THE DIAGRAM IN
THE MIDDLE THAT IS COMING FROM
THE COHORT WHERE WE HAVE HAIR,
BLOOD AND BRAIN SAMPLES, WE SEE
LESS THAN 20% OF THE METABOLITES
SHOW CONSISTENT ASSOCIATIONS
ACROSS COMPARTMENTS.
AT THE SINGLE METABOLITE LEVEL
THESE ARE MORE COMPLEX.
THIS IS ALSO TRUE IF YOU COMPARE
THE RESULTS WE GET FROM BLOOD
METABOLOMICS FROM ONE COHORT
COMPARED TO ANOTHER.
WE WERE ASKING OURSELVES WHAT
MIGHT CONTRIBUTE TO THE
HETEROGENEITY WE'RE SEEING.
WE INVESTIGATED IF THIS COULD BE
LINKED TO DISEASE HETEROGENEITY.
WE INVESTIGATED TWO AND LOOKED
IF THE METABOLITE ASSOCIATIONS
WITH ALZHEIMER'S DISEASE WE
OBSERVED AND THE MAJORITY OF
ASSOCIATIONS WERE DIFFERENT.
HOW CAN WE USE IT TO COME UP
WITH SOMETHING THAT COULD BE
USED AS A BIOMARKER IN
ALZHEIMER'S DISEASE AND I'LL
GIVE ONE EXAMPLE.
HERE WE HYPOTHESIZED CAPTURING
HETEROGENEITY AND USING PRIOR
KNOWLEDGE USING A CLASS OF
METABOLITES THAT ARE ESTABLISHED
MARKERS FOR MITOCHONDRIA AND
THOSE METABOLITES ARE MEDIATORS
OF THE CYCLE TRANSPORTED IN AND
OUT OF MITOCHONDRIA AND
BIOMARKERS FOR COMPLEX
CONDITIONS LIKE TYPE II DIABETES
AND ALZHEIMER'S DISEASE.
IN ADDITION THEY'RE IN ROUTINELY
USED TO DETECT ERRORS AND SO
AREN'T CLINICAL ASSAYS AVAILABLE
AND THERE'S A STRONG COMPLEX
COMPONENT TO THE METABOLITES
WHICH ALLOW US TO INVESTIGATE
HOW MUCH OF THE DYSREGULATION IN
THIS PARTICULAR PATHWAY IS
LINKED TO GENETICS AND
MODIFIABLE FACTORS.
WHAT WE DID WAS WE USED FASTING
SERUM LEVELS OF 23 L-CARNITINE
AND THEN PERFORMED
IDENTIFICATION AND THAT SHOWED
THESE METABOLITES CLUSTER
PARTICIPANTS INTO GROUPS OF RISK
AND RESILIENCE TO ALZHEIMER'S
DISEASE.
WE SAW GENETIC EFFECTS TO
IMPAIRMENT OF THE TCA CYCLE LATE
IN THE DISEASE AND THE GENETIC
MARKERS CAN BE USED FOR SUB
STRATIFICATION AND MODIFIABLE
EFFECTS POINT TO A KEY ROLE OF
BETTER OXIDATION THAT MAY BE
MODIFIED FOR INSTANCE WITH
THERAPEUTIC INTERVENTIONS AND
NON THERMALOGIC INTERVENTIONS
AND WANTED TO COME UP WITH A
COMPOSITE MARKER AND CAME UP
WITH A FITNESS METRIC OR AGING
CLOCK DERIVED IN A HEALTHY
POPULATION-BASED COHORT AND
TRANSFERRED WHICH SHOWED US THIS
CORE WAS FOLLOWING THE
CLUSTERING STRUCTURE WE OBSERVED
AND ALSO ASSOCIATED
CROSS-SECTIONALLY WITH
BIOMARKERS INCLUDING ENERGETIC
STATUS IN THE BRAIN AFTER A PET
AND PREDICTIVE FOR FUTURE
COGNITIVE PROJECTIONS.
IN ORDER TO ESTIMATE WE
CONDUCTED A CLINICAL TRIAL USING
THE MOST EXTREME FIT QUARTILE OF
INDIVIDUALS AS A TREATMENT GROUP
AND CONTROL GROUP WERE THOSE
LEAST FIT AND THEN LOOKED AT HOW
THE TWO GROUPS ARE DIFFERENT
AFTER 18 MONTHS.
WHAT WE OBSERVED THERE IS WE GET
TO ESTIMATE WHAT WAS PUBLISHED
IN THE TRIAL.
AND WHAT IS ALSO NOTEWORTHY HERE
IS WE HAVE MUCH LESS IN OUR
STUDIES.
LESS THAN 200 INDIVIDUALS PER
ARM OF THE SIMULATED TRIAL AND
THE POWER CALCULATION INDICATED
WE NEED MORE THAN 800 AND THE
TRIAL HAD MORE THAN 800
INDIVIDUALS PER TREATMENT ARM.
IN ADDITION WE WANTED TO SEE IF
THERE ARE RISK FACTORS THAT
INFLUENCE POTENTIAL TREATMENT
BENEFIT IF YOU WOULD FIND A
TREATMENT THAT ACTS ON THE
SCORE.
WHAT WE SAW THERE IS WHILE APOE
4 HAD NO ROLE UP THIS, WE SAW
ACTUALLY FEMALES WOULD BENEFIT
MUCH MORE FROM MODULATING BIO
ENERGETIC AGE BY A FACTOR OF
ALMOST 2 THAN MALES IN CONTRAST
TO RECENT PUBLICATIONS SHOWED
FEMALES HAD MUCH LESS OR NO
BENEFIT.
SO WHAT I TRIED TO CONVEY IN THE
TALK IS THE BLOOD METABOLOME IS
A HUMAN PHYSIOLOGY THAT
NEVERTHELESS PROVIDERS ROBUST
MARKERS FOR HUMAN DISEASE
INCLUDING ALZHEIMER'S DISEASE
AND RESILIENCE AND THE TARGETING
SUCH METABOLIC ASPECTS LIKE THE
CAPACITY WITH PHARMACOLOGIC
INTERVENTIONS CAN BE A PROMISING
TREATMENT STRATEGY FOR
ALZHEIMER'S DISEASE AND SIMILAR
COMPOSITE MEASURES LIKE THIS FOR
OTHER PATHWAYS FOR ALZHEIMER'S
DISEASE NOT ONLY HAVE THE
POTENTIAL AS PRECISION MEDICINE
BIOMARKERS BUT CAN ACCELERATE
CLINICAL TRIALS BECAUSE OF THE
DYNAMIC NATURE OF THE METABOLOME
AND IDENTIFY NOVEL THERAPIES FOR
ALZHEIMER'S DISEASE.
THANK YOU.
>> NEXT IS ERIK JOHNSON FROM
EMORY UNIVERSITY.
THANK YOU.
>> THANK YOU FOR SETTING UP MY
PRESENTATION SO NICELY.
I'LL TALK ABOUT BIOMARKERS FROM
A PROTEOMIC ANGLE.
I'LL START WITH WORK WE DID A
FEW YEARS AGO IN BRAIN.
WE LOOKED AT THE PROTEOME IN THE
ROSS MAP AND COHORT ACROSS THE
SPECTRUM OF ALZHEIMER'S DISEASE
BY MASS SPECTOMETRY AND WE USED
TMTMS TO MEASURE OVER 1500
PROTEEPZ AND OVER 500 INDIVIDUAL
TISSUES.
THAT'S A VERY LARGE SET OF DATA
AND THE WAY WE TRY TO INTERPRET
THAT TO UNDERSTAND THE DISEASE
WE USE A PROTEIN COEXPRESSION
THAT CLUSTERS PROTEINS INTO
GROUPS WE CALL MODULES.
AND YOU CAN ANNOTATE THEM THE
DIFFERENT GROUPS BY THEIR
PRIMARY BIOLOGICAL PROCESSES OR
ONCOLOGIES.
THAT IS WHAT IS SHOWN AROUND THE
CIRCLE IN THE SPOKES ON THE
OUTSIDE OF THE ONTOLOGY AND
DIFFERENT MODULES.
YOU CAN SEE A VERY DIVERSE SET
OF ONTOLOGIES HERE.
I WANT TO TALK ABOUT TWO OF THEM
PARTICULARLY TODAY AND THAT IS
THE M42 MODULE AND ALSO THE M7
SIGNALLING AND METABOLISM
MODULE.
THE REASON IS THIS MODULE WE
IDENTIFIED WAS ONE WITH THE
STRONGEST CORRELATION TO
ALZHEIMER'S DISEASE PATHOLOGY IN
THE BRAIN.
AND THE MAP KINASE MODULE HAD
THE STRONGEST CORRELATION TO
FUNCTION.
IT WASN'T LARGE BUT THEY HAD A
COLLECTION OF PROTEINS THAT
SEEMED TO BE HIGHLY ASSOCIATED
WITH AMYLOID BETA DEPOSITION IN
THE BRAIN SHOWN ON THE LEFT.
AND THEHISTO CHEMISTRY HAS BEEN
PERFORMED BY A NUMBER OF GROUPS
DEMONSTRATING THIS.
ONE PROTEIN WAS FROM A MODULE
THAT STANDS FOR SPARK RELATED
MODULE PROTEIN 1.
AN EXTRA CELLULAR MATRIX
PROTEIN.
IT'S NOT SOMETHING WE TYPICALLY
ASSOCIATE OR HAVE KNOWN IN THE
PAST TO BE ASSOCIATED WITH
ALZHEIMER'S.
IT'S A MORPHOGENIC PROTEIN
SIGNALLING AND INVOLVES THE
SIGNALLING PATHWAY AND PROMOTES
ANGIOGENESIS AND A HEPARAN
BINDING PROTEIN AS WELL AS
OTHERS IN THE MODULE.
IF YOU LOOK AT BIO FLUIDS IN
ALZHEIMER'S DISEASE BY MULTIPLE
TECHNIQUES YOU CAN SEE IT'S
INCREASED.
CSF AND PLASMA AND SEEMS TO BE
RATHER SPECIFIC FOR ALZHEIMER'S
DISEASE WHICH MAKES SENSE
BECAUSE IT'S ASSOCIATED WITH
AMYLOID BETA.
WE'VE LOOKED AT ALS AND
PARKINSON'S DISEASE TO SEE THE
SPECIFICITY.
NOW, WE'RE INTERESTED IN LOOKING
AT HOW THIS PROTEIN CHANGED OVER
TIME AND ONE WAY YOU CAN DO THAT
IS TO LOOK IN A COHORT LIKE THE
THIS COHORT THE POWER OF ADAD IS
YOU KNOW WITH FAIRLY GOOD
PRECISION WHEN PEOPLE WILL
DEVELOP THE DISEASE AND PUT THIS
INTO A LONGITUDINAL CONTEXT AND
I'M SHOWING TWO MEASURES HERE.
FIRST IS THE A BETA 42 OVER 40
RATIO A GOOD MARKER OF PLAQUE
DEPOSITION AND THE PEOPLE WITH
AUTOSOMAL MUTATION CARRIERS HAVE
INCREASED LEVELS EARLY ON IN
LIFE BECAUSE THEY PRODUCE MORE
42 COMPARED TO 40 AND AS THEY
DEVELOP PLAQUE THAT DECREASES.
IF YOU LOOK AT WHEN THE CHANGE
OCCURS COMPARED TO A CONTROL OR
NON-CARRIER, THAT'S ABOUT 18
YEARS PRIOR TO SYMPTOM ONSET
COMPARED TO ONSET OF 0.
THAT STARTS TO INCREASE IN
CARRIERS EARLY AS THE A BETA 42
TO 40 IS CHANGES AND IF YOU LOOK
AT THE ABSOLUTE CHANGE THAT
OCCURS ABOUT 29 YEARS PRIOR TO
SYMPTOM ONSET.
AND SO IF WE THEN PUT THIS INTO
THE BROADER CONTEXT OF SOME OF
THE OTHER PROTEINS WE MEASURED
IN THE COHORT YOU CAN SEE THE
PROTEINS ARE CHANGING VERY EARLY
ALONG WITH A BETA 42 OVER 40.
EARLIER THAN P TAU 217 AND CSF
THE RED IS SHOWING THE INCREASE
UP CARRIERS.
YOU CAN SEE IT'S INCREASING EVEN
EARLIER THAN P TAU 217 AND USE
OTHER MARKERS WE ASSOCIATE WITH
HOW THEY'RE RELATED TO THE BRAIN
MODULES WE MEASURE TRANSLATING
THE BRAIN TO THE CSF.
THESE ARE PROTEINS WE MAP TO THE
BRAIN MODULES TO UNDERSTAND OVER
TIME HOW THE BRAIN IS CHANGING
IN THE EVOLUTION OF AUTOSOMAL
ALZHEIMER'S DISEASE.
WE SEE EARLY CHANGES IN A BETA
PLAQUE FOLLOWED BY SYNAPTIC
CHANGES IN GLUCOSE METABOLISM
AND RESPONSE AND INTEGRITY AND
IMMUNE CHANGES ASSOCIATED WITH
COGNITIVE DECLINE AND CORTICAL
ATROPHY AND METABOLISM CHANGES.
PUTTING THESE BIOMARKERS THEN
INTO CONTEXT TO UNDERSTAND THE
NATURAL HISTORY OF AUTOSOMAL
DOMINANCE.
IT'S SUMMARIZED IN A FIGURE LIKE
THIS SEEING THE EARLY CHANGES
WITH A BETA PLAQUE AND FOLLOWED
BY METABOLISM THAT CHANGE OVER
TIME AND PATTERNS.
GETTING BACK TO SMOC1 WE THINK
THE PROTEINS ARE NOT INCIDENTAL
BIOMARKERS AND MAY BE GOOD
THERAPEUTICS.
I'M GOING TO SHOW YOU SOME NEW
DATA FROM THE COHORT WHERE WE
HAVE A PERSON WHO HAS SHOWN
EXTREME RESILIENCE TO THE
MUTATION THAT CAUSES ONE OF THE
MUTATIONS THAT CAUSES AUTOSOMAL
DOMINANCE AND NOW 20 YEARS PAST
WHEN WE EXPECTED THEM TO DEVELOP
THE DISEASE AND A CLEAR OUTLIER
FROM THE REST OF THE MUTATION
CARRIERS.
IF YOU LOOK AT THE AMOUNT OF
AMYLOID IN THIS INDIVIDUAL'S
BRAIN IT'S VERY HIGH.
HERE'S THE ESTIMATE HERE.
IN FACT THIS IT WILL BASICALLY
WHERE THE COHORT ENDS,
UNFORTUNATELY FOR THESE
INDIVIDUALS BUT HE'S AT THE TOP
OF THE ESTIMATE HERE AT 100% AND
BASICALLY DRIVING THE REST OF
THIS BECAUSE HE'S THE ONLY
PERSON OUT HERE.
IF YOU LOOK AT THE LEVELS OF
SMOC THEY'RE NOT THE SAME LEVEL
AS THE AMYLOID BETA.
IT'S SUGGESTIVE AND THIS COULD
BE AN MOLECULE IN THE
PATHOGENESIS OF THE DISEASE.
WE CAN THEN TAKE THE SAME
APPROACH WE'VE DONE IN BRAIN AND
APPLY IT TO CSF AND MEASURE
THOUSANDS OF PROTEINS IN THE CSF
AND HAVE DONE THIS IN A RECENT
STUDY USING TWO PROTEOMIC
PLATFORMS MASS SPEC AND BUILD
THE SAME TYPE OF NETWORKS AND
UNDERSTAND WHAT'S CHANGING IN
ALZHEIMER'S DISEASE.
TO HIGHLIGHT HERE WE CAN
IDENTIFY MODULES STRONGLY
ASSOCIATED WITH APOE 4 IN CSF.
THIS DETOXIFICATION OF THE
KINASE SIGNALLING AGAIN
METALATION WHICH IS SIMILAR TO
YOU BICK WIT INATION AND
ASSOCIATED WITH APOE 4 RAND CSF
AND WANTED TO FOCUS ON THE
GLYCOLYSIS MODULE.
THIS WAS RELATED TO COGNITIVE
FUNCTION IN CSF NOT JUST BRAIN
WE CAN OBSERVE AND SEE HOW IT'S
INCREASED IN ALZHEIMER'S DISEASE
COMPARED TO CONTROLS AND THIS IS
TRYING TO USE THIS IN A CLINICAL
TRIAL CONTEXT TO USE THIS CSF
PROTEOMIC ANALYSIS TO REALLY TRY
TO TRANSLATE THAT INTO POTENTIAL
BIOMARKERS AT A PROTEOMIC LEVEL
IN CSF.
THE WAY WE'RE THINKING OF DOING
THIS I'LL DESCRIBE BRIEFLY AN
EXAMPLE THE MEDICATION CALLED
ATAMO X ITINE APPROVED FOR
ATTENTION DEFICIT HYPER ACTIVITY
DISORDER MAINLY IN CHILDREN AND
NOREPINEPHRINE REUP TAKE
INHIBITOR AND IN ALZHEIMER'S
DISEASE ONCE OF THE EARLIEST
CHANGES IS LOCUS SER EELIUS AND
THERE'S PRE CLINICAL WORK THAT
SHOWED THIS COULD POTENTIALLY BE
A DISEASE MODIFYING PATHWAY
TARGETED.
SO THERE WAS A CLINICAL TRIAL AT
EMORY A SMALL ONE WHERE WE
TESTED THIS COMPOUND AND CROSS
OVER OF THE DESIGN TRIAL.
WE LOOKED AT AND IF WE LOOKED AT
A COMBINATION OF PROTEINS THAT
GAVE US A BETTER PREDICTION IN
TERMS OF A RATIO.
ILLUSTRATING THE PROTEOMIC
APPROACH AND TO WRAP UP I KNOW
I'M OUT OF TIME WE'LL DO WORK
HERE IN SPORADIC EARLY ONSET
ALZHEIMER'S DISEASE LOOKING AT
BRAIN CSF AND PLASMA.
WE'RE SEEING INTERESTING
FINDINGS IN EARLY ONSET COMPARED
TO OTHER TYPE OF ALZHEIMER'S
DISEASE FINALLY IN DOWN SYNDROME
WHICH HAS ALREADY BEEN TALKED
ABOUT AT THE CONFERENCE TO LOOK
AT THE PROTEOMIC CHANGES FOR
DOWN SYNDROME.
AND FINALLY THE GNPC IS AN
EFFORT YOU'LL HEAR ABOUT OVER
THE NEXT YEAR AND IT'S USING
COHORTS AROUND THE WORLD WITH
PLASMA-BASED PROTEOMICS TO
BETTER UNDERSTAND THE DISEASE
AND ITS BIOMARKERS.
MORE TO COME.
THANKS.
>> OUR NEXT SPEAKER IS ROB
RISSMAN FROM THE UNIVERSITY OF
SOUTHERN CLINICAL RESEARCH.
>> THANK YOU FOR THAT.
I WANT TO THANK ERIKA AND LAURIE
FOR INVITING ME AND HELPING ME
ASSEMBLE MY SLIDES.
I'LL TALK ABOUT ATNV BIOMARKERS
HOW TO USE IN BIOMARKER TO
INCREASE INCLUSIVITY IN CLINICAL
TRIALS.
AND THIS IS PROBABLY THE LARGEST
COHORT STUDY OF DIVERSE ETHNIC
GROUPS IN THE COUNTRY.
THUS FAR WE'VE COLLECTED A HUGE
AMOUNT OF DATA.
WE HAVE THOUSANDS OF PEOPLE FROM
DIFFERENT DIVERSE GROUPS A WIDE
VARIETY OF AGES.
ALL KIND OF BIO SPECIMENS AND
IMAGING SAMPLES WHICH ARE ALL
AVAILABLE FOR SHARING THROUGH A
DATA LINK YOU CAN SEE AT THE
BOTTOM THERE.
SO ONE VERY IMPORTANT PART ABOUT
THIS COHORT IS THE ABILITY TO
EXPAND DATA FROM NON-DIVERSE
COHORTS FROM SOME OF OUR
CLINICAL TRIALS TO BE ABLE TO
ESTABLISH CUT OFFS AND RANGES
THAT CAN BE POTENTIALLY USED TO
HELP THESE ETHNIC GROUPS GET
INTO CLINICAL TRIALS.
JUST AS AN EXAMPLE OF HOW THE
DATA CAN BE USED USING SOME
IMAGING STUFF.
AS WE ALL KNOW TAU IS VERY MUCH
RELATED TO CELL LOSS AND
COGNITIVE CHANGE IN NON-HISPANIC
WHITES.
WE'VE KNOWN THIS FOR A LONG
TIME.
IT'S NOT NECESSARILY THE CASE IN
ALL ETHNIC GROUPS.
INDEED IN HER STUDY SHE FOUND
THERE WAS SOMETHING ELSE DRIVING
COGNITIVE IMPAIRMENT THAT
DOESN'T SEEM TO BE TAU.
SO WITH THE ABILITY OF THIS
COHORT BEING SO SENSITIVE TO
DETECTION OF DIFFERENCES BETWEEN
ETHNIC GROUPS WE THOUGHT TO
LEVERAGE THIS AND UNDERSTAND HOW
TO USE THESE DEVELOPS TO
INCREASE CLINICAL TRIAL
RECRUITMENT.
AND AS AN EXAMPLE OF WHAT
HAPPENS WHEN YOU DON'T DO ANY
SPECIAL WORK YOU JUST BRING
PEOPLE IN, YOU TEST THEM
COGNITIVELY AND DO PET SCANS YOU
GET A HIGH LEVEL OF SCREEN AND
THIS IS WITHOUT PLASMA
SCREENING.
WE ALL HEARD A LOT ABOUT PLASMA
NOT ONLY IN THE LITERATURE BUT
IN THE CONFERENCE.
WE'RE TALKING ABOUT USING PLASMA
P TAU 217 OR A BETA 242/40 TO
UNDERSTAND HOW MUCH AMYLOID IS
IN SOMEONE'S BRAIN.
SCREEN FAIL IS VERY HIGH.
PART OF THE REASON THAT IS, IS
BECAUSE AND WE BRING PEOPLE IN
AND TAKE ALL COMERS.
WE DON'T DO SPECIAL PROCEDURES
TO SEE WHETHER OR NOT TO
PRESCREEN.
AGAIN BECAUSE WE HAVE DONE THIS
IN THE PAST ALL THESE TRIALS
SUCH AS A4 HAD A HIGH LEVEL OF
SCREEN YEARS AND TOOK ALMOST
FOUR YEARS TO TAKE THE TRIAL NO
WITH STANDING COVID BUT THE MAIN
CAUSE WAS DUE TO TWO NEGATIVE
PET SCANS.
WE WANT TO GET PEOPLE IN MORE
QUICKLY USING A PLASMA BIOMARKER
AND SEE HOW WE CAN IMPROVE THIS.
AND WE'RE USING THIS RIGHT NOW
IN THE HEAD TRIAL IT'S A NOT
ONLY TO REDUCE SCREENING TIME
AND BURDEN AND REDUCE INCLUSION
OF DIVERSE PARTICIPANTS TO GET
MORE THAN JUST NON-HISPANIC
WHITES INTO THE TRIALS IS THE
MAIN GOAL.
THIS IS HOW IT LOOKED.
AGAIN, THIS IS PREDOMINANTLY IN
NON-HISPANIC WHITES AND USING
PLASMA BIOMARKERS WE CAN DO WELL
AT PREDICTING AMYLOID PET.
YOU CAN SEE THE PTAU 217 RATIO
WITH MASS SPECTOMETRY.
YOU CAN SEE A HIGH LEVEL OF THIS
AND ABLE TO DETECT PEOPLE WITH
AMYLOID AND BRAIN.
WHEN WE COMBINE THAT WITH A BETA
42 AND 40 IT GOES HIGHER.
WE PRACTICALLY HAVE AN
IDENTIFICATION.
A TREMENDOUS TOOL TO GET PEOPLE
THROUGH QUICKLY INTO THE
SCREENING PROCESS AND GET THEM
HOPEFULLY TREATED.
BEING THIS IS A BLOOD BIOMARKER
YOU DON'T NECESSARILY HAVE TO GO
TO A CLINIC.
YOU CAN HAVE IT DONE REMOTELY
AND GO IT ALL KINDS OF PLACES
FOR IT, IT COULD BE SOMETHING TO
ATTRACT ETHNIC GROUPS AND
DIVERSE COMMUNITIES TO GET
INVOLVED IN TRIALS AND GET THE
HELP THEY NEED.
SO SURE ENOUGH WHEN WE USE
PLASMA PRESCREENING SEE IN THE
ORANGISH REDDISH LINE WE REDUCED
SCREEN FAILS DRAMATICALLY.
WE'RE UP PRACTICALLY LIKE 75
PLUS PERCENT SCREEN FAILS.
THAT'S OUTRAGEOUS NO WONDER A4
TOOK US 10 YEARS.
IT WASN'T JUST COVID.
WE'RE ABLE TO REALLY REDUCE THE
NEGATIVE PET SCANS AND GET
PEOPLE IN THROUGH THE SCREENING
PROCESS QUICKLY.
SO AGAIN THE POINT ISN'T REALLY
TO REDUCE THE NUMBER OF
POSITIVE PET SCANS BUT REDUCE
THE NUMBER OF NEGATIVE PET SCANS
AN DO NOT INCREASE THE BURDEN
FOR PEOPLE AND HOW DO WE LEVEL
THE PLAYING FIELD FOR DIFFERENT
GROUPS?
HERE'S DATA FROM HENRY FROM USC
AND YOU CAN SEE HERE BY USING
PLASMA BIOMARKERS WE CAN REALLY
START TO INCREASE THE NUMBER OF
PEOPLE WHO ARE PET ELIGIBLE.
SO AGAIN WE DID A PRESCREENER
AND EVERYONE DEEMED POSITIVE
WOULD GET A CONFIRMATORY PET
SCAN AND NOT AT THE POINT
BELIEVING WE CAN USE PLASMA
BIOMARKERS AS THE SOLE SCREENING
TECHNIQUE FOR GETTING PEOPLE
INTO A LOWER AMYLOID TREATMENT
AND WE DRAMATICALLY INCREASE THE
NUMBER OF PEOPLE WHO WERE PET
ELIGIBLE AND WERE ABLE IT COME
INTO THE TRIAL.
BASED ON ALL THESE DATA WE
PROPOSED TO TAKE SOME NEXT STEPS
TO EXPAND UPON THESE.
AGAIN, WHEN WE HAVE DONE THIS IN
THE PAST WE'VE HAD MOSTLY
NON-HISPANIC WHITES AND NEED TO
IMPROVE THAT AND GET THIS OUT TO
ALL THE DIFFERENT COMMUNITIES.
OUR INITIAL WORK DID NOT INCLUDE
DIVERSE PARTICIPANTS.
THE IDEA HERE FOR USING THE
HATCH COHORT AND OUR ONGOING
WORK IS TO CHANGE THIS.
WE'RE GOING TO ESTABLISH CUT
OFFS AND RANGES FOR ALL KINDS OF
ETHNIC GROUPS AND DO THAT WITH
THE FOLLOWING AIMS.
THIS IS AN RO1 SENT YESTERDAY.
IT'S ACTUALLY GOING TO HAPPEN
THANKS TO HER.
SHE DID KEEP ME IN SUSPENSE FOR
A LONG TIME AND KNOWS HOW TO
TORTURE ME.
WE'RE GOING TO LOOK AT NOVEL AND
EMERGING PLASMA BIOMARKERS
AMONGST THE DIFFERENT ETHNIC
GROUPS.
LOOKING AT THE PHOSPHO TAU
SPECIES AND A BETA SPECIES AND
LOOKING AT NTBR AND
PREDOMINANTLY USING MASS SPEC
AND WITH AMINO ASSAYS BECAUSE
THEY'RE SO HIGH THROUGHPUT.
THE IDEA IS TO TAKE A LOOK AND
EXAMINE HOW THEY RELATE TO
AMYLOID AND TAU PET.
WE'RE GOING TO BE USING OUR
CUT-OFFS AND THINGS WE USED FOR
NON-HISPANIC WHITES AND SEEING
HOW THEY MEASURE UP AND WHERE
THEY ARE IN OTHER ETHNIC GROUPS.
IN ADDITION TO LOOKING AT THESE
THINGS CROSS SECTIONALLY FROM A
SCREENING BASIS AND PREDICTION
BASIS WE'LL ALSO LOOK AT THEM
LONGITUDINALLY.
OVER THE NEXT FIVE YEARS WE'RE
GOING TO BE LOOKING AT HOW
PLASMA BIOMARKERS ARE CHANGING
AND HOW THOSE CHANGE IN TERMS OF
CHANGES IN COGNITION.
HOW THEY CHANGE IN TERMS OF
AMYLOID PET WORSENING AND TAU
PET WORSENING USING THE COHORT.
IT SHOULD BE AN EXCITING FIVE
YEARS AND I THINK IT WILL BE A
SEMINOLE STUDY TO TELL US HOW
BLOOD BIOMARKERS CHANGE AND
EVERYTHING ENDS UP IN GROUPS
BECAUSE WE HAVE SUCH A
TREMENDOUSLY CHARACTERIZED
COHORT.
ANYWAY I'LL STOP THERE.
THANK YOU FOR YOUR ATTENTION.
>> WE'RE NOW GOING TO SHIFT TO
OUR FIVE-PARENT PRESENTATIONS.
THE REST OF THE PANELISTS COULD
COME UP IT WILL BE IPSIT AND
NILUFER AND JESSICA AND ERIN.
COME UP AND BRING YOUR NAME
TAGS.
WE'LL GET STARTED HERE.
>> WE'LL START THIS PANEL OFF
WITH IP SET VAHIA FROM HARVARD
UNIVERSITY.
>> I'M A GERIATRIC SCIENTIST AND
PRESENT A CLINICIAN RESEARCHER
PERSPECTIVE ON OUR WORK IN
DIGITAL BIOMARKERS.
AND REALLY TEE OFF FROM WHERE
THE REST OF THE PANEL HAS GONE
WHICH IS DEMONSTRATING HOW THESE
ARE MOVING FROM THE INITIAL
PROOF OF CONCEPT VALIDATION
QUICKLY INTO AND I'M GOING TO
FOCUS LARGELY ON MOTION BASED
BIOMARKERS THOUGH AS WE'VE HEARD
THERE'S A NUMBER OF DIGITAL
BIOMARKERS USING SENSORY
MODALITIES INCLUDING VOICE AND
SOUND.
I HAVE MORE DATA THAN I'M
PRESENTING HERE BUT THIS WAS AT
THE SUGGESTION OF THE ORGANIZERS
AND RECOGNIZING THE ABSORPTION
CAPACITY FOR MORE DATA IS NOT
WHAT IT WAS ON DAY ONE.
YOU CAN SEE IN THE FIRST FIGURE
ON THE TOP LEFT BY GATHERING
DATA FROM RADIO WAVE BASED
SENSOR THAT EFFECTIVELY
FUNCTIONS AS AN IN-ROOM SAUNA IN
PEOPLE'S NATURAL LIVING
ENVIRONMENT WE'RE ABLE TO MAP
MOTION BASED ON HOW THE WAVES
BOUNCE OFFER THE BODY AND LAYER
IT AGAINST SPATIAL LOCATION AND
TIME STAMPING IT.
THE FIRST FIGURE DEMONSTRATES
HOW WE WERE ABLE TO DO AN N OF 1
STUDY DEMONSTRATING INCREASE IN
APATHY BY MAPPING LONGITUDINALLY
BY HOW MUCH TIME THE PERSON
SPENDS ON THE COUCH IN THE ROOM
AND AS THE TIME SPENT INCREASED
WE WERE ABLE TO MEASURE AGAINST
AN APATHY MARKER AND RADIO WAVE
SENSING CAN CAPTURE ACTIVATION.
WE TRACK ALL THE MOVEMENT THIS
PERSON MAKES IN THE ROOM FOR 24
HOURS LONGITUDINALLY GOING
FORWARD.
ONCE YOU PROCESS THE DATA USING
A SIGNAL PROCESSING APPROACH YOU
CAN DIFFERENTIATE A LOW ACTIVITY
FROM A HIGH ACTIVITY DAY AND
PICK UP QUITE EARLY WHETHER THIS
IS BECOMING PATHOLOGICAL AND
DRIFTING TO AGITATION.
WITH THIS EARLY VALIDATION IN
PLACE WE RECENTLY RESO LY RECEI
THE N RAT STUDY WHICH IS NIA
FUNDED.
WE'RE ADDING DATA FROM THE
MARKER INTO A STUDY LOOKING AT
WHETHER IT IMPACTS BRAIN BIO
ENNER GENETICS AND WITH THE
BIOMARKER IT'S ONE OF THE EARLY
STUDIES WITH DIGITAL PHENOTYPING
WITH GENETIC MARKERS AND THE
STUDY ASSOCIATIONS BETWEEN
THESE.
AND LOOKED AT THE A2 COLLECTIVE
TO PUT MOTION-BASED BIOMARKERS
IN THE CLINICAL SERVICE.
HERE WE USE WEARABLES AND THE
FIGURE ON THE BOTTOM LEFT IS A
MARK UP OF A DASHBOARD AS PART
OF THE STUDY AND HERE WE'RE
GOING TO LOOK AT WHETHER GIVING
CLINICIANS ACCESS TO MOTION DATA
IMPACTS THE PRACT IS AND SEEING
IF ADDING WEARABLE DATA ON THE
DASHBOARD IN SESSION LETS
CLINICIANS BETTER IDENTIFY
MEDICATION EFFECTS AND SIDE
EFFECTS AND NON-EFFECTS.
IT'S GOING TO FOCUS ON HIGH-RISK
PSYCHOTICS AND MOOD DISORDERS IN
PEOPLE WITH DEMENTIA.
AS IT PLAYS OUT IT'S THROWING
OUT IN REAL TIME COMPLICATED
QUESTIONS.
I'VE SPOTLIGHTED SOME OF THE
CHALLENGES AND OPPORTUNITIES
THAT HAVEN'T BEEN DISCUSSED SO
FAR.
A BIG ONE IS HAVING ALL THE DATA
DOES IT ACTUALLY TRANSLATE TO
ANYTHING IN TERMS OF CHANGING
CLINICAL PRACTICE.
WHAT'S THE IMPACT OF ACCESS TO
DATA ON CLINICAL DECISION
MAKING.
WHAT ARE THE RIGHT DATA SCREENS
TO USE FOR SPECIFIC USE CASES OR
INDICATIONS.
WHEN DO WE USE VOICE.
WHEN DO WITH USE SOUND AND
MOTION?
AND UPDATE TRAINING CURRICULA
AND REFLECT HOW ALL THE DATA
SHOULD BECOME PART OF STANDARD
OF CARE.
FINALLY THE BIG ONE IS GOING TO
BE AS WE START GETTING USED TO
USING HIGHLY INTRUSIVE
TECHNOLOGIES IN PEOPLE'S NATURAL
LIVING ENVIRONMENTS WE HAVE TO
THINK OF WHAT MALFEASANCE MEANS
AND THERE'S MUCH WORK TO BE
DONE.
THANK YOU.
>> THE NEXT PANELIST I THINK
WILL BE TAG TEAMED WITH MY
CO-CHAIR, DONNA WILCOCK AND
ERIN.
>> SO GOOD MORNING, EVERYONE.
I WAS TALKING ABOUT VASCULAR
CONTRIBUTIONS TO COGNITIVE
IMPAIRMENT AND DEMENTIA.
AND SPECIFICALLY THE MARK VACD
CONSORTIUM AND THE PROGRESS MADE
BY THAT CONSORTIUM.
FIRST I THOUGHT IT WOULD BE A
GOOD INTRODUCTION TO GIVE AN
OVERVIEW OF WHAT WE THINK ABOUT
WHEN WE THINK ABOUT VASCULAR
CONTRIBUTIONS TO COGNITIVE
IMPAIRMENT AND DEMENTIA FROM NOW
ON I'LL SAY VCID.
THE PATHOLOGIES IS AN UMBRELLA
FOR MANY VASCULAR PATHOLOGIES
RANGING FROM INFARCTS AND MICRO
BLEEDS AND SMALL VESSEL
HEMORRHAGIC STROKE TO LARGE
VESSEL ISCHEMIC AND HEMORRHAGIC
STROKE CONTRIBUTING TO COGNITIVE
FUNCTION.
SO THE MARK VCID IS A CONSORTIUM
IN ITS SECOND PHASE AND IN YEAR
EIGHT AT THIS POINT AN NINDS
FUNDED CONSORTIUM.
WE HAVE SEVEN SITES AROUND THE
NATION AND THE NEW ITERATION
FUNDED A COUPLE YEARS AGO WE NOW
HAVE NINE SITES WITHIN THE
CONSORTIUM THAT COORDINATING
CENTER IS HOUSED AT MGH.
AND THE GOAL OF MARK VCID IS NOT
ONLY TO IDENTIFY CANDIDATE
BIOMARKERS FOR VCID IN
PARTICULAR CEREBRAL SMALL VESSEL
DISEASE AND CROSS-SITE VALIDATE
AMONG THE NINE SITES THESE
BIOMARKERS TO ENSURE ROBUSTNESS
AND VALIDITY.
WHAT ARE THE MARK VCID
BIOMARKERS.
THERE'S A NUMBER OF NEURO
IMAGING BIOMARKERS AND I'M NOT A
NEURO IMAGIST SO I CAN'T GO INTO
DETAIL BUT THESE ARE THE KITS
BEING CROSS-SITE VALIDATED
INCLUDING AN IMAGING BASED
ALGORITHM FOR ARTERIAL SCLEROSIS
AND VASCULAR REACTIVITY GIVING
US INFORMATION ABOUT THE
FUNCTION OF THE VESSEL AND HOW
FUNCTIONAL THE IMPROVED
CHARACTERIZATION FOR WHITE
MATTER CHANGE AND FREE WATER
WHICH IS ANOTHER MEASURE OF
INFLAMMATION AND WHITE MATTER
INTEGRITY.
MARK VCID HAD A PLACENTAL GROWTH
FACTOR AND THAT LOOKS LIKE A
PROMISING BIOMARKER FOR CEREBRAL
SMALL VESSEL DISEASE ON THE
BOTTOM RIGHT AND THE GRAPH IS
YOU CAN SEE THE DIAGNOSTIC
ACCURACY OF PLACENTA GROWTH
FACTOR FOR VASCULAR DEMENTIA WAS
POINT 89 AND FOR VCI IT WAS .74.
IT'S A PROMISING BIOMARKER WE'RE
CONTINUING TO LOOK AT.
IN THINKING OF THE CHALLENGES OF
BIOMARKER FOR VCI D WE HAVE A
LACK OF BIOMARKERS TO VALIDATE
BEYOND NEUROPATHOLOGY OUR
IMAGING OF ESPECIALLY THE SMALL
SELF INSULTS IN THE BRAIN IS
QUITE POOR AND USED WHITE MATTER
INNENCE TI AS AN INDICATOR --
INTENSITY AS AN INDICATOR AND
IT'S THE TIP OF THE ICEBERG WHEN
IT COMES TO VASCULAR
PATHOLOGIES.
AND AMYLOID ACCUMULATION
INDEPENDENTLY CONTRIBUTE TO
WHITE MATTER INTENSITY.
WHEN WE THINK ABOUT THE REAL
WORLD MANY TIMES WE HAVE
PATIENTS WHO HAVE BOTH VASCULAR
CONTRIBUTIONS TO THEIR COGNITIVE
IMPAIRMENT AS WELL AS ALZHEIMER
CONTRIBUTIONS.
UNDERSTANDING HOW MUCH OF THAT
WMH IS BEING CONTRIBUTED TO
AMYLOID VERSUS VASCULAR INSULTS
IS CHALLENGING.
EVEN OUR PARENT PATHOLOGIC
ASSESSMENT OF PATHOLOGIES IS
MINIMALLY INFORMATIVE BECAUSE WE
DO A LOT OF RANDOM SAMPLING IN
NEURO PATHOLOGY SO IT'S HIT OR
MISS WHETHER IN THAT PIECE OF
TISSUE YOU WILL FIND A MICRO
INFARCT OR NOT IT'S DEFINED AS
PRESENCE OR ABSENCE OF THE
HALLMARKS ARE NOT QUANTIFIABLE.
WE HAVE A LACK OF QUANTIFY WITH
CAA AND WE'RE MISSING PATHOLOGY.
WITH THAT I'LL WRAP UP AND WE'LL
MOVE ON.
THANK YOU.
>> THANK YOU.
SO I'M GOING TO TALK ABOUT THE
CLEAR AD U19 LONGITUDINAL
BIOMARKERS OF ALZHEIMER'S
DISEASE IN MULTI-ETHNIC
POPULATIONS.
AND AS WE HEARD IN THE PREVIOUS
TALK THIS IS A LARGE CONSORTIUM
EFFORT LED BY THE MAYO CLINIC
AND INDIANA UNIVERSITY WITH 13
SITES AND OVER 100
INVESTIGATORS.
ON THE TOP LEFT THERE YOU SEE
THE PRECISION BIOMARKER
FRAMEWORK.
WE ALL HEARD ABOUT AMYLOID TAU
NEURODEGENERATION AS BIOMARKERS
OF KEY NEUROPA PAPATHOLOGIES AN
THERE'S MORE UNDER THE ICEBERG
IT'S A COMPLEX DISEASE AND WE
HEARD ABOUT IT THROUGHOUT THE
TALKS.
I WON'T BELABOR THAT.
THE PREMISE OF CLEAR AD IS THERE
ARE COMPLEX MOLECULAR
PERTURBATIONS IN THE BRAIN AND
WE HEARD ABOUT THESE
PERTURBATIONS IN MANY
MULTI-OMICS TALKS.
AND CLEAR AD AIMS TO IDENTIFY
NOT ONLY THE CENTRAL MOLECULAR
SIGNATURES OF DISEASE BUT ALSO
TO CAPTURE THEM IN PERIPHERY IN
THE SO CALLED CENTRALLY LINKED
PERIPHERAL MOLECULAR SIGNATURES.
ON THE TOP RIGHT IS THE
FRAMEWORK FOR THE PROGRAM.
THE MOLECULAR PERTURBATIONS WILL
BE CAPTURED USING A PENTAOMICS
APPROACH LOOK AT THE BIOLOGICAL
PATHWAYS THAT THESE
PERTURBATIONS FALL INTO IN A
TIERED MECHANISM.
THE CENTER OF THE TIER ARE THOSE
BIOLOGICAL PATHWAYS THAT ARE
MOST PROVEN IN ALZHEIMER'S
DISEASE.
THE OUTER TIER PATHWAYS ARE 20
MORE AND THE OUTER MOST TIER IS
THE DISCOVERY SPACE.
WE'LL BE TAKING A LOOK AT THESE
PERTURBATIONS IN THE CONTEXT OF
THE ENVIRONMENT IN THE CONTEXT
OF ALZHEIMER'S DISEASE
COPATHOLOGIES AND COMORBIDITIES
IN MULTI-ETHNIC POPULATIONS
COMPRISING AFRICAN AMERICAN AND
LATIN AMERICANS AND NON-HISPANIC
WHITES AND WE'LL BE CORRELATING
THE MULTI-OMICS MEASURES AND
BIOLOGICAL PERTURBATIONS TO A
VARIETY OF ENDO PHENOTYPES
INCLUDING BUT NOT LIMITED TO
COGNITIVE IMAGING AND THE
ROUTINELY MEASURED PERIPHERAL
BIOMARKERS OF ATN.
SO THE LOWER LEFT ARE THE
EXPECTED OUTCOMES OF IDENTIFYING
THE SIGNATURES WHERE IN THE
FUTURE THE SIGNATURES WILL THEN
BECOME THE PRECISION BIOMARKERS.
THE PROGRAM AIMS TO ESTABLISH AN
APPROACH, A PIPELINE FOR
PRECISION BIOMARKERS IN
ALZHEIMER'S DISEASE.
WE'LL IDENTIFY NOT ONLY THE
PRECISION SIGNATURES BUT THAT
THESE SIGNATURES CAN THEMSELVES
BECOME THERAPEUTIC TARGETS AS WE
HEARD FROM OTHER SPEAKERS TODAY.
AND IMPORTANTLY THE PROGRAM ALSO
OFFERS A TWO-YEAR SCHOLARSHIP.
IF YOU'D LIKE TO LEARN MORE
ABOUT IT, PLEASE CHECK OUT OUR
WEBSITE CLEAR AD.org.
SOME OUTCOMES OF THE PROGRAM YOU
CAN FIND ON THE WEBSITE AND
EXAMPLES ON THE LOWER RIGHT HAND
CORNER AND HIGHLIGHT A
PUBLICATION FROM OUR GROUP P
PUBLICATION USING SINGLE NUCLEI
RNA SEQ IN A BRAIN TISSUE.
WE HAVE IDENTIFIED A MOLECULAR
DUO, A SMAT 3NGEEFA PERTURBED
AND MAY UNDER LIE BLOOD BRAIN
BARRIER DYSFUNCTION IN
ALZHEIMER'S DISEASE.
BOTH BASED ON OUR DATA EXTERNAL
DATA AS WELL AS MODEL SYSTEMS
INCLUDING INDUCED PLURIPOTENT
STEM CELL DERIVED PERICYTES.
THE SMAT 3 WHICH IS PERTURBED IN
PERICYTES WHEN MEASURED IN BLOOD
ALSO DOES CORRELATE WITH NEURO
IMAGING BIOMARKERS OF
ALZHEIMER'S DISEASE SPECIFICALLY
AMYLOID DEPOSITION AND CORTICAL
ATROPHY THEREBY PROVIDING A LINK
BETWEEN ALZHEIMER'S DISEASE AND
CENTRAL PERIPHERY LINK.
WITH THAT I'LL STOP.
>> SO OUR NEXT SPEAKER IS
JESSICA FAUL FROM THE UNIVERSITY
OF MICHIGAN.
I HAVE TO SAY, GO BLUE.
>> SO WE'LL SWITCH GEARS A
LITTLE BIT AND TAKE A BIG
PICTURE VIEW.
WHAT WE FELT WAS NEEDED WAS TO
REPLICATE THE WORK DONE ON BLOOD
BRAIN BARRIER BUT USING A
REPRESENTATIVE POPULATION BASED
AND DIVERSE SAMPLE AND WE HAD A
LONGITUDINAL PANEL STUDY WITH A
REPRESENTATIVE SAMPLE OF ADULTS
IN THE U.S. OVER AGE 50 EVERY
TWO YEARS WITH AN OVERSAMPLING
OF RACE AND ETHNIC MINORITIES.
WE MEASURED A BETA 42/40 RATIO
AND P TAU 181 AND REPRESENTATIVE
SUBSET OF PARTICIPANTS BORN IN
1959 AND EARLIER.
SO THE SUB SAMPLE WAS ABOUT
4,000 PEOPLE.
BEFORE THIS WE HAD TO SHOW THIS
WAS FEASIBLE AND WE'RE
COLLECTING BLOOD IN PARTICIPANTS
HOME SHIPPED TO A LABORATORY AND
DEVIATING FROM CLINICAL BEST
PRACTICE.
THIS LINKS TO THE PUBLICATION
FROM THE PILOT STUDY.
WE LEARNED IT WAS POSSIBLE WITH
SOME CAVEATS.
WE WERE ABLE TO USE PLASMA FOR
THE A BETA 42 AND 40 MEASUREMENT
BUT COULD ONLY LOOK AT IT AS A
RATIO BECAUSE THE TOTAL AMOUNT
OF A BETA DECLINED BECAUSE OF
THE DELAY PROCESSING ABOUT THE
THE RATIO REMAINED CONSTANT.
NFL AND G FAB WERE UNCHANGED AN
FOR P TAU WE HAD TO SWITCH TO
SERUM BECAUSE OF THE THEY ARE IN
PROCESSING LEADS TO ARTIFICIALLY
HIGH PHOSPHORYLATION AND WEREN'T
ABLE TO USE THE PLASMA SAMPLE.
WE USED THE ASSAY AND THEN IN
THE STUDY WE COMPARED IT TO OUR
COGNITIVE TESTS.
HERE WE'RE LOOKING AT MEDIA AND
ADELAY RECALL AND BACKWARDS
COUNTING AS A TOTAL SCORE FROM 0
TO 27 AND APPLIED THE DIAGNOSTIC
ALGORITHM VALIDATED IN OTHER
STUDIES TO PREDICT DEMENTIA
STATUS.
ON THE FAR SIDE YOU CAN SEE SOME
DESCRIPTIVES AND I WANTED TO
POINT OUT WE ALSO HAD APOE E4
ALLELE STATUS FROM PRIOR
GENOTYPING EFFORTS AND WHAT WE
FOUND THE MARKERS GENERALLY WERE
MODERATELY CORRELATED.
SO SPECIFICALLY NFL G FAB AND A
BETA 42/40 WAS ONLY WEAKLY
RELATED TO PAV OF P TAU FOR THE
MOST PART THEY MEASURE
DISTINCTIVE THINK AND SAW THE
AGE-RELATED PATTERNS WE EXPECTED
BUT NO DIFFERENCES FOR THE A
BETA 42/40 RATIO.
WE WERE LOOKING FOR RACE AND
ETHNIC DIFFERENCES AND WE DIDN'T
SEE DIFFERENCES IN MEANS ACROSS
THE BIOMARKERS BUT SEE A
DIFFERENCE IN HOW WELL THEY
PREDICTED OUTCOMES.
SO IN OUR SAMPLE NFL P TAU AND G
FAB WERE PREDICTIVE OF COGNITIVE
SCORE CROSS SECTIONALLY IN THE
ENTIRE SAMPLE AND THE A BETA
42/40 WAS PREDICTIVE OF
COGNITIVE SCORE IN THE WHITE
SAMPLE.
AND NFL WAS REALLY THE ONLY
MARKER THAT CONSISTENTLY
PREDICTED COGNITIVE FUNCTIONING
ACROSS ALL THE RACE/ETHNIC
GROUPS.
THIS SLIDE LOOKS WONKY SHOWING
THE RELATIONSHIP WITH THE CROSS
SECTIONAL COGNITIVE SCORE.
WHEN WE LOOKED AT THE MARKERS
TOGETHER, NFL COMES OUTS THE
STRONGEST PREDICTOR OF COGNITIVE
FUNCTION.
WE ALSO HAD THE ABILITY TO LOOK
LONGITUDINALLY FOUR YEARS OUT
FROM THE TIME OF MEASUREMENT AND
THE TABLE SHOWS WHAT THAT LOOKS
LIKE AND AGAIN NFL WAS THE
MARKER THAT WAS ABLE TO PREDICT
DEMENTIA AND DEATH TWO AND FOUR
YEAR AFTER THE MEASUREMENT OF
THE BIOMARKER.
AND AGAIN CONSISTENT ACROSS RACE
AND ETHNIC GROUPS IN CONCLUSION
THE MARKERS CAN BE MEASURED IN
POPULATION-BASED STUDIES WITH
CAVEATS AND APPROPRIATE
PROTOCOLS.
THE BIOMARKERS RELATED TO
CROSS-SECTIONAL AND LONGITUDINAL
FUNCTIONING AND SAW LITTLE
EVIDENCE OF RACE AND ETHNIC
DIFFERENCES IN MEANS BUT SOME
ABILITY TO PREDICT OUTCOMES.
NFL FOR US WAS THE STRONGEST
PREDICTOR OF COGNITION CROSS
SECTIONALLY AND LONGITUDINAL TO
PREDICT DEMENTIA ONSET BUT AS
ROB MENTIONED THE STRENGTH OF
THE BIOMARKERS IS TO HELP
DIFFERENTIATE BETWEEN DIFFERENT
KINDS OF DEMENTIAS.
WE HAVE MEASURED THESE
LONGITUDINALLY AND MEASUREMENTS
SIX YEARS LATER NOW AND JUST
STARTING TO LOOK AT THOSE AND
THINK THAT WILL HELPFUL IN
UNDERSTANDING HOW THEY CHANGE
OVER TIME.
ONE THING WE NEED IN THE FIELD
IS A PLATFORM COMPARISON.
WE'RE ALL USING DIFFERENT TYPES
OF TECHNIQUES TO MEASURE THESE
THINGS AND I THINK FOR US TO
BEGIN TO UNDERSTAND HOW ALL OF
THESE STUDY RELATE TO ONE
ANOTHER THAT TYPE OF WORK WOULD
BE HELPFUL.
I ALSO WANTED TO MAKE A PLUG
THAT ALL THE DATA WE PRODUCE ARE
PUBLICALLY --
[NO AUDIO]
RELEASED LATER THIS YEAR.
>> I'LL TRY THAT AGAIN.
>> I WANT TO START BY THANKING
THE NIA FOR THE SIN INVITATION.
WE HAVE A NON FOR PROFIT TO
SUPPORT THE MISSION OF THE NIH
AND ONE OF THE KEY SUCCESSES IN
TACKLING THE MOST PRESSING
HEALTH CHALLENGES IS PARTNERING
WITH WORLD CLASS ORGANIZATIONS
AND SCIENTIST AND CREATES
PUBLIC-PRIVATE PARTNERSHIPS AND
ADVOCACY GROUPS TO ACCELERATE
BIOMEDICAL INNOVATION ACROSS A
RANGE OF DISEASES.
AND THE FNIH HAS LED SEVERAL
INITIATIVES RESPONSIVE TO THE
UNMET NEEDS IN ALZHEIMER'S
DISEASE RESEARCH AND IN LINE
WITH PET TRACERS, FLUID
BIOMARKERS AND THE DISEASE
MODIFYING THERAPEUTICS RECENTLY.
THESE INCLUDE OVERSIGHTS OF THE
AD
ADNI PUBLIC-PRIVATE PARTNERSHIPS
AND WITH THE CONSORTIUM IN I AM
PROVING HEALTH THROUGH MEASURES.
WE LEAD A CROSS-SECTOR EFFORTS
TO IDENTIFY AND VALIDATE AND
QUALIFY POTENTIAL BIOMARKERS TO
ADVANCE DRUG DEVELOPMENT AND
ALSO SUPPORT REGULATORY DECISION
MAKING.
AMONG THE GOALS ARE TO DEVELOP
EVIDENCE TO QUALIFY BIOMARKERS
FOR SPECIFIC APPLICATIONS IN
DIAGNOSING DISEASE AND IMPROVING
CLINI
CLINICAL PRACTICE AND WITHIN THE
THEMES OF THE SUMMIT IS THAT THE
DATA THAT IS GENERATED OR
FINDINGS GENERATED WITHIN THE
BIOMARKER CONSORTIUM PROJECT ARE
MADE BROADLY AVAILABLE TO THE
SCIENTIFIC COMMUNITY.
THERE ARE FOUR THERAPEUTIC AREAS
UNDER THE BIOMARKER CONSORTIUM
BUT FOR THE PURPOSES OF MY
PRESENTATION I'LL FOCUS ON OUR
NEUROSCIENCE COMMITTEE WHICH IS
COMPRISED OF REPRESENTS FROM THE
NIH, FDA, BIO TECHNOLOGY AND BIO
PHARMACEUTICAL COMPANIES AND
PATIENT ADVOCACY ORGANIZATIONS.
THE FNIH HAS CONCEPT IDEATION TO
COMPREHENSIVE PROJECT PLANNING
AND THROUGH PROJECT EXECUTION.
SO WE HAVE A NUMBER OF ACTIVE
PROJECTS THAT ARE INVESTIGATING
ANALYTICAL VALIDATION OF FLUID
AND IMAGING BIOMARKERS AND FOR
THE INTEREST OF TIME I DO
ENCOURAGE YOU TO UTILIZE THAT QR
CODE TAKING US TO THE BIOMARKER
CONSORTIUM WEBSITE FOR
INFORMATION ON THE PROJECTS.
AND I DID WANT TO MENTION TOO
THE NEUROSCIENCE STEERING
COMMITTEE IS ENGAGED IN
PRIORITIZING AND OUTLINE NEW
PROJECT CONCEPTS DONE IN THE
COMING MONTHS AND A FEW OF THE
POTENTIAL AREAS THROUGH
DISCUSSIONS WITH OUR PARTNERS
THAT HAVE BEEN HIGHLIGHTED FOR
NEURAL INFLAMMATION, DIGITAL
MEASURES AND TDP43 AND I WANTED
TO TOUCH ON IN DEVELOPMENT
PROJECTS.
THE FIRST BEING THE AD BIO
SIGNATURE PROJECT AND A
SIGNATURE OF AMYLOID POSITIVE
COHORTS OF M INDIVIDUALS.
THE IDEA WE WOULD LEVERAGE DATA
EXISTING WITHIN PRE CLINICAL AND
AD COHORTS WITH A FOCUS ON
DIVERSITY WITHIN THE SELECTION
OF PARTICIPANTS, PERFORM
ADDITIONAL BIOMARKER ASSESSMENTS
TO FILL IN ANY DATA GAPS,
HARMONIZE TO THE POINT MADE OF
DIFFERENT PLATFORMS AND
INVESTIGATE EMERGING BLOOD
BASED BIOMARKERS.
IF YOU WAND MORE INFORMATION
COME FIND ME.
YOU HAVE MY E-MAIL IF YOU'D LIKE
TO CONNECT OUTSIDE THE SUMMIT
AND I'LL END BY BRIEFLY
INTRODUCING OUR WORK TO
COMPREHENSIVELY INVESTIGATE THE
CLINICAL RELEVANCE AND
BIOLOGICAL CONTEXT OF VARIOUS
SYNAPTIC MARKERS IN ALZHEIMER'S
DISEASE AND PSYCHOSIS SPECTRUM
DISORDERS AND ELUCIDATING THEIR
ASSOCIATION WITH DISEASE
PATHOLOGY.
THAT WILL ENTAIL META-ANALYSIS
AS WELL AS COMPARISONS BETWEEN
THE FLUID SYNAPTIC MARKERS AND
VALIDATING THEM AGAINST PET
IMAGING AND MEASUREMENTS IN
BRAIN TISSUE.
YOU ENCOURAGE TO YOU REACH OUT
KNOW COLLEGIATE THE FNIH AND HER
E-MAIL IS HERE IF YOU ARE
INTERESTED.
THANK YOU SO MUCH.
>> OKAY.
SO I THINK WE DID A GREAT JOB ON
TIME WITH THAT SESSION.
SO TO KICK OFF THE DISCUSSION
PORTION OF THIS SESSION
DR. RHODA AU AND I PRIMARILY
RHODA PUT TOGETHER SOME TALKING
POINTS FOR US TO THINK ABOUT
WHEN WE THINK ABOUT GAPS IN
OPPORTUNITIES AND WITH RESPECT
TO DISCOVERY I THINK THE THEMES
THAT CAME ACROSS TODAY FROM ALL
OF OUR SPEAKERS ARE THAT WE NEED
TO DIVERSIFY AND IDENTIFY NOVEL
BIOMARKERS, NEXT GENERATION
BIOMARKERS AND WE NEED TO BE
REPRESENTATIVE IN OUR SAMPLE
WHEN WE ARE LOOKING AT
BIOMARKERS.
WE ALSO NEED CLEAR VALIDATION
AND I THINK JESSICA BROUGHT THIS
UP WE'RE ALL USING DIFFERENT
PLATFORMS TO MEASURE OUR PLASMA
BIOMARKERS WHEN WE'RE WORKING IN
INDIVIDUAL GROUPS.
WE'VE GOT TO MAKE SURE THAT'S
REPRODUCIBLE.
IT'S GOOD TO DO INDIVIDUAL WORK
BUT WE THESE MULTI-MODAL
VALIDATION ACROSS DIFFERENT
PLATFORMS TO REALLY VALIDATE
THESE BIOMARKERS BEFORE WE ROLL
THEM OUT IN CLINIC.
THE EXPOSOME I THINK HAS BEEN
DISCUSSED BY SEVERAL SPEAKERS.
WE KNOW IT'S CONTRIBUTORY BUT I
THINK WE NEED TO CONSIDER
EXPOSOME AS INTEGRATIVE AND
MULTIDIMENSIONAL AND THINK OF
THE CLINICAL UTILITY OF OUR
BIOMARKERS FOR DIAGNOSIS AND
CONSIDER HOW WE'LL GET THEM TO
FDA APPROVAL AND THEN HOW ARE WE
GOING TO INTEGRATE THEM AND
WHERE ARE WE GOING TO INTEGRATE
THEM WITHIN THE HEALTH CARE
SYSTEM.
THE OPPORTUNITIES ARE SCALABLE
ACCURATE ASSESSMENT AND
BIOMARKERS REPRESENT SUCH AN
OPPORTUNITY IN THIS AREA FOR US
TO BE SCALABLE AND ALSO
INCLUSIVE IN OUR SCIENCE AND
CARE.
AND WE NEED TO BE DOING TRUE
COMPREHENSIVE CHARACTERIZATION
OF BIOMARKERS.
SO GAP AND OPPORTUNITIES WITH
THE SCIENTIFIC ENGINE.
THE FRONT END INFRASTRUCTURE
LOW-COST DATA COLLECTION IS
IDEAL.
WE NEED DATA INGESTION AND NEED
TO BE WORK WITH THE FDA AS EARLY
AS POSSIBLE TO REALLY MOVE THESE
BIOMARKERS FORWARD TO THE
CLINIC.
ON THE BACK HAND WE NEED DATA
PREPARATION, DATA
DEIDENTIFICATION, DATA
HARMONIZATION IS KEY FOR SO MANY
OF THESE STUDIES.
DATA SHARING AND RE-USE I THINK
WE'RE ALL IN AGREEMENT.
OPEN DATA SHARING IS THE WAY
FORWARD FOR THE WHOLE FIELD.
SO WE NEED TO THINK IN THOSE
TERMS.
WE NEED TO THINK ABOUT HOW WE
CONSENT OUR PARTICIPANTS.
WE NEED TO THINK ABOUT THE
ETHICS OF THE DATA SHARING AND
CLINICAL STUDIES AND TRIALS.
I KNOW THERE'S BEEN A LOT OF
FRUSTRATION FROM THE ACADEMIC
COMMUNITY ABOUT ACCESS TO
SAMPLES FROM CLINICAL TRIALS SO
WE CAN APPLY OUR OWN SCIENTIFIC
HYPOTHESES AND MOVE THOSE FIELDS
FORWARD.
I THINK IF WE HAD SOME MORE OPEN
SCIENCE AROUND CLINICAL TRIALS
THAT WOULD MOVE THE SCIENCE MORE
RAPIDLY.
INTEROPERABILITY IS IMPORTANT.
ON THE DATA ANALYTICS SIDE AS WE
GET THESE BIG DATA SETS IT'S
GOING TO BE MULTI-DIMENSIONAL
DATA.
WE'LL HAVE A LOT OF MODELLING
AND CLEARLY THERE'S A SPACE HERE
FOR THE USE OF A.I. AND
OBVIOUSLY WE NEED TO RAMP UP OUR
DATA SCIENTIST WORKFORCE WHO CAN
SPEAK ALZHEIMER'S AND DEMENTIA.
THAT'S BEEN A CHALLENGE IS
FINDING DATA SCIENTISTS WHO CAN
HAVE ENOUGH UNDERSTANDING OF THE
SCIENCE WE'RE TRYING TO DO.
WE HAVE A LOT OF OPPORTUNITIES.
THERE'S A LOT OF NON-PROPRIETARY
TOOL AND YOU DON'T HAVE TO BUY
LICENSE AND EXPENSIVE SOFTWARE
TO DO SOME OF THIS WORK.
AND MANY PEOPLE ARE PUTTING
THEIR DATA ANALYTIC CODES OUT
ONLINE SO YOU CAN REPRODUCE
THEIR ANALYSIS ON YOUR OWN DATA
SETS.
WE NEED ACCESSIBLE AND GLOBALLY
REPRESENTATIVE DATA RESOURCES
AND I THANK THE NIH FOR TRYING
TO BUILD A LOT OF THESE
INTERNATIONAL AS WELL AS
NATIONAL REPOSITORIES.
WE NEED TO ADVANCE COMPUTATIONAL
APPROACHES AND I SEE THIS AS
BEING A RAPIDLY ACCELERATING
AREA OVER THE NEXT FEW YEARS.
WE NEED EQUAL OPPORTUNITY
SCIENCE.
SO WITH THAT AND WITH THOSE
BROAD GAPS IN OPPORTUNITIES WHEN
IT COMES TO BIOMARKERS WE'LL
OPEN THIS UP FOR A DISCUSSION
WITHIN THE PANEL BUT ALSO
OBVIOUSLY IDEALLY WE WOULD HAVE
QUESTIONS FROM THE AUDIENCE.
PLEASE COME TO THE MICROPHONES
WITH ANY QUESTIONS OR POINTS
YOU'D LIKE TO MAKE.
>> HI THERE.
SOME MIND BLOWING PRESENTATIONS
THIS MORNING.
MY QUESTION DIRECTED TO THE
ONES -- PLEASE DON'T TAKE THIS
PERSONALLY AND MIKE SNYDER AND
RHODA AU AND THE DIGITAL
BIOMARKERS.
THE CAPABILITIES AND POTENTIAL
IS AMAZING BUT WONDERING IF YOU
MIGHT BE WILLING THERE'S A
DIFFERENCE BETWEEN RESEARCH AND
CLINICAL PRACTICE.
BIG DIFFERENCE.
COULD YOU ADDRESS, PLEASE, THE
ISSUES OF THE RISKS, SAFETY AND
PRIVACY?
>> WHO WOULD LIKE TO TAKE THAT
QUESTION?
>> THANK YOU.
I THINK ABOUT PRIVACY, GET OVER
IT.
NOTHING'S REALLY PRIVATE.
YOU HAVE CAMERAS ON TRAFFIC
LIGHTS.
WE ALL HAVE CREDIT CARDS AND
THEY'RE HAVE PRIVATE INFORMATION
IS THE ANSWER BY THE WAY AND
THERE'S PRIVATE DATA OUT THERE
AND THE QUESTION IS WE'LL GET
THEM USED AND OBVIOUSLY MY
THINKING IS WE SHOULD HAVE LAWS
AND WE WANT TO PROMOTE DATA.
I THINK DATA ARE INCREDIBLY
VALUABLE.
IT'S A LOT OF WORK ACTUALLY TO
GO THROUGH ALL THESE PRIVACIES
TO RUN THE STUDIES BECAUSE
PEOPLE ARE VERY CONCERNED BUT I
CAN'T SAY I'VE NEVER SEEN ANYONE
WHO'S BEEN ABUSED BY THEIR
WEARABLE DATA.
I MAY BE WRONG ABOUT THAT BUT I
HAVEN'T SEEN IT MUCH AND THE
BENEFITS OUT WEIGH THE RISK.
I GUESS I'M SAYING I THINK THE
DATA IS SUPER VALUABLE.
SOME ARE QUITE ACCURATE.
SOME LESS SO BUT THE DELTAS ARE
USUALLY FINE WITH CHANGES.
I JUST THINK IT'S INCREDIBLY
VALUABLE THINGS TO BRING IN.
I THINK WE CAN SECURE AS MUCH AS
WE CAN AND GENOMIC DATA AND FIRE
WALLS AND ALL THIS SORT OF
STUFF.
HOPEFULLY IT WON'T BE ABUSED BUT
NOTHING IS TOTALLY UNHACKABLE.
SO I THINK AGAIN THE BENEFITS
OUTWEIGH THE RISKS.
I MYSELF AS A PERSONAL LEVEL
HAVE ABOUT TWO PETABYTES OF MY
DATA ONLINE INCLUDING ANY GENOME
SEQUENCE AND SO FAR NO ONE HAS
ABUSED ME FOR IT AND I'VE GOTTEN
INTERESTING ADVICE OUT THERE BUT
THAT'S MY TWO CENTS ON IT.
>> I ASSUME YOU HAVEN'T APPLIED
FOR LONG-TERM CARE YET?
>> NOT YET.
>> THIS IS AN EXAMPLE OF ONE OF
THE RISKS.
>> IT COULD BE, YEAH.
>> IPSIT DO YOU HAVE ANYTHING TO
ADD TO THIS DISCUSSION?
>> AS SOMEONE WHO GIVES MY
PATIENTS WEARABLES THIS IS WITH
MY CLINICIAN HAT ON,
TRANSPARENCY IS KEY AND
ENGENDERS TRUST AND IF YOU CAN
TELL SOMEONE EXACTLY WHAT YOU'RE
COLLECTING AND CAN CONTROL AND
CAN'T CONTROL AND EXPLAIN WHAT
THEY'RE GOING TO GET OUT OF IT,
I THINK PEOPLE ARE QUITE WILLING
TO SHARE THEIR DATA IF YOU CAN
CONVEY TO THEM EXACTLY HOW THIS
IS GOING TO HELP THEM.
THIS IS THE ONE-ON-ONE
DOCTOR-PATIENT LEVEL.
IT'S HARDER AT SCALE.
THE OTHER POINT IS THE QUALITY
OF DATA AND PRECISION YOU NEED
FOR CLINICAL PRACTICE IS QUITE A
LOWER STANDARD BAR THAN FOR
RESEARCH.
WE USE THE TERM DIGITAL
CO-LATERAL INFORMATION TO
CAPTURE WHAT WE DO WITH PATIENTS
WHERE YOU WANT ADDITIONAL
SOURCES OF INFORMATION.
THEY DON'T NEED TO BE PERFECT.
THE WORK OF CLINICAL PRACTICE
OFTEN COMES TO INTEGRATING
VARIOUS SOURCES OF DATA AND WHAT
THE PATIENT TELLS YOU TO GENETIC
MARKERS AND COMING UP WITH A
PLAN.
AND IN THE END WE HEARD TRUST IS
KEY.
>> RHODA ANYTHING TO ADD?
>> VALUE PROPOSITION IS WHAT
YOU'RE TALKING ABOUT.
YOU NEED TO GIVE VALUE BACK FROM
THE RESEARCH SAMPLING AND ALSO
ON THE CLINICAL STANDPOINT.
I DO THINK WE'RE GOING TO MOVE
TO A CASE WHERE OUR WEARABLE
APPLICATIONS WILL GIVE DATA.
FITBIT GIVES YOU STEPS AND SO
FORTH AND FROM A CLINICAL CARE
STANDPOINT I THINK WE'LL START
WITH THEM AS MEASURES NOT
BIOMARKERS.
I THINK THERE'S VALUE IN GETTING
THIS INFORMATION.
SHARING IT WITH YOUR CLINICAL
CARE TEAM WITH A LOWER LEVEL OF
ACCURACY DEPENDENCY AT THAT
POINT.
THAT'S WHY I DIFFERENTIATE
BETWEEN DIGITAL PHENOTYPING
MEASURES VERSUS BIOMARKERS WHICH
WILL TAKE US A KWLIEL TO GET
THERE BUT AT LEAST WE'LL BE ABLE
TO PENETRATE.
WE'RE ALREADY STARTING TO
PENETRATE WITH THE DIGITAL
DEVICES.
THE OTHER THING WE DO IS AT
LEAST IN THE RESEARCH WE'RE
DOING IS GIVING PARTICIPANTS A
CHOICE.
SO WE WILL HAVE A SET OF
DIFFERENT APPLICATIONS,
WEARABLES AND IN-HOME SENSOR AND
ALLOW THEM TO CHOOSE WHAT THEY
FEEL COMFORTABLE WITH TO GIVE
THEM THE VALUE PROPOSITION
THAT'S IMPORTANT TO THEM AND WE
MAKE SURE TO COLLECT THE RAW
DIGITAL DATA STREAMS.
IT TURNS OUT ACROSS ALL THESE
SMARTPHONE, WEARABLE, THEY'RE
ALL THE SAME SENSORS AND
COLLECTING THE SAME KIND OF DATA
JUST WITH DIFFERENT KINDS OF
DEVICES.
SO WE GET THE RAW IT'S GOING TO
BE OVERLAPPING.
SO THEY GET THEIR CHOICE IN
ORDER TO MAKE SURE IT BRINGS
VALUE TO THEM AND WE'RE GETTING
DATA.
THIS IS WHERE THE DATA
HARMONIZATION COMES IN TO
AGGREGATE AND GET TO THE SAME
MEASURES EVEN THOUGH IT'S COMING
FROM DIFFERENT SOURCES.
>> THANK YOU FOR YOUR THOUGHTFUL
RESPONSES.
LET'S KEEP THAT PART OF THE
DIALOGUE.
>> MICROPHONE TO MY RIGHT,
PLEASE.
>> YES, WONDERFUL PRESENTATIONS.
I ENJOYED IT SANDIN JONES.
I DRUTH THE CLINICAL BIOMARKERS
LABORATORY AND WHEN I STARTED IT
I REALIZED IT'S ALMOST MYTHICAL
TO CONSIDER BIOMARKERS AND
WONDERFUL TO SEE THE PROGRESS.
I'M INTERESTED IN THE
CONNECTIVITY TO MODIFIABLE
OUTCOMES.
THAT'S WHERE WE WANT TO GO.
THAT'S SOMETHING I DIDN'T HEAR A
LOT ABOUT BUT I KNOW YOU ALL
HAVE TERRIFIC IDEAS ON THAT.
HOW WE CAN USE THESE MORE
DIRECTLY TO CONNECT TO
MODIFIABLE OUTCOMES.
>> YEAH, I CAN LET OTHER
PANELISTS CHIME IN.
ROB PROBABLY HAS THOUGHTS ON
THIS TOO.
I THINK THE FLUID BIOMARKERS ARE
IMPERFECT WHEN IT COMES TO
TRACKING THE EFFICACY OF THE
APPROVED DRUGS.
EVEN THOUGH THOSE PLASMA
BIOMARKERS ARE VERY GOOD
DISTINGUISHING WHO HAS AND
DOESN'T HAVE AMYLOID AND ONCE
THEY'RE ON THE DRUG THEY DON'T
HELP US TRACK THE CLEARANCE AS
WELL AS WE WOULD LIKE.
AND SO WE'RE STILL STUCK WITH I
THINK PET LIKE ENDS AT THIS
POINT.
I THINK AS WE DEVELOP NEW
THERAPEUTICS IT'S GOING TO BE
CRITICALLY IMPORTANT THAT WE
DEVELOP IN PARALLEL TARGET
ENGAGEMENT BIOMARKERS SO THAT WE
CAN HAVE THE READ OUT THAT
YOU'RE TALKING ABOUT.
AND SO I WOULD ENCOURAGE ANYONE
WITH A DRUG DEVELOPMENT PROGRAM
TO ALSO BE THINKING ABOUT A
CLEAR TARGET ENGAGEMENT
MODIFIABLE OUTCOME BIOMARKER
THAT THEY WILL DEVELOP IN
PARALLEL WITH THE DRUG.
>> I AGREE WITH WHAT YOU'RE
SAYING DONNA DEFINITELY.
I THINK WE'RE GETTING THERE IN
TERMS OF USING PLASMA BIOMARKERS
OR CSF BIOMARKER PHARMACO
DYNAMICALLY WATCHING THEM CHANGE
AS AMYLOID CHANGE.
WE'RE STILL EARLY DAYS.
IT'S IN DEVELOPMENT.
I AGREE PERHAPS AT THE MOMENT
PET IS STILL NEEDED.
FOR EXAMPLE IN THE A4 TRIAL
WHICH WAS NEGATIVE, WE DID SEE
SOME CHANGE IN AMYLOID
ACCUMULATION THAT WAS ONLY
VISIBLE BY PET.
WHEN YOU LOOK AT P TAU, 217 IT
WAS NOT SIGNIFICANT.
I THINK AS THE ASSAYS GET
REFINED AND BETTER BUT WE'RE NOT
QUITE THERE YET.
>> ERIN.
>> FOR THE AD BIOSIGNATURE IT'S
BEEN DISCUSSED AT A HIGH LEVEL
WE COULD AS DATA SETS BECOME
AVAILABLE SO ACCESS MAY BE A
CHALLENGE BUT IF WE GET
INTERVENTION TRIAL DATA WE CAN
LOOK AT OTHER CONTEXT OF USE
INCLUDING THOSE WITH THE
MODIFIABLE OUTCOMES.
I APPRECIATE YOUR QUESTION.
THANK YOU.
>> I THINK IN THE INTEREST OF
TIME WE HAVE 12 MINUTES TO GET
TO THESE QUESTIONS.
I'M GOING TO ALTERNATE THE
MICROPHONE TO MY LEFT, PLEASE.
>> IAN KRIEGER.
REMARKABLE SESSION AND I'LL
OFFER A COMMENT BUT A PREAMBLE
IS I'M WILDLY ENTHUSIASTIC ABOUT
EVERYTHING YOU'RE DOING BUT -- I
HOPE THAT ALL OF YOU THAT WORK
IN THE BIOMARKER SPACE AND NIA
AND ITS ROLE IN LEADERSHIP WITH
PARTNERS LIKE FDA AND CMS WHILE
DIVE DEEPLY INTO THE ETHICS AND
APPLYING THIS IN REAL WORLD
SETTINGS.
THERE'S ENORMOUS POWER IN WHAT
YOU ARE OFFERING TO NOT ONLY
CLINICIANS BUT TO THEIR CURRENT
AND FUTURE PATIENTS, WHOLE HUMAN
BEINGS.
IN THE SAME WAY THIS CONFERENCE,
THIS SUMMIT IS FOCUSSED ON
PRECISION MEDICINE, WE NEED TO
WORK HARD REALLY HARD TO MAKE
SURE WE HAVE PRECISION IN THE
WAY INFORMATION IS DISCLOSED AND
THEN ACTION OF THE DISCLOSURE
DIRECTED THE RECIPIENTS OF THE
BIOMARKER IS AT LEAST AS
SIGNIFICANT IN TERMS DISEASE
PROCESSES AND THE RELEVANT
APPLICATIONS OF HOW TO TACKLE
THOSE DISEASES AND THE
MANIFESTATIONS OF SYMPTOMS.
THERE IS ENORMOUS DANGER THAT
WE'RE ALREADY LIVING WITH IN
UNLEASHING THIS KIND OF DATA
DIRECT TO CONSUMER NEVER MIND
WHEN IT'S FILTERED THROUGH
CLINICIANS THE PATIENT MAY OR
MAY NOT HAVE A DEEP MEANINGFUL
RELATIONSHIP.
AND FEW OF US ACTUALLY HAVE A
DEEP PERSONAL RELATIONSHIP.
WE HAVE THIS MASSIVE TURNOVER ON
WHICH CLINICIAN WE SEE ON WHICH
VISIT ABOUT WHICH SPECIFIC
COMPLAINT OR RISK FACTOR.
SO IF WE ARE GOING TO GO DOWN
THIS COURSE, YOU CAN'T GET THE
HORSE BACK INSIDE THE BARN.
BUT WE CAN CHOOSE WHETHER WE
PERSONALIZE IN A CULTURALLY
SENSITIVE AND RESPONSIVE WAY
WHEN PEOPLE GET THIS
INFORMATION, ARE THEY EQUIPPED
TO INTERPRET IT OR ASSISTED IN
INTERPRETING IT AND KNOWING WHAT
TO DO WITH THE INFORMATION AND
WHAT GOD HELP US AND THEM, THEY
OUGHT NOT DO WITH THE
INFORMATION.
I'LL END ON THIS.
WE ALL KNOW DISCLOSURE OF A
DIAGNOSIS OF ALZHEIMER'S CAN BE
DONE WELL OR DONE BADLY AND WHEN
IT IS DONE BADLY THE LITERATURE
IS RICH ABOUT THE ELEVATION IN
SUICIDALITY.
SO LET'S DO THIS WELL.
LET'S PLAN BEFORE ALL OF THE
HORSES ARE OUT OF ALL THE BARNS
AND MAKE SURE THAT WE'RE BEING
PERSONALIZED IN A WAY DISCLOSURE
IS DONE AND PROACTIVE IN GIVING
PEOPLE TOOLS TO UTILIZE THE
INFORMATION THAT'S DISCLOSED IN
A SCIENTIFICALLY ACCURATE AND
MEANINGFUL WAY TO IMPROVE THEIR
QUALITY OF LIFE.
>> SO, I 110% AGREE WITH
EVERYTHING YOU JUST SAID.
I WAS RELIEVED TO SEE THE QUEST
DIRECT TO CONSUMER WAS PULLED
BACK.
THERE WAS A BACKLASH.
I KNOW SOMEONE ELSE IS PUTTING
OUT DIRECT TO CONSUMER WHICH IS
WORRYING.
I THINK THIS IS A MOVING FIELD
AND A MOVING TARGET AND SO RIGHT
NOW I DON'T KNOW THAT THERE'S A
NEED TO DO PLASMA BIOMARKERS
CLINICALLY UNLESS SOMEONE HAS A
COGNITIVE COMPLAINT BECAUSE THEN
THEY CAN POTENTIALLY BE
CANDIDATES FOR THE NEW DRUGS.
I THINK AS THE HEAD TRIAL READS
OUT IN A COUPLE YEARS WHERE
WE'RE LOOKING AT WHETHER
TREATMENT'S EFFECTIVE THAT WILL
CHANGE THE LANDSCAPE OF HOW WE
DO BIOMARKERS CLINICALLY IF
PRE-CLINICAL A.D. TREATMENT IS
NOW APPROVED.
SO I THINK WE HAVE -- I THINK WE
ALL APPRECIATE YOUR POINT ABOUT
HOW ETHICALLY AND RESPONSIBLY WE
HAVE TO MANAGE THE DATA AND WHAT
WE SHARE WITH THE PATIENTS BUT I
WILL SAY A LOT OF OUR RESEARCH
PARTICIPANTS WANT THIS
INFORMATION BACK.
I THINK IT'S JUST A CASE OF HOW
WE GIVE IT BACK TO THEM AND THE
KIND OF COUNSELLING THEY ARE GET
AHEAD OF HEARING THOSE RESULTS.
>> I TOO AGREE.
HAVING SAID THAT THERE ARE
FRAMEWORKS ALREADY IN PLACE.
WE SEE PATIENTS IN THE PRIMARY
CARE SETTING.
WE TELL THEM THEY HAVE PROSTATE
CANCER.
WE MEASURE THEIR LIPIDS AND LOOK
AT THEIR EKG AND TELL THEM
YOU'RE AT RISK OF STROKE, A
HEART ATTACK.
WE DELIVER THESE THINGS AND DONE
IN A FRAMEWORK.
WE CAN BORROW FROM THE SAME
FRAME WORK BUT WE NEED TO ALSO
BE COGNIZANT OF THE FACT THE
BIOMARKERS CANNOT BE JUST THE
PROPERTY OF THE SUB, SUB, SUB
SPECIALIST.
IT UP TO PRIMARY CARE
PHYSICIANS BECAUSE WE'RE DEALING
WITH AN EPIDEMIC AND DEALING
WITH POTENTIALLY DANGEROUS
INFORMATION WHICH IT COULD BE WE
CAN BORROW FROM THE EXISTING
FRAMEWORKS.
WE NEED TO BE COGNIZANT OF THE
FACT THAT IT CANNOT JUST BE THE
SUB SPECIALIST AND TERTIARY CARE
CENTERS.
WE NEED TO TRAIN PHYSICIANS
APPROPRIATELY AND TRAIN MORE
NEUROLOGISTS, MORE BEHAVIORAL
NEUROLOGISTS, MORE NEURAL
PATHOLOGISTS WHO ARE WELL VERSED
IN THE SCIENCE AND NEED TO TRAIN
MORE SCIENTISTS WELL VERSED IN
THE REAL LIFE APPLICATIONS.
>> I JUST WANT TO ADD QUICKLY IN
THE REALM OF DIGITAL IT'S
ALREADY OUT THERE.
I TOLD YOU IT'S $35 BILLION AND
GLOBAL.
THERE AREN'T RESOURCES AVAILABLE
AND I THINK WE ALSO NEED TO
THINK ABOUT HOW WE TURN THIS
AROUND INTO SORT OF THINKING
ABOUT THE CITIZEN SCIENTISTS.
GENETICS ALREADY DID THAT WITH
THE COMMERCIALIZATION.
WE NEED TO DO A BETTER JOB OF
PUSHING THIS OUT THERE IN THE
GREATER CONTEXT IN MY CASE I
LIKE TO THINK ABOUT PRECISION
BRAIN HEALTH SO YOU'RE THINKING
ABOUT YOUR HEALTH ACROSS YOUR
ENTIRE LIFE SPAN.
WE THINK OF THIS AS LIFE COURSE
ANYWAYS.
SO YOU'RE LEARNING HOW TO USE
THESE DIFFERENT DEVICES YOU
ALREADY ARE FEEDING BACK
INFORMATION AND EDUCATING.
SO THIS IS SORT OF A PUBLIC
AWARENESS, PUBLIC EDUCATION
MOVEMENT THAT NEEDS TO GO.
I DO THINK WE HAVE SOME OF THESE
DIRECT TO CONSUMER PRODUCTS TO
LEARN LESSONS FROM THAT.
I WANT TO MAKE SURE WE
DIFFERENTIATE BETWEEN WHAT CAN
BE DRIVEN THROUGH OUR HEALTH
CARE VERSUS WHAT'S HAPPENING
ALREADY.
>> THANK YOU.
IN THE INTEREST OF TIME WE ARE
GOING TO DO QUICK QUESTIONS,
QUICK ANSWERS.
SO GO AHEAD.
>> DR. RISSMAN AS WE EMBARKED IN
THE PAST DECADE IMPROVING
SAMPLES AND BLOOD BIOMARKERS.
YOU HEARD ABOUT METABOLOMICS AND
THE FANTASTIC POWER THAT IT CAN
INFORM AND WE ARE ADDING OUR
PARTNERS WITH THE PROTEOME.
I HOPE WE CAN TAKE THE LESSONS
FROM THE ADNI AND LINKAGES TO
THE MARKERS AND BE ABLE TO APPLY
TO THE FANTASTIC DIVERSE COHORT
YOU ARE WORKING ON WITH THE
FANTASTIC TEAM.
HOW CAN WE BRIDGE THIS KNOWLEDGE
SO WE CAN QUICKLY MOVE AND
DEFINE WHAT IS DIFFERENT IN
DIVERSE POPULATIONS.
>> THANKS, REMA.
>> IT'S A GOOD QUESTION.
THE KEY HERE IS THROUGH DATA
SHARING AND ALL THE AND THERE'S
FREE SHARING SOON IT'S
GENERATED.
SO ALL THE THINGS CAN BE
COMPARED TO DATA SETS SUCH AS
ADNI OR EVEN OTHER CLINICAL
TRIAL DATA SETS LIKE THE A4 JUST
RELEASED OR HEAD SCREENING
SAMPLE.
>> WORKING ON HARMONIZATION OF
THE METABOLOMICS AND SURE OUR
PARTNERS WITH PROTEOMICS IF
WE'RE ABLE TO DO THIS WE CAN
COMPARE AND CONNECT THE DATA
SETS.
>> I AGREE.
>> SOUNDS GREAT.
PLEASE GO AHEAD.
>> HI.
IT'S A QUESTION FOR LEE.
I LIKE THE APPROACH OF USING
OCULAR IMAGING TO DIAGNOSE.
I THINK IT'S FANTASTIC.
MORE PEOPLE GO REGULARLY THROUGH
THEIR LIFE TIME TO HAVE THESE
TESTS.
I WANTED TO KNOW GIVEN THAT AN
AMYLOID IS ASSOCIATED WITH AMD
THAT RPE CELLS EXPRESS ALPHA B
CYST TALIN.
IS THERE AN ASSOCIATION WITH AND
IN THE PATIENTS AND NUMBER 2,
GIVEN THERE'S CLEAR GENETIC
ANCESTRY ASSOCIATION WITH AMD
INCIDENTS, ARE YOU SEEING THAT
IN YOUR STUDIES?
HAVE YOU DONE A DIVERSE
POPULATION STUDY?
>> YES.
THE SITUATION IN THE RETINA IS A
BIT MORE COMPLEX.
ACTUALLY DR. RISSMAN AND OTHERS
HAVE DONE WORK IN THAT AS WELL.
IT'S A LITTLE BIT MORE COMPLEX.
AND IT'S NOT AT ALL AS CLEAR AS
IT IS IN THE LENS, NO PUN
INTENDED THERE WHERE IT'S VERY
STRAIGHTFORWARD.
THERE'S AD ASSOCIATED AMYLOID
DEVELOPMENT IN THE LENS WE
WORKED OUT IN MOLECULAR
PHENOTYPE AND WE'VE SEEN IT IN
DOWN SYNDROME AND TRANSGENIC
MICE AND IT'S AN A DIRECT AND
EARLY MARKER.
IT'S NOT INFLUENCED BY OTHER
COMPLICATIONS IN THE RETINA, FOR
EXAMPLE.
I THINK THERE'S STILL WORK TO BE
DONE AND OTHER COMPARTMENTS
INCLUDE THE AQUEOUS AND
COLLEAGUES HAVE SHOWN A BETA IN
BOTH.
I THINK IT'S AN OPTICALLY
ACCESSIBLE COMPARTMENT TO LOOK
AT THE KINETICS AND DYNAMICS OF
THE FRONT OF OF THE EYE THAT MAY
GIVE US SOME TOOLS NOT ONLY FOR
DOING DISCRIMINATION FOR STUDIES
BUT ALSO LOOKING AT DYNAMICS
WHERE WE DON'T HAVE TO DO LPs
AND SUCH.
I THINK THERE'S WORK TO DO.
ROBERT I THINK YOU AGREE WITH
THAT.
>> OKAY MAYBE YOU CAN DISCUSS
OFFLINE DURING THE BREAK.
THESE ARE GOING TO BE THE LAST
TWO QUESTIONS SO WE'LL GET TO
BOTH OF YOU, I HOPE IF THEY'RE
QUICK QUESTIONS AND ANSWERS.
ON MY RIGHT, PLEASE.
>> THANKS, DONNA.
I WAS ENCOURAGED BY YOUR
STATEMENT ABOUT THE AVAILABILITY
OF DATA KNOW THAT PEOPLE CAN GO
AND LOOK FOR REPRODUCIBILITY AND
FIND THEIR SIGNAL AND SEE
WHETHER IT VALIDATES.
WITH MY PHILANTHROPY FUNDER HAT
ON IT'S AN IMPORTANT PART OF
CONFIRMING THE CONFIDENCE IN THE
SCIENCE AND RESEARCH THAT WE DO.
ON THE OTHER HAND IF I PUT MY
RESEARCHER HAT ON, IT'S SO HARD
TO FIND THE TIME TO ANALYZE YOUR
OWN DATA, GOSH, WHERE DO YOU
FIND THAT TIME TO VALIDATE AND
TAKE ADVANTAGE OF THE WEALTH OF
DATA OUT THERE AND IF YOU THINK
OF WHAT JOURNALS AND FUNDERS DID
AND SUZANNA LOOKING AT YOU AS
WELL FROM A POLICY POINT OF VIEW
OR CULTURE POINT OF VIEW THERE
WAS A TIME WHEN SHARING WASN'T
MANDATED BUT THEN IT BECAME THE
NORM.
PEOPLE HAD TO DO IT AND FIGURE
OUT A WAY TO DO IT TO GET THEIR
GRANT AND THEIR PAPER AND THEN
SIMILARLY TO DATA BEHIND THE
FIGURE AND YOU WERE SAYING THE
NICE PAPER YOU JUST HAD COMING
OUT WITH THE TAU PET AND GWAS
REQUIRES THE UNDERLYING DATA AND
NOBODY WAS DOING THAT IN
GRADUATE SCHOOL AND TRAINING.
I'M WONDERING IS THERE A NEED
FOR A PUSH HERE WHETHER IT'S
FROM THE JOURNALS AND/OR THE
FUNDERS TO SAY YOU NEED TO
ACTUALLY GO AND LOOK AT THE DATA
THAT'S OUT THERE AND VALIDATE
WHAT YOU FOUND IN AT LEAST TWO
DIFFERENT DATA SETS BECAUSE
GOSH, AS A WES LAB BIO CHEMIST
WITHOUT A PUSH I PROBABLY WON'T
DO THAT COMPUTATIONAL WORK
BECAUSE IT'S NOT WHAT I'M GOOD
AT.
>> I THINK IT'S JOURNAL TO
JOURNAL BUT AS EDITOR-IN-CHIEF
ON ALZHEIMER'S AND DEMENTIA WHEN
WE GET BIOMEDICAL SUBMISSIONS WE
REQUIRE A VALIDATION COHORT IN
ANY OF THE FLUID BIOMARKER WORK.
SO I KNOW IT'S GOING TO VARY
JOURNAL TO JOURNAL BUT GENERALLY
WE LOOK FOR THAT AS A ROBUSTNESS
OF THE SCIENCE.
>> YEAH, I WOULD JUST SAY
THERE'S CHALLENGES ON THE
DIGITAL FRONT BECAUSE MANY OF
THE PLATFORM CAN'T ACCEPT THE
DIGITAL DATA STREAM TO CONNECT
WITH THE CLINICAL DATA.
ONE, WE HAVE TO SOLVE THAT AND
FIGURE OUT THE INTEROPERABILITY
BETWEEN PLATFORMS TO BRING IT
BECAUSE WE DON'T HAVE AS MUCH AS
DATA YET ON THE DIGITAL FRONT.
SO WE'RE SORT OF A LITTLE BIT
FURTHER BEHIND IN TERMS OF BEING
ABLE TO PUSH THIS FORWARD.
>> THANKS, RHODA.
I THINK WE CAN DISCUSS THIS ALL
DAY BUT I ACTUALLY THINK A.I.
MAY HAVE A PLACE IN HELPING US
DO THESE RAPID VALIDATION AND
EXISTING DATA SETS AND TAKE AWAY
SOME BURDEN ON THE INDIVIDUAL
SCIENTISTS BUT THAT MAY BE IN
THE FUTURE.
>> SO WE ACTUALLY HAVE TWO
QUESTIONS FROM ONLINE
PARTICIPANTS AND I'M HAPPY TO
LEAVE THEM AS FOOD FOR THOUGHT
IF THERE ISN'T TIME TO ADDRESS
BOTH.
ONE QUESTION IS HOW LONG CAN A
SAMPLE BE STORED AT MINUS 80
DEGREES CELSIUS FOR THE
ASSESSMENT AND THE OTHER
QUESTION IS SEVERAL OF THE
PRESENTATIONS FOCUSSED
SPECIFICALLY ON AD OR VASCULAR.
HOW DO WE LEVERAGE THIS EXCITING
WORK IN THINKING ABOUT THE
REALITY WHICH IS PRESENTED AT
THE BEGINNING FROM PATRICIA
BOYLE'S WORK SHOWING MOST OLDER
ADULTS AT AUTOPSY HAVE MULTIPLE
PATHOLOGIES AND IN DIFFERENT
COMBINATIONS?
>> I'LL SPEAK TO THE SECOND
QUESTION REAL QUICK BECAUSE I
ORIGINALLY THOUGHT I HAD MORE
THAN FIVE MINUTES SO THE SLIDES
I WENT WERE COVERING BIOMARKERS.
I THINK THERE'S INCREDIBLE
PROGRESS BEING MADE ON
IDENTIFICATION OF BIOMARKERS FOR
TDP43.
WE DO HAVE THE ALPHASIN IT'S A
YES OR NO ANSWER.
IT'S NOT QUANTIFIABLE AND
DOESN'T GIVE REGIONAL
INFORMATION BUT AT LEAST
PROGRESS.
THERE'S NOVEL APPROACHES FOR
TDP43 ONE OF WHICH IS LOOKING AT
CRYPTIC PEPTIDES PRODUCED
BECAUSE THE TDP IS NOW
DYSFUNCTIONAL IN THE BRAIN.
YOU GET PEPTIDE CAN BE MEASURED
IN CSF AND PLASMA.
THAT'S AN INTERESTING BIOMARKER
APPROACH.
THERE'S GOING TO BE MANY OTHERS.
I WOULD SAY THERE'S INCREDIBLE
PROGRESS BEING MADE ON THESE AND
IF WE'RE GOING TO GET TO A
PRECISION MEDICINE PLACE WE'RE
GOING TO NEED BIOMARKERS FOR ALL
OF THESE DIFFERENT PATHOLOGIES
SO THAT WE CAN CONSIDER WHAT THE
RELATIVE CONTRIBUTION OF EACH OF
THOSE ARE TO THE OVER ALL
COGNITIVE CLINICAL PRESENTATION
OF THE PATIENTS.
>> SOMETHING ABOUT THE SECOND
QUESTION IT'S MORE COMPLICATED
THAN THAT BECAUSE IF YOU LOOK AT
THE DIFFERENT BRAIN REGIONS
YOU'LL SEE HETEROGENEITY IN THE
SAME PERSON ABOUT THE AMOUNT AND
TYPE OF PATHOLOGIES.
THOUGH IT CONTINUES TO BE THE
DEFINITIVE DIAGNOSES FOR THE
DISORDERS MAYBE THERE'S A SECOND
LAYER BECAUSE THE SECOND
PATHOLOGY COULD BE ARRIVED UPON
BY DIFFERENT MOLECULAR PATHWAYS.
UNDER CLEAR AD WE'LL LOOK AT
COHORTS IN WHICH WE HAVE BOTH
AUTOPSY MATERIAL AND
ANTI-MORTEM, LONGITUDINALLY
COLLECTED PERIPHERAL BLOOD AND
WE'LL BE ABLE TO CONNECT THE
MOLECULAR PATHWAYS WHICH IS
GOING TO BE ESSENTIAL AND FOR
THE DONORS IN SEVEN BRAIN
REGIONS.
COMPARISON FROM DONOR TO DONOR
AND FROM EACH WITH A DIFFERENT
REGION.
AS TO THE MINUS 80 QUESTION IT
DEPENDS ON WHAT YOU'RE
MEASURING, HOW YOU'RE MEASURING
AND ALL OF THAT.
I THINK SOMETHING THAT WE NEED
TO BE THINKING VERY CAREFULLY
ABOUT WAS WHAT MATHIAS MENTIONED
IT COMES BEFORE THE INNOVATIVE
QUESTIONS OF THE DATA AND HOW DO
WE GET AND STORE THE SAMPLES.
WE NEED TO PAY CAREFUL ATTENTION
TO THE STANDARD OPERATING
PROCEDURES.
THEY MAY NOT BE GLORIOUS BUT
THEY'RE ESSENTIAL FOR US TO BE
ABLE TO GET USABLE DATA.
WE NEED TO MAKE THESE BROADLY
AVAILABLE.
WE NEED TO MAKE AVAILABLE OUR
METADATA OF HOW WE COLLECTED THE
SAMPLES AND HOW WE PROCESS THEM
AND THEN HOW WE ANALYZE THEM.
WE NEED TO CAREFULLY THINK ABOUT
THE VARIABLES THAT CONTRIBUTE TO
THE VARIABILITY OF THE SIGNAL
WE'RE GETTING, TAKE THAT INTO
ACCOUNT BEFORE WE DO ALL SORTS
OF COMPARISONS.
NOT A DEFINITIVE ANSWER OF DON'T
USE ANYTHING BEYOND THIS MANY
YEARS BECAUSE IT'S VARIABLE AND
YOU NEED TO DETECT THE EXTENT OF
VARIABILITY.
>> I'M GOING TO GIVE ERIN 10
SECONDS AND RHODA 10 SECONDS AND
THEN WE'RE WRAPPING UP SO WE GET
A BREAK.
>> I COMPLETELY AGREE.
I ENCOURAGE THE PERSON ASKING TO
REACH OUT TO THE ASSAY PLATFORM
PROVIDER.
THEY SHOULD HAVE THAT DATA
AVAILABLE.
IT'S PART OF THE ANALYTICAL V
VALIDA
VALIDATION.
>> ON THE DIGITAL FRONT, DIGITAL
IS THE NEW BLOOD.
YOU'LL BE ABLE TO TAKE THE
DIGITAL DATA AND BE ABLE TO
RE-ANALYZE IT MANY DIFFERENT
WAYS IN ORDER TO DEVELOP THESE
BIOMARKERS OF INTEREST.
>> OKAY.
WITH THAT WE'LL CLOSE THE
SESSION AND RECONVENE AT 11:00.
IS THAT RIGHT?
SO 11:00.
THANK YOU SO MUCH.
>> WE'VE SEEN BRILLIANT
ENGINEERING TO REMOVE AND
CONNECT PARTS AND IN THIS
SESSION I HOPE WE CAN BRING THE
POWER OF THIS BIG DATA AND THE
DEVELOPMENTS THAT CAME OUT OF
OPEN SCIENCE TO EVEN ACCELERATE
DUE TO OPEN SCIENCE WE'VE SEEN
REPOSITORIES OF BIG DATA
GENERATED WITH SIGNIFICANT
FUNDING, OMICS DATA I COPY FROM
THE SLIDE AND WE ARE GOING TO
TALK ABOUT WHAT WE LEARNED AND
HOW DID WE SHARE AND WHAT ARE
LIMITATIONS WE ENCOUNTERED AND
WHAT CAN BE DONE BETTER.
WE'LL HEAR FROM A SERIES OF
SPEAKERS ON THE ADVANTAGES AND
LIMITATIONS THAT REMAIN FROM THE
INITIAL SERIES OF REPOSITORIES
THAT HAVE BEEN PUT TOGETHER THAT
ENABLE SHARING OF BIG DATA AND
CERTAINLY RESULTED IN MAJOR NEW
INSIGHTS.
AS WE LOOK FORWARD WE ALREADY
HEARD FROM THE SESSION
PROCEEDING THIS AND THROUGHOUT
THE PAST TWO DAYS THE DATA THAT
WE ENVISION THAT IS GOING TO
COME NEXT IS A WHOLE AREA OF
DATA FROM CHEMICAL EXPOSURES,
DATABASES ON PHOTOMICS AND
THINGS WE INGEST AND THINGS WE
TAKE AND ASSOCO -- SOCIO
ECONOMIC AND SLEEP PATTERNS AN
MOVE FROM STATIC DATA THAT IS
MORE DYNAMIC AND TRULY
REPRESENTATIVE ON OUR METABOLIC
HEALTH AND I'M A BIG ADVOCATE
FOR METABOLOMICS BECAUSE WE LEAD
A METABOLOMICS CONSORTIUM AND
IT'S DYNAMIC AND CAPTURES
INFLUENCES ON HEALTH IN REAL
TIME.
THE ELECTRONIC MEDICAL RECORDS,
THE DIGITAL RECORDINGS AND POWER
OF CONNECTING OUR SENSORS WHEN
OF US HAVE INCLUDING MYSELF.
I MONITOR A LOT OF THINGS ABOUT
MY HEALTH, CONNECTING ALL THIS
WITH MY METABOLOMIC PROFILE
TAUGHT ME PERSONALLY HOW TO LIVE
AND EAT BETTER.
I HOPE THIS WILL OVERCOME MY
GENETIC SUSCEPTIBILITIES.
WE'LL SEE A WHOLE AREA OF NEW
DATA COMING IN.
DRUGS RESPONSE AND VARIATIONS OF
RESPONSE, CLINICAL TRIALS THAT
FAILED OR SUCCEEDED AND DRUGS ON
THE MARKET, WHO IS ON IT?
HOW ARE THEY DOING?
WE'LL HEAR ABOUT THIS AS PART OF
THE FUTURE AND MOVING FORWARD
AND THINKING GLOBALLY IT'S
CRITICAL NO MATTER HOW BIG DATA
WE PRODUCE THE POWER OF
CONNECTING ALL OF US AND OUR
DATA SETS IS POWERFUL.
AS WE LOOK FORWARD, PART OF THE
THINGS WE WANT TO DISCUSSION IN
THE SESSION ARE WE READY TO
THINK ABOUT DATA THAT DOESN'T
MOVE?
DATA THAT IS STATIONARY AND
WHERE WE CAN VISIT THE DATA, DO
WHAT WE NEED TO DO IN THE CLOUD
AND ALL OF OUR COMPUTATIONS.
IS THIS THE RIGHT THING TO DO
MOVING FORWARD.
OUR EXPERTS WILL TACKLE THIS AND
WE HAVE TO ADOPT WHAT WAS
INITIALLY PIONEERED AND
INNOVATED BY THE DUTCH.
WE WORKED CLOSELY WITH THE DUTCH
ON TE THE DATA AND THE CONCEPT
OF THE DIGITAL TWINNING TO
PARTICIPATE AND SHARE THE DATA
THEY WANT AND THE ISSUE OF
EMPOWERING INDIVIDUALS.
AND WE INTO HE HAD TO GIVE MORE
POWER TO THE INDIVIDUALS IN
CONTROLLING THEIR DATA WITHOUT
DISRUPTING ANALYSES WE WANT TO
DO.
THE CLOUD COMPUTING AND
RESOURCES NEEDED.
WHO IS LIKE ME WAS AN ISSUE
BROUGHT UP BY THE ADVOCACY
GROUPS.
WE BELIEVE IN IT.
WE WORK ON IT.
WE WANT TO BE ABLE TO CONNECT,
INFORM THE PATIENTS THROUGH THIS
BIG DATA AND WHO MIGHT RESPOND
LIKE THEM IS KEY.
INTEROPERABILITY BETWEEN THE
MEGA PLATFORMS ARE IMPORTANT.
SUSTAINABILITY OF THE RESOURCES
AND WHAT IT TAKES TO SUSTAIN
THEM IS A TOPIC OF DISCUSSION.
ENFORCING STANDARDS DOESN'T
WORK.
WE CANNOT FORCE SPEAKERS TO
FOLLOW STANDARDS.
THE NEXT BEST THING IS TO COME
UP WITH DATA HARMONIZATION
APPROACHES FOR ALL THE DATA WE
GENERATE INCLUDING OUR
METABOLOMICS AND OTHER OMICS IS
SOMETHING WE ARE WORKING ON SO
THIS TOPIC IS KEY THE DYNAMIC
DATA WE TALKED ABOUT IT GLOBAL
AND MOVING BOUNDARIES SO WE CAN
ACCELERATE AND REAL LIFE DATA OF
COURSE IS CENTRAL BUT MOVING
FORWARD WHAT I HAVE SEEN IN THE
SUMMIT AND WHAT I HAVE SEEN AS
BRILLIANT ENGINEERING THROUGH
THE PAST DECADE BY WORK WITH NIA
AND BEING FUNDED THROUGH LARGE
INITIATIVES WE ARE MOVING
BOUNDARIES.
ALZHEIMER'S ALL OF A SUDDEN IS
DEPRESSION AND PARKINSON'S AND
THE MORE WE LOOK AT BIG DATA
MORE COMMON AND HAVING INSTITUTE
SUPPORT THIS OR NOT IS PERHAPS
NOT OPTIMAL.
THERE'S A LOT OF COMMON AND
LEARN FROM THE EXPERIENCES,
CONNECT DATA AND RESEARCH
COMMUNITIES, WORK AS
COMMUNITIES.
IT'S A NEW PARADIGM OF DOING
RESEARCH THAT HAS TRANSFORMED
AND WE'RE THOUGHT GOING TO GO
BACK.
I THINK IT ALREADY WE HAVE MOVED
FORWARD AND IT'S NO WAY BACK
INDEED.
CONNECTING GLOBALLY AND THEN
FROM DATA TO KNOWLEDGE.
WE GATHER BIG DATA AT THE END OF
THE DAY.
IF WE CANNOT TRANSLATE THIS TO ,
INFORM EACH INDIVIDUAL ABOUT
THEIR HEALTH, THEIR TRAJECTORY
FOR DISEASE WE HAVEN'T REALLY
DONE WHAT WE'RE SUPPOSED TO DO.
AND HOW WE MOVE FROM BIG DATA TO
KNOWLEDGE.
WITH THIS I'M GOING TO MOVE ON
TO THE FIRST SPEAKER, DR. METTE
PETERS FROM HIRN AND PRIOR WAS
AT SABLING AND ENABLED ALL OF US
THROUGH MANY YEARS.
>> WE HAVE DATA ENABLEMENT WHEN
IT COMES TO INFRASTRUCTURE AND
INTRAOPERABILITY AND HOW TO
IMPROVE THE USE OF DATA ACROSS
ALL THESE DATA RESOURCES.
NOW, THE NIA IS SUPPORTING A
WHOLE VARIETY OF DIFFERENT
RESEARCH DATA THAT IS BROADLY
AVAILABLE TO THE COMMUNITY.
THIS IS CLEARLY NOT LIMITED TO
WHAT I HAVE ON THE SLIDE AS YOU
HEARD OVER THE PAST COUPLE OF
DAYS.
THERE'S MANY MANY OTHER DATA
RESOURCES OUT THERE.
THIS VARES FROM MOUSE AND ANIMAL
MODELS.
IT'S ABOUT THE AVAILABILITY OF
IN TISSUE RESOURCES AND CELL
LINES AND CELL TYPE SUCH AS
IPSCs.
IT'S DATA FROM LARGE STUDIES AN
SUPPORTING THE MANAGEMENT AND
DISTRIBUTION OF THAT DATA.
THERE'S A WHOLE VARIETY OF TOOLS
OF DATA PROCESSING AND ANALYSIS
TOOLS AND DATA VISUALIZATION OR
QUERY TOOLS THAT AGAIN ARE
AVAILABLE TO THE RESEARCH
COMMUNITY.
WHAT WE'VE HEARD OVER THE PAST
COUPLE DAYS IS THE IMPORTANCE OF
THE DATA RESOURCES BEING FAIR.
SO IS THE DATA AVAILABLE IS IT
FINDABLE BY HUMANS AND COMPUTERS
AND MACHINES?
ONCE YOU FIND THE DATA, IS IT
ACCESSIBLE?
IS THERE A STANDARDIZED WAY THAT
A USER HAS AUTHORIZATION?
IS THE DATA INTEROPERABLE.
CAN YOU INTEROPERATE THAT DATA
WITH SAY OTHER STUDIES OR ACROSS
DATA MODALITIES.
CAN YOU OPERATE THAT DATA WITH
TOOLS THAT IS NECESSARY FOR THE
ANALYSIS?
IS THE DATA FORMAT MACHINE
READABLE FOR EXAMPLE?
AND CAN YOU REUSE THAT DATA?
DOES IT HAVE THE NECESSARY STUDY
METHODS, DESCRIPTION METADATA,
QC INFORMATION, THE BATCH
VARIABLES YOU'LL NEED IN ORDER
TO REALLY TAKE ADVANTAGE OF THAT
DATA?
AND THOSE HAVE BEEN VIEWED FROM
TWO DIFFERENT VIEWS.
ONE IS FAIRNESS WITHIN DATA
RESOURCES AND FAIRNESS BETWEEN
THE DATA RESOURCES.
AND I WOULD ARGUE THAT NIA
SUPPORTED DATA RESOURCES MORE OR
LESS MEET THE FAIR PRINCIPLES
WITHIN BUT THE FAIRNESS BETWEEN
IS A MUCH MORE COMPLICATED
QUESTION.
AND THERE IS WORK BEING DONE IN
THAT AREA THAT WE ARE MOVING
TOWARDS THE ECO SYSTEM AND I
WANT TO MENTION A COUPLE
EXAMPLES.
ONE IS THE NATIONAL ALZHEIMER'S
DATA CENTER AND SHARING PLATFORM
ORIGINATING AND INTEGRATING DATA
FROM IMAGING DATA FROM
GENOTYPING DATA AND OTHER OMICS
DATA AND LINKED TO THE SAME
IDENTIFIER AND MAKE THE DATA
AVAILABLE FOR RESEARCH USE.
TO HAVE THE ABILITY TO LINK DATA
ACROSS RESOURCES.
SARAH BIBER WILL TALK MORE ABOUT
THAT IN A BIT.
THERE'S ALSO EXAMPLES OF LINKING
DATA FROM RELATED STUDIES.
THERE'S EFFORTS LINKING DATA
FROM THE SAME INDIVIDUALS FROM
AD KNOWLEDGE PORTAL.
AND DATA IN LONI THAT IS INDEXED
AND DISCOVERABLE THROUGH THE AD
KNOWLEDGE PORTAL AND MULTIPLE
PORTALS HAVE OR IN THE PROCESS
OF ENABLING THE ACCESS WITH DATA
FROM THE PORTALS INTO CLOUD WORK
SPACES.
AND ENABLE ACCESS TO OTHER DATA
RESOURCES NOT LIMITED TO AD/A
DRD DATA.
AND WE HAVE ADDRESSED IF HE
QUESTIONS OF FAIRNESS AND CRASS
THE DATA INFRASTRUCTURES.
THAT QUESTION OF
INTEROPERABILITY AND HERE'S
COMMUNITY INPUT WE GOT THROUGH
THE WORKSHOP.
ONE IT'S IMPORTANT TO BUILD ON
EFFORTS.
THE QUESTION OF FINDABILITY.
DOESN'T MATTER WHAT DATA
RESOURCES ARE OUT THERE IF YOU
CAN'T FIND THEM.
AND THAT CAME UP VERY
FREQUENTLY.
IT'S IMPORTANT TO THINK ABOUT
BUILDING CENTRALIZED DATA
DISCOVERY AND SEARCH.
WE HAD AN IN DEPTH DISCUSSION
OF A.I. AND ENHANCING FOR DATA
LINKAGES THINKING THE WHOLE LIFE
SPAN EXPOSOME AND DIGITAL HEALTH
TECHNOLOGIES.
THE LINKING TO IMAGING AND OMICS
DATA.
WE NEED A WAY OF PRESERVING THE
PRIVACY OF THAT DATA BUT ALSO
ENABLE THAT ABILITY TO LINK THE
DATA TOGETHER.
AND EDUCATION ON TRAINING
RESOURCES WHEN IT COMES TO CLOUD
COMPUTE AND TO MAKE THE MODEL
SYSTEM DATA TO MAKE THEM BETTER
KNOWN AND ACCESSIBLE AND
INTEROPERABLE AND LAST BUT NOT
LEAST THE IMPORTANCE OF
FOSTERING DIVERSITY, EQUITY,
INCLUSIVITY AND ACCESSIBILITY
BOTH IN REPRESENTATION OF THE
COMMUNITIES THE DATA REPRESENT
AND THE USERS OF THE DATA AND
ALSO BEYOND CARE.
DON'T FORGET THE COLLECTIVE
BENEFITS OF THE DATA AND THE
AUTHORITY TO CONTROL THE
RESPONSIBILITY AND THE AFFECTS.
NOW, IF WE ARE GOING TO MANAGE
THIS WE DO NEED STANDARDS.
SO LOOKING AT THE STANDARDS AN
PEOPLE TO ADOPT SOME STANDARDS.
THE NIA DATA RESOURCES ARE
DISTRIBUTED ACROSS A VARIETY OF
REPOSITORIES AND THERE'S DATA
BEYOND THE ECO SYSTEM.
SO WE NEED THE ABILITY TO LINK.
WE NEED STANDARDS THAT CAN LINK
THIS DATA.
AND THERE ARE MULTIPLE
INITIATIVES DEVELOPING THE
STANDARDS AND GENOMICS AND
HEALTH THE POLICY ORGANIZATION
AND THE NIH CLOUD PLATFORM
INTEROPERABILITY PROGRAM AND
NCBI SORT OF IMPLEMENTING OTHER
STANDARDS IN CREATING A
FEDERATED SYSTEM AND STANDARDS
THE HL7 FIRE STANDARD
FACILITATES THE EXCHANGE OF
HEALTH CARE INFORMATION.
NOW, I'LL TALK ABOUT A SPECIFIC
EXAMPLE OF DATA INTEGRATION IN
APPLICATION OF STANDARDS.
THAT IS BASED ON THE
ACCELERATING MEDICINE
INITIATIVE.
IT'S GENERATED UNPRECEDENTED
AMOUNTS OF DATA FROM
ALZHEIMER'S, PARKINSON'S AND
SCHIZOPHRENIA AND OTHER
DISEASES.
THIS PROVIDES AN OPPORTUNITY TO
TAKE ADVANTAGE OF THE DATA TO
LOOK AT COMMONALITIES ACROSS
THESE DISEASES AND ALSO
DIFFERENCES ACROSS THE DISEASES
BY TAKING A LARGE SCALE NETWORK
ANALYSIS APPROACH.
TO DO THIS THOUGH WELL FIRST OF
ALL THIS HAS LED TO WHAT IS
CALLED THE BIOLOGY OF
INFLAMMATION WHICH IS A CONCEPT
PROPOSED TO LEVERAGE DATA FROM
EXISTING PROGRAMS AND BIOLOGY
AND ANALYSIS AND INCREASE THE
INTEROPERABILITY OF DATA AND
BEING ABLE TO IDENTIFY OR BUILD
THE PROTECTIVE MODEL OF
INFLAMMATION COMMON AND SPECIFIC
TO DISEASES IN IDENTIFY
INFLAMMATORY AND IMMUNE
SIGNATURES -- THE NIH TO ADDRESS
CHALLENGES HAS INVESTED UP A
PROTOTYPE OF INFRASTRUCTURE.
THIS IS FUNDING OVER THREE YEARS
THROUGH THE COMMON FUND VENTURE
PROGRAM WHICH WILL FUND A
PLATFORM THAT WILL CREATE A
CENTRALIZED SYSTEM ARCHITECTURE
FOR FEDERATED DATA SHARING AND
START DEVELOPING A DATA MODEL
SCALABLE AND DATA HARMONIZATION
AND DATA QUERIZATION.
THE INTENT IS FOR THIS TO BE A
POWERFUL TOOL ITSELF BUT BE ABLE
TO SCALE WHAT IS DEVELOPED TO
AMP SBI AND NEEDS GOING IN THE
FUTURE
>> THE NEXT SPEAKER FROM OXFORD
UNIVERSITY IS DR. GALLACHER AND
HAVE SEEN EXAMPLES OF SUCCESS OF
DATA SHARING IN THE U.K. WITH
THE U.K. BIO BANK AND MORE.
>> THANK YOU FOR INVITATION AND
ORGANIZATION AND IT'S A
PRIVILEGE TO JOIN YOU IN WHAT A
DESCRIBE AS A VIBRANT COMMUNITY.
YOU CAN BUILD DIFFERENT
KNOWLEDGE NETWORKS.
WE'LL BE TALKING ABOUT HOW WE
HAVE DEVELOPED DATA PLATFORM
FOCUSSED ON DATA TRANSLATION AND
THIS MEANS BRINGING TOGETHER
COHORT AND BEGINNING TO EXTEND
INTO LABORATORY DATA.
FOR INTEREST OF BACKGROUND
THERE'S THREE LEGS TO THE
TRIPOD.
WE HAVE A FRAMEWORK WHICH IS
ABOUT 64 SITES.
A LARGE REGISTRY PROBABLY THE
LARGEST IN THE U.K.
WE HAVE AN EXPERIMENTAL MEDICINE
PROGRAM BRIDGING THE GAP BETWEEN
DISCOVERY AND HELPING COMPANIES
MAKE DECISION IN TERMS OF DRUG
DEVELOPMENT.
I'LL BE TALKING ABOUT OUR DATA
PORTAL TRYING TO IMPLEMENT MANY
OF THE THINGS METTE WAS
DESCRIBING AND WE'RE A
PUBLIC-PRIVATE PARTNERSHIP AND
THERE ARE ARE OUR PARTNERS.
IF YOU'RE A GRAND OLD MAN OR
WOMEN OF SCIENCE YOU CAN DO WHAT
YOU WANT.
IF YOU'RE AN EARLY CAREER
RESEARCHE
RESEARCHER IN MALAWI YOU NEED
PLATFORMS LIKE THIS AND OUR USE
IS VERY MUCH WITH THE EARLY
PRE-RESEARCHERS AND RESEARCHERS
WHO DID NOT COME FROM HIGH END
COMPUTING ACCESS BACKGROUNDS.
LET'S LOOK AT THE ARCHITECTURE.
WE'LL TAKE DATA IN ANY FORMAT
YOU WANT TO PROVIDE IT.
THE GOAL IS TO MAKE IT AS EASY
AS POSSIBLE FOR YOU.
WE THEN CURATE IT TO STANDARDS
AND IT DEPEND ON THE MODALITY.
YOU IT'S INTEROPERABLE WITH
OTHER PLATFORMS.
FROM A USERS POINT OF VIEW THE
DATA BECOMES DISCOVERABLE
THROUGH A SUITE OF
DISCOVERABILITY AND BROKER
ACCESS BETWEEN THE USER AND DATA
CONTROLLER OR THE DATA PROVIDER.
SO IF YOU NEEDED TO ACCESS FIVE
DAT SETS YOU WOULD NEED TO
CONTACT US ONCE.
WE THEN DISTRIBUTE THE ACCESS
REQUEST TO THE DATA CONTROLLERS
AND BRING REPLIES BACK TO YOU.
IT MAKES IT A MORE STREAMLINE
OPERATION BUT THE MEAT IS IN THE
DATA ANALYSIS LAYER YOU CAN HAVE
YOUR OWN PRIVATE LABORATORY
SPACE AND CONFIGURE AND THAT'S
YOUR PRIVILEGE.
THE CONFIGURATION IS MORE OF AN
EXERCISE WE CAN DO ON YOUR
BEHALF.
AND WE WILL THEN PROVIDE YOU
WITH THE TOOLS SO YOU CAN COME
TO THE DATA.
DATA NEVER LEAVE AS IN NEVER
LEAVE THE DATA PORTAL.
AND WITHIN THE DATA WE CAN
PROVIDE YOU WITH THE TOOLS YOU
REQUIRE.
I DON'T THINK WE'VE COME ACROSS
ANY SOFTWARE REQUESTS SO FAR
THAT WE HAVEN'T BEEN ABLE TO
PROVIDE.
THIS REALLY REDUCES A
DUPLICATION OF EFFORT AND COST
ON BEHALF OF THE SCIENTIFIC
COMMUNITY.
AND THEN THE MORE DIFFICULT
ACCESS IS KNOWLEDGE MANAGEMENT
ENVIRONMENT BECAUSE IT'S HARD TO
GET HOLD OF THE KNOWLEDGE IN ANY
SENSE OF COMPLETENESS.
TO REITERATE SOME OF THE
COMMENTS OTHER PEOPLE HAVE MADE
DATA IS ONE THING AND MEANING IT
WILL DATA ANOTHER AND DEVELOPED
PREPROCESSING PIPELINES TO DATA
THAT RELEVANT TO THE SPECIALISTS
CAN BE RELEVANT TO A BROADER
HYPOTHESIS.
IF YOU'RE A GENETICISTS YOU'D
LIKE TO SEE THE SEQUENCE POWER
BUT IF YOU WANT TO LOOK AT
GENETICS DATA YOU JUST WANT TO
KNOW THE GENOTYPE AND CAN ARGUE
THAT IN MANY WAYS.
I WAS INTERESTED IN THE CORE
DIGITAL PHENOTYPES.
THEY'RE CONFUSED AND PEOPLE CAN
STANDARDIZE THE DATA.
SO WE NEED TO CREATE RESEARCH
FOR COHORTS.
WE HAD SEVERAL GOES AT THIS AND
FAILED MICHELLY UNTIL WE DECIDED
TO FOCUS ON DATA DISCOVERY.
AT THAT POINT THE PROBLEM BECAME
MANAGEABLE.
AND CURATE TO A PARTICULAR
STANDARD AND HAVE 18 THEMES
BROKEN INTO DOMAINS, FAMILIES
AND OBJECTS AND THE COGNITIVE
DATA AND THE VARIABLES.
THIS HAS INCREDIBLE UTILITY.
IF YOU WERE TO GO TO A BRAND NEW
DATA SET WITH AN EXPERIMENT
WE'VE DONE AND SAY WE WANT TO
IDENTIFY 25 VARIABLES OF
INTEREST IT WILL PROBABLY TAKE
YOU FROM SCRATCH BECAUSE YOUR
NOT FAMILIAR WITH THE DATA SET
AND IT'S USUALLY ANNOTATED AND
IF IT'S IN A STANDARD FORMAT YOU
ARE FAMILIAR WITH THE SAME WORK
LOAD TAKES AROUND 15 MINUTES.
NOW, THIS MEANS WE DEAL WITH THE
HARD WORK AND DO THE HEAVY
LIFTING BUT IT HAS INCREDIBLE
BENEFITS FOR YOURSELVES IN THE
COMMUNITY.
THE REAL QUESTION HERE IS DOES
IT WORK?
HERE WE HAVE A DASHBOARD WE MAKE
AVAILABLE PUBLICLY.
THIS IS AVAILABLE TO OUR FUNDERS
AND THE USING COMMUNITY.
WE HAVE AND MANAGE COHORTS AND A
THOUSAND USERS IN DIFFERENT
COUNTRIES AND RECEIVED ACCESS
REQUEST.
THEY'RE GROWING YEAR ON YEAR.
WE HAD A DIP IN 2020 WITH COVID
BUT SO FAR THIS YEAR SURPASSED
THE 2023 LEVELS OF INTEREST.
INTERESTINGLY THE STATISTIC I
LIKE MOST IS THIS ONE HERE BY
PUBLISHING THE DATA WE GET
RELATIVELY RAPID TURNAROUND
TIMES FOR DECISIONS BY THE
COHORT P.I.s AND THAT IS REALLY
HELPFUL TO EVERYBODY INVOLVED.
SO WHAT ABOUT THE ?
THE FUTURE IS DIVERSIFYING THE
RESEARCH COMMUNITIES TO AREAS OF
INTEREST IN TERM OF DATA
MODALITY OR RESEARCH QUESTION.
THOUGH YOU MIGHT HAVE ONE BIG
POOL OF DATA WE CUT IT INTO BITS
TO MAKE IT MORE ACCESSIBLE AND
COMMUNITIES HAVING AN IDENTITY
AND CREATE SPECIALISMS.
AND ANOTHER FUTURE WE'RE WORKING
ON IS METADATA AND DATA LED
FEDERATION.
THE IDEAL IS YOU HAVE MANY
PLATFORMS BUT THEY HAVE A
SIBLING RELATIONSHIP IN TERMS OF
DATA ACCESS.
IF YOU LOOK TO THE RIGHT YOU
HAVE TO HAVE EFFECTIVELY A
SINGLE DATA PLATFORM TO AGREE A
SUBMISSION LAYER PROCESS.
ONLY THEN CAN THEY ACT AS
SIBLINGS AS EQUALS IN THE DATA
SHARING.
WE HAVE A SOLUTION BUT REQUIRES
TRUST BEING DEVELOPED ACROSS
DATA PLATFORMS.
ONE WAY OF DEVELOPING THIS TRUST
AND THIS IS PARTICULARLY HAVE
GOVERNANCE NEUTRAL SECURE
ENVIRONMENTS.
ONE PLATFORM CAN PROVIDE THE
INFRASTRUCTURE BUT BASICALLY
LOOKING AT THE PLATFORMS AN AND
IT'S ERASED AND THERE'S NO
LEGACY IN TERMS OF GOVERNANCE.
.
WE TRIED TO BE USER FACING.
THE QUESTIONS ARE TOUGH AND NEED
TO BE PERSISTENT.
THOUGH WE LOOK FOR SPECIFICS WE
DEVELOPED GENERIC SOLUTIONS,
STANDARDIZATION OF STREAMLINING
AND INCREMENTAL IMPROVEMENT AND
THINK STRATEGICALLY.
THERE'S A BROADER FOCUS HERE.
AND I JUST LEAVE YOU WITH THE
COLLABORATION RAPID DATA ACCESS,
TRUSTWORTHINESS AND USER-LED
DEVELOPMENT AND OPTIMIZING
INFORMATION BECAUSE IT'S NOT
ABOUT THE TECHNOLOGY IT'S ABOUT
THE PEOPLE.
THANK YOU.
>> NEXT IS DR. ANNA GREENWOOD
FROM SAGE BIO NETWORKS.
THANK YOU.
>> I WANT TO TALK ABOUT A NODE
OF REPOSITORIES.
THE PREVIOUS ALZHEIMER'S SUMMITS
EMPHASIZED A NEED FOR OPEN
SCIENCE.
THIS HAS BEEN A RECURRING THEME
WE HEARD STARTING IN 2012 AND
THROUGH THE THREE DAYS WE'VE
BEEN MEETING SO FAR.
THE MORE WE CAN MAKE SCIENCE
ACCESSIBLE AND REPEATABLE AND
TRANSPARENT WE CAN ACCELERATE
DISCOVERIES AND BRIDGE THE
TRANSLATIONAL GAP.
DATA SHARING IS ONE OF THE MANY
TOOLS IN THE TOOL KIT OF OPEN
SCIENCE BUT IT'S REALLY NOT EASY
TO SHARE DATA.
THIS IS ANALYSIS FROM YEARS AGO
AND IN MANUSCRIPTS WHERE PEOPLE
SAID THEY'D SHARE DATA ON
REQUEST, LESS THAN 10% OF THOSE
AUTHORS ACTUALLY FOLLOWED
THROUGH WITH THAT REQUEST.
IT'S REALLY DIFFICULT TO SHARE
DATA.
THE REASON IS MULTIFACETS BUT WE
NEED A VARIETY OF INCENTIVES AND
PROCESSES.
GRANTS AND DEDICATED FUNDING TO
SUPPORT THE CURATION AND SHARING
OF DATA IS REQUIRED THEN
INCENTIVES WHETHER THOSE BE
COMPETITION LEADER BOARDS TO GET
PEOPLE EXCITED ABOUT SHARING
DATA OR WHAT WE FIND AS THE
COORDINATING CENTER TO BE THE
MOST EFFECTIVE IS A HEAVY STICK
TO MAKE SURE THAT PEOPLE REALLY
ARE SHARING THE DATA REQUIRED BY
THEIR FUNDING SOURCES.
PEOPLE AND INFRASTRUCTURE ARE
ANOTHER CORE COMPONENT OF
SUPPORTING DATA SHARING.
AND LOOK AT DATA CENTERS FOR
EXCEPTIONAL LONGEVITY.
YOU HEARD ABOUT THE EXCEPTIONAL
LONGEVITY STUDIES ON THE FIRST
DAY OF THE CONFERENCE.
TOGETHER THESE CONSORTIA ARE
GENERATING A RICH RESOURCE OF
MULTI-OMIC PROFILING DATA ON
LONGITUDINAL COHORTS AND
CROSS-SECTIONAL COHORTS AND ALSO
ANIMAL MODELS AND EARLY
TRANSLATIONAL STUDIES WE
DEVELOPED AN INTERCONNECTED
SUITE OF PLATFORMS TO HELP SHARE
THE DATA FROM THESE PROGRAMS.
I'LL TELL YOU ABOUT THESE TODAY.
AT THE HEART ARE TWO DATA
PORTALS ENABLING ACCESS TO
LONGEVITY DATA RELIED ON A
SHARED INFRASTRUCTURE OUR
SYNAPSE PLATFORM.
THE ELITE PORTAL AND EXCEPTIONAL
RESOURCES PORTAL AND AD
KNOWLEDGE PORTAL.
THE ELITE PORTAL IS CURRENTLY IN
A BETA VERSION.
IT'S PUBLICALLY ACCESSIBLE.
AND THE OFFICIAL LAUNCH WILL
HAPPEN THIS FALL.
IT HAS DATA FROM CENTENARIANS
AND COGNITIVE TRAITS AND
MULTI-OMICS DATA FROM HUMAN AND
ANIMAL MODEL SYSTEMS.
AND THE AD KNOWLEDGE PORTAL HAS
BEEN AROUND A LOT LONGER.
OVER SO YEARS OLD NOW.
AND HAVE DATA FROM DATA TYPES
AND HUMAN SUBJECTS FROM OVER
30,000 HUMAN SPECIMENS AND THIS
HAS BEEN WIDELY USED.
JUST SINCE 2022 WE HAD 4800
UNIQUE USERS WHO HAVE DOWNLOADED
OVER 3. 8 MILLION FILES.
AND THIS IS REALLY A RICH SET OF
DATA.
IT'S QUITE DIVERSE REFLECTING
THE DIVERSITY OF PROGRAMS THAT
IT'S SHARING DATA FROM AND HUMAN
AND MODEL SYSTEM DATA.
A WIDE DIVERSITY OF DATA TYPES
AND TRANSCRIPTOMIC DATA AND
PROTEOMICS AND METABOLOMICS AND
MANY STUDIES YOU HEARD ABOUT
OVER THE PAST FEW DAYS YOU CAN
FIND THE DATA IN THE AD
KNOWLEDGE PORTAL.
A LARGE FOCUS IS MULTI-OMIC DATA
FROM HUMANS.
FROM AN INDIVIDUAL POSTMORTEM
BRAIN THERE'S RICH MULTI-LAYERED
DATA FROM THE SAME SUBJECTS.
YOU CAN GET GENETIC DATA,
EPIGENETIC DATA, TRANSCRIPTOMICS
FROM THE SAME INDIVIDUAL WHY
ALLOWSES FOR A RICH DISSECTION
OF THE UNDER PINNING OF
ALZHEIMER'S DISEASE.
WE WORKED HARD TO MAKE THE
PORTAL PRETTY EASY FOR USERS TO
FIND RESOURCES.
THERE'S A SIMPLE PROCESS TO
EXPLORE THE DATA THAT'S
AVAILABLE AND THEN BROWSING AND
LOCATING THE DATA OF INTEREST.
THEN WE ALLOW DATA TO BE
ACCESSED IN MULTIPLE WAYS.
WE PERMIT USERS TO DOWNLOAD THE
DATA ONCE THEY'VE GONE THROUGH
THE CONTROLLED ACCESS REQUEST
PROCESS THEY CAN DOWNLOAD DATA
OR OUT IT ON THEIR OWN CLOUD
SYSTEMS BUT WE'RE WORKING WITH
EXISTING BIO INFORMATICS
PLATFORMS TO BUILD BRIDGES WHERE
THE DATA IN THE AD KNOWLEDGE
PORTAL CAN BE ANALYZED IN THESE
POWERFUL PLATFORMS.
ONE OF THE THINGS WE WORK HARD
TO DO IS NOT JUST GET THE DATA
OUT THERE AND HAVE THE PORTAL,
BUT WE FOUND THAT PROVIDING USER
SUPPORT HELPS FACILITATE DATA
REUSE.
WE HAVE A DISCUSSION FORUM WHERE
PEOPLE CAN ASK ANY QUESTION
ABOUT THE DATA AND SOMETIMES
USERS WILL EVEN ANSWER OTHER'S
QUESTIONS AND HAVE EXAMPLES HOW
TO WORK WITH THE DATA.
WE HAVE A NEWS LETTER AND DATA
RELEASE NOTES SAYING WHENEVER
DATA HAS BEEN UPDATED AND THEN
WE HAVE HANDS ON WORKSHOPS.
WE HAD ONE AT THE ALZHEIMER'S
ASSOCIATION CONFERENCE THIS
SUMMER AND HAVE THEM THROUGHOUT
THE YEAR VIRTUALLY OR IN PERSON
TO GET PEOPLE FAMILIAR WITH HOW
TO WORK WITH THE DATA.
AND THESE EFFORTS HAVE BORNE
FRUIT.
WITH FIND MOST THE DATA REUSE
HAS DEMONSTRATED BY PUBLICATIONS
THAT REFERENCE THE AD KNOWLEDGE
PORTAL COMES FROM SECONDARY DATA
USE.
THOUGH DATA CONTRIBUTORS ARE
FAMILIAR WITH THE DATA AND
PUBLISH AS WELL THE MAJORITY
REPRESENT PEOPLE IN THE
COMMUNITY AS WE SEE AS A TRUE
TESTAMENT TO THE POWER OF OPEN
SCIENCE.
WE'RE CONTINUING TO IMPROVE
THESE PORTALS AND
INFRASTRUCTURE.
SOME OF THE NEW IMPROVEMENTS
COMING IN THE NEXT PHASE OF OUR
COORDINATING CENTER GRANTS
INCLUDE THE ABILITY TO SEARCH
FOR DATA BY PROPERTIES OF AN
INDIVIDUAL BY CHARACTERISTICS OF
AN INDIVIDUAL AND IMPROVED
NAVIGATION WE'RE CONTINUALLY
TRYING TO MAKE THIS EASIER FOR
USERS.
AND WE ARE CONTINUING TO EXPAND
THE DATA AS NEW TECHNOLOGIES AND
DATA ARE MADE AVAILABLE.
A BIG FOCUS ON IMPROVING
DIVERSITY IN OUR SAMPLES.
AND IN MY LAST COUPLE MINUTES I
WANTED TO MENTION A
COMPLEMENTARY PLATFORM CALLED
AGORA TO HELP DEMOCRATIZE THE
RESOURCES TO A BROADER
COMMUNITY.
IT'S AN DATA EXPLORER WHERE WE
HAVE TAKEN THE DATA FROM THE AD
KNOWLEDGE PORTAL AND REANALYZED
THAT AND PROCESSED IT AND
SUMMARIZED IT IN A CURATED WAY.
YOU CAN GO TO AGORA AND LOOK AT
ANY GENE OF INTEREST AND SEE HOW
IT'S ASSOCIATED WITH ALZHEIMER'S
DISEASE AND COMPARE ACROSS THE
GENES USING THE GENE COMPARISON
TOOL.
ONCE YOU FIND A GENE OF INTEREST
WE HAVE A RICH SET TO HELP YOU
UNDERSTAND HOW THE GENE MAY BE
INTERACTING WITH ALZHEIMER'S
DISEASE.
AND INFORMATION HOW TRACTABLE
THE INFORMATION MIGHT BE.
AND WITH THAT I WANTED TO
QUICKLY ACKNOWLEDGE THE LARGE
TEAM OF PEOPLE AT SAGE WHO
CONTRIBUTED TO THE WORK AND
PARTICULARLY I WANTED TO THANK
ERICA, LAURIE AND SUSANA FOR HER
AMAZING VISION AND LEADERSHIP.
>> THE NEXT SPEAKER IS MY
CO-CHAIR GUSTAVO
JIMENEZ-MAGGIORA FROM UNIVERSITY
OF SOUTHERN CALIFORNIA.
>> THANK YOU.
>> I WANTED TO START BY THANKING
THE SUMMIT ORGANIZERS FOR
INVITING ME TO PRESENT ON ACTC
AND OUR APPROACH TO CLINICAL
TRIALS DATA AND RESOURCE
SHARING.
IT'S THE ALZHEIMER'S CLINICAL
TRIALS CONSORTIUM.
IT'S AN NIA PROGRAM THAT IT LED
JOINTLY BY THE UNIVERSITY OF
SOUTHERN CALIFORNIA AND HARVARD
AND THE MAYO CLINIC TO ESTABLISH
A STANDING INFRASTRUCTURE THAT
IS COMPOSED OF 35 SITES AS WELL
AS EXPERT-LED UNITS AND
COMMITTEES.
ACTC HAS A LONG STANDING
COMMITMENT TO OPEN SCIENCE
ALIGNED WITH NIA EXPECTATIONS AS
WELL AS WITH THE PRINCIPLES OF
FAIR DATA AND COLLABORATION FOR
ALZHEIMER'S PREVENTION.
TO MEET THIS COMMITMENT WE
SUPPORT BROAD AND TIMELY TRIAL
DATA DESIGN TO PROTECT INTEGRITY
AND PRIVACY AND HAS ANONYMIZED
BIO SPECIMEN AND ANALYSIS,
INSTRUMENTS AND EXPERTRY IN
TRIAL DESIGN AND DOCUMENTS.
OUR GOAL IS TO SHARE DATA AT TWO
CRITICAL TIME POINTS IN THE
STUDY LIFE CYCLE.
THE FIRST OF WHICH IS ONE YEAR
AFTER THE COMPLETION OF
ENROLLMENT WHERE WE SHARE ALL
THE SCREENING DATA FOR A TRIAL.
AND THE SECOND TIME POINT IS ONE
YEAR AFTER THE REPORTING OF THE
TRIAL RESULTS WHERE WE SHARE THE
DATA SET.
TO FACILITATE OUR APPROACH I'D
LIKE TO QUICKLY SHARE CASE STUDY
OF OUR EFFORT TO SHARE THE A4
TRIAL DATA.
IT WAS A PHASE III RANDOMIZED
CLINICAL TRIAL LOOKING AT
EFFICACY AND SAFETY OF THE USE
OF SOLEANEZEW ZUMAB AND SCREENED
PARTICIPANTS BETWEEN THE AGES OF
65 AND 85 CLINICALLY NORMAL OF
THE PARTICIPANTS WHO FAILED TO
BE ENROLLED IN THE MAIN STUDY
WERE ENROLLED INTO AN
OBSERVATIONAL COHORT AND WERE
FOLLOWED UP FOR THE SAME PERIOD
USING THE SAME PROTOCOL.
IF LEWD LIKE MORE INFORMATION
ABOUT THE TRIALS, I ENCOURAGE
YOU TO VISIT CLINICAL TRIALS DOT
GOV.
WE SHARED THE SCREENING DATA SET
FOR A4 AT THE END OF 2018.
AND THE FINAL DATA SET WHICH
INCLUDES PLACEBO AND TREATMENT
ARMS DATA WAS SHARED RECENTLY A
FEW WEEKS AGO.
THIS DATA SET INCLUDES CLINICAL,
COGNITIVE AND LAB DATA AS WELL
AS BIOMARKER DATA THAT INCLUDE
FLUID AS WELL AS IMAGING
BIOMARKER DATA.
AN ENORMOUS AMOUNT OF NEURAL
IMAGING DATA ACROSS MODALITIES
AND GENETIC DATA.
I'D LIKE TO SHARE RESULT OF THE
EFFORTS WITH YOU AT THIS POINT.
FOR SCREENING DATA THE DATA WAS
SHARED USING LONI AND THE TWO
PANELS ON THE RIGHT-HAND SIDE OF
THE SLIDE QUANTIFY THE NUMBER OF
APPROVED REQUESTS THAT WE HAVE
RECEIVED OVER THE PAST FIVE
YEARS.
MORE THAN 1500 REQUESTS HAVE
BEEN APPROVED BY INVESTIGATORS
FROM OVER 60 COUNTRIES AND THEY
DOWNLOADED IMAGING DATA AND
ULTIMATELY A LITTLE BIT MORE
THAN 2,000 AL ALOE ALLO QUATS
HAVE BEEN SHARED AND CLOSE TO 70
PEER-REVIEWED PUBLICATIONS HAVE
REFERENCED THE SCREENING DATA
AND WHAT WE LEARNED WAS
SOMETHING OTHER SPEAKERS HAVE
MENTIONED IS THE DATA
PREPARATION PROCESS WAS
EXTREMELY LABOR INTENSIVE
ESPECIALLY BECAUSE WE WANTED TO
MAKE SURE WE APPLIED THE STATE
OF THE ART IN TERMS OF METHODS
TO DE-EYE -- DE-IDENTIFY AND
DEFACE THE DATA TYPE WE'RE
SHARING.
FAST FORWARDING FIVE YEARS WE
RECENTLY SHARED THE A4 FINAL
STUDY DATA.
I'M HAPPY TO REPORT WE APPROVED
MORE THAN 100 REQUESTS FROM
INVESTIGATORS FROM 15 COUNTRIES.
THIS INCLUDES MORE THAN 15,000
LONGITUDINAL MULTI-MODAL IMAGING
STUDIES.
ANOTHER THING WE LEARNED IS
DIFFERENT COMMUNITIES WITHIN THE
ALZHEIMER'S FIELD TEND TO
GRAVITATE TOWARDS DIFFERENT
PLATFORMS.
SO TO TRY TO MEET INVESTIGATORS
WHERE THEY ARE WE DECIDED TO
SHARE THE DATA FOR THIS ROUND ON
MULTIPLE PLATFORMS.
SO WE'VE SHARED THE DATA ON THE
GRIP PLATFORM WHICH IS A
COLLABORATION WITH OUR PARTNERS
AT GATES VENTURES AND SHARED THE
DATA ON SYNAPSE WHICH TENDS TO
BE FAIRLY FIM FAMILIAR TO THE
OMICS AND SHARING THE DATA ON
LONI AS WELL BECAUSE WE KNOW
IMAGEERS ARE ESPECIALLY
COMFORTABLE USING THE APPROACH.
AND TO SHARE THE LESSONS LEARNED
WE DEVELOPED A MANUSCRIPT TO TRY
TO DOCUMENT SOME 69 LESSONS
LEARNED IN THE EXPERT PART OF
THE SPECIAL ISSUE PUBLISHED IN
JPAD A FEW WEEKS AGO.
THERE'S PUBLICATIONS THAT
REFERENCED THE A4 SCREENING
DATA.
SO THIS IS AN ARTICLE THAT THAT
EXPLORE THE RELATIONSHIP BETWEEN
AD BIOMARKERS AND ANCESTRALLY
DIVERSE INDIVIDUALS.
THE INVESTIGATORS FOUND
NON-HISPANIC BLACK PARTICIPANTS
HAD LOWER MEASURES OF AMYLOID
RELATIVE TO NON-HISPANIC WHITE
PARTICIPANTS AND THIS AFFECT WAS
STRONGEST IN PARTICIPANTS THAT
WERE APOE 4 CARRIERS.
THE FINDINGS HAVE IMPLICATIONS
FOR FUTURE AD PREVENTION TRIALS
AND I THINK ARE ONE EXAMPLE OF
PRECISION MEDICINE APPROACHES
THAT MAY BE APPLICABLE TO
TRIALS.
TO CONCLUDE WITH NEXT STEPS IN
OUR TRIAL SHARING EFFORTS.
FIRST, WE PLAN TO CONTINUE TO
DEVELOP OUR TOOLS AND
INFRASTRUCTURE TO SUPPORT
PRECISE REQUEST FOR DATA
DOCUMENTATION ACROSS DATA TYPES
AND PLAN TO PARTNER TO IMPROVE
PRIVACY PROTECTING APPROACHES
FOR THE DIFFERENT TYPE OF
COMPLEX DATA TYPE AND ONE
EXAMPLE WOULD BE WORK WE'RE
HOPING TO DO WITH RHODA AND HER
GROUP TO DE-IDENTIFY A LARGE
COLLECTION OF AUDIO DATA WE HAVE
FOR THE TRIAL AND TRYING TO
PROVIDE AN OPEN SOURCE TOOL TO
SUPPORT ANALYSIS AND
VISUALIZATION AND AN APPROACH WE
USE A.I. DATA EXPLORATION TOOLS
VIA NATURAL LANGUAGE PROMPTS TO
SUPPORT MORE ACCESSIBLE
APPROACHES TO EXPLORING THESE
COMPLEX DATA.
WE WANT IT INTEGRATED INTO THE
BROADER ECO SYSTEM THROUGH THE
FAIR PRINCIPLES AND MAKE SURE WE
ARE PROMOTING SECONDARY USE OF
TRIAL DATA AND RESOURCE TO DRIVE
PRECISION MEDICINE APPROACHES TO
ACCELERATE THERAPEUTIC
DEVELOPMENT.
I WANT TO CONCLUDE BY
ACKNOWLEDGING THE PARTICIPANTS
AND THEIR FAMILIES AND STUDY
PARTNERS.
THANK YOU FOR YOUR ATTENTION.
>> THE NEXT TALK IS FROM MARIA
CARRILLO WITH THE ALZHEIMER'S
ASSOCIATION.
>> THANK YOU FOR THE NATIONAL
INSTITUTE ON AGING FOR
LEADERSHIP AND PLANNING OUT SO
MANY SUMMITS THAT HAVE LAID OUT
THE MILESTONES WE WORK WITH AND
PROGRESS WE'RE MAKING AND FOR
THE TALK I WANT TO THANK
DR. SNYDER AT THE ALZHEIMER'S
ASSOCIATION AND DR. EDDELMIER.
THEY'RE THE LEADS FOR ALZ NET.
YOU'D LIKE TO THANK CO-PRINCIPLE
INVESTIGATORS.
I THINK WE HEARD THROUGHOUT THE
THREE DAYS WE HAVE THE POTENTIAL
FOR PRECISION MEDICINE WE HAVE
BEEN SUPPORTIVE OF NOT ONLY
PRECISION MEDICINE BROADLY BUT
OF THE AMP AD PROGRAM SINCE THE
INCEPTION.
AND CONTINUE TO BE THERE'S GREAT
VALUE AND PROMISE STARTING TO
DELIVER AS YOU HEARD OVER THE
LAST FEW DAYS.
YOU HEARD ABOUT SHARING REAL
WORLD DATA AS MUCH AS WE CAN AND
HOW DO WE GATHER THE KNOWLEDGE
AND SHARE IT IN A WAY THAT IS
OPEN AND HAS THE APPROPRIATE
CONSENT AND MAXIMIZING FOR THE
PANEL THAT DRIVE HOME WHAT WE
NEED TO DO AND WHY.
WHEN WE FUND RESEARCH KNOW IT
IMPACTS DIAGNOSIS AND TREATMENT
AND LEADS TO BETTER CARE BUT
THAT BETTER CARE DRIVES MORE
RESEARCH BECAUSE IT'S A CIRCLE
THAT WE HAVE TO CONTINUE TO IT
RATE ON TO IMPROVE PRACTICE AND
IMPROVE QUALITY CARE AND PATIENT
EXPERIENCE ITSELF AND DRIVE
HEALTH EQUITY AND WHO SHOULD
TALK THEM AND SHOULDN'T AND WHY.
WE WANT TO DO A LOT OF THESE
THINGS WITH ALZ NET ON THE
RIGHT.
I WON'T BELABOR THEM BECAUSE OF
TIME BUT IT'S A VOLUNTARY HEALTH
CARE PROVIDER NETWORK.
THEY ENROLL THEM IN BEING
EVALUATED FOR TREATMENT WITH A
NOVEL TREATMENT APPROVED BY FDA
AFTER 2021.
THE KEY TO THE MIDDLE PORTION IS
EVALUATED FOR TREATMENT.
WE WANT TO FOLLOW THEM EVEN
AFTER THE EVALUATION WHETHER
THEY DECIDE ON TREATMENT OR NOT
BECAUSE SOMETIMES YOU GET MORE
INFORMATION WHEN YOU FOLLOW
THOSE WHO CHOSE OR COULD NOT BE
ELIGIBLE FOR THE TREATMENT.
HERE'S A SNAPSHOT OF THE
QUESTIONS WE CAN ADDRESS WITH
ALZ NET.
YOU CAN PROBABLY THINK OF
QUESTIONS THAT ARE BETTER ONES
THAN WE AND THE NETWORK WILL BE
AVAILABLE FOR YOU TO DOWNLOAD
DATA.
I WON'T GO THROUGH THEM BECAUSE
YOU CAN READ AND ACCESS THE
SLIDES THESE ARE QUESTIONS WE'VE
BEEN ASKING THE LAST THREE DAYS.
ALZ NET CONTINUES TO DPROE.
IT'S A VOLUNTARY PROVIDER
REGISTRY.
OUR LARGEST SITE IS AT INDIANA
UNIVERSITY.
THEY'LL START ENROLLING WE HAVE
PATIENTS ENROLLED THAT WILL BE
FOLLOWED EVERY SIX MONTHS WITH
THEIR PROVIDERS GIVING US
INFORMATION WE ARE PROVIDING
MONETARY INCENTIVE TO PROVIDERS
AND CLINICS TO PAY FOR THEIR
TIME FOR PARTICIPANTING IN ALZ
NET.
IF WITH YOU WANT MORE DETAILS
LOOK AT THE QR CODE OR E-MAIL
ANY OF US AT THE END OF THE
CONVERSATION.
THIS IS THE TYPE OF DATA WE'RE
COLLECTING.
WE TRIED OUR HARDEST TO PUT A
WISH LIST IN.
AT THE SAME TIME NOT MAKE IT SO
ONEROUS FOR THE CLINICIANS TO
NEED MORE THAN 15 MINUTES TO
INPUT THIS WHOEVER THEY
DESIGNATE IN THEIR CLINIC.
SO IMPORTANT TO HAVE INFORMATION
BUT NOT TOO MUCH WE CAN'T MAKE
THIS A USABLE FORMAT FOR THOSE
PARTICIPATING THIS IS MORE THAN
THE MEDICARE AND MEDICAID
REGISTRY USES.
WE ACKNOWLEDGE THAT.
WE DO THINK THAT REGISTRY IS
FAIRLY UNHELPFUL ABOUT SAFETY
AND OTHER EVENTS WE THINK WILL
BE VERY IMPORTANT.
WE ARE ENGAGED IN THINKING ABOUT
HOW WE CAN CREATE A BROADER
PLATFORM AND THIS WAS ACTUALLY
VERY WELL SPELLED OUT IN A
RECENT PROPOSAL WE PUT TOGETHER
AND WE CONTINUE TO WORK TOWARDS
HOPING THAT THIS WILL BECOME OUR
VISION AND RIGHT NOW THE
ALZHEIMER'S VISION IS THE ONLY
INVESTOR.
WE DON'T HAVE ANY PUBLIC-PRIVATE
PARTNERS YET.
DEEPLY PHENOTYPED DATA IS
ANYTHING UNDERWAY AND WORKING
CLOSELY TO DO THAT AND HAPPY TO
TALK ABOUT THAT LATER THOUGH
SARA WILL BE UP HERE HERSELF
TALKING.
IF YOU HAVE ANY QUESTIONS ABOUT
THAT, PLEASE LET ME KNOW.
SO ALZ NET IS DESIGN TO WORK
COLLABORATIVELY WITH OTHER
STUDIES.
I HAVE TWO I WANT TO SHARE
INFORMATION ABOUT.
THE FIRST IS COVERAGE WITH
DEVELOPMENT AND THE CENTER FOR
MEDICARE AND MEDICAID
REQUIREMENT FOR PHASE IV
INFORMATION ON SAFETY AND
EFFICACY.
THE PRIMARY PURPOSE OF THIS
STUDY IS TO INVESTIGATE THAT
LONG-TERM EFFECTIVENESS AND
SAFETY OF NEW TREATMENTS.
THIS IS OUR FIRST AFFILIATED
STUDY BECAUSE CLINICIANS CAN
UTILIZE ALZ NET TO ENROLL.
OF PATIENTS AND NO THE DO DOUBLE
DUTY OF ENROLLING THEM IN CMS
AND ALZ NET AND WE KNEW THAT WAS
THE REASON WHY WE HAD IT APPLY
FOR A CD THOUGH WE AT THE
ASSOCIATION PUBLICLY STATED WHEN
THERE'S TRADITIONAL APPROVAL WE
DID NOT FEEL COVERAGE WITH
EVIDENCE DEVELOPMENT WAS
APPROPRIATE FOR CMS TO LAUNCH
HOWEVER WE ARE HERE.
ON THE RIGHT SIDE YOU SEE THE
LATEST ASSIGNED AS A CONTRACT
WITH AN AFFILIATED STUDY THAT
FULFILLS THE APPROVAL OF IT TO
FOLLOW SAFETY OUTCOMES.
WE'RE COLLABORATING WITH THEM
AND ARE GOING TO BE CONDUCTING
REGULAR ALMOST MONTHLY REPORT
OUTS ON SAFETY DATA TO REPORT
BACK TO THE FDA.
WE HAVE BEEN COLLABORATING
CLOSELY WITH THE FDA THE PAST
THREE YEARS ON ALZ NET AND THEY
HAVE IT AS A RECOMMENDED
REGISTRY FOR THE CLINGS AND
PROVIDERS TO PUT THEIR PATIENT'S
DATA IN TO HELP FDA AND ALL THE
COMMUNITY UNDERSTAND HOW THESE
DRUGS ARE BEHAVING IN REAL WORLD
SETTING AND ALIGNED WITH THE
WORK WE'RE DOING.
I THINK WE'LL HEAR FROM THE FDA
LATER TODAY.
ONE THING I WANTED TO FOCUS ON
IS ARIA.
I'LL BREEZE THROUGH THIS BECAUSE
WE KNOW WHAT IT IS.
IT'S A SAFETY THINGS WE'RE
MANAGING TO LOOK AT THROUGH NOT
ONLY THE PMR REGISTRY BUT THE
COVERAGE STUDY.
IN 2010 THE FDA DID NOTICE THERE
WERE ANOMALIES HAPPENING ACROSS
THE CLASS OF MONOCLONAL
ANTIBODIES.
WE CREATED A WORK GROUP THAT IN
2011 PUBLISHED THE PAPER IN
ORDER TO NAME ARIA E AND H.
TODAY WE'RE RE-EVALUATING WHAT
THE WORK GROUP LOOKED AT THAT
TIME.
WE HAVE NOT A LOT OF INFORMATION
ABOUT WHAT THE EDEMA WAS YOU
CAUSED IN THE DRUG STUDIED AN
STILL DON'T KNOW AS MUCH AS WE
WANT BUT WANT TO KNOW MORE.
WE HAVE TWO FEDERAL PARTNERS THE
NIA WITH THE WORK GROUP MEMBERS
AND THEY'RE INSIGHTS BUT THEY'RE
NOT OFFICIAL WORK GROUP MEMBERS
AND WHY THERE'S AN ASTERISK
THERE.
THESE ARE QUESTIONS WE'RE
ASKING.
YOU THINK WE UNDERSTAND WE KNOW
MORE NOT ENOUGH.
WE'RE WORKING WITH THE FDA TO
UNDERSTAND PATIENT LEVEL DATA
AND HAVE MANY COMPANIES ASKING
THEM TO SHARE THEIR DATA WITH US
ON ARIA.
YOU CAN IMAGINE THERE ARE SUM
RELUCTANCE FOR COMPANIES TO
SHARE DATA BUT WE'RE WORKING
HARD ON TRYING TO GET IT.
THIS IS MY FINAL SLIDE.
I WANTED TO SHARE OUR VISION.
YOU CAN PUT ANY DEMENTIA IN THE
MIDDLE BUT WE'LL DO ALZHEIMER'S
BECAUSE THIS IS THE SUMMIT.
WE KNOW THERE ARE BRAIN CHANGES
THAT HAPPEN AND TALKED ABOUT
THEM AND NOT ONLY WITH
BIOMARKERS BUT PERHAPS OMICS
DATA WE WILL BE ABLE TO
DETERMINE WHAT UNDER LIES THE
CHANGES.
AND ULTIMATELY WE WANT THERAPIES
FOR EACH OF THOSE.
AND THAT IS GOING TO BE A
PERSONALIZED APPROACH AND WE'RE
CLOSER THAN EVER AND I'VE COME
OUT WITH MORE HOPE AND THIS IS A
SLIDE MODIFIED FROM RON
PETERSON.
IN PARTICULAR WE HAVE SOME DRUGS
THAT ARE GOING TO TACKLE THIS
SIDE OF THE CIRCLE BUT ON TOP OF
THAT YOU HEARD FROM LAURA BAKER
AND OTHERS RISK FACTOR
INTERVENTIONS CAN OFFER GREAT
HOPE.
THAT IS A GOOD WRAP AROUND HOW
WE AT THE ALZHEIMER'S
ASSOCIATION AND EXCITED TO
PARTICIPATE IN THE PANEL AND
THANK YOU FOR THE LEADERSHIP AND
LOOKING FORWARD TO THE
DISCUSSION.
I WANT TO THANK OUR PARTNERS AND
GILL AND MIKE AND DR. SNIDER AND
EDELMIER.
THANK YOU VERY MUCH.
>> I'D LIKE TO INVITE THE
FIVE-PARENT PRESENTATION
SPEAKERS.
LIKED TO INVITE DR. CHRIS
SWANSON-FISHER TO START THE
FIRST PRESENTATION.
>> THANK YOU AND GOOD MORNING OR
GOOD AFTERNOON TO EVERYBODY.
I'M PROGRAM DIRECTOR AT NINDS
THANK YOU FOR THE LEADERSHIP OF
THE SUMMIT AND PUTTING TOGETHER
THIS CRUCIAL SESSION TODAY.
I KNOW MANY HAVE HEARD OVER THE
LAST TWO DAYS AS WELL AS WE
BELIEVE JUST NOW FROM ANNA ABOUT
THE BREADTH OF THE DATA TO BE
EXPLORED IN THE ANG 80 KNOWLEDGE
PORTAL AND PROVIDE AN OVERVIEW
WHERE THE ACCELERATING MEDICINE
PARTNERSHIP FOR PARKINSON'S
DISEASE IS AND WHERE WE'RE
HEADING NEXT.
AMP AD IS A PUBLIC-PRIVATE
PARTNERSHIP AS WELL AS INDUSTRY
PARTNERS AND THE MICHAEL J FOX
FOUNDATION AND ALLIANCE FOR
PARKINSON'S.
IT WAS LAUNCHED IN 2018 WITH THE
GOAL TO HELP ADVANCE PATHWAYS
AND BIOMARKERS FOR PARKINSON'S
DISEASE TO ENABLE CLINICAL TRIAL
DESIGN BY DEVELOPING AND LAMPING
THE AMP KNOWLEDGE PLATFORM.
WE'RE FAMILIAR WITH PLATFORMS WE
HEARD ABOUT OVER THE LAST COUPLE
DAYS AND IN THE SESSION.
WE GENERATED ROBUST MOLECULAR
CHARACTERIZATION AND IDENTIFYING
NOVEL BIOMARKERS AN TARGETS.
YOU CAN SEE ON THE RIGHT WE HAVE
EIGHT UNIFIED COHORT WITHIN THE
PLATFORM.
THEY HAVE LONGITUDINAL
HARMONIZED CLINICAL DATA AND WE
HAVE RNA SEQUENCING DATA FROM
BLOOD AS WELL AS MATCH PLASMA
AND LONGITUDINAL PROTEOMICS DATA
AND RNA SEQUENCING DATA AS WELL.
AND FEDERATED DATA FROM THE
PARKINSON'S GP2 YOU HEARD FROM
MONDAY AS WELL TO PROVIDE
GENOTYPING FROM PEOPLE WITH
PARKINSON'S DISEASE AND RELATED
DISORDERS.
A CORNERSTONE IS DATA
DEMOCRATIZATION.
I THINK IT'S BEEN ENABLED
THROUGH OUR AMP PLATFORM AND AN
ENVIRONMENT WORK WITH PARTNERS
TO LEVERAGE TERRA WORK SPACES IN
THE CLOUD AND ABLE TO FEDERATE
THE DATA THROUGH GP2 AND
CURRENTLY HAVE OVER 800 USERS
WHO HAVE ACCESSED THE DATA FROM
AROUND THE WORLD AND AT THE SAME
TIME WE WANT TO BUILD UPON THE
KNOWLEDGE PORTAL BY RECENTLY
LAUNCHING THE TARGET EXPLORER
TOOL MODELLED AT THE PLATFORM TO
SERVE AS A PUBLIC RESOURCE FOR
OPEN ACCESS TO NOMINATE GENES
AND PROTEINS FROM MODELLED FROM
THE DATA THAT CAN BE IMPLICATED
IN PARKINSON'S DISEASE.
AND THERE'S WORK STREAMS
FOCUSSING ON THE BIOMARKERS AND
KNOX DRUG TARGETS AND CURRENTLY
WE HAVE OVER 13,000 TRAR --
TARGETS ON PROTEOMIC DATA SETS.
BASED ON RESOURCES ESTABLISHED
THROUGH THE AMP PHASE FROM 2018
TO THE LAST YEAR A NUMBER OF KEY
STAKEHOLDERS INCLUDING THE AC
FIX PARTNERS AND SUBJECT MATTER
EXPERTS AND KEY OPINION LEADERS
STARTED TO LOOK AT THE SUCCESS
OF PHASE 1 AND START TO THINK
WHERE WE CAN MOVE NEXT WHICH WE
WANT TO ENABLE THE PRECISION
MEDICINE APPROACH.
WE DECIDED TO LOOK BEYOND
PARKINSON'S DISEASE COHORTS AND
LOOK INTO OTHER DISEASES AND
PRODROMAL PARKINSON'S DISEASE
AND OTHER ATYPICAL
PARKINSONISMS.
THE NEW PARTNERSHIP CALLED THE
AMP PARKINSON'S DISEASE AND ED
DISORDER OR AMP PDRD WAS
OFFICIALLY LAUNCHED THIS PAST
JULY AND SIGNED ON NINDS AND
INDUSTRY PARTNERS.
WE ARE GROWING.
IF YOU'RE INTERESTED IN LEARNING
MORE ABOUT THE INITIATIVE ARD
CONTRIBUTING DATA FOR
PARKINSON'S OR OTHER RELATED
DISORDER COHORTS, PLEASE DO
REACH OUT TO ME AND IF YOU'RE
INTERESTED AS A PRIVATE PARTNER
AND POTENTIALLY JOINING THE
ORGANIZATION I CAN CERTAINLY
ANTIBIOTIC -- INTRODUCE YOU TO
MY COLLEAGUES TO FACILITATE THE
COVERINGS.
WE'LL EXPAND THE WORK IN PHASE 1
INCLUDING DISCOVERY AND
VALIDATION OF BIOMARKERS.
WE'VE BEEN HEARING ABOUT THE
SEED AMPLIFICATION ASSAY.
I WILL NOTE MY COLLEAGUE DIANNE
STEVENSON IS IN THE AUDIENCE AND
THE CRITICAL PATH TO PARKINSON'S
DISEASE SUBMITTED A LETTER OF
SUPPORT TO THE FDA WHICH
RECEIVED A SUPPORT FROM THE FDA
TO ENABLE THE UTILITY OF THE CSF
AMPLIFICATION ASSAY TO ENRICH
FOR CLINICAL TRIAL DESIGN AS A
RISK SUSCEPTIBILITY MARKER AND I
THINK THERE'S SYNERGY WITH THAT
WORK FOR WHERE WE'RE GOING IN
THE NEXT PHASE OF AMP PRAD AND
ENABLE MULTI SCALE ANALYSIS
NETWORK.
>> OUR NEXT SPEAKER IS
DR. TIMOTHY HOHMAN FROM
VANDERBILT UNIVERSITY.
>> IT'S MY PRIVILEGE TO PRESENT
ON THE ALZHEIMER'S SEQUENCING
PROJECT PHENOTYPE HARMONIZATION
CONSORTIUM.
YOU HEARD EARLIER THIS WEEK
ABOUT THE ALZHEIMER'S SEQUENCING
PROJECT AND THE AMAZING DIVERSE
DATA BEING COLLECTED AS PART OF
THE PROJECT.
AND A LOT OF THE DATA SETS THAT
COME IN TO THE SEQUENCING
PROJECTS COME FROM DIFFERENT
COHORTS THAT USE DIFFERENT
PROTOCOLS IN DATA COLLECTION.
WE'VE HAD TO TACKLE THE
CHALLENGE OF HOW DO WE INTEGRATE
THOSE DATA COLLECTED IN VERY
DIFFERENT WAYS AND MAKE THEM
AVAILABLE TO RESEARCHERS FOR
GENOMIC DATA ANALYSIS.
WE ESTABLISHED A TEAM OF ABOUT
13 DOMAIN EXPERTS AROUND THE
COUNTRY WHO ALREADY HAD
ESTABLISHED METHODOLOGIES FOR
THE DIFFERENT DOMAINS WE HAVE
LISTED ON THE LEFT.
WE HARMONIZED DATA AND DOMAINS
OF RISK FACTORS AND COGNITIVE
DATA WITH DIFFUSION AND
STRUCTURAL IMAGE AND NEURAL
PATHOLOGY DATA.
WHEN WE DO THE DATA
HARMONIZATION THE GOAL IS TO
MAKE AVAILABLE FOR SEQUENCE
ANALYSIS AND INCLUDE EVERYONE IN
THE COHORT.
WE ALREADY HARMONIZED COGNITIVE
DATA FOR MORE THAN 80,000
PARTICIPANTS AND MADE THEM
AVAILABLE TO THE COMMUNITY.
ALL THE DATA ARE AVAILABLE AND
SEND THEM BACK TO THE INDIVIDUAL
COHORTS FOR PEOPLE USING THE
DATA AND JUST WANT HARMONIZED
PHENOTYPES FOR YOUR COHORT FOR
ADNI OR THE A4 STUDY YOU HEARD
ABOUT TODAY.
THERE'S DIFFERENT PLATFORMS SET
UP TO SOLVE DIFFERENT TYPES OF
PROBLEMS AND ONE WAS SET UP TO
DEAL WITH SHARING GENOMIC DATA
AND SHARE IMAGING DATA.
WE HELPED FACILITATE A NICE
COLLABORATION TO MAKE IT EASIER
ON THE USERS AND MAKE IT
POSSIBLE TO ACCESS RAW DATA FOR
USERS OF THAT.
AND WE HEARD AN OPPORTUNITY TO
DO WORK SHOP AND WEBINARS.
EACH YEAR WE PUT ON A WORKSHOP
WHERE WE GIVE HANDS ON TRAINING
TO THE RESEARCH COMMUNITY TO
LEARN HU TO DO DATA
HARMONIZATION, HOW TO TAKE THE
PHENOTYPES WE GENERATED AN USE
THEM IN YOUR OWN ANALYSES AND
WINDOW TO THE TYPE OF WORK WE
DO.
AND ON THE TOP RIGHT WE
INTEGRATED WITH GREAT PROGRAMS
YOU HEARD ABOUT TODAY.
WE WORKED WITH THE AD KNOWLEDGE
PORTAL FOR NEURAL PATHOLOGY DATA
AND STARTED WORKING WITH CARD
AND THE GPT 2 PLATFORM ON COMMON
DATA ELEMENTS TO BE EXTRACTED
FROM NEURAL PATH OLOGY SLIDES
AND INTEGRATE ACROSS DISEASES.
WE WORKED WITH THE NATIONAL
ALZHEIMER'S COORDINATING CENTER
YOU'LL HEAR MORE ABOUT IN
MINUTES AND HAD A CHANCE TO WORK
WITH FOLKS WHO DO ARTIFICIAL
INTELLIGENCE AND MACHINE
LEARNING.
THEY'RE HELPFUL FOR DATA
HARMONIZATION.
WE USE THE APPROACHES UP OUR
HARMONIZATION METHODS BUT THE
REASON WE WERE ESTABLISHED WAS
BECAUSE A LOT OF PEOPLE WHO DO
A.I. AND M.L. WORK WATCH THE TO
USE DATA FROM GENOMICS AND
NEURAL IMAGES BUT MAY NOT HAVE
THE EXPERTISE.
ONE HUGE DELIVERABLE ARE THE
A.I. READY DATA SETS THAT CAN GO
INTO WORK GROUPS THAT HAVE
EXPERTISE IN THAT AREA AND
ACCELERATE SOME OF THE
DISCOVERIES THAT CAN COME FROM
THAT AND YOU'LL HEAR MORE ON
THAT IN A FEW MINUTES.
ONE OTHER COLLABORATION IS WITH
A MILLION VETERANS PROGRAM AS
PART OF THE V.A.
THIS IS ONE OF THE FIRST
COLLABORATIONS BETWEEN THE V.A.
AND NIA TO MAKE IT POSSIBLE TO
DO GENOMIC DATA ANALYSIS ACROSS
THAT REALLY CDC PROGRAM IN THE
V.A. AND THE ADSP.
WE JUST STARTED THIS PROJECT AND
GOT UNDERWAY AND EXCITED TO
INTEGRATE ELECTRONIC HEALTH
REPORT DATA TO GET PHENOTYPES
AND PULLING IN CLINICAL IMAGES
TO PULL IN AD RELEVANT FROM DATA
AND WITH THE GOAL OF DOING JOINT
ANALYSIS IN THE FUTURE.
FINALLY YOU CAN READ MORE ABOUT
THE DATA WE HAVE HERE ON OUR
DATA EXPLORER TOOL AND WE TRY TO
MAKE THE DATA ACCESSIBLE TO
FOLKS ACROSS DIFFERENT LEVELS OF
EXPERTISE.
IF YOU'RE AN IMAGEER AND WANT TO
WORK WITH RAW IMAGING DATA IT'S
AVAILABLE BUT IF YOU NEVER
LOOKED AT AN IMAGE BUT
INTERESTED IN GENOMIC ANALYSIS
ON AMYLOID STAT STATUS AND
THOUGH THE DATA ARE COMING FROM
COMPLEX IMAGING ANALYSES.
AND SO HOPEFULLY YOU'LL CHECK
US -- US OUT AND THE
PARTICIPANTS WHO MAKE THEIR DATA
AVAILABLE FOR US TO MAKE AN
IMPACT ON THE DISEASE.
THANK YOU VERY MUCH.
>> THE NEXT SPEAKER IS DR. BIBER
FROM THE UNIVERSITY OF
WASHINGTON.
>> HELLO.
THANKS SO MUCH TO THE ORGANIZERS
FOR INVITING ME.
I'M THRILLED TO HAVE THE
OPPORTUNITY TO LEARN FROM ALL OF
YOU AND TO HIGHLIGHT THE WORK TO
REVOLUTIONIZE INTEROPERABILITY
AND DISCOVERY AND ACCESS FOR
ADRC PROGRAM DATA.
IT'S THE CENTRALIZED
COLLABORATORY AND COMMUNICATION
HUB FOR THE ALZHEIMER'S DISEASE
RESEARCH CENTERS PROGRAM OF 35
CENTERS ACROSS 24 STATES.
OVER THE PAST 2R5 YEARS WE BUILT
ONE OF THE LARGEST AND
COMPREHENSIVE LONGITUDINAL
NEUROPATHOLOGICAL DATA SETS IN
THE WORLD.
WE HAVE DATA ON MORE THAN 51,000
PARTICIPANTS WITH UP TO 19 YEARS
OF DATA ON SOME.
THIS INCLUDES PARTICIPANTS
HEALTHY, AT RISK AND WITH
DEMENTIA SYSTEMS.
THE UNIFORM DATA SET WHICH HAS
COLLECTED WITH ADRC SINCE 2005
IS STANDARDIZED AND LONGITUDINAL
AND CONSISTS OF ROBUST CRITERIA
BASED DIAGNOSES CONSIDERED GOLD
STANDARD BY THE FIELD.
IT HOUSES NEURAL PATHOLOGY DATA.
60% OF PARTICIPANTS ARE BRAIN
DONORS WITH PURE AND MIXED
ETIOLOGY.
IT HAS ENABLED MAJOR
BREAKTHROUGHS IN THE FIELD AND
USED TO GENERATE OVER 1300
PUBLICATIONS TO DATE.
ADDITIONALLY OVER THE PAST THREE
YEARS THREES BEEN OVER 100%
INCREASE IN THE AVERAGE NUMBER
OF DATA REQUESTS PER MONTH.
WE'RE NOW AT MORE THAN 100.
MUCH OF THE DATA IS STANDARDIZED
AND THERE'S DATA DRIVEN STANDARD
ALIGNED WITH THE DEVELOPMENTS.
THE LATEST VERSION WILL NOW
CAPTURE DATA ON USE OF DISEASE
MODIFYING DRUGS, SOCIAL
DETERMINATES OF HEALTH AND MILD
BEHAVIORAL IMPAIRMENT,
BIOMARKERS AND DIGITAL VOICE
RECORDINGS.
OUR CURRENT TOOLS HAVE BEEN
TRANSLATED INTO OVER 32
LANGUAGES AND USED IN 140
INTERNATIONAL RESEARCH STUDIES
OVER THE PAST FIVE YEARS.
TO FURTHER EMPOWER THE RESEARCH
COMMUNITY TO TACKLE THE MOST
COMPLEX AND PRESSING CHALLENGES
WE'VE ESTABLISHED A ONE STOP
SHOP FOR PARTICIPANT DATA.
THE FLEXIBLE AND MODERN CLOUD
BASED DATA PLATFORM IS MORE
MULTI-MODAL AND INTEROPERABLE
AND PROVIDES EASY ACCESS TO
INCREASING QUANTITIES OF DATA
STANDARDIZED AND HARMONIZED AND
INTEGRATE.
GO TO NACC DATA DOT ORG TO LEARN
MORE.
WE MIGRATED OUR EXISTING DATA
PLATFORM WITH PET DATA.
WE'RE ALSO IN THE PROCESS OF
BUILDING OUT NEW PIPELINES TO
INTEGRATE DIGITAL DATA AND
BIOMARKERS AND E.H.R. AND CLAIMS
DATA.
WE'RE EXPANDING INTEROPERABILITY
TO INTEGRATE MORE MODALITIES.
SO FAR INCLUDES FLUID DATA AND
MULTIOMICS DATA.
LASTLY, IT'S PROVIDING THE
INFORMATICS AND INFRASTRUCTURE
TO ENABLE MAJOR CROSS PROGRAM
INITIATIVES SUCH AS SCAN AND
CLARITY.
THIS TOO HAS MADE DATA STREAMS
AVAILABLE INCLUDING AT
STANDARDIZED MRI AND PET, FLUID
BIOMARKER AND IT WILL SERVE AS A
ONE STOP SHOP FOR RESEARCHERS TO
SEARCH, VISUALIZE ALL MODALITIES
FOR PARTICIPANTS ACROSS
REPOSITORIES.
THE DATA FRONT DOOR SELF-SERVICE
COMPONENTS INCLUDE QUICK ACCESS
FILES, REAL TIME DASH BOARDS AND
SELECTION TOOL FOR BUILDING DATA
SETS.
WE'RE ALSO PILOTING A SECURE
ENVIRONMENT WITH THE LINKAGE
PLATFORM.
OUR QUICK ACCESS FILE ENABLES
RESEARCHERS TO ACCESS DATA
WITHIN 24 HOURS BY SIGNING A
DATA USE AGREEMENT AND
SUBMITTING A 15-MINUTE DATA
REQUEST.
IT PROVIDES REAL TIME
INFORMATION HOW MUCH MRI AND PET
DATA IS AVAILABLE.
OUR NEW NEW SECURE ENCLAVE
ENABLES RESEARCHERS PART OF OUR
PILOT STUDY TO ANALYZE E.H.R.
AND CLAIMS DATA FROM CONCEPTS
PARTICIPANTS.
OUR COHORT BROWSER TOOL ONLINE
IN THE NEXT YEAR WILL ENABLE
RESEARCHERS TO BUILD THEIR OWN
MULTI-MODAL DATA SETS WITH
PARTICIPANT DATA AVAILABLE ON
THE PLATFORM OR PARTNER
REPOSITORIES.
WE EXPECT MAKING ALL THESE DATA
MODALITIES AVAILABLE FOR THE
PARTICIPANTS WILL EMPOWER
RESEARCHERS TO ANSWER NEW
QUESTIONS TO ADVANCE THE FIELD.
AND DE-UTILIZATION.
WE'RE TALKING NEARLY 20,000
PARTICIPANTS WITH MORE THAN 12
DATA TYPES AVAILABLE FOR EACH.
I'M ALSO SXIETED TO SHARE HOW WE
PLAN TO FURTHER LEVERAGE DATA TO
DRIVE DISCOVERY AND TRANSLATION
AS PART OF OUR RENEWAL
APPLICATION.
WE'LL LAUNCH A RESEARCH
NAVIGATOR TEAM TO SUPPORT
RESEARCHERS IN MATCHING THE DATA
TO QUESTIONS AND PROVIDER
ONRAMPS TO RESPONSIBLE A.I.
WE'LL FACILITATE COMPUTATIONAL
ANALYSIS BY PROVIDING A SECURE
ENVIRONMENT EQUIPPED WITH BUILT
IN TOOLS LIKE JUPYTER NOTEBOOKS
AND GPUs AVAILABLE TO DEVELOP
AND TEST ALGORITHMS TO
SUBSIDIZED FEE FOR SERVICE MOLE
AND THE ENCLAVE WILL ENABLE
DISCOVERIES THROUGH
COLLABORATION WITH PARTNERS AND
GATE VENTURES AND CATTLE AND
SAGE BIO NETWORKS.
TO SUPPORT TRANSPARENT,
RESPONSIBLE AND EXPLAINABLE
RESEARCH IT WILL PARTNER TO HAVE
AN OPEN REPOSITORY OF A.I.
ALGORITHMS.
IT WILL ENABLE THE RESEARCH
COMMUNITY TO VALIDATE ALGORITHMS
CONDUCT DEEPER MULE TIE MODEL
ANALYSIS AND TEST DIFFERENT
POPULATIONS AN SAVE RESOURCES BY
ENABLING RESEARCHERS TO BUILD
OFF EACH OTHER TOOLS RATHER THAN
RECREATING THE WHEEL.
WE HOPE THESE INITIATIVES WILL
FURTHER DEMOCRATIZE AND BUILD
TRUST IN THE RESEARCH.
>> THANK YOU.
OUR NEXT SPEAKER IS ANDY SAKIN
FROM INDIANA UNIVERSITY.
>> WE'VE BEEN HEARING ABOUT A
TREMENDOUS VOLUME OF DATA FOR
TWO AND A HALF DAYS ESPECIALLY
IN THIS SESSION.
JUST EXTRAORDINARY.
IT USED TO BE WHAT MY COLLEAGUE
CALLED DATA PENIA AND HAVE RAIN
EXPLOSION OF EXTREMELY VALUABLE
DATA.
HOW DO WE ANALYZE AND EXTRACT
THE IMPORTANT INFORMATION FROM
THIS COMPLEX MATRIX?
HOW DO WE PUT CUTTING PLANES TO
THE HAIR BALL OF THE
CONNECTIVITY OF THE DATA
DIFFERENT SETS?
ONE IMPORTANT PROGRAM TRYING TO
BRING ADVANCED ANALYTIC
STRATEGIES TO THE FIELD IS A.I.
AND MACHINE LEARNING CONSORTIUM.
I MENTIONED GIVING A TELEGRAPHIC
DESCRIPTION OF THE GENETICS
INITIATIVES ON MONDAY, THAT WAS
ADDED LATER IN THE GAME OF 2021.
THE FIRST TWO PROJECTS AND
THERE'S A LIST IN THE UPPER
CORNER OF THE EIGHT PROGRAMS
FUNNED THROUGH THE INITIATIVE.
THE FIRST TWO INCLUDING WHAT WE
CALL A.I. FOR AD CONSORTIUM WITH
FIVE P.I.s AND MANY OTHER
INVESTIGATORS WAS FUNDED AND
ANOTHER AND SIX ADDITIONAL
JOINED A YEAR LATER.
WITH HAVE REGULAR MEETINGS AND
DO DATA SHARING CROSS GROUPS
WHICH HAS BEEN EXCITING.
I WANTED TO GIVE A FEEL FOR SOME
OF THE WORK GOING ON.
ONE OF THE MAJOR FOES DID BE
FOSI IS THE IMAGING AND FLUID
BIOMARKERS AND SO ON.
THE CONSORTIUM FOR PHENOTYPE
HARMONIZATION CAME A YEAR INTO
THIS.
WE HAD TO START AND DO SOME OF
THIS WITHIN A.I. M.L. AND DO
THIS ON A LARGE SCALE BASIS.
TAKING IMAGE WE CAN USE DEEP
LEARNING APPROACHES AND ASK THE
INFORMATIVE FEATURES AND DOING
GROUP ANALYSES AND VARIOUS
STRATEGIES BUT NOW WE HAVE OTHER
TOOLS THAT COULD TELL US WHAT
FEATURES MAY BE MAXIMALLY INFORM
AND MAY SERVE AS BETTER
PHENOTYPES FOR CLINICAL TRIALS
AND SO ON.
IN THE UPPER RIGHT IS AN EXAMPLE
OF ANALYSIS OF TAU PET BY DEEP
LEARNING AT INDIANA UNIVERSITY.
THE LOWER IMAGE SHOWS A
CONVENTIONAL GROUP ANALYSIS WITH
TAU PET.
THE UPPER IMAGE IS WHAT A DEEP
LEARNING ALGORITHM IDENTIFIES AS
THE MOST INFORMATIVE FEATURE
AREA AROUND THE INTER-RHINAL
CORTEX AND MAY BE A BETTER
PHENOTYPE.
WE HAVE 3 BILLION BASE CARES OF
PAIRS IN THE GENOME AND 60,000
GENOMES BY THE RELEASE THIS YEAR
AND ANOTHER 80,000 THE YEAR
AFTER.
HOW DO WE INTERROGATE 3 BILLION
BASES TIMES 80,000 INDIVIDUALS
OR MORE AGGREGATING DATA FROM
U.K. BIO BANK AND OTHER
SEQUENCING SOURCES?
ONE WAY IS TO USE DEEP LEARNING
APPROACHES OR LARGE LANGUAGE
MODEL STRATEGIES.
ONE EXAMPLE SHOWN IN THE LOWER
LEFT PANEL WAS SOMETHING WE
CALLED SWAT CNN A SLIDING WINDOW
THROUGH THE GENOME AND DOES
CONVOLUTIONAL ANALYSIS TO FIND
INFORMATIVE FEATURES AND GETTING
COMPARED TO THE
AT
UNIVERSITY OF PENNSYLVANIA
STUDY PUBLISHED IN NATURE
COMMUNICATIONS EARLIER THIS
YEAR BY YAN ET AL, LOOKED AT
MRI FROM 28,000 INDIVIDUALS
AND LOOKED FOR MOLECULAR
SUBTYPES, MORPHOLOGIC
SUBTYPES MAXIMALLY
ASSOCIATED WITH GENETIC DATA
AND FOUND FOUR SUBTYPES.
THERE'S MANY WAYS TO SLIGHTS
THEM UP, WE NEED TO FIND THE
MOST ACTIONABLE AS WE TALKED
ABOUT MONDAY. THIS IS A
STRATEGY FOR EXTRACTING THE
INFORMATIVE INFORMATION FROM
VERY LARGE VERY HIGH
DIMENSIONAL DATA SETS. AND
WE'LL HAVE MUCH PROMISE. ONE
IMPORTANT PRINCIPLE THOUGH
IS WE CAN'T JUST RUN THIS AS
A BLACK BOX THROW THINGS
INTO THE HOPPER AND SEE WHAT
COMES OUT OF THE OTHER END
AND WHAT ARE THESE
MULTI-LAYERED NETWORK ANAL
SEE. WE NEED TO UNDERSTAND
WHY THEY, WHO. IF I FINDS A
DRUG TARGET WHICH IS DRUG
REPURPOSING TARGET ONE OF
THE STRATEGIES THAT
(INDISCERNIBLE) IS LEADING
FOR THE GROUP OR FINDS
INFORMATIVE REGION, OR A NEW
GENETIC LOCI THAT'S
DETECTED, WE HAVE TO
UNDERSTAND WHY IT WORKS. SO
WE NEED MAXIMALLY
INFORMATIVE OPEN STRATEGIES
FOR THAT. THAT'S A MAJOR
PRINCIPLE FOR THE GROUP. I
WILL STOP THERE. BUT I THINK
YOU CAN SEE THE POTENTIAL
PROMISE OF THESE APPROACHES
AND CONSORTIUMS.
>> THANK YOU, DR. SAYKIN. OUR
NEXT SPEAKER IS DR. EUGENE
HINDERER FROM TUFTS UNIVERSITY.
>> THANKS. GOOD AFTERNOON. MY
NAME IS EUGENE HINDERER, FROM
TUFTS CLINICAL AND TRANSLATIONAL
SCIENCE INSTITUTE. SINCE 2019
OUR TEAM HAS BEEN HARD AT WORK
DEVELOPING TAP DISCOVERY. AI
PLACED PLATFORM FOR MULTI-SCALE
CLINICAL AND LABORATORY DATA
ANALYSIS, AUTOMATED DATA MINING,
AND KNOWLEDGE ENHANCED MACHINE
LEARNING. OUR AIM IS TO PROVIDE
ACADEMIC RESEARCHERS WITH
COMMERCIAL GRADE TOOLS AN
INNOVATIVE INFRASTRUCTURE TO
ACCELERATE RESEARCH AND CREATE
ACTIONABLE METRICAL DISCOVERIES.
FIRST AND MOST MOW WE DESIGNED
AN OPEN SCIENCE PLATFORM WITH
FEATURES AND PERFORMANCE OF
COMMERCIAL GRADE INFORMATICS
SYSTEM. TO NAME MANY KEY ASPECTS
OF THIS PLATFORM FIRST IT IS
DESIGNED FOR ALL TYPES OF U
CRUISERS FROM CLINICS EYE
BIOLOGISTS TO CHEMISTS. T IT
INCLUDES SEAMLESS ACTS IS TO
BILLIONS OF KNOWLEDGE
ASSOCIATIONS FOR USER IN YOUR
MODELS, CONTAINS DATA RANGELING
TOOLS WITH INTERNAL CALL CHECKS,
USE BEST IN CLASS MACHINE
LEARNING MODELS TO HANDLE
MULTI-SCALE CLINICAL OMIC AND
IMAGING DATA USED TOGETHER IN A
MODEL THAT GOES BEYONDS COMMON
MACHINE LEARNING ALGORITHMS TO
ADAPT WORKLOADS AND MILLION
SCALE REASONING. ALLOWING DATA
DRIVEN MULTI-SCALE ANALYTICS AND
BIOMEMECAL INFORMATICS IN ONE
DISCOVERY. WHAT WE CALL THE
VIRTUOUS LOOP AT TOP RIGHT. TAP
DISCOVERY ALSO SAVES WORKLOADS
TO USE WITH EXISTING DATA SETS
FOR REPRODUCIBILITY AND NEW DATA
SETS FOR EXPERIMENTAL
CONSISTENCY. TO SHARE WITH
COLLABORATORS. EVERYTHING TO
REINFORCE BEST SCIENTIFIC
PRACTICES. FOR ADVANCED
ANALYSIS, A PLATFORM INCLUDES
INTEGRATED EXMANGE AI METHODS,
WHAT IF SCREENS AND AUTOED MATED
RURAL GENERATOR ON COUNTER
FACTUALS. WE INCLUDED
BIOINFORMATICS INDIVIDUALS TO
ASSIST USER IN UNDERSTANDING AND
SHARING RESULTS 6789 DOMAIN
SPECIFIC TOOLS LIKE GENOME
BROWSERS, VIEWERS CHEMICAL EDIT
TORRS AND PATHWAY VISUALS. ALL
LIVE LINKERRED WITHIN ALL AI AND
ML RESULTS AND BIOCHEMICAL
INFORMATICS CAPABILITIES. IN
ADDITION, USER DEFINED KNOWLEDGE
GRAFTS SUPPORTED BY INTERNAL
KNOWLEDGE REPOSITORY OF OPEN
SCIENCE KNOWLEDGE HELP PLACE
RESULTS IN CONTEXT OF DISEASE
AND PHENOTYPES, PATHWAYS AND
HALLMARKS, AND ALL THE WAY DOWN
TO PROTEINS AND CHEMICALS AND
PROCESSES. THIS AGE
UNDERSTANDING GIVING NEXT STEPS
TO EXPLORATION TOWARDS NEW
DISCOVERIES. LASTLY, TWO
FEATURES THAT ARE ON THE HORIZON
BEFORE U OUR Q1 PUBLIC REELS
WILL INCLUDE ADDING POWERFUL LLM
CAPABILITIES TO FURTHER ENHANCE
EXPLANATION AND CONTEXT
BUILDING, AND FEATURES TO
AUTOMATICICALLY GENERATE METHOD
SECTION IN SUPPORTING FIGURES TO
ASSIST IN EASE OF PUBLICATIONS.
TO FULLY APPRECIATE TAP
DISCOVERIES CAPABILITIES I WANT
TO POINT OUT BUN OF OUR PILOT
PROJECTS, WHICH IDENTIFIED
POTENTIAL DRUG TARGETS
ASSOCIATED WITH SIGNIFICANT
COGNITIVE DECLINE IN
ALZHEIMERALZHEIMER'SDISEASE. WEA
FROM THE ROZ MAP STUDIES MOST
MODEM RNA SEQ DEMOGRAPHICS AND
COGNITIVE DECLINE ASSESSMENTS
FROM 146 INDIVIDUALS AND
CONTAINED OVER 56,000 FEATURE
VARIABLES.
WE TRAIN NINE MACHINE LEARNING
ALGORITHMS WITH HYPERFEATURE
OPTS MYIZATION WITH SELECTED
PREDICTIVE AND HIGH COGNITIVE
DECLINE AMONG SUBJECTS. WHILE WE
IDENTIFIED MANY DISEASE RELATED
FEATURES THE SYSTEM FLAGGED ONE
FEATURE CONSISTENTLY ACROSS THE
NINE MODELS WHICH WAS THE
EXPRESSION OF GENE CALLED
QUINNOID DIQDPR. MORE ON THAT IN
A MOMENT. USING THE PLATFORM
CAPABILITIES I MENTIONED
EARLIER, WE WERE ABLE TO
INVESTIGATE OUR RESULTS IN REAL
TIME RATHER THAN NEEDING TO END
THE STORY HERE OR MOVE TO
EXTERNAL TOOLS. USING OUR
MATHEMATICAL H H EQUIPOISE SCRE,
WE EXAMINE THE MODEL CONFIDENCE
AND PREDICTIONS ALLOWING US TO
UNDERSTAND THE ROBUSTNESS OF OUR
MODEL. WE USE PLATFORMS RURAL
GENERATOR FEATURE TO IDENTIFY
MINIMUM SET OF RULES BE MINIMUM
PERTURBATIONS TO CHANGE
PRETICKETED OUTCOMES. THE
CLINICAL OBSERVATION OF COG ANY
GIVE DECLINE. WE EXPLORED GENES
LIKE REQUEST,DPR, RELATE TO
KNOWN PHENOTYPES PATHWAYS SMALL
MOLECULE LIGANDS, USING OUR
KNOWLEDGE GRAPH TOOL, WHICH
GIVES US BETTER INSIGHT IN TO
POSSIBLE DISEASE MECHANISMS.
OUR NETWORK GRAPH ALLOWED TO
FURTHER VISUALIZE COMMONALITIES
AMONG SHARED GENE FEATURES,
CELLULAR LOCATION AND REGULATORY
PROCESSES. AND THIS IS CRITICAL
FOR ZEROING MECHANISMS AT PLAY
THAT INVOLVE OUR TARGET FEATURES
IN THE CONTEXT OF ALZHEIMER'S
PATHOLOGY. FINALLY, WE USE MANY
DOMAIN STANDARD BIOINFORMATICS
TOOLS INCLUDING A GENOME BROWSER
CHEMICAL VIEWER AND EDITOR AND
3-D PROTEIN VISUALIZER TO
FURTHER EXPLORE AND VET OUR
MODELS. CIRCLING BACK TO
IDENTIFICATION OF QDPR, WE WERE
ABLE TO USE THE TOOLS I JUST
DESCRIBED ALONG WITH THE
TRANSCRIPTOMICS MODEL OF AD TO
IMPLICATE KEY COMPONENTS OF THE
OXIDATIVE STRESS RESPONSE AND
MITOCHONDRIAL DYSFUNCTION AS
DRIVING FACTORS FOR OUR COG I
INTIVE DECLINE IN OUR MODEL.
PROMISINGLY A PARALLEL STUDY
CONNECTED BY MIT INVESTIGATING
SINGLE CELL TRANSCRIPT OMICS
USING THE SAME CORTAID FEWED
QDPR AS ONE OF FOUR GENES
EXPRESSION SIGNATURES
CONSISTENTLY DEFINED A
SUBPOPULATION OF PATHOLOGICAL
OLIGODENDROCYTES IN ALZHEIMER'S
POSITIVE SUBJECTS. SO TO
CONCLUDE, AS AI ENABLED
TECHNOLOGY IS LIKE TAP DISCOVERY
CONTINUE TO EVOLVE AND ENTER THE
MAINSTREAM, WE BELIEVE THEY WILL
DRIVE ACCELERATED INSIGHT AND
ACTIONABLE INFORMATION. WHAT WE
LIKE TO CALL AI 3. WE BELIEVE
TAP DISCOVERY IS A PIONEER IN
THIS REGARDS. AND WE PREPARE TO
GO LIVE -- I'M SORRY. WE INVITE
YOU TO JOIN US IN THIS CHART.
THANK YOU.
>> THANK YOU. SO NOW WE WOULD
LIKE TO DESCRIBE SOME OF THE
GAPS AND OPPORTUNITIES THIS
GROUP OF EXPERTS IDENTIFIED. SO
FIRST AND FOREMOST, WE DIVIDED
GAPS AND OPPORTUNITIES INTO
MULTIPLE DOMAINS. AND I THINK
THAT MANY OF THE TALKS ALREADY
TOUCHED ON SOME THESE ISSUES BUT
I WILL TAKE A MINUTE TO
HIGHLIGHT SOME OF THOSE ISSUES
THAT WERE DISCUSSED. SO IN THE
DOMAIN OF DATA DISCOVERY --
DISCOVERABILITY INTEROPERABILITY
AND SUSTAINABILITY, WE
IDENTIFIED OPPORTUNITIES TO
IMPROVE THE FINDIBILITY OF DATA
SETS, TO ENCOURAGE
STANDARDIZATION OF BOTH DATA AND
METADATA. AS WELL AS TO
ENCOURAGE HARMONIZATION APPROACH
SUCH AS THOSE DECLINED BY DR.
HOHMAN. WE ALSO DISCUSSED
ESTABLISHING TECHNICAL
STANDARDS, THAT FOR DATA
FEDERATION, FEDERATED LEARNING,
AND DIGITAL TWINS TECHNOLOGIES.
AND FINALLY WE DISCUSSED THE
OPPORTUNITIES AVAILABLE TO
ENSURE DATA SHARING PROGRAMS ARE
SUSTAINABLE OVER THE LONG RUN BY
DEVELOPING FUNDING MODELS THAT
CAN SUPPORT DATA STORAGE
SECURITY AND CURATION. IN TERMS
OF DATA OPPORTUNITIES FOR DATA
DIGITAL DATA PLATFORMS THERE WAS
QUITE A BIT OF CONSIST CUSHION
ABOUT THE DIFFERENT MODELS THAT
ARE AVAILABLE AND INTEREST IN
SUPPORTING HYBRID DATA ACCESS
MODELS WHERE THEY MIGHT BE A
COMBINATION OF ENCLAVE APPROACH,
DOWNLOAD OR AGGRAVATED OR
FEDERATED APPROACHES. IN TERMS
OF THE OPPORTUNITIES AVAILABLE
FOR REAL WORLD DATA INTEGRATION
WITH SOME OF OUR COHORT DATA,
SOME OF THOSE OPPORTUNITIES
DESCRIBED BY DR. COREO IN HER
RELATION, WE DISCUSSED THE
OPPORTUNITIES AVAILABLE TO
INTEGRATE INFORMATION ABOUT THE
CLINICAL USE OF FIRST GENERATION
DISEASE MODIFYING THERAPIES FROM
NATIONAL TREATMENT REGISTERS,
SUCH AS ALSNET TO DEVELOP
THERAPIES TREATMENT PLANS AN
PRICING MODELS AND USE OF
PRIVACY PREPRESERVING RECORD
LINKERRING APPROACHES LINKS
BETWEEN REAL WORLD DATA AND
RESEARCH COHORT. IN TERMS OF
DATA RELATED TO OPPORTUNITIES
AVAILABLE FOR AI AND MACHINE
LEARNING AND DEEP LEARNING, WE
DISCUSSED THE YOU ARE GENERAL
NEED TO DEFINE GUIDELINES FOR
THE ETHICAL RESPONSIBLE
REPRODUCIBLE EXPLAINABLE
CRITICAL AND TRUSTWORTHY USE OF
AI. AND ALSO THINKING ABOUT THE
ENVIRONMENTAL IMPACTEDS OF USING
AI ESPECIALLY FOR MODEL TRAINING
AND INFERENCE. IN MANY TERMS OF
OPPORTUNITIES FOR THE EX ANDED
USE OF CLINICAL TRIALS DATA WE
DISCUSSED THE OPPORTUNITY TO
INCENTIVIZE THE DEVELOPMENT OF
PRECISION MEDICINE APPROACH IN
TRIAL DESIGN AND IMPLEMENTATION
IN THE DOMAIN OF OPEN SCIENCE
AND TEAM SCIENCE PRACTICES WE
WERE ALL VERY MUCH IN SUPPORT OF
THINKING ABOUT THE OPPORTUNITIES
TO ENGAGE ALL STAKEHOLDERS IN
THE DATA SHARING PROCESS TO
ENSURE THAT THERE'S EQUITY IN
TERMS OF THE BENEFITS AND RISKS
ASSOCIATED WITH DATA SHARING.
AND WE SEE THAT AS ALSO
INCLUDING PARTICIPANTS IN THAT
DISCUSSION AS WELL AS
COMMUNITIES. WE TALKED ABOUT
EXPANDING TRAINING PROGRAMS IN
DATA SCIENCE TO PROMOTE THE
EXPANSION OF SKILLS NECESSARY TO
WORK WITH THESE COMPLEX DATA
SETS. AND ALSO TO DEVELOP
REALLY RESEARCH INTO TEAM
SCIENCE SPECIFICALLY SO THE
SCIENCE OF TEAM SCIENCE IF YOU
WILL, TO BETTER UNDERSTAND
STRATEGIES THAT CAN EFFICIENTLY
AND COST EFFECTIVELY USE THE
LARGE TECHNICAL AND HUMAN
RESOURCES WITHIN AN OPEN SCIENCE
FRAMEWORK. FINALLY, THERE WAS
QUITE A BIT OF DISCUSSION ABOUT
ENSURING THAT THE TRANSPARENCY
AND RECIPROCITY WHEN SHARING
WITH INVESTIGATORS BOTH IN THE
U.S. AS WELL AS OUTSIDE THE U.S.
MAKING SURE THAT US-BASED
INVESTIGATORS CAN ACCESS
INTERNATIONAL DATA AND SAMPLES.
SO WITH THAT, I WOULD LIKE TO
OPEN UP THE SESSION FOR
QUESTIONS, BOTH OUR SPEAKERS AS
WELL AS TO THE AUDIENCE AND FOR
QUESTIONS FROM THE AUDIENCE, I
WANTED TO ASK IF THE INDIVIDUAL
COULD PRESENT THEMSELVESES WITH
HAIR NAME AS WELL AS
AFFILIATION. SO MAYBE WE CAN
START WITH --
>> WE HAVE AN ONLINE PARTICIPANT
ASKING A QUESTION ABOUT THE A
FORCE STUDY. AND ACTC.C. THE A
FORCE IS IT DI IS VALUABLE TO
RESEARCH ERGS. DOES ACTK
CONSIDER SHARING DATA FROM OTHER
CLINICAL TRIALS?
>> THAT IS AN EXCELLENT
QUESTION. THANK YOU. SO WE ARE
WORKING ON APPLYING THE SAME
METHODS THAT I DESCRIBED HAVE
BEEN USED FOR THE A FORCE STUDY
RESPECTIVELY AND PERSPECTIVELY.
ONE EXAMPLE OF PROSPECTIVE
PROJECT WE WILL BE EMBARKING ON
SOON IS SHARING THE
PRE-RANDOMIZATION DATA FOR THE
HEAD STUDY SCHEDULED TO COMPLETE
ENROLLMENT BEFORE THE ENDS OF
THIS YEAR. SO WE EXPECT
PRE-RANDOMIZATION DATA FOR AHEAD
WILL BE AVAILABLE BY THE END OF
NEXT YEAR.
>> INCENTIVIZING -- PUTTING OUT
THERE MANY OF THE CLINICAL
STUDIES THAT WERE COMPLETED,
THOSE THAT FAILED AND THOSE THAT
ENABLED APPROVAL OF SOME DRUGS,
WHATEVER IF WE START WITH THE
ONES AND PUT THIS BIG DATA OUT
THERE, I'M SURE THERE'S GOING TO
BE MUCH MORE TO LEARN FROM THE
BIG DATA ON THIS INDIVIDUALS AND
RESPONSES AND VARIATIONS AND
PERHAPS DEFINING SOME SUBGROUPS
OF INDIVIDUALS WHOP MIGHT BE
FUNDERS WHO ARE MISSED IN THE
ACTION SO THESE DRUGS COULD BE
PROVES INTO BIOLOGY WHICH IS
VERY POWERFUL.
>> CONTAINER MAYOR CLINIC. QUICK
COMMENT AND A QUESTION. COMMENT
IS I APPRECIATED THE FACT
SHARING DATA ACCORDING TO NOT
ONLY FAIR BUT ALSO CARE
PRINCIPLES WAS HIGHLIGHTED HERE.
AND THAT'S SOMETHING THAT WE
NEED TO CONTINUE TO HARP UPON.
THANK YOU FOR BRINGING THAT UP.
THE QUESTION PERTAINS TO ALL THE
DATA RESOURCES, IT IS WONDERFUL
TO SEE THE INITIATIVES BRINGING
TOGETHER THE VARIETY OF DATA
RESOURCES IS EXEMPLIFIED IN THE
NAC DATA FRONT DOOR THAT
BRINGING TO NAC AND THE AD
KNOWLEDGE PORTAL BUT THERE IS
FAR MORE BEYOND THAT. AT THESE
MEETINGS WE HAVE BEEN DISCUSSING
IT WILL BE USEFUL TO HAVE A
DATABASE OF DATABASES. ARE THERE
PLANS FROM THE NIH, ALZHEIMER'S
ASSOCIATION AND OTHER FUNDERS TO
BUILD SOMETHING LIKE THAT
BECAUSE WE ONLY KNOW WHAT WE
KNOW.
>> I THINK YOU DID ONE OF OUR --
DO YOU WANT TO TAKE THAT
QUESTION?
>> I THINK THAT IS AN EXCELLENT
SUGGESTION. THE DEVIL IN THE
DETAIL OF COURSE. WHAT SORT OF
INFORMATION WOULD BE INFORMATIVE
FRANKLY, PARTICULAR RESEARCH
QUESTIONS? HOW FORTHCOMING WOULD
THE DIFFERENT DATABASES BE IN
ALLOWING THAT TO HAPPEN? I WOULD
REALLY WELCOME THIS, THE TROUBLE
IS HAVING WHAT YOU MIGHT
DESCRIBE AS A TRUSTED THIRD
PARTY, WHICH CAN BE GOVERNMENT
FUNDED BUT IT DOESN'T MATTER,
THE POINT IS THEY ARE TRUSTED AS
INDEPENDENT THIRD PARTIES TO
REPRESENT ALL DIFFERENT
DATABASES. THE ISSUE THEN COMES
DOWN TO CONSISTENT DATA MODELS,
SO YOU ARE COMPARING APPLES WITH
APPLES EXPLICITLY. I THINK IT
WOULD WORK BUT I WOULD CERTAINLY
SUPPORT IT.
>> AID DO WANT TO POINT OUT
THERE IS A EFFORT IN BETA BY NLM
TO CATALOG DATA SETS ACROSS ITS
FOCUSING PRIMARILY ON DB GAP AND
ALL THE DATA RESOURCES. IT IS
IN BETA, THAT NEEDS TO BE SCOPED
BEYOND THAT BUT FINDING THE DATA
IS CLEARLY A BEGINNING.
>> IT IS A GREAT QUESTION, I
JUST THINK ONE OF THE THINGS
THAT WOULD BE REALLY IMPORTANT
IS TO TRY TO CONNECT THE
CLINICAL DATA THAT WE HAVE IN
SOME OF OUR CLINICAL DATA SETS,
TO THE OMICS DATA THAT WE HAVE
ON AGORA AND SAGE AND ET CETERA
THOSE LINKS WE ARE TRYING TO
TEST WITH SARAH AND DR.
(INDISCERNIBLE) WITH THE
TREATMENT LEVEL DATA WE ARE
TRYING TO GATHER IN ALSNET. BUT
THAT IS SOMETHING THAT I DON'T
KNOW IF WE HAVE MANAGED TO DO.
I'M NOT A DATA SCIENTIST. I KNOW
WE WILL ATTEMPT TO DO IT WITH
NAC. BUT I MEAN, I THINK IT IS
REALLY GREAT POINT.
>> WE HAVE SEEN BIG INTEREST
FROM THE NON-PROFIT
ORGANIZATIONS IN BRINGING
TOGETHER SOME OF THESE BIG
REPOSITORIES, CREATING A
DIALOGUE AND WORKING, MAYBE WE
MENTIONED ISSUE OF
STANDARDIZATION AND USE IT IN
DIFFERENT WAYS, META, WHEN I
TALK ABOUT STANDARDIZATION, I --
THE OMICS DATA WE REPRODUCE
OMICS DATA THIS IS NOT GOING TO
HAPPEN IN ME TAN LOAMICS BUT
STANDARD DIEDING EVERYTHING ELSE
TO MAKE BIOREPOSITORIES WORK,
COLLABORATE, LEARN TOGETHER, AND
IMPROVE THE WHOLE PROCESS, IS
THIS HAPPENING? ANNA? ARE THESE
REPOSITORIES MEETING,
COLLABORATING, DISCUSSING THE
FUTURE HOW IT CAN WORK FOR ALL
OF US?
>> YES. I THINK THE IN HIA HAS
BEEN DOING A GREAT JOB AND THIS
IS LED BY META OVER THE PAST
YEAR BRINGING TOGETHER THESE
REPOSITORIES TO START HAVING
THESE CONVERSATIONS ABOUT WHAT
IS REALLY REQUIRED. THERE IS
THIS EFFORT TO ACCEPTOR
EVERYTHING AROUND USE CASES.
BECAUSE AS JOHN WAS POINTING
OUT, THE DEVIL IS IN THE DETAILS
HERE. SO WHAT ARE THE REARS
TRYING TO ASK AND HOW CAN WE
HELP ANSWER IT WITH THE WAY WE
BILL OUR SYSTEMS AND DEVELOP OUR
INTEROPERABILITY.
>> QUESTION FROM THE AUDIENCE.
>> HI. SARAH (INDISCERNIBLE)
FROM MICHIGAN STATE UNIVERSITY.
FIRST THANK YOU TO EVERYBODY
INVOLVED IN THIS CONFERENCE. I'M
RELATIVELY NEW TO THE FIELD AND
IT'S BEEN REALLY GREAT TO HEAR
ALL THE RESOURCES AND ALL THE
THINGS THAT ARE AVAILABLE AND
HEAR FROM SUCH WONDERFUL EXPERTS
AND TO GET A GREAT IDEA OF WHERE
THE FIELD IS HEADING IN THE
FUTURE AS WELL. TO MY QUESTION,
IT KIND OF BUILDS OFF THE
PREVIOUS QUESTION, IN IN TERMS
OF MAKING NEW INVESTIGATORS OR
OTHER INVESTIGATORS IN THE FIELD
AWARE OF THESE RESOURCES, APART
FROM COMING TO WONDERFUL
CONFERENCES AND SYMPOSIUMS SUCH
AS THIS, ARE THERE EFFORTS WHICH
TO REACH OUT AND TO MAKE PEOPLE
AWARE OF WHAT IS AVAILABLE,
CONNECT RESEARCHERS THAT MIGHT
HAVE SIMILAR FIELDS OR SIMILAR
INTERESTS SO THAT WE CAN START
TO BRING THE PEOPLE TOGETHER NOT
JUST THE DATA?
>> MAYBE I CAN START. ONE OF THE
WAYS IN WHICH WE TRY TO DO THAT
IS TO PROVIDE PLATFORMS A THE
ALZHEIMER'S ASSOCIATION
INTERNATIONAL CONFERENCE. SO EF
WITH FOR EXAMPLE SHARED BOOTH
WITH GAIN.ORG WITH ADDI
ALZHEIMER'S DATA INITIATIVE, AND
WE ALSO HAVE SESSIONS FOR THE
PRECISION MEDICINE PROGRAMS, IT
IS A LOT OF DAYS PRE-MEETINGS AT
AIC AND WE HAVE HAD SUCCESSFULLY
HAD THEM A FEW YEARS IN A ROW.
SO THERE'S LOTS OF OPPORTUNITIES
AT THE CONFERENCES IN ORDER TO
ENGAGE WITH ALL OF THESE GROUPS
INCLUDING THE EDST AND NAC AND
SO MANY OTHERS, THERE'S
WORKSHOPS AND YOU HEARD DR.
HOHMAN MENTION WORKSHOPS TO
TEACH PEOPLE HOW TO USE THESE
BECAUSE THESE ARE BIG DATA SETS,
IF YOU ARE NOT A DATA SCIENTIST
LIKE ME YOU GET LOST AND YOU
DONE KNOW WHERE TO START. SO
THESE ARE SOME EFFORTS. PERHAPS
THERE'S -- ONE OF THE CHALLENGES
WE CAN TAKE ON IS TO TRY TO
FIGURE OUT HOW TO CENTRALIZE
THOSE IN ONE PLACE SO THEY
ADVERTISE AND NOT JUST -- THEY
ARE SCATTERED ACROSS LIKE THAT
TYPE OF A CONFERENCE AND MAIN WE
CAN MAKE MORE AN EFFORT TO
CENTRALIZE ALL OF THE
OPPORTUNITIES AVAILABLE FOR
PEOPLE. THANK YOU FOR THAT
COMMENT.
>> I WANT TO ADD TO THAT. I
THINK PART OF BRINGING PEOPLING
TO INVOLVES ENCOURAGING AND
EMPOWERING BIOMEDICAL
RESEARCHERS TO USE AI ENABLED
TOOLS BECAUSE IT IS A BARRIER TO
ENTRY TO A LOT OF THEM, THEY GET
INTIMIDATED. THIS IS ALL NEW
SCIENCE. SO ONE OF THE THINGS
THAT WE TRY TO INCORPORATE INTO
OUR PLATFORM ARE SORT OF
EXTENSIVE GUIDANCE SYSTEM AND
JUST BASICALLY ON BOARDING
PEOPLE INTO THE PROCESS AND
GUIDING THEM THROUGH IT. WE SET
ASIDE A LOT OF TIME FOR ONE ON
ONE MEETINGS OR HELP SESSIONS AS
WELL. SO THERE IS A LOT
OUTREACH WHEN YOU ARE BUILDING A
PLATFORM THAT NEEDS TO BE
CONSIDERED JUST TO SORT OF BREAK
DOWN BARRIERS TO ENTRY FROM
PEOPLE WANTING TO -- THAT WANT
TO USE THE TECHNOLOGY BUT FEEL
LIKE MAYBE THEY AREN'T READY.
>> BUILDING ON THAT, I WANT TO
GIVE -- FIRST OF ALL, GRATITUDE
TO EVERYONE WHO IS CREATING
THESE RESOURCES THAT BENCH
SCIENTISTS CAN NOW ENTER INTO
THE DATA SCIENCE WORLD. AND I
WANT TO GIVE A SPECIAL SHOUT OUT
TO ANNA GRE GREENWOOD WHO HAS SE
BIONETWORKS, EVERY TIME WE OFFER
COURSE IN NIAT PRE-DONNING GRANT
FOR PRE-FELLOWS GIVES A LECTURE
ON THE AMP AD RESOURCE. AND HOW
WE UTILIZE THAT RESOURCE TO
ACTUALLY -- THIS IS CATHY ROGERS
COURSE, AND DEVELOPMENT WHERE
THE GRADUATE STUDENTS,
PRE-DOCTORAL FELLOWS AND
GRADUATE STUDENTS AT LARGE USE
THE AMP AD TO SELECT A TARGET,
BUILD A PROGRAM OR RESEARCH
AROUND THAT, AND ACTUALLY MOVE
THAT INTO A COMMERCIALIZATION
PLAN. SO THE POINT HERE IS IS
THAT, THE NEXT GENERATION OF
DATA SCIENTIST, BENCH SCIENTISTS
COMING TOGETHER, IS ACTUALLY
BEING BUILT THROUGH SOME OF
THESE TRAINING PROGRAMS. I KNOW
IT IS A LOT MORE WORK FOR ALL OF
YOU BUT IF YOU CAN FOLLOW ANNA'S
LEAD HERE, THAT WOULD BE GREAT.
>> WE SECOND THIS AND MUCH
GRATITUDE, AMAZING WORK YOU HAVE
DONE AND GREAT DEDICATION
THROUGHOUT THE YEARS. THANK YOU
>> A QUESTION ON THE RIGHT.
>> I'M MARINA FROM UCSF, I ONLY
A COMPUTATIONAL SCIENTIST. I AM
AMAZING AD ALL THE AMAZING DATA
SHARING EFFORTS THAT WERE
MENTIONED DURING SESSION AND I
HAVE BEEN SLACKING MY GRADUATE
STUDENTS AND TAKING PICTURES
THROUGHOUT THE PRESENTATIONS.
ALSO THE COMPUTATIONAL TOOLS
THAT WERE PRESENTED. I HAVE A
THOUGHT AND A QUESTION. THOUGHT
WAS STEMMING FROM THE QUESTION
ASKED EARLIER, ONE APPROACH TO
CONSIDER MIGHT BE, I DON'T KNOW
IF THIS HAS BEEN DONE IN THE
ALZHEIMER'S SPACE IS TO LAUNCH
SOME COMPUTATIONAL CHALLENGES
BASED ON SOME OF THESE
INCREDIBLE RESOURCES. WE HAVE
BEEN TALKING A LOT ABOUT
BRINGING THE DISCOVERY SCIENCES
OR CLINICIANS TO THE DATA BUT WE
ALSO WANT TO ATTRACT
COMPUTATIONAL PEOPLE WHO MIGHT
NOT BE WORKING MANY THE
ALZHEIMER'S SPACE AND THIS MIGHT
BE AN OPPORTUNITY TO EXPLORE.
THE QUESTION THAT I HAVE IS IN
THE CONTEXT OF THE PATIENT
SESSION YESTERDAY MORNING, WHAT
ARE YOUR THOUGHTS? I DON'T KNOW
THE ANSWER TO THIS, ABOUT
BRIDGING THE COMPUTATIONAL
EFFORTS THE DATA SHARING TO ALSO
BRING BACK TO THE COMMUNITY AND
THE PATIENTS AND HOW DO WE GO --
>> ANNA, DID YOU WANT TO TALK
ABOUT THE PETITION?
>> SURE. SAGE BIONETWORKS THEY
HAVE THEIR JUNE CHALLENGE
PLATFORM WHICH IS AMAZE. AT NAC
ONE THING WE ARE PUSHING FORWARD
ARE SOME OF THESE DATA
CHALLENGES, PARTICULARLY DURING
RENEWAL PERIOD TO HELP BUT WE
WANT TO BRING TOGETHER SOME OF
THESE LONG STANDING DATA STREAMS
LIKE UNIFORM DATA SET WITH RICH
PHENOTYPIC DATA WITH NEW DATA
STREAMS, BIOMARKER DATA, ET
CETERA. SO WE WANT TO BRING
TOGETHER KNOWING THESE
CHALLENGES ARE INCREDIBLY
EFFECTIVE WAY THE CREATE
DEMOCRATIZE RESEARCH PROCESS
GREAT NEW ON LAMPS. WE ARE
INCREDIBLY EXCITED -- ONRAMPS
AND WE ARE EXCITED TO DRIVE
THOSE FORWARD. OVER THE NEXT
COUPLE OF YEARS.
>> MARINA WANT TO -- YOU HAVE
ANYTHING?
>> YEP. SO I THINK WHAT WE WOULD
LOVE TO BE ABLE DO AND AGAIN
ALSMAP JUST BUILDING OUT ALL OF
THESE PORTIONS OF IT, IS TO
CREATE AN OPPORTUNITY FOR
PATIENTS THEMSELVES WHO ARE IN
THESE -- TAKING THESE
MEDICATIONS, TO COMMUNICATE
AMONG EACH OTHER. TO CREATE A
COMMUNITY OF AND EMPOWER THEM
NOT ONLY TO PERHAPS ASK
QUESTIONS OF EACH OTHER BUT THEN
EVEN LOOK AT THE DATA AVAILABLE.
THEY ARE PART OF IT. THEY
CONTRIBUTE TO IT. SO THAT IS
SORT OF I WOULD SAUCY ALSNET
2.0, WE ARE TRYING TO BUILD IT
AND CREATE OPPORTUNITIES FOR A
COMMUNITY. AND TO GIVE BACK TO
THEM AND HAVE THEM GIVE EVEN
MORE, BECAUSE THEY PROBABLY
WOULD BE MORE THAN WILLING TO
TALK TO EACH OTHER ABOUT WHAT
THEY ARE EXPERIENCING. THANK
YOU.
>> I THINK IT IS A HUGE POINT.
WHO IS LIKE ME AND HOW CAN I
LEARN FROM OTHERS -- THE ISSUE
THAT WAS RAISED BY THE ADVOCACY
GROUPS, WAS INCREDIBLY
IMPORTANT. THERE IS THE
QUESTION, WHAT -- HOW CAN I
LEARN AND WHO IS LIKE ME? AND WE
ARE REALLY BUILDK PLATFORMS AN
RESOURCES TO GET COMMUNITIESING
TO TO FIND OTHERS WHO ARE LIKE
THEM -- COMMUNITIES TOGETHER TO
FIND OTHERS LEARN TOGETHER AND
OPTIMIZE TREATMENT STRATEGIES
AND CARE MOVING FORWARD SO WE
TAKE THIS VERY SERIOUSLY AND
THERE IS MORE THAT IS INSPIRING
US FROM THE EUROPEAN MODELS.
AGAIN THE DUTCH ARE PUTTING THE
POWER BACK IN THE HANDS OF THE
PEOPLE THAT CONTRIBUTE THE DATA
SO THAT THROUGH THE DIGITAL
PRINTS THEY CAN ENABLE AND
DECIDE WHAT DATA TO SHARE AND
THEY ARE PART OF LEARNING, WE
IMMEDIATE TO MAKE DATA SIMPLE
ENOUGH TO LEARN AND TO
UNDERSTAND. FROM US METABOLISM
IS CARDIOVASCULAR HEALTH, THERE
IS A LOT WE CAN SHARE. I HOPE WE
CAN DO THIS WITH A POINTER. AS
WE START TO LOOK AT THE POINTER
BASELINE WITH THE TEAM, TO BE
ABLE TO REDUCE COMPLEXITY OF A
THOUSAND THINGS WE MEASURE AND
BE ABLE TO TELL THEM I CAN GIVE
YOU SOMETHING MORE THAN GLUCOSE
THAT WOULD TELL YOU SOMETHING
ABOUT THAT.
>> I JUST BRIEFLY ALSO MENTION
THAT FOR THE ACCELERATING
MEDICINES PARTNERSHIP AT THE
NEXT PLACE FOR PARKINSON DISEASE
AND RELATED DATES ORDERS WE ARE
INTEGRATED PERSONS WITH LIVED
EXPERIENCE PATIENTS AND
CAREGIVERS INTO OUR STEERING
COMMITTEE AS WELL AS BOSHING
GROUPS AND THIS IS A MODEL WE
RECENTLY -- WORKING GROUPS. THIS
IS ALSO A MODEL FOR ACCELERATING
MEDICINE.
>> MIGHT MAKE A COMMENT ON
REDUCING COMPLEXITY. COMPLEXITY
BRINGS INFORMATION, YOU CAN
REDUCE COMPLEXITY AND REDUCE THE
FORMATIVENESS OF THE DATA. I
THINK THE REALLY SUIT IS
MAXIMIZING SCIENTIFIC
OPPORTUNITY. THAT DOES MEAN THAT
THERE IS A TRADE OFF HERE OF
CONSTRAINING SOME INTELLECTUAL
FREEDOM. ONE EXAMPLE. IF YOU GO
TO THE UK AND YOU HAVE TO GET A
PLUG ADAPTER. IT IS A REAL PAIN.
JUST IMAGINE EVERY CITY IN THE
UK HAD A DIFFERENT PLUG ADAPTER.
YOUR OPPORTUNITY WOULD BE
LIMITED BUT YOUR FREEDOM WOULD
BE WONDERFUL IF YOU LIVE IN THAT
CITCITY. THERE REALLY IS A CASER
CENTRALIZATION DISCUSSION
COMMUNITY-LED LIMITATION OF %-
LIKE CONSTRAINING OF INNOVATION
IN ORDER TO MAINTAIN AND
MAXIMIZE OPPORTUNITIES. BECAUSE
IT WILL BE OPPORTUNITY WHICH
ACTUALLY BRINGS RESULT AND
GENERATES THE WORK, NOT SOME
CRACK POT ACADEMIC HAVING A
BRIGHT IDEA HOW WE WOULD LIKE TO
MAKE THIS DATA, IT IS
HYPOTHESIS. I KNOW THE THOUGHTS
ARE NOT NORMALLY ENCOURAGED, BUT
I DO PUT TO YOU WOULD YOU RATHER
HAVE TO HAVE ONE IN PLACE OR 50
IN PLACE.
>> I THINK WE HAVE TIME FOR ONE
LAST QUESTION.
>> NO.
>> WE DON'T. OKAY.
>> COULD I JUST MAKE A POINT
THOUGH THAT I WAS OF
(OVERLAPPING SPEAKERS) FOR THOSE
OF YOU THAT ARE NEW TO THE
FIELD, AND ALSO YOU THAT ARE
WONDERING WHAT RESOURCES ARE OUT
THERE. AS YOU HEAR, THERE IS A
LOT OF COLLABORATIVE WORK GOING
ON BETWEEN THESE DATA
REPOSITORIES. REACH OUT TO ONE
OF THEM. REACH OUT TO THE AD
KNOWLEDGE PORTAL DISCUSSION
FORUM, POSE A QUESTION AND THEY
CAN HELP YOU NAVIGATE THIS
ECOSYSTEM.
>> THANK YOU. WITH THAT WE WANT
TO THANK OUR SESSION 7 SPEAKERS.
>> THANKS TO ALL THE SPEAKERS
AND THANK YOU TO THE AUDIENCE.
>> THANK YOU.
>> WE ARE GOING TO TAKE AN HOUR
BREAK FOR LUNCH, BUT BEFORE WE
DO, SARAH WOULD YOU LIKE TO
BRIEFLY TALK ABOUT THIS FLASH
SIGHT THAT IS UP?
>> ACTUALLY I JUST THANK YOU FOR
THE OPPORTUNITY TO MENTION THIS.
SO ANDY AND MYSELF AND CATHY ARE
SPECIAL EDITORS FOR -- I'M
SORRY, GUEST ED TOFERS FOR
SPECIAL INTERVIEW OF ALZHEIMER'S
DEMENTIA, WILL BE FOCUSED ON THE
40TH ANNIVERSARY OF ADRC PROGRAM
AND 25TH OF NAC. THE GOAL IS TO
HIGHLIGHT IMPACT THESE PROGRAMS
HAVE HAD ON ADVANCING ADRD
TRANSLATION DISCOVERY AND
ONGOING CLINICAL ROLE IN
TACKLING THE PRESSING CHALLENGES
IN THE FIELD MANY WHICH
DISCUSSED TODAY SO IF YOU ARE
INTERESTED IN SUBMITTING TO THE
OPEN CALL FOR THAT, THAT IS DUE
ON DECEMBER 31 AND WE THOUGHT IT
WOULD BE A BIG OPPORTUNITY, SO
MANY PEOPLE TALKED ABOUT USING
MAP DATA AS WELL AS OTHER ADRC
DATA, VERY INTERESTING WAYS AT
THIS CONFERENCE SO THANKS,
EVERYONE.
>> GOOD AFTERNOON, EVERYONE,
WELCOME TO THE NEAR FINAL
SESSION OF THIS ABSOLUTELY
FANTASTIC MEETING.
IT'S SUCH AN HONOR TO WITNESS
FIRSTHAND THE TRUE
TRANSFORMATION TAKING PLACE IN
THE FIELD OF ALZHEIMER'S DISEASE
THANKS ON THE PIONEERING EFFORTS
OF ALL OF YOU THAT HAVE BEEN
SHARED AT THIS GROUNDBREAKING
MEETING.
THESE LAST THREE DAYS HAVE MEANT
SO MUCH FOR ME ON MY JOURNEY,
THE LAST ALZHEIMER'S DISEASE
SUMMIT I ATTENDED WAS IN 2015 25
AND THE WORLD WAS A DIFFERENT
PLACE.
FOR MANY OF YOU WHO HAVE BEEN IN
THIS FIELD FOR SO LONG, YOU
REMEMBER IF YOU THINK BACK TO
TEN YEARS AGO, THE NAPA
INITIATIVE WAS JUST KICKING OFF,
THE BAPANUS TRIALS WERE JUST
READING OUT AND WE WERE
STARTING TO USE TERMS LIKE DATA
SHARING, BACK IN 2015.
TEN YEARS AGO, I WAS ASKED TO
WRITE A MANUSCRIPT AROUND MY
PERSONAL AND PROFESSIONAL
JOURNEY, AND IT WAS A CALL TO
ACTION PUBLISHED AS A
PERSPECTIVE REVIEW ENTITLED:
ALZHEIMER'S DISEASE, FROM
RESEARCHER TO CAREGIVER, A
PERSONAL JOURNEY AND CALL TO
ACTION.
THAT WAS WHEN MY MOTHER WAS
STILL ALIVE, AND STILL TO THIS
DAY, IT KEEPS ME UP AT NIGHT,
OFTENTIMES IN THE PAST FEELING
HOPELESS THAT I COULDN'T HELP
HER, BUT TODAY I'M JUST SO
INVIGORATED TO SEE THE PROGRESS
IN THIS FIELD AND TRULY HAVE
HOPE FOR THE FUTURE.
TODAY, WE GATHER IN THIS UNIQUE
SESSION TO FOCUS ON REGULATORY
SCIENCES, A TOPIC THAT IS SO
OVERLOOKED AND WAY TOO OFTEN
MISINTERPRETED.
SO WHAT DOES THE TERM REGULATORY
INNOVATION TRULY MEAN?
TODAY, IN THIS UNIQUE PANEL, YOU
WILL HEAR FROM DISTINGUISHED
LEADERS ACROSS DIFFERENT CENTERS
AND DIVISIONS AT THE FDA TO
SHARE THEIR INSIGHTS AND
EXAMPLES.
THE THEMES OF MODEL INFORMED
DRUG DEVELOPMENT, PATIENT
FOCUSED DRUG DEVELOPMENT,
COMPLEXIN NOTICE VAI TV TRIAL
DESIGNS, BIOMARKERS INCLUDING
REASONABLY LIKELY SURROGATE
ENDPOINTS, AND ACCELERATED
APPROVAL, WERE PIONEERED IN
NEARLY ALL CASES IN ALZHEIMER'S
DISEASE AT THE FDA.
SUCH NOVEL STRATEGIES HAVE PAVED
THE PATH IN THAT OTHER DISEASE
AREAS ARE FOLLOWING.
THE PRINCIPLES YOU WILL HEAR
ABOUT IN THIS SESSION ARE BEING
APPLIED ACROSS MANY DISORDERS,
INCLUDING RARE CHRONIC
PROGRESSIVE DISORDERS THAT ARE
HAVING APPROVALS FOR THE FIRST
TIME.
HOW UNPRECEDENTED IS THAT?
DETERMINING THE SAFETY AND
EFFECTIVENESS OF NEW MEDICATIONS
IS VERY, VERY HARD TO DO.
TWHEAN FROM MY YEARS THERE -- I
KNOW THAT FROM MY YEARS IN
INDUSTRY, BUT THE REGULATORY
SIDE OF THIS I THINK VERY FEW
APPRECIATE HOW DIFFICULT THIS
IS.
OUR AGENCY COLLEAGUES ARE
PARTNERS WITH US AT CRITICAL
PATH INSTITUTE, AND WE'RE SO
GRATEFUL FOR THE LONG TIME
SUPPORT AND FUNDING OF THE
NEARLY 20 YEARS SINCE CPATH WAS
FOUNDED.
IN ALZHEIMER'S DISEASE THE C
PATH COALITION AGAINST MAJOR
DISEASES WAS ONE OF THE FIRST TO
TAKE ON THE TASK OF SHARING
CLINICAL TRIAL DATA FROM
ALZHEIMER'S TRIALS MOST OF WHICH
HAD FAILED IN THEIR GOAL TO
ACHIEVE DISEASE-MODIFYING
ACTIVITY.
THIS DATA WAS USED TO ACHIEVE
THE FIRST-EVER IN SILICO DRUG
DISEASE TRIAL MODEL IN 2013.
THIS ACHIEVEMENT SET THE
LANDSCAPE OF WHAT YOU'RE GOING
TO HEAR ABOUT TODAY ON THE FDA'S
NEW QUANTITATIVE CENTER,
QUANTITATIVE MEDICINE CENTER OF
EXCELLENCE THAT YOU'RE GOING TO
HEAR OF.
WE ALSO ACHIEVED IN 2015 THE
FIRST EVER LETTER OF SUPPORT FOR
ALZHEIMER'S BIOMARKERS, WAY A
LONG TIME AGO WHEN IT WAS A BETA
AND CFS AND TAONCFS AND WE KNOW
HOW THAT'S BEEN TRANSFORMED TO
BLOOD BASED BIOMARKERS.
JUST A FEW WEEKS AGO,
FAST-FORWARD TO TODAY, THE FDA
JUST SIGNED A LETTER OF
SUPPORT,IC CHRISTINE MENTIONED
THIS, FOR THE USE OF CFSS OFFICE
NEW CLEE INTO SUPPORT CLINICAL
TRIALS OF DISORDERS THAT SHARE A
COMMON BIOLOGY OF SINUCLIIN,
THIS WAS A LANDMARK BECAUSE IT
TOOK ONLY THREE MONTHS AND SHOWS
THE URGENCY ACROSS DIVISIONS.
IN THIS SESSION, YOU WILL HEAR
FROM LEADERS AT THE CENTERS OF
EXCELLENCE IN MULTIPLE DIVISIONS
AND HOW THEY'RE APPROACHING AND
ADVANCING THERAPEUTIC INNOVATION
AND REGULATORY SCIENCE.
IT'S MY HOPE THAT YOU CAN
GENERATE IDEAS FROM THIS
DISCUSSION TODAY AND GENERATE
WAYS THAT YOU CAN WORK IN
PARTNERSHIP WITH THE AGENCY TO
ACCELERATE YOUR PROGRESS IN YOUR
OWN RESEARCH AND TRIALS.
THANK YOU.
JUST SPEAKING FOR THE FIRST
SPEAKER IN THE SESSION I THINK
IS DR. B DR. BU BURACCHIO.
>> I'M TERESA BURACCHIO, I'M THE
DIRECTOR OF NEUROSCIENCE IN THE
CENTER FOR DRUGS.
OTHER NEUROLOGIC DISEASES AS
WELL WHEN WE'RE TALKING ABOUT
PRECISION THERAPIES.
SO, THIS MANTRA, RIGHT DRUG SHES
RIGHT PERSON, RIGHT TIME, I HAVE
SEEN ON A COUPLE SLIDES HERE
ALREADY AND HAS BEEN AROUND FOR
WHILE, BUT I USE THIS AS
SHORTHAND A LOT WHEN I THINK
ABOUT PRECISION MEDICINE IS WHAT
DOES IT MEAN TO ME AT THE
AGENCY, AND THIS IS WHAT I
THINK.
I THINK ABOUT THE RIGHT DRUG, IS
IT TARGETING THE RIGHT TARGETS
IN THE PATHOLOGIC PROCESS OF THE
DISEASE, ARE WE TREATING A
PERSON WHO HAS THOSE TARGETS,
WHO MANIFESTS THOSE PATHOLOGIC
PROCESSES, IN ALMOST ALL OF OUR
NEUROLOGIC I GO DISEASES THE
RIGHT TIME IS AS SOON AS
POSSIBLE -- NEUROLOGIC DISEASES,
THE RIGHT TIME IS AS SOON AS
POSSIBLE IF NOT YESTERDAY.
SO WE WANT TO GO AS EARLY AS
POSSIBLE.
IT'S IMPORTANT TO NOTE, THOUGH,
THAT WE CAN ONLY ADDRESS THIS TO
SOME EXTENT IN DRUG DEVELOPMENT
AND APPROVING A DRUG IS ONLY THE
FIRST STEP IN THE PROCESS.
A LOT OF WHAT HAPPENS WITH
PRECISION MEDICINE HAPPENS AFTER
DRUG APPROVAL, AND WHEN WE SEE
HOW THE DRUG IS USED IN THE REAL
WORLD.
SO A LOT OF THE DISCUSSION THAT
IS WE'VE HAD TODAY ARE HOW TO
LEVERAGE DATA THAT'S ACCRUING
BOTH IN THE REAL WORLD AND
THROUGH RESEARCH STUDIES, SO
IT'S IMPORTANT TO UNDERSTAND HOW
TO APPLY THOSE PRINCIPLES EVEN
AFTER A DRUG IS APPROVED.
THERE'S ONLY SO MANY THINGS WE
CAN ACCOUNT FOR WITHIN THE
SETTING OF A CLINICAL TRIAL, BUT
WHEN IT GOES OUT, A DRUG GOES
OUT INTO THE REAL WORLD IS WHEN
WE REALLY START TO SEE HOW WE
CAN USE THESE DRUGS OPTIMALLY IN
THE CLINIC.
SO AS I MENTIONED, WE THINK
BROADLY AT THE AGENCY, ALTHOUGH
ALZHEIMER'S DISEASE IS A REALLY
LARGE PORTION OF OUR PORTFOLIO
WITHIN THE OFFICE OF
NEUROSCIENCE, WE SEE ALL
NEUROLOGIC DISEASES.
SO WE HAVE A LOT OF EXAMPLES OF
TARGETED THERAPIES IN NEUROLOGY,
AND THNTS AN EXHAUSTIVE LIST --
THNTS AN EXHAUSTIVE LIST -- THIS
IS NOT AN EXHAUSTIVE LIST, IT'S
SOME OF THE MORE RECENT
APPROVALS.
ALZHEIMER'S DISEASE IS ONE OF
THE MORE RECENT APPROVALS THAT
WE'VE HAD IN A LONG LITANY OF
DRUGS OF TARGETED THERAPIES, AND
I'LL POINT OUT A FEW NOTABLE
ONES THAT I THINK HAVE BEEN
PRETTY EXCITING FOR US, WHICH IS
THE ALS SOD1 MUTATION WHICH IS
AN ANTI-SENSE AL GOA NUCLEOTIDE
THAT BINDS SOD1 mRNA AND SOD1
TROWKS GIVE AN ACCELERATED
APPROVAL TO THAT DRUG AND THAT
GOT A LOT OF PRESS AT THE TIME
AND IT WAS A PRETTY EXCITING
APPLICATION FOR US TO REVIEW AS
WELL.
AND ANOTHER JUST EXAMPLE OF A
TARGETED THERAPY THAT HAS HAD A
BIG EFFECT IS THE HEREDITARY
TRANCETHYRETEN-MEDIATED
AMYLOIDOSIS FOR POLYNEUROPATHY,
AN EXAMPLE WHERE WE'VE BEEN ABLE
TO HAVE A HIGH QUALITY BIOMARKER
THAT'S VERY RELIABLE AND
REDUCTIONS WERE REALLY
PREDICTIVE OF BENEFITS.
THAT RECEIVED A STANDARD
APPROVAL, NOT AN ACCELERATED
APPROVAL, BUT I THINK IT REALLY
SHOWED HOW A VERY TARGETED
THERAPY COULD HAVE A LARGE
IMPACT.
NOW, WE KNOW ALSO, THOUGH, THAT
DISEASES ARE COMPLEX, AND EVEN
THOUGH WE TARGET ONE PIECE OF
THE DISEASE, IT'S REALLY A PIECE
OF THE PUZZLE.
AND THERE'S A LOT, MANY OTHER
TARGETS THAT COULD BE TARGETED.
SO WE RECOGNIZE THAT IN A
SETTING OF ALZHEIMER'S DISEASE,
ALTHOUGH WE NOW HAVE SOME
AMYLOID TARGETED THERAPIES, THAT
THAT'S NOT GOING ON CURE THE
DISEASE AND WE NEED TO CONTINUE
TO UNDERSTAND OTHER TARGETS AS
WELL.
AND IT'S GOING TO BE, AND IT MAY
NOT JUST BE DRUGS THERE, MAY BE
OTHER MODIFIABLE FACTORS IN
LIFESTYLE THAT WILL ALSO COME
INTO PLAY.
SO WE DO RECOGNIZE THAT, AND,
YOU KNOW, IT'S NOT THAT THE
AMYLOID BETA DIRECTED ANTIBODIES
ARE GOING TO BE THE ANSWER, BUT
THEY'LL BE ONE PIECE OF THE
ANSWER.
SO WHAT IS CRITICAL FOR DRUG
DEVELOPMENT AND HAVING PRECISION
THERAPIES OR TARGETED THERAPIES
IS HAVING A BIOLOGIC BASED
DEFINITION OF A DISEASE, AND
THIS HAS REALLY ONLY BEEN
POSSIBLE IN THE LAST 20 YEARS OR
SO IN ALZHEIMER'S DISEASE WHEN
WE'VE HAD THE DEVELOPMENT
ACCURATE AND RELIABLE BIOMARKERS
THAT PROVIDE AN INCREASED
UNDERSTANDING OF THE DISEASE
PROCESSES IN VIVO.
AND MORE RECENTLY WEEIVEL ABLE
TO -- WE'VE BEEN ABLE TO MOVE
USING THESE BIOMARKERS FROM
DIAGNOSES BASED ON PHENOTYPE OR
CLINICAL SYMPTOMS TO DIAGNOSES
THAT ARE INFORMED BY ACTUAL
BIOMARKERS OF DISEASE PATHOLOGY
THAT WE CAN MEASURE IN LINE.
AND IT'S REALLY CRITICAL TO DRUG
DEVELOPMENT BECAUSE FOR A NUMBER
OF REASONS, AND I HIGHLIGHTED A
FEW OF THEM HERE, WHICH IS, YOU
KNOW, ALLOWS US FOR MORE PRECISE
DEFINITIONS OF DISEASE
POPULATIONS, IT FACILITATES THE
DEVELOPMENT OF TARGETED
THERAPIES, THE KEY PIECE OF THIS
IS REDUCING HETEROGENEITY IN
CLINICAL TRIALS, THE MORE
HOMOGENOUS WE CAN HAVE A
POPULATION, THE BETTER WE'LL BE
ABLE TO DEDUCT A SIGNAL,
ALTHOUGH AS I SAID WE DO
RECOGNIZE THAT WHEN THIS ROLLS
OUT INTO THE REAL WORLD, THERE
WILL BE MORE HETEROGENEITY THAT
WE'LL NEED TO UNDERSTAND.
IT'S INFORMATIVE TO PRESCRIBERS
TO IDENTIFY OPTIMAL THERAPIES
FOR PATIENTS, AND A CRITICAL
PIECE OF THIS IS THAT IT'S GOING
ON ALLOW US TO MOVE AS EARLY AS
POSSIBLE IN TREATING THESE
DISEASES AND IDEALLY I THINK WE
ALL WANT TO MOVE BEFORE SYMPTOMS
EVEN BEGIN.
WE WANT TO INTERVENE AS EARLY AS
POSSIBLE.
SO SOME EXAMPLES OF THIS IN
ALZHEIMER'S, WHICH I THINK
EVERYONE KNOWS ARE THE REVISED
CRITERIA FOR DIAGNOSING AND
STAGING PUBLISHED EARLY THIS
YEAR, AND IN BOTH OF THESE OUR
GUIDANCE IS ALIGNED VERY WELL
FOR THE CRITERIA FOR DIAGNOSIS
AND STAGE AND GO OUR GUIDANCE IS
BASED ON HAVING A BIOLOGIC BASED
DEFINITION OF DISEASE, WHICH IS
INFORMED BY BIOMARKERS, AS WELL
AS CLINICAL STAGING, AND IN OUR
GUIDANCE WE'RE ABLE TO, WE DO
GIVE SOME SPECIFIC OUTLINES FOR
WHAT DIFFERENT CLINICAL STAGES
OF DISEASE ARE.
WE DON'T ENDORSE ANY SPECIFIC
BIOMARKERS IN THE ALZHEIMER'S
DISEASE GUIDANCE BECAUSE WE
DOMENT IT TO BE FLEXIBLE AND WE
DO WANT IT TO BE ABLE TO BE
ADAPTABLE AND EVOLVE AS THE
SCIENCE EVOLVES, BUT THE
CLINICAL STAGING IS PRETTY WELL
UNDERSTOOD ALREADY BY THE
PUBLIC, SO WE DO HAVE THAT IN
OUR GUIDANCE.
BUT IT DOES OVERALL ALLOW FOR
TIE TO THE CURRENT REVISED
CRITERIA FOR DIAGNOSIS AND
STAGING OF ALZHEIMER'S DISEASE,
AND IT ALSO ALLOWS AS THOSE
CRITERIA TO EVOLVE AND GROW
SWINE TISK KNOWLEDGE THAT OUR
GUIDE -- SCIENTIFIC KNOWLEDGE
THAT OUR GUIDANCE WILL ALLOW FOR
THAT.
IT'S IMPORTANT TO NOTE THAT THIS
IS ALSO HAPPENING IN OTHER
NEURODEGENERATIVE DISEASES AS
WELL, SO THERE ARE INTEGRATED
STAGING SYSTEMS THAT HAVE BEEN
PROPOSED FOR HUNTINGTON'S
DISEASE AND MOST RECENTLY FOR
NEURONALLING SYNUCL HE IN
DISEASE WHICH INCLUDES
PARKINSON'S WITH NEURO BODIES
AND WE FIND THESE STAGING ARE
VERY USEFUL TO US TO HELP US
GIVE ADVICE ON DRUG DEVELOPMENT
AND HELPS US COME UP WITH COMMON
LANGUAGE THAT WHEN WE TALK WITH
ACADEMIA, WITH INDUSTRY, WITH
ADVOCACY GROUPS AND OTHER
GOVERNMENT AGENCIES AS WELL,
THAT WE KNOW THE POPULATION THAT
WE'RE TALKING ABOUT THAT WAS
ENROLLED IN THE CLINICAL TRIALS,
AND THEN WE KNOW HOW TO INFORM
PRESCRIBERS LATER ON HOW TO
OPTIMALLY USE THOSE, USE THE
DEFINITIONS THAT WERE USED IN
THE CLINICAL TRIALS AND CLINICAL
PRACTICE.
SO THESE GUIDELINES OR THESE
STAGING SYSTEMS ARE REALLY A
BRIDGE BETWEEN RESEARCH AND
CLINICAL PRACTICE, AND EVEN IF
CLINICAL PRACTICE ISN'T THERE
YET, AS WE DEVELOP NEW DRUGS AND
THE SCIENCE EVOLVES, CLINICAL
PRACTICE WILL GET THERE.
SO THESE ARE REALLY FORWARD
LOOKING DOCUMENTS, BUT WHAT IS
THE FUTURE IN CLINICAL PRACTICE
IS SORT OF OUR CURRENT TIME IN
DRUG DEVELOPMENT RIGHT NOW.
SO THESE ARE, I CONSIDER THEM
ESSENTIAL FOR THE WORK THAT WE
DO.
NOW, THERE ARE A LOT OF
DIFFERENT USES OF BIOMARKERS IN
DRUG DEVELOPMENT, AND I LISTED
THE MAIN USES THAT WE SEE HERE.
THERE'S A LOT OF FOCUS ON
SURROGATE ENDPOINTS AS PRIMARY
END POITS, AND THAT'S A PRETTY
HIGH BAR.
BUT I THINK BIOMARKERS CAN BE
USED IN ANY STAGE OF DEVELOPMENT
REALLY, AND WE FIND THEM
INFORMATIVE FOR A VARIETY OF
PURPOSES.
FOR INDUSTRY, PROOF CONCEPT IS
WHERE THEY COME IN A LOT, AND
THAT'S MAYBE A LITTLE LESS
IMPORTANT FOR US BECAUSE THAT
USUALLY HAPPENS AT THE STAGE
BEFORE THEY COME AND ENGAGE WITH
US AT THE AGENCY.
BUT DIAGNOSTIC BIOMARKERS ARE
USED FOR ENROLLMENT IN CLINICAL
TRIALS, FOR ENRICHMENT IN
POPULATIONS THAT ARE MORE LIKELY
TO PROGRESS OR DEVELOP THE
OUTCOME OF INTEREST DURING A
TRIAL, FOR MONITORING FOR
SAFETY, AND THEN OF COURSE THERE
IS THE SURROGATE ENDPOINT BUT
ALSO WE DO CONSIDER BIOMARKER AS
WELL WHEN WE'RE LOOKING AT
CLINICAL OUTCOME MEASURES, SO
THEY CAN BE SUPPORTIVE AND SHOW
UP ON A DYNAMIC RESPONSE THAT IS
SUPPORTIVE OF ANY IMPACT WE SEE
ON CLINICAL OUTCOME MEASURES.
DID I WANT TO HIGHLIGHT TWO
IMPORTANT THINGS THAT HAVE
ALREADY BEEN DISCUSSED.
DIANE MENTIONED ONE ABOUT WE
RECENTLY ISSUED A LETTER OF
SUPPORT ENCOURAGING THE USE OF
SYNUCLEAN BASED BIOMARKERS, THE
ASSAY IN CLINICAL TRIALS RISK OF
SUSCEPTIBILITY BIOMARKER AND
ALSO WITHIN NIH WE HAVE ACCEPTED
A LETTER OF INTENT TO QUALIFY
NEURO FILAMENT AS A BIOMARKER OF
RARE NEURODEGENERATIVE DISEASES.
THIS REALLY HIGHLIGHTS THE
IMPORTANT ROLES THAT
PUBLIC/PRIVATE PARTNERSHIPS AND
DATA SHARING AND ALL OF THE
GREAT THINGS WE HEARD ABOUT
EARLIER IN THE LAST SESSION H
THE IMPORTANCE OF THESE TO US AT
THE FDA TO DRUG DEVELOPMENT AT
LARGE, THAT WE CAN, YOU KNOW,
THESE ARE THINGS THAT YES, WE
CAN ACCEPT NEURO FILAMENT AND
CLINICAL TRIALS WITHOUT
NECESSARILY HAVING THESE
INITIATIVES UNDERWAY, BUT I
THINK THIS IS -- IT'S A LOT MORE
WORK FOR US AND FOR EVERYBODY
ELSE IF WE'RE DOING THESE ALL IN
SILOS, SO HAVING THESE SORT OF
PUBLIC/PRIVATE PARTNERSHIPS,
HAVING THESE INITIATIVES WHERE
PEOPLE ARE WORKING TOGETHER
REALLY HELPS MOVE THE FIELD AND
BRINGS EVERYBODY ALONG WITH IT
AND MAKES OUR JOB A LITTLE BIT
EASIER TOO.
I ALSO WANT TO HIGHLIGHT THE
IMPORTANCE OF DIVERSE
POPULATIONS.
WE REALLY, YOU KNOW, PRECISION
MEDICINE NEEDS TO CONSIDER THE
POPULATIONS THAT WE'LL BE USING
WITH DRUGS P IN THE REAL WORLD.
OFTEN OUR CLINICAL TRIALS ARE
LIMITED TO, YOU KNOW, PEOPLE WHO
ARE WILLING TO PARTICIPATE IN
CLINICAL TRIALS, SO THERE'S AN
INHERENT SELECTION BIAS THERE,
BUT WE REALLY NEED TO UNDERSTAND
HOW BIOMARKERS PERFORM IN A REAL
WORLD POPULATION, AND WE DO HAVE
A GUIDANCE THAT I HIGHLIGHTED
HERE.
IT'S NOT CURRENTLY A REQUIREMENT
BUT WE DO ASK COMPANIES, WE
RECOMMEND THAT THEY DEVELOP A
DIVERSITY ACTION PLAN TO IMPROVE
ENROLLMENT AND PARTICIPANTS FROM
UNDERREPRESENTED POPULATIONS AND
CLINICAL STUDIES, AND THIS MAY
BE INFORMATIVE FOR CLINICAL
RESEARCH BEYOND JUST CLINICAL
TRIALS.
I ALSO WANT TO HIGHLIGHT SOME
RECENT COLLABORATIVE WORK WE'VE
HAD WITH THE NIA, MY OUTSTANDING
COLLEAGUES HERE, SUZANNA AND
LAURA AND NADA ARE IN THE
EXPROOM WE WORK -- IN THE ROOM
AND WE CLOSELY WITH THEM.
ABOUT A YEAR AGO WE HAD A
COLLABORATIVE MEETING AND THOSE
OF US WHO WORK IN THE
ALZHEIMER'S DISEASE SPACE CAME
TOGETHER AND DISCUSSED COMMON
CHALLENGES WE'RE FACING BOTH IN
RESEARCH AND DRUG DEVELOPMENT
AND EARLIER THIS YEAR WE
EXECUTED A MEMORANDUM OF
UNDERSTANDING BETWEEN NIA AND
FDA AND SPECIFICALLY WITH CD HE
R AND CBER AND CDRH AND THIS
WILL ALLOW US TO DISCUSS
RESEARCH PRIORITIES ACROSS THE
AGENCY AND WILL FURTHER
FACILITATE COLLABORATION AND
WE'RE HAVING ONGOING DISCUSSIONS
ABOUT MORE COLLABORATIVE
INTERACTIONS TO COME.
SO I'LL WRAP IT UP HERE WITH THE
TAKE HOME POINTS THAT WE FEEL
THAT BIOLOGIC BASED DEFINITIONS
OF DISEASE ARE REALLY CRITICAL
FOR DRUG DEVELOPMENT.
THEY ALLOW FOR MORE PRECISE
CHARACTERIZATION OF DISEASE
POPULATIONS, AND IT'S IMPORTANT
THAT THE FRAMEWORKS TO DEFINE
END STAGE DISEASES FOR
STANDARDIZATION THAT THEY ARE
FLEXIBLE AND ALLOW FOR ADDITION
AND IS REVISIONS AS SCIENTIFIC
KNOWLEDGE EVOLVES, AND WE DO
FOLLOW THOSE, FOLLOW 9 SCIENCE
AND MAKE SURE THAT WE'RE AWARE
OF ALL THE LATEST THINKING ON,
YOU KNOW, HOW TO DEFINE AND
STAGE DISEASES, THAT INCLUSION
OF DIVERSE POPULATIONS IS
ESSENTIAL, AND KEY POINT HERE,
PRE-COMPETITIVE EFFORTS AND DATA
SHARING ARE CRITICAL TO SUCCESS
IN THIS SPACE.
THANK YOU.
>>
>> SORRY, WE'RE LOOKING FOR THE
FDA SLIDES ON QUANTITATIVE
MEDICINE, CENTER OF EXCELLENCE.
HERE WE ARE.
THE NEXT ONE AFTER THIS.
HERE WE ARE.
INTRODUCTION TO CD HE R
QUANTITATIVE MEDICINE CENTER OF
EXCELLENCE.
OKAY.
>> THANK YOU VERY MUCH.
THANK YOU, EVERYONE, FOR GIVING
US AN OPPORTUNITY TO COME AND
SHARE WITH YOU ALL ONE OF THE
RECENT CDER INITIATIVES, C DE R
QUANTITATIVE MEDICINE CENTER OF
EXCELLENCE.
CDER.
ALL RIGHT.
IT DID MOVE.
OKAY.
WELL, I THINK THERE ARE A NUMBER
OF DIFFERENT DEFINITIONS THAT
ARE OUT THERE FOR WHAT IS
QUANTITATIVE MEDICINE.
OUR OPERATING DEFINITION IS THAT
THIS INVOLVES DEVELOPMENT AND
APPLICATION OF EXPOSURE-BASED
MODELS THAT ARE ROOTED IN OUR
UNDERSTANDING OF BIOLOGY AND
PHYSIOLOGY AND USE THE
QUANTITATIVE METHOD TO USE THIS
INFORMATION ACROSS WIDE VARIETY
OF SOURCES OF INFORMATION,
COMING FROM NONCLINICAL,
CLINICAL, ALL THE WAY UP TO REAL
WORLD DATA.
THE PURPOSE OF DOING THIS
EXERCISE IS TO INFORM DRUG
DEVELOPMENT AND MORE
IMPORTANT -- REGULATORY DECISION
MAKE AND GO MORE IMPORTANTLY AT
THE END OF THE DAY, INFORM THE
PATIENT CARE.
IN OUR OPINION, WE HAVE SEEN
DOING THIS HELPS STREAMLINE P
AND ACCELERATE DRUG DEVELOPMENT
THROUGH ALL THE PRODUCT LIFE
CYCLE.
DURING THE PREMARKET STAGE, IT'S
USEFUL FOR IDENTIFYING AND
QUANTIFYING UNCERTAINTIES AND
HELP ADDRESS THOSE UNCERTAINTIES
IN THE LIFE CYCLE, AND MOST
IMPORTANTLY IN REGULATORY MAKING
SPACE, CONTRIBUTE TO THE
TOTALITY OF UNDERSTANDING OF A
DRUG'S BENEFITS AND RISKS.
WE HAVE HAD A RICH HISTORY OF
APPLICATION OF QUANTITATIVE
MEDICINE APPROACHES AT CDER.
HERE ARE FIVE OF THE EXAMPLES,
I'M PRETTY SURE THERE ARE A LOT
MORE.
I'LL TOUCH BRIEFLY ON SEVERAL OF
THESE.
SPHIRTS MODEL INFORMED DRUG
DEVELOPMENT.
-- FIRST IS MODEL INFORMED DRUG
DEVELOPMENT.
THIS INITIATIVE HAS BEEN AROUND
FOR CLOSE TO TWO DECADES BUT SIX
AND SEVEN IT WAS IDENTIFIED AS
ONE OF THE ENHANCEMENTS AS PART
OF -- AND WE HAVE A REGULATORY
ENGAGEMENT PATHWAY FOR APPLYING
MODEL INFORMED APPROACHES FOR
VARIOUS DRUG DEVELOPMENT
DECISION-MAKING.
SECOND IS COMPLEXIN NOTICE
VAITIVE TRIAL DESIGN, THIS IS A
PROGRAM ALONG WITH MODEL
INFORMED DRUG DEVELOPMENT AT THE
OFFICE OF CLINICAL PHARMACOLOGY,
RUN OUT OF THE OFFICE OF
STATISTICS, PRIMARILY FOCUSING
VERY COMPLEX AND INNOVATIVE
TRIALS WHICH INVOLVE ADAPTIVE
DESIGNS, YOU NAME IT, ALL THESE
UNIQUE FEATURES, IT BE ABLE TO
BEST LEVERAGE THE TRIALS TO BE
ABLE TO INFORM THE DRUG
DEVELOPMENT.
THE THIRD AND PROBABLY MORE
RELEVANT TO THIS PARTICULAR
AUDIENCE THE FIT FOR PURPOSE
INITIATIVE, A JOINT PROGRAM RUN
OUT BY THE OFFICE OF CLINICAL
PHARMACOLOGY, IN COLLABORATION
WITH THE OFFICE OF NEW --
WHEREIN VARIOUS APPROACHES,
EITHER TECHNICAL APPROACHES FOR
CONDUCTING DATA ANALYSIS OR FOR
DEVELOPING DISEASE PROGRESSION
MODELS FOR SPECIFIC APPLICATIONS
THAT ARE DEEMED TO BE FIT FOR
APPLICATION IN A SPECIFIC
CONTEXT.
ONE OF THE EXAMPLES THAT WE HAVE
UNDER THIS IS IN THE ALZHEIMER'S
DISEASE FOR INFORMING CLINICAL
TRIALS USING SIMULATION
APPROACHES.
THESE ARE ALL WHAT I MENTIONED
ARE IN THE NEW DRUG SPACE.
WE ALSO HAVE SIMILAR EFFORTS OF
APPLICATION OF QUANTITATIVE
APPROACHES IN THE LIFE CYCLE
SPACE, IN OUR OFFICE OF
GENERATIVE DRUGS WHERE THEY HAVE
A SPECIFIC PROGRAM FOR MODEL
INTEGRATED EVIDENCE WHERE
MODELING APPROACHES ARE USED FOR
BIOAVAILABILITY, IN VERY COMPLEX
SITUATIONS WHERE YOU CANNOT
CONDUCT THE ROUTINE CLINICAL
STUDIES THAT INFORM THE APPROVAL
OF GENERATIVE PRODUCTS.
SIMILARLY BEING IN THE OFFICE OE
OF QUALITY, THERE'S BEEN
PHYSICIAN LOGICS BASED MODELING
APPROACHES TO BE ABLE TO HELP
INFORM THE PRODUCT QUALITY,
INFORMING THIS SPECIFICATIONS
UPON RELEASE AND THINGS OF THAT
NATURE.
SO THIS IS NOT NEW IN A SENSE,
EVEN THOUGH WE ARE USING NEW
TERMS HERE.
SO GIVEN THIS KIND OF A RICH
HISTORY, WE THOUGHT WE ARE IN
VERY INTERESTING TIMES WHERE WE
CAN BRING ALL THESE EFFORTS TO
BE ABLE TO ACTUALLY MAKE MUCH
PROGRESS TO LEARN FROM ONE
ANOTHER, AND THAT WAS THE
MOTIVATION FOR US TO COME UP
WITH THE CDER QUANTITATIVE
MEDICINE CENTER FOR EXCELLENCE.
THE VARIOUS FOCUS AREAS WHICH I
HAVE MENTIONED HERE ARE THE ONES
WHERE WE WOULD COME TOGETHER TO
COORDINATE, COLLABORATE AND
OPERATIONALIZE APPLICATION OF
MANY OF THESE APPROACHES,
APPLYING PHARMACOSTATISTICAL
MODELS, MECHANISTIC MODELING,
MACHINE LEARNING AND ARTIFICIAL
INTELLIGENCE, YOU HAVE HEARD
ABOUT THAT THIS MORNING, THIS IS
THE THING THAT IS UP AND COMING
ADDING TO THE TOOLKIT OF
QUANTITATIVE RESEARCH THAT WE
HAVE, APPLYING THEN FOR BETTER
UNDERSTANDING OF BIOMARKER
ENDPOINT RELATIONSHIPS,
DR. BURACCHIO TALKED ABOUT
BIOMARKERS IN THE SPAN OF NEW
DRUG DEVELOPMENT AND LASTLY TO
BE ABLE TO APPLY THESE MODELS TO
ANTICIPATE HOW TO, HOW WOULD THE
TRIALS PLAY OUT IF WE WERE TO
RUN IN SILICO PREDICTIONS OF
THOSE SO WE ARE BETTER INFORMED
WITH RESPECT TO WHAT INFORMATION
TO COLLECT, WHEN TO COLLECT AND
HOW TO ACTUALLY DESIGN THESE
TRIALS AND OPERATIONALIZE THEM.
SO WE BELIEVE WITH THE
ESTABLISHMENT OF THE CDER
QUANTITATIVE MEDICINE CENTER OF
EXCELLENCE, WE WILL HELP
FACILITATE CONTINUOUS EVOLUTION
CONSISTENT APPLICATION OF
APPROACHES FOR DRUG DEVELOPMENT
AND REGULATORY DECISION-MAKING.
THIS EFFORT BRINGS TOGETHER FIVE
DIFFERENT SUPER OFFICES WITHIN
THE CENTER -- CD HE R OFFICES,
WITH SPONSORSHIP COMING FROM OUR
CENTER DIRECTOR, AND IT PULLS IN
ALL THE RELEVANT DISCIPLINES
ENGAGED IN THE NEW DRUG SPACE,
AS WELL AS IN THE LIFE CYCLE,
RANGING FROM OFFICE OF
TRANSLATIONAL SCIENCES WITH
OFFICE BIOSTATISTICS AND OFFICE
OF CLINICAL PHARMACOLOGY, OFFICE
OF NEW DRUG POLICY, QUALITY
RESEARCH AS WELL AS QUALITY
ASSESSMENTS, AND LASTLY FROM THE
OFFICE OF GENERIC DRUGS WITH THE
OFFICE OF RESEARCH STANDARDS.
SO THIS PROVIDES AN OPPORTUNITY
TO PULL TOGETHER THE EFFORTS
THAT ARE ACROSS ALL THESE
OFFICES TO BE ABLE TO
COORDINATE, COLLABORATE AND
LEARN FROM ONE ANOTHER AND BE
ABLE TO OPERATIONALIZE MANY OF
THESE CONCEPTS FOR CONSISTENT
APPLICATION THROUGHOUT THE
LANDSCAPE.
SO THE PRIMARY FOCUS.
CDER QUANTITATIVE MEDICINE
CENTER OF EXCELLENCE CAN BE
BUCKETED INTO THESE THREE MAIN
AREAS AND I'LL TALK THROUGH EACH
ONE OF THESE VERY QUICKLY.
THE FIRST IS WITH APPLIED
SCIENCE POLICY.
SO WE HAVE GATHERED A LOT OF
EXPERIENCE AND COMFORT LEVEL
WITH APPLICATION OF QUANTITATIVE
APPROACHES IN DIFFERENT AREAS,
WHICH CAN HELP US FOSTER
DEVELOPMENT OF GOOD PRACTICES
WHICH ARE EVIDENCE-BASED AND TO
HELP INFORM NEW GUIDANCES, WHICH
WILL IN TURN HELP WITH THE
CONSISTENT APPLICATION OF
APPROACHES.
WE'LL ALSO BE EMBARKING UPON
KNOWLEDGE MANAGEMENT WHICH
INVOLVES CATALOGING VARIOUS
PRECEDENCES WHICH BECOME THE
SUBSTRATES FOR EVENTUAL
DEVELOPMENT OF POLICIES AS WE
DID FORWARD AND BE ABLE TO
DISSEMINATE THIS SO THAT WE CAN
RAISE THE AWARENESS OF THE
APPLICABILITY OF THESE
APPROACHES AND IN WHICH CONTEXT
THEY MIGHT BE USEFUL, AND THAT
CONNECTS TO THE SECOND FOCUS
AREA, WHICH IS MULTIDISCIPLINARY
EDUCATION AND EXCHANGE.
THE FIRST IS THE EDUCATIONAL
ENRICHMENT.
THE EFFORTS HERE IS TO BE ABLE
TO MAKE SURE THAT THE LEARNINGS
ARE MADE AVAILABLE TONT ONLY
STAFF -- TO NOT ONLY STAFF
WITHIN THE CENTER BUT ALSO THE
VARIOUS STAKEHOLDERS SO THAT
THERE IS AN INCREASED AWARENESS
ABOUT THE AVAILABILITY OF
VARIOUS APPROACHES, WHEN THEY
CAN BE USEFUL TO BE APPLIED, AND
WHAT ARE THE PROS AND CONS OF
SPECIFIC APPLICATIONS.
AND TO THIS END, WE'LL ALSO BE
ENGAGING WITH THE COMMUNITY
THROUGH STAKEHOLDER ENGAGEMENT
ACTIVITIES WHEREIN WE'RE TRYING
TO LEARN FROM THE PEOPLE ON THE
OUTSIDE, ACOMPLYING IS
DEVELOPING SOME OF THESE
APPROACHES TO BE ABLE TO BE
PREPARED FOR THE FUTURE WHERE WE
WILL BE -- AS PART OF SUBMISSION
SO WE CAN HAVE AN INFORMED
DIALOGUE.
LASTLY, THIS IS PREDOMINANTLY AN
IN-HOUSE ACTIVITY WITH RESPECT
TO STRATEGIC PLANNING AND
COORDINATION, SO WE ARE
CURRENTLY IN THE PROCESS OF
PULLING TOGETHER ALL THE VARIOUS
ACTIVITIES THAT ARE HAPPENING
ACROSS DIFFERENT OFFICES AND PUT
FORTH A PLAN FOR COORDINATING
ALL THESE EFFORTS AS WE GO
FORWARD.
SO I HOPE THIS PROVIDES A HIGH
LEVEL OVERVIEW OF THE CENTER AND
THE FOCUS AREAS, AND BEFORE I
CLOSE, I WOULD LIKE TO TOUCH UP
ON SOME OF THE KEY HIGHLIGHTS OF
THE OPPORTUNITIES FOR
QUANTITATIVE MEDICINE APPROACHES
IN ADVANCING NEW THERAPIES
ESPECIALLY IN THIS AREA OF
NEURODEGENERATIVE DISEASES.
I THINK THERE IS GOING TO BE
SOME OVERLAP IN WHAT
DR. BURACCHIO PRESENTED.
THE QUANTITATIVE MEDICINE
APPROACHES CAN BE VERY USEFUL IN
UNDERSTANDING THE PROGRESSION OF
DISEASE AND ALSO VARIOUS SOURCES
OF AVAILABILITY TO BE ABLE TO
IDENTIFY -- OF VARIABILITY TO BE
ABLE TO IDENTIFY AND HELP
ADDRESS THEM.
THE SECOND ASPECT IS AROUND
IDENTIFICATION OF BIOMARKERS AND
CHARACTERIZING THEIR
RELATIONSHIPS WITH THE ENDPOINTS
OF INTEREST.
SOMETIMES THESE ARE PROGNOSTIC
IN NATURE, SOMETIMES THEY ARE
PREDICTIVE IN NATURE, BUT I
THINK FUNDAMENTALLY WE WILL HAVE
ESPECIALLY IN AREAS WHERE THESE
ARE SLOW MOVING OR SLOWLY
PROGRESSING AREAS, THAT IT IS
ESSENTIAL FOR US TO BE ABLE TO
HAVE A GOOD UNDERSTANDINGS OF
VARIOUS MARKERS AND THE PATHWAY
AND HOW THEY ARE RELATED TO ONE
ANOTHER TO BE ABLE TONT ONLY
TARGET THOSE, BUT ALSO TO BE
ABLE TO MEASURE -- TO NOT ONLY
TARGET THOSE BUT ALSO TO BE ABLE
TO MEASURE AND USE THEM TO
IDENTIFY TREATMENT OR EVEN
INFORM PATIENT SELECTION, WHICH
COMES TO THE NEXT POINT, WHERE
QUANTITATIVE MEDICINE APPROACHES
CAN BE VERY USEFUL FOR INFORMING
CLINICAL TRIAL DESIGN,
ENRICHMENT, IDENTIFYING THE
RIGHT PATIENTS WHO MIGHT BENEFIT
FROM THE TREATMENT.
ONE OF THE RIGHT -- ON WHAT
DR. BURACCHIO ADDED, FIND THE
RIGHT PATIENT AND AT THE RIGHT
TIME.
SO QUANTITATIVE MEDICINE
APPROACHES ARE OFTEN USEFUL FOR
INFORMING THOSE SELECTION.
THEY CAN BE VERY USEFUL FOR
INFORMING THE ENDPOINT SELECTION
AS WELL AS TIMING OF ASSESSMENTS
DEPENDING UPON THE TRAJECT RIDS
OF RESPONSE EFFORTS AS WELL AS
TREATMENT EFFORTS AND LASTLY
OFTEN USED FOR OPTIMIZING DOSE,
DOSING REGIMENS, BRIDGING
BETWEEN PRESENTATIONS, MIGHT
COME WITH FROM ONE DRUG ROUTE OF
ADMINISTRATION, IF THEY WERE TO
CHANGE FOR OTHER ROUTES OF
ADMINISTRATIONS, THESE
APPROACHES BRING IN A CERTAIN
ELEMENT OF EFFICIENCY SUCH THAT
WE CAN LEVERAGE IF OUR
UNDERSTANDING FROM PREVIOUS
EFFORTS TO BE ABLE TO HELP
INFORM THESE MODIFICATIONS.
SO LASTLY, BEFORE I CLOSE, I
WOULD POINT OUT SEVERAL
RESOURCES THAT ARE OUT THERE,
THE QUANTITATIVE MEDICINE CENTER
OF EXCELLENCE, AS WELL AS OUR
CONTACT INFORMATION, SO IF YOU
HAVE A GOOD IDEA AND YOU ARE
INTERESTED IN REACHING OUT TO
US, THAT COULD BE THE INBOX, AND
WE ALSO HAVE A SUITE OF
EDUCATIONAL RESOURCES THAT WE
WORK CLOSELY WITH THE CRITICAL
PATH INSTITUTE TO MAKE THEM
ONLINE, THIS IS THE CONTENT THAT
IS AVAILABLE ON OUR WEBSITE AND
ALSO INFORMATION FOR HEARING
ABOUT VARIOUS PRIORITIES AND
OPPORTUNITIES HA WE SHOULD
PROBABLY START THINKING ABOUT
AND PRIORITIZE AS WE GO FORWARD.
>> THANK YOU SO MUCH.
WHAT A GREAT EXAMPLE OF THE
CROSS-CENTER COLLABORATIONS.
I THINK NEXT I'LL TURN IT OVER
TO DR. LIU WHO IS GOING TO TALK
ABOUT THE CENTER FOR BIOLOGICS
EVALUATION AND RESEARCH AND
>> ALL RIGHT.
GOOD AFTERNOON.
FIRST I WOULD LIKE TO THANK THE
ORGANIZERS FOR THE INVITATION.
IT HAS BEEN A FANTASTIC MEETING
AND IT'S A PRETTY GREAT PLEASURE
TO BE HERE.
SO WE HAVE HEARD QUITE A BIT
ABOUT -- IN THE PAST THREE DAYS
AND IN FACT THE OFFICE OF
THERAPEUTIC PRODUCTS ACTUALLY
OVERSEES A LOT OF THESE
PRODUCTS.
SO FOR TODAY, I WOULD LIKE TO
JUST GIVE A VERY HIGH LEVEL
OVERVIEW OF OPPORTUNITIES TO
INTERACT WITH THE OFFICE OF
THERAPEUTIC PRODUCTS, AND I HOPE
THIS INFORMATION WILL BE HELPFUL
TO ALL THE GREAT WORK THAT YOU
ARE DOING.
SO THE OFFICE OF THERAPEUTIC
PRODUCTS OTP IS A SUPER OFFICE
THAT WAS ESTABLISHED BACK IN
2023.
THIS OFFICE OVERSEES A VARIETY
OF PRODUCTS, INCLUDING CELL
THERAPY, GENE THERAPY,
THERAPEUTIC VACCINES,
TRANSPLANTATION, HUMAN TISSUE
PRODUCTS, COMBINATION PRODUCTS
AND DEVICE, YOU NAME IT.
WE HAVE SIX OFFICES AND THREE OF
THE OFFICES ARE FOR
MANUFACTURING REVIEW, AND ONE
OFFICE IS FOR CLINICAL REVIEW
AND THEN ONE OFFICE IS
PHARMACOLOGY TOXICOLOGY REVIEW
AND ALSO OFFICE OF REVIEW
MANAGEMENT AND REGULATORY
REVIEW.
THERE ARE MANY OPPORTUNITIES TO
INTERACT WITH OTP DURING THE
PRODUCT DEVELOPMENT.
WE HIGHLY ENCOURAGE OUR SPONSORS
TO UTILIZE ALL THE MILESTONES,
FOR EXAMPLE THE PRE-IND AND ONE
AND TWO, IN ADDITION, EARLY IN
THE NONBINDING REGULATORY ADVICE
CAN BE OBTAINED FOR
MANUFACTURING, FOR ANIMAL
STUDIES, FOR CLINICAL
DEVELOPMENT THROUGH THE INDIRECT
MEETING WHICH STANDS FOR INITIAL
TARGETED ENGAGEMENT FOR
REGULATORY DEVICE ON C DE R
PRODUCTS.
WE ALSO HAVE MANY OTHER
OPPORTUNITIES AND FOR ENHANCED
COMMUNICATION WITH OTP FOR ALL
STAKEHOLDERS, AND THIS SLIDE
PROVIDES SOME EXAMPLES OF SUCH
OPPORTUNITIES.
THE PATIENT FOCUSED DRUG
DEVELOPMENT MEETINGS, PATIENT
LISTENING SESSIONS, AND
REGENERATIVE MEDICINE EDUCATION
WEBINARS ARE ALL PART OUR
COLLABORATIVE EFFORT TO CONNECT
WITH PATIENT COMMUNITIES AND TO
BETTER UNDERSTAND PATIENT
PERSPECTIVES, EXPERIENCE.
FOR RARE DISEASES, THE RDEA
PROGRAM IS DESIGNED TO PROVIDE A
PLATFORM FOR OUR SPONSORS TO
COLLABORATE WITH THE FDA THROUGH
THE DEVELOPMENT OF NOVEL
ENDPOINTS AND START WAS VERY
WELL RECEIVED AND CAN PROVIDE
ANOTHER PATHWAY FOR RARE DISEASE
DRUG THERAPEUTICS -- DRUG
DEVELOPERS TO ENGAGE WITH THE
FDA AND TO ACCELERATE DRUG
DEVELOPMENT.
FOR TECHNOLOGY FOCUSED PROGRAMS,
WE HAVE THE PLATFORM TECHNOLOGY
DESIGNATION.
THIS ONE IS DESIGNED FOR
TECHNOLOGIES THAT ARE WELL
UNDERSTOOD AND REPRODUCIBLE AND
WE HOPE TO LEVERAGE THE
NONCLINICAL DATA AND
MANUFACTURING DATA OF THESE
TECHNOLOGIES AND FOR
ACCELERATING PRODUCT DEVELOPMENT
FOR OTHER PRODUCTS.
ON THE OTHER HAND, THE CBER
ADVANCED TECHNOLOGY TEAM
MEETINGS FOCUS ON NOVEL
TECHNOLOGIES THAT HAVE THE
POTENTIAL TO HAVE SIGNIFICANT
IMPACT ON PRODUCT DEVELOPMENT.
THE ENHANCED COMMUNICATIONS ARE
ALSO OFFERED THROUGH OUR
EXPEDITED PROGRAMS, FOR EXAMPLE,
FAST TRACK, BREAK THROUGH
THERAPY AND RMAT.
I'M GOING TO TALK A LITTLE BIT
MORE ABOUT THE RMAT DESIGNATION
AS IT IS RATHER UNIQUE TO OTP
REGULATED PRODUCTS.
SO RMAT STANDS FOR REGENERATIVE
MEDICINE ADVANCED THERAPY.
THE PROGRAM WAS ESTABLISHEDS BY
THE 21ST CENTURY CURES ACT IN
2016 AND IS BASICALLY
REGENERATIVE MEDICINE ADVANCED
THERAPIES.
THE FOLLOWING PROVIDES A
DEFINITION OF REGENERATIVE
MEDICINE THERAPY.
LTS DEFINED BY THE FACT AS CELL
THERAPY, THERAPEUTIC TISSUE
ENGINEERING PRODUCTS, HUMAN CELL
AND TISSUE PRODUCTS, OR ANY
COMBINATION PRODUCT USING SUCH
THERAPIES OR PRODUCTS.
COMBINATION PRODUCT CAN BE
ELIGIBLE FOR RMAT DESIGNATION
WHEN THE BIOLOGICAL COMPONENT
PROVIDES THE GREATEST
CONTRIBUTION TO THE OVERALL
INTENDED EFFECTS OF THE
COMBINATION PRODUCT.
IN ADDITION, GENE THERAPIES,
INCLUDING GENETICALLY MODIFIED
CELLS, THAT LEAD TO A SUSTAINED
EFFECT ON CELLS OR TISSUES, SUCH
AS ANTI-VIRAL GENE THERAPY,
MEDIATED GENE THERAPY ARE ALSO
CONSIDERED AS REGENERATIVE
MEDICINE THERAPY.
FOR RMAT DESIGNATION AN
INVESTIGATIONAL DRUG MUST MEET
THE DEFINITION OF REGENERATIVE
MEDICINE THERAPY.
THE DRUG MUST BE INTENDED TO
TREAT, MODIFY, REVERSE OR CURE A
SERIOUS OR LIFE-THREATENING
DISEASE OR CONDITION, IN
ADDITION, PRELIMINARY CLINICAL
EVIDENCE NEEDS TO SUPPORT THAT
THE DRUG HAS THE POE TECIALG TO
ADDRESS UNMET -- POTENTIAL TO
ADDRESS UNMET NEEDS FOR SUCH
DISEASE OR CONDITION.
MUCH THE VANGDZ OF THE RMAT
DESIGNATION INCLUDE ALL OF THE
BENEFIT OF THE FAST TRACK AND
BREAKTHROUGH DESIGNATION
PROGRAMS, INCLUDING EARLY
INTERACTIONS WITH FDA TO DISCUSS
ANY POTENTIAL SURROGATE OR
INTERMEDIATE ENDPOINTS TO
SUPPORT ACCELERATED APPROVAL.
THE STATUTE ALSO ADDRESSES
POTENTIAL WAYS TO SUPPORT
ACCELERATED APPROVAL AND SATISFY
POST-APPROVAL REQUIREMENTS.
I DON'T HAVE TIME TO GO INTO ALL
THE DETAILS OF ALL THE WONDERFUL
PROGRAMS, BUT I DOMENT TO SHARE
THIS PIE CHART WITH YOU -- BUT I
DO WANT TO SHARE THIS PIE CHART
WITH YOU.
AS OF DECEMBER 2023, WE RECEIVED
270 RMAT DESIGNATION REQUESTS.
OF THESE, 99 WERE GRANTED.
AND AS SHOWN IN THIS PIE CHART,
NEUROLOGY HAS THE MOST RMAT
DESIGNATION REQUESTS.
I THINK THIS IS A GREAT
REPRESENTATION FOR THE INTEREST
FOR THE DEVELOPMENT OF
REGENERATIVE MEDICINE, PRECISION
MEDICINE FOR NEUROLOGICAL
DISORDERS INCLUDING ALZHEIMER'S
DISEASE.
WITH THAT, HERE IS OUR CONTACT
INFORMATION AND A LOT OF
WEBSITE, THE RESOURCES PROVIDED
THERE.
THANK YOU.
>> THANK YOU SO MUCH, DR. LIU.
I'M HAPPY TO TURN IT OVER TO MY
COLLEAGUE AND PARTNER
DR. MICHELLE CAMPBELL WHO WORKS
SO MUCH ACROSS NEURAL PROGRAMS,
PATIENT FOCUSED DEVELOPMENT.
>> THANK YOU.
I'LL SPEND THE NEXT COUPLE
MINUTES TALKING ABOUT HOW WE
WANT TO CAPTURE THE LIVED
EXPERIENCE.
I'M IN THE OFFICE OF
NEUROSCIENCE IN C DE R BUT THE
PROGRAMS I'LL BE TALKING ABOUT
ARE ACROSS ALL THREE MEDICAL
PRODUCT CENTERS INCLUDING CBER
AS WELL.
PATIENT FOCUSED DRUG DISWOMENT A
SYSTEM ABILITY APPROACH TO HELP
ENSURE THAT THE PATIENT'S
EXPERIENCES, PERSPECTIVES AND
NEEDS ARE CAPTURED AND
MEANINGFULLY INCORPORATED INTO
DRUG DEVELOPMENT AND EVALUATION.
SO FIRST AND FOREMOST IN OUR
EVERY DAY AS DR. BURACCHIO SAID
WHAT, WE THINK ABOUT, SO FOR US,
WE ALSO THINK ABOUT AS WE WANT
TO HAVE TREATMENTS THAT ARE
CLINICALLY MEANINGFUL TO
PATIENTS THAT DEMONSTRATES THAT
THEY IMPROVE HOW THEY FEEL,
FUNCTION OR SURVIVE.
PATIENT FOCUSED DRUG DEVELOPMENT
IS REALLY CAUTERIZED AND PULLED
OUT AND SPECIFICALLY LISTED.
BACK IN 2012 THIS REALLY CAME
ABOUT, AND SO IT'S BEEN A
PLEASURE TO WORK IN THIS SPACE
SINCE ITS INFANCY OF REALLY HOW
DO WE APPLY THIS TO DRUG
DEVELOPMENT, BECAUSE IT HAS
GROWN AMAZINGLY IN THE LAST
DECADE WITH HOW DO WE
INCORPORATE PATIENT FOCUSED DRUG
DEVELOPMENT THROUGHOUT THE DRUG
DEVELOPMENT LIFE CYCLE.
ILT IMPORTANT TO NOTE THAT FOR
PATIENT FOCUSED DRUG DEVELOPMENT
FDA IS JUST ONE STAKEHOLDER.
INDUSTRY, ACADEMIA EXPSK
PATIENTS AND THEIR FAMILIES ARE
OTHER KEY STAKEHOLDERS THAT NEED
TO BE THOUGHT ABOUT WHEN WE'RE
CONSIDERING HOW TO DEVELOP DRUGS
AND THERAPIES FOR ALZHEIMER'S,
AND I THINK YOUR PANEL YESTERDAY
MORNING REALLY HIGHLIGHTED THAT
ABOUT HOW PEOPLE TALKED ABOUT
THEIR EXPERIENCE WS THEIR LOVED
ONES AND WHAT WERE THOSE
OPPORTUNITIES FOR THEM TO LEARN
MORE ABOUT IF THEY HAVE A RISK
FOR DEVELOPMENT, AND I THINK
THAT WAS A REALLY GREAT EXAMPLE
AND THEY WERE PROVIDING SOME
REALLY GREAT EXAMPLES OF HOW TO
INCORPORATE THEIR THOUGHTS INTO
EITHER CLINICAL PRACTICE,
CLINICAL RESEARCH AND CLINICAL
TRIALS.
SPECIFIC.
LY FOR FDA, SPECIFIC THINGS WE
HAVE LED IN OUR UNDERTAKING
FIRST AND FOREMOST WAS OUR FDA
LED PATIENT FOCUSED DRUG
DEVELOPMENT MEETINGS THAT CAME
OUT OF FIVE, WE WERE MANDATED TO
HAVE SO MANY MEETINGS AND WITH
SO MANY DISEASES AND DISORDERS,
WE HAD TO FIGURE OUT WHICH ONES
TO START WITH.
WE DID DO SUCCESSFULLY EXCEED
OUR MANDATES AND WE LEARNED FROM
DISEASES THAT HAVE MAYBE A
LARGER POPULATION OF FOLKS, AND
RARE DISEASE AS WELL.
WHAT WE LEARNED, WHICH I THINK
FOR A LOT OF US IN THIS AUDIENCE
WE KNOW, BUT IT REALLY, REALLY
RANG TRUE AND IS THE HALLMARK OF
HOW WE PRACTICE PFDD IS PATIENTS
ARE THE EXPERTS OF THEIR
CONDITIONS, AND WE SHOULD REALLY
BE TALKING TO THEM BECAUSE WE
KNOW THAT IN DRUG DEVELOPMENT,
SOMETIMES WHAT IS BEING CAPTURED
IS ACTUALLY NOT WHAT'S
MEANINGFUL TO PATIENTS.
SO WE REALLY NEED TO MAKE SURE
WE'RE TAKING INTO THOSE
EXPERIENCES INTO OUR DRUG
DEVELOPMENT.
IT'S ALSO IMPORTANT TO NOTE THAT
WHEN WE'RE APPLYING PATIENT
FOCUSED DRUG DEVELOPMENTS INTO
CLINICAL TRIAL DESIGN, WE ALSO
HAVE TO BALANCE ALL THE OTHER
THINGS WE'VE BEEN TALKING ABOUT,
WHAT DO WE THINK THE DRUG GOING
TO DO, DHUNG WE THINK WE'LL SEE
AN EFFECT, WILL WE BE ABLE TO
CHANGE THIS CONCEPT THAT IS
REALLY IMPORTANT TO FAMILIES AND
TO PATIENT FROM THAT TREATMENT.
WE HAVE SUCCESSFULLY
TRANSITIONED FROM FDA LED PFFD
MEETINGS WHICH WE STILL WILL
HOST AS NEEDED TO A VERY
SUCCESSFUL EXTERNALLY LED
PATIENT FOCUSED DRUG DEVELOPMENT
PROGRAM WHERE PATIENT GROUPS
WILL SUBMIT LETTERS OF INTENT TO
CDER, WANTING TO HOST MEETINGS,
AND ONCE YOU ENGAGE WITH THE
PATIENT FOCUSED DRUG DEVELOPMENT
STAFF ON HOW TO DO THAT, SO THEY
DO HAVE SOMEONE TO WORK WITH,
THEY WORK WITH US, AND REVIEW
DIVISIONS ABOUT HOSTING THESE
MEETINGS.
AGAIN, WHILE SOME OF THESE ARE
HOSTED OUT OF C DE R, ALL THREE
OF THE MEDICAL PRODUCT CENTERS
ARE FULLY INVOLVED AND
PARTICIPATE IN THESE MEETING AS
WELL.
SO THAT IS A GREAT VENUE FOR
THAT.
SO WE HAVE SOME UPCOMING
MEETINGS.
WE HAVE A MEETING IN I WANT TO
SAY TWO WEEKS, MAYBE THREE AT
THIS POINT, IF I CAN REMEMBER
CORRECTLY MY CALENDAR, FOR
DEMENTIA WITH LEWY BODY ON
OCTOBER 15 AND THEN THERE'S ONE
ON HUNTINGTON'S IN NOVEMBER,
WE'VE ALSO HAD SOME OTHER
EXTERNAL PATIENT MEANS AND SOME
OF THE OTHER ADRD RELATED
DEMENTIAS.
WE HAVE A PATIENT FOCUSED DRUG
DEVELOPMENT METHODOLOGICAL
GUIDANCE SERIES, AND THIS IS, I
WILL SAY, AS SOMEONE WHO HELPED
CONTRIBUTE TO IT, IT WAS A LABOR
OF LOVE, AND YOU'LL PROBABLY
NEVER SEE A GUIDANCE SERIES EVER
LIKE THAT AGAIN.
SO I'M GOING TO HOLD OFF, I
THINK MY NEXT SLIDE IS ACTUAL ON
THAT SERIES, AND I'LL TALK A
LITTLE BIT MORE ABOUT THAT.
WHILE WE ARE NOT A FUNDING
AGENCY LIKE OUR COLLEAGUES AT
NIA AND NIH, WE DID FUND A PILOT
PROGRAM IN TRYING TO ADVANCE
DEVELOPMENT OF CLINICAL OUTCOME
ASSESSMENTS IN SPECIFIC DISEASE
AREAS OR CONCEPT AREAS.
SO REALLY WE ARE FULLY TRENCHED
IN PUSHING FORWARD PATIENT
FOCUSED DRUG DEVELOPMENT IN MANY
WAYS.
THE OTHER PIECE IS PATIENT
EXPERIENCE DATA.
THIS ALSO CAME OUT OF 21ST
CERTAIN TRI CURES AND HAS A
REALLY BIG DEFINITION -- REALLY
BROAD DEFINITION OF WHAT IS IT.
PATIENTS HAVE A PLETHORA OF
INFORMATION THAT THEY WANT TO
SHARE, AND THEY WANT US TO SEE
IT AND TO BE INFORMED BY IT.
REALLY PATIENT EXPERIENCE DATA,
THIS IS NOT THE FINAL LIST.
IT IS JUST A SNIPPET OF WHAT
THAT CAN LOOK LIKE.
SO IT CAN BE SOMETHING SUCH AS
PATIENT LISTENING SESSIONS OR
PATIENT FOCUSED DRUG DEVELOPMENT
SESSIONS, PATIENT EXPERIENCE
DATA IS THE CLINICAL OUTCOME
ASSESS THAMENTS ARE USED IN
CLINICAL TRIALS TO SUPPORT OUR
CLINICAL TRIAL ENDPOINTS, IT
COULD BE PATIENT PREFERENCE
STUDIES PARTICULARLY ON SAFETY
THAT A LOT OF WORK PARTICULARLY
IN GENE THERAPIES WITH MY CBER
COLLEAGUES LOOKING AT SAFETY
PROFILES AND WHAT IS SOMEONE'S
RISK TOLERANCE FOR THESE
NEUROTHERAPIES.
THEY CAN INCLUDE QUALITATIVE
INFORMATION ON BENEFIT/RISK AND
CLINICAL MEANINGFULNESS, WHICH
IS REALLY A CONVERSATION WE HAVE
EVERY DAY ABOUT WHAT WE'RE
REVIEWING DATA, IT'S IMPORTANT
TO NOTE THAT WHEN WE TALK ABOUT
CLINICAL MEANINGFULNESS, WE ARE
REALLY INTERESTED IN MEANINGFUL
WITHIN PATIENT CHANGE.
SO WHAT IS HAPPENING AT THE
PATIENT LEVEL, AND IS IT
MEANINGFUL TO THEM, BECAUSE WE
KNOW THAT SOMETIMES THE MINIMAL
AMOUNT OF CHANGE IS OFTEN MAY
NOT BE MEANINGFUL TO THEM.
SO THERE ARE MULTIPLE WAYS THAT
WE CAN ACTUALLY EXPLORE THIS,
AND PATIENT EXPERIENCE DATA
THROUGH QUALITATIVE METHODS IS
ONE OF THOSE WAYS.
SO THE METHODOLOGICAL GUIDANCES
SERIES, YOU WILL NEVER SEE AN
FDA GUIDANCE EVER LOOK LIKE THIS
AGAIN.
I'M JUST GOING TO TELL YOU THAT
RIGHT NOW.
IT IS A FOUR PART GUIDANCE
SERIES, AND IT IS AN EXTREMELY
LENGTHY GUIDANCE SERIES.
EACH GUIDANCE IS ABOUT 40 PAGES.
SO NOT TO SCARE YOU ANY MORE OFF
OF THAT, WHY IS THIS SO
REVOLUTIONARY THOUGH FOR PATIENT
FOCUSED DRUG DEVELOPMENT?
BECAUSE WE BASICALLY WROTE AN
ENCYCLOPEDIA/COOKBOOK FOR
EVERYONE, SO WHAT WE DID AND WE
WERE UNDER OUR 281ST CENTURY
CURES WE WERE MANDATED TO PUT
THIS TOGETHER BUT IT WAS ALREADY
SOMETHING WE WERE ALREADY
THINKING ABOUT DOING OURSELVES
WITHOUT HAVING HAD IT ADDED INTO
PADUFFA EFER, WE WERE REALLY
THINKING ABOUT HOW DO WE
APPROACH THIS.
FIRST TWO GUIDANCE IS ABOUT HOW
DO WE COLLECT COMPREHENSIVE AND
REPRESENTATIVE INPUTS,
YESTERDAY'S PANEL WAS A GREAT
WAY TO SHOW THE DIVERSITY IN THE
SPACE AND WHY WE NEED TO DO THIS
QUALITATIVE WORK.
FROM GUIDANCE ONE YOU GO INTO
GUIDANCE TWO WHICH IS HOW DO WE
START APPLYING SCIENTIFIC RIGOR
TO CAPTURING QUALITATIVE
INFORMATION.
FIRST TWO GUIDE ANS ONE AND TWO
WERE WRITTEN, IF YOU LOOK AT
THEM, FOR PATIENT GROUPS IN MIND
BECAUSE WE KNOW THAT THEY'RE
OFTEN STARTING A LOT OF THIS
DATA COLLECTION EFFORTS.
GUIDANCES THREE AND FOUR SHIFT A
LITTLE BIT AND THEY'RE
DEFINITELY MORE TECHNICAL, I
WILL SAY, AND THESE WERE
DEFINITELY FOR INDUSTRY, BECAUSE
WHAT GUIDANCE THREE DOES, EACH
GUIDANCE BUILDS UPON THEMSELVES.
SO GUIDANCE THREE IS SAYING,
WELL, YOU'VE TAKEN WHEUF DONE IN
ONE AND TWO -- TAKEN WHAT YOU'VE
DONE IN ONE AND TWO AND
COLLECTED ALL THIS INFORMATION,
BUT NOW HOW DO WE SELECT A: CAL
OUTCOME ASSESSMENT, DO WE NEED
TO DEVELOP ONE OR MODIFY ONE AND
WHAT IS THE EVIDENTIARY
STANDARDS HA WE NEED FOR ALL
FOUR TYPES OF CLINICAL OUTCOME
ASSESSMENTS WHERE WE WANT TO USE
THEM TO SUPPORT OUR TRIAL
ENDPOINTS, AND THEN GUIDANCE
FOUR REALLY TALKS ABOUT HOW DO
WE GO FROM THE ENDPOINTS OR FROM
THE OUTCOME ASSESSMENT INTO IT
SUPPORTING THE CLINICAL TRIAL
ENDPOINT.
I WILL TELL YOU RIGHT NOW THEY
ARE A HEAVY READ.
I COMPLETELY ADMIT TO THAT.
BUT DON'T BE AFRAID OF THEM.
THERE ARE FOLKS OUT THERE WHO
COMPLETELY UNDERSTAND THEM.
WE UNDERSTAND THEM.
SO IF YOU COME AND GET ADVICE TO
US EARLY WE CAN HELP PROVIDE
SOME UNDERSTANDING OF WHAT'S IN
THERE.
AND I CAN'T GO TOO FAR WITHOUT
QUICKLY MENTIONING DIGITAL
HEALTH TECHNOLOGY, WHICH IS
ALONG WITH AI AND MACHINE
LEARNING ARE SOME OF THE
NEUROOPPORTUNITIES FOR US TO
COLLECT INFORMATION, AND I KNOW
WE HAD THE MORNING SESSION
HIGHLIGHTED SOME ASPECTS WITH
DIGITAL HEALTH TECHNOLOGY.
SO THIS IS OUR DEFINITION OF
DIGITAL HEALTH TECHNOLOGIES FOR
ALL THREE MEDICAL PRODUCT
CENTERS AND YOU CAN FIND THIS IN
THE FDA NIH BEST GLOSSARY.
BUT OUR DEFINITION IS AN
EXTREMELY BROAD DEFINITION AS
IT'S A SYSTEM THAT USES
COMPUTING PLATFORMS,
CONNECTIVITY, SOFTWARE AND
SENSORS FOR HEALTHCARE USES, AND
YOU CAN SEE ON THE RIGHT-HAND
SIDE WHAT SOME OF THOSE
POTENTIAL USES COULD BE.
SO IT IS AN EXTREMELY BROAD
THING.
BUT WHAT DO I WANT YOU TO KNOW?
FIRST AND FOREMOST, WE HAVE A
GUIDANCE OUT.
WE'VE MENTIONED A COUPLE
GUIDANCES TO EVERYONE TODAY,
PLEASE KNOW THAT THESE GUIDE ANS
SHOULD NEVER BE READ AS A SINGLE
GUIDANCE.
THERE IS PROBABLY A GUIDANCE OF
A NUMBER OF 207 IKS THAT
COMPLEMENT THE OTHER GUIDANCE
THAT YOU'RE READING.
SO OUR FINAL GUIDANCE CAME OUT
IN DECEMBER, AND IT REALLY
FOCUSES ON WHAT IS NEEDED FOR
COLLECTING REMOTE DATA IN
CLINICAL INVESTIGATIONS.
IT REALLY TALKS ABOUT THE HAVE
ADDITION AND VERIFICATION WORK
THAT IS NEEDED FROM THE DEVICE
THAT THE DIGITAL HEALTH
TECHNOLOGY STANDPOINTS.
IT DOES NOT TALK ABOUT HOW YOU
TAKE THE DATA THAT'S BEEN
COLLECTED AND HOW IS THAT DATA
THEN EITHER GOING TO BE USED TO
SUPPORT A DIGITALLY DERIVED
BIOMARKER OR A DIGITALLY DERIVED
ENDPOINT.
AND WE KNOW THAT THERE'S A BIG
FOCUS IN WANTING TO USE DHT'S TO
SUPPORT DIGITALLY DERIVED
ENDPOINTS AND WE WOULD SAY THAT
ONCE THE CONTEXT OF USE HAS BEEN
DETERMINED, WE WILL THEN NEED TO
THROW IN WHAT WE KNOW ABOUT THE
EVIDENCE WE NEED FOR ENDPOINTS
IN THERE AS WELL.
SO MY FINAL REMARKS, HOW DO WE
REALLY IMPLEMENT PATIENT FOCUSED
DRUG DEVELOPMENT IN ALZHEIMER'S.
FIRST AND FOREMOST AS
DR. BURACCHIO SAID, WE NEED TO
INCORPORATE AND LEVERAGE WHAT IS
KNOWN WITH THE BIOLOGY OF THE
DISEASE, AND I WOULD SAY EVEN MY
CLINICAL PHARMACOLOGY
COLLEAGUES, THE INFORMATION
THEY'RE DOING, THIS IS GOING TO
BE EXTREMELY IMPORTANT IN HOW
WE'LL APPROACH PATIENT FOCUSED
DRUG DEVELOPMENT.
WE NEED TO EMPLOY QUALITATIVE
METHOD OLINGSZ TO COLLECT THE
LIVED -- METH ODOLOGIES TO
COLLECT LIVED EXPERIENCE
INFORMATION THROUGHOUT THE
SPECTRUM AND STAGES OF AD AND TO
WANT HEAR FROM BOTH PERSONS WITH
AD PARTICULARLY IF IT'S BEEN
EARLIER IDENTIFIED AND THOSE
THAT MAY BE AT A HIGHER RISK OF
DEVELOPING, WE HEARD FROM THOSE
FOLKS YESTERDAY AND THAT'S A
GREAT OPPORTUNITY, AS WELL AS
FAMILIES AND CAREGIVERS AND THE
FULL SPECTRUM IS CRITICALLY
IMPORTANT TO KIND OF KNOW
BECAUSE WHAT MAY BE IMPORTANT AT
ONE POINT MOST LIKELY WILL SHIFT
OVER TIME FROM WHAT WE'VE HEARD
FROM OUR EXPERIENCES TALKING TO
FAMILIES.
AND FINALLY, WE WANT TO CONSIDER
IMPLEMENTING ALL DIFFERENT TYPES
OF CLINICAL OUTCOME ASSESSMENTS
P WHEN WE CAN INTO OUR CLINICAL
TRIALS.
THIS ALSO CAN INCLUDE INCLUDING
USE OF DIGITAL HEALTH
TECHNOLOGIES, SO THIS IS WHEN WE
ALWAYS SAY COME EARLY AND OFTEN
AND TALK TO US SO WE CAN GIVE
THE BEST ADVICE AND APPROACHES
ON HOW TO LEVERAGE AL TYPES HAD
OF ASSESSMENTS.
WITH THAT, I TURN IT BACK TO
YOU.
S.
>> SO I THINK WE HAVE FIVE
MINUTES, IF ANYBODY IN THE
AUDIENCE HAS ANY QUESTIONS, THEY
CAN COME UP TO THE MICROPHONE
AND ASK QUESTIONS OF ANY OF THE
PANELISTS.
WE MIGHT HAVE A FEW ONLINE.
>> THANK YOU.
SO WE HAVE AN ONLINE QUESTION
ABOUT FDA GUIDELINES.
SO SOME FDA GUIDELINES AVAILABLE
ONLINE ARE DRAFTS.
MY UNDERSTANDING IS THAT THEY'RE
NOT THE FINAL OR OFFICIAL
VERSIONS, SO HOW SHOULD THE
AUDIENCE LOOK AT THEM
CRITICALLY?
>> SO THE DRAFTS, WE I SHALL
INITIALLY PUT OUT GUIDE ANS AS
DRAFTS.
THEY EMPLOY OUT FOR A PUBLIC
COMMENT PERIOD.
WE THEN WILL -- THEY GO OUT FOR
A PUBLIC COMMENT PERIOD.
WE THEN WILL TAKE THE PUBLIC
COMMENT AND DISCERN IF WE NEED
TO MAKE REVISIONS TO THE
GUIDANCE BASED ON THE PUBLIC
COMMENTS THAT WE RECEIVE.
SOMETIMES WE WILL MAKE REVISIONS
PRETTY QUICKLY DEPENDING ON THE
TYPE OF COMMENTS WE GOT.
OTHER TIMES, WE WILL TAKE THOSE
COMMENTS UNDER CONSIDERATION,
BUT WE MAY NOT FEEL THAT ANY
IMMEDIATE CHANGES ARE NEEDED.
WE TYPICALLY DO REVISIT
GUIDANCES EVERY FEW YEARS, I
CAN'T REMEMBER, I THINK THERE'S
A RECOMMENDATION OF, YOU KNOW,
EVERY FIVE YEARS OR SO WE SHOULD
REVISIT THEM AND SEE IF THEY
NEEDED TO BE UP2K5EU9D AND WE
WILL UP-- UPDATED AND WE WILL
UPDATE THEM AS NEEDED.
IF IT IS AN AREA OR FIELD WHERE
THERE'S STILL A LOT OF EVOLVING
THINKING AND CHANGES IN
SCIENTIFIC KNOWLEDGE, GUIDE ANS
CAN REMAIN IN DRAFT FOR A FAIR
AMOUNT OF TIME, BECAUSE WE KNOW
THAT THEY'RE GOING TO NEED TO BE
CONTINUED TO BE UPDATED, AND WE
MAY IN SOME CASES WE MAY NEVER
BE ABLE TO ISSUE A FINAL
GUIDANCE.
I'LL SAY THAT IN PARTICULAR WITH
THE ALWAYS ALZHEIMER'S DISEASE
GUIDANCE, WE'VE HAD NOW THREE
DRAFTS.
IT WILL BE UPDATED AGAIN HAD THE
FUTURE, I THINK AS WE CONTINUE
AS OUR KNOWLEDGE CHANGED, YOU
KNOW, AND WE MOVE ALONG.
BUT THAT IS ONE THAT I FIND IS
PARTICULARLY, WILL BE
PARTICULARLY CHALLENGING TO MAKE
IN A FINAL FORM BECAUSE THE
FIELD IS SO RAPIDLY EVOLVING
RIGHT NOW.
SO, YOU KNOW, I THINK THE DRAFT
GUIDANCES THAT ARE OUT THERE,
EVEN THOUGH THEY SAY DRAFT, DO
REPRESENT OUR CURRENT THINKING,
AND JUST BECAUSE IT DOESN'T SAY
FINAL DOESN'T MEAN THAT IT'S,
YOU KNOW, NOT REPRESENTATIVE OUR
THINKING.
IT'S JUST THAT IT MAY BE UPDATED
AGAIN IN THE FUTURE.
>> MAYO CLINIC.
THANK YOU VERY MUCH.
THANK YOU, NIA, FOR BRINGING OUR
COLLEAGUES AT FDA TO US.
SO WE'VE HEARD AT THESE MEETINGS
THAT THERE ARE HUNDREDS OF
POTENTIAL THERAPEUTIC TARGETS,
AND INVESTIGATORS ARE WORKING ON
HUNDREDS OF THEM, MAYBE TENS OF
THEM OR TOWARDS A HUNDRED OF
THEM ARE IN LATER STAGES IN OUR
LABS, AND I ALSO APPRECIATED THE
PIPELINE OF ENCOURAGING
INVESTIGATORS TO MEET WITH FDA
IN THE PRE-PREIND STAGES, BUT
CONSIDERING THAT, EVEN FROM FDA
THERE ARE 600 THERAPEUTIC
TARGETS, WHEN IS A REALLY GOOD
TIME TO GET TOGETHER WITH OUR
COLLEAGUES AT THE FDA TO DISCUSS
THE NEXT STEPS?
>> SO IN THE EARLIEST STAGES
WHEN YOU'RE STILL IN DISCOVERY,
WE WEREN'T ABLE TO GIVE TOO MUCH
SPECIFIC FEEDBACK ON A GIVEN
DRUG DEVELOPMENT PROGRAM AT THE
DISCOVERY STAGE.
THOSE SORTS OF STAGES ARE BETTER
FOR BROADER SCIENTIFIC MEETINGS,
YOU KNOW, SUCH AS MEETINGS
ORGANIZED BY NIA OR OTHER GROUPS
WHERE THE SORT OF STATE OF THE
SCIENCE IS DISCUSSED AND WE CAN
GIVE MORE BROADER FEEDBACK.
IT'S USUALLY WHEN A PRODUCT IS
READY TO MOVE INTO ITS FIRST
HUMAN STUDIES THAT WE START
BECOMING ENGAGED.
IF THERE ARE PARTICULAR ISSUES
WITH THE INTERACT MEETINGS, WE
ALSO DO HAVE THE INTERACT
MEETINGS, THEY STARTED IN CBER
BUT WE DO HAVE THEM IN CDER AS
WELL NOW, WHERE IF THERE'S
REALLY UNIQUE ASPECTS OF
DEVELOPMENT PERHAPS, YOU KNOW,
UNIQUE CHALLENGES THAT ARE NOT
COMMON AND ARE NOT ALREADY
ADDRESSED BY SOME OF THE
GUIDANCES THAT COME OUT, THOSE
ARE WHAT THOSE MEETINGS ARE
INTENDED FOR FOR REALLY UNIQUE
SITUATIONS, BUT EVEN THEN,
THAT'S USUALLY AT A STAGE WHERE
A DRUG OR A COUPLE OF DRUGS THAT
MEET A SPECIFIC TARGET ARE BEING
CONSIDERED FOR FURTHER
DEVELOPMENT.
SO THAT'S, WE USUALLY GET
INVOLVED A LITTLE AFTER THE
DISCOVERY PHASE, BUT WHEN WE'RE
STILL AT THE DISCOVERY PHASE,
YOU KNOW, THERE IS STILL
OPPORTUNITIES FOR ENGAGEMENT,
BUT THAT'S USUALLY GOING TO BE
AT A MORE GENERAL FORUM.
>> I JUST WONDERED, FOR INTERACT
MEETINGS, OFTENTIMES WE ADVISE
OUR SPONSORS TO COME TO US WHEN
THEY FINISH THEIR FIRST APPROVAL
CONCEPT STUDY.
HAVING STARTED ENABLING ANIMAL
STUDIES, SO THAT TYPICALLY IS A
GOOD TIME TO COME TALK TO US FOR
YOUR INTERACT MEETING.
REALLY THERE'S NO BAD TIME TO
COME TALK TO US.
DOESN'T MATTER WHERE IN THE
CLINICAL DEVELOPMENT STAGE YOU
ARE, AND JUST COME AND TALK TO
US, WE'LL FIGURE OUT A WAY.
>> -- FOR DR. BURACCHIO OR
ANYONE WHO CHOOSES TO FIELD IT.
I'M WONDERING HOW YOU WOULD
ENCOURAGE US TO BE THINKING
ABOUT THE INVOLVEMENT OF WHAT
BIOMARKER PANELS, AS THE
TECHNOLOGIES EVOLVE AND AS THE
COMPLEXITY OF POTENTIAL
THERAPIES EVOLVE, IN A PRECISION
MEDICINE CONTEXT BECAUSE THAT'S
THE THEME OF THE SUMMIT HERE.
>> I'LL START AND OTHERS CAN
JOIN ME.
P I THINK THAT'S A VERY GOOD
QUESTION WITH RESPECT TO HOW
SCIENCE WILL EVOLVE AND HOW
TECHNOLOGIES WILL ENABLE US.
HISTORICALLY WE HAVE BEEN TRYING
TO IDENTIFY THAT CRITICAL
BIOMARKER, THAT ONE KEY
BIOMARKER, AND WE DO REALIZE
THAT DISEASES ARE VERY
HETEROGENEOUS, THERE IS NO -- I
SHOULD NOT SAY THERE IS NO.
RARELY THERE IS INSTANCES THERE
IS ONLY ONE CHOKE POINT IF
EXPIEFD ADDRESSED THAT WOULD --
IDENTIFIED AND ADDRESSED THAT
WOULD HELP TREAT A DISEASE KIND
OF SITUATION.
SO OBVIOUSLY APPEARS THE SCIENCE
EVOLVES AND TECHNOLOGIES COME
UP, MAYBE THERE WILL BE A SHIFT
TOWARDS PANELS OF BIOMARKERS
WHICH ARE GOING TO HAVE A -- AS
OPPOSED TO A SINGLE STAND ALONE
BIOMARKER BY ITSELF MAY NOT HAVE
THE ABILITY TO INFORM US, AND I
THINK WE'LL HAVE TO START
GETTING COMFORTABLE WITH THE
VARIOUS QUANTITATIVE AREAS TO BE
ABLE TO ANALYZE SUCH
INFORMATION.
WE KNOW HOW TO CREATE A SINGLE
RESPONSE.
WE KNOW HOW TO LOOK AT COMPOSITE
OF ENDPOINTS, FOR EXAMPLE.
SO THERE ARE SOME LEARNINGS
THERE AND PROBABLY THERE ARE
METHODOLOGIES WHICH WE WILL HAVE
TO START GETTING COMFORTABLE AT
SOME POINT OR TIME AS TO HOW TO
BEST INTEGRATE THE INFORMATION
ACROSS THE PANEL OF BIOMARKERS,
FIGURE OUT WHAT THEY MEAN, AND
CORRELATE THEM TO THE CLINICAL
OUTCOMES.
SO I THINK THIS WILL BE
SOMETHING THAT WE LOOK FORWARD
TO AND WILL BE SOMETHING THAT IT
WILL EVOLVE OVER A PERIOD OF
TIME.
OTHERS?
>> WE ALREADY ARE USING
BIOMARKERS WITHIN OUR CLINICAL
TRIALS AS FAR AS I MENTIONED FOR
ENRICHMENT, FOR ENROLLMENT
CRITERIA, FOR ENRICHMENT, AND IF
IT'S BEING USED IN DEVELOPMENT,
YOU KNOW, THERE'S ALWAYS
EXPLORATORY ENDPOINTS, IF IT'S
GOING TO BE USED TO SORT OF
TRACK CHANGES DURING THE COURSE
OF A CLINICAL TRIAL, WE
GENERALLY RECOMMEND THAT THOSE
BE INCLUDED AS EXPLORATORY
OUTCOME MEASURES IN THE TRIALS
HELP GENERATE THE DATA THAT WE
NEED TO THEN FURTHER SUPPORT
THEIR USE AS EITHER HIGHER IN
THE HIERARCHY OR EVEN AS A
SURROGATE ENDPOINT EVENTUALLY.
>> THANK YOU.
>> SAYS BEING AROUND DATA
SHARING THAT I THINK EVERYBODY
MAY NOT SRN OUR PREDICTIVE
SAFETY TESTING CONSORTIUM WAS
ABLE TO ACHIEVE A LETTER OF
SUPPORT IN SIX MONTHS, THEY HAVE
A MICRORNA PANEL TO PROJECT
PANCREATIC DRUG INDUCED TOXICITY
IN NONCLINICAL SPECIES.
THE REASON WHY IT TOOK SO FAST,
SIX MONTHS, IS SEVEN INDUSTRY
SPONSORS CONTRIBUTED DATA TO
SUPPORT THAT SUCCESS.
SO LTS A COMPOSITE, IT'S
MICRORNAS WHICH IS PRETTY
EXCITING AND I THINK IT SENDS
THE MESSAGE THAT WE'RE ALL
SAYING HERE ABOUT DATA SHARING.
>> I THINK WE'RE OUT OF TIME SO
WE'LL PASS IT TO THE NEXT PANEL,
LAST PANEL.
SO THANKS MY FELLOW COLLEAGUES.
>> GOOD AFTERNOON.
AS WE'RE TRYING TO CONCLUDE THE
SUMMIT FEST IT'S AND --
FESTIVITIES AND WALK AWAY REALLY
BOTH HUMBLED AND INSPIRED AND
FULL OF REALISTIC OPTIMISM, IT
IS MY PLEASURE TO INTRODUCE OUR
COLLEAGUES, DR. STACY
CARRINGTON-LAWRENCE FROM ACTING
DIRECTOR AT THE DIVISION OF
AGING BIOLOGY, WHO IS GOING ON
SHARE WITH US THE HIGHLIGHTS AND
KEY TAKE AWAYS OF THE
GEROSCIENCE SUMMIT THAT WAS HELD
RECENTLY.
FOLLOWING HER PRESENTATION,
DR. ERIN HARRELL, DIRECTOR OF
BEHAVIORAL SOCIAL RESEARCH WILL
SHARE WITH US THE KEY TAKE AWAYS
AND HIGHLIGHTS FROM THE
COGNITIVE AGING SUMMIT THAT WAS
ALSO HELD RECENTLY.
AND THE REASON BEING WE REALLY
WANT TO ILLUSTRATE NIA'S
COMPREHENSIVE APPROACH AND
INTEGRATIVE APPROACH IN BRINGING
TOGETHER THE INVESTIGATION OF
AGING, AGE RELATED DISORDERS,
OUTSIDE OF ALZHEIMER'S AND
RELATED DEMENTIAS, AND IN ALL
THESE DIMENSIONS, INCLUDING
OBVIOUSLY -- SO THANK YOU,
STACY, AND THE PODIUM IS YOURS.
>> GREAT, THANK YOU, SUZANNA.
I HOPE EVERYONE IS ABLE TO HEAR
ME OKAY.
>> YES.
>> OKAY.
SO AGAIN, GOOD AFTERNOON,
EVERYONE.
I WANT TO THANK SUZANNA, ERIKA,
AS WELL AS LAURIE FOR INVITING
ME OR GIVING ME THE OPPORTUNITY
SHARE A BRIEF SUMMARY OF THE
FOURTH GEROSCIENCE SUMMIT THAT
WAS SPONSORED BY NIA BACK IN
2023.
SO FIRST, I'LL GIVE SORT OF A
BRIEF OVERVIEW OF GEROSCIENCE.
I KNOW MANY OF YOU PROBABLY
ALREADY KNOW WHAT IT IS, BUT FOR
THOSE WHO DON'T, I'LL JUST
BRIEFLY GO THROUGH IT, THEN I
WILL TALK ABOUT SOME ACTIVITIES
THAT ARE GOING ON AT NIH IN
RESPONSE TO GEROSCIENCE, AS WELL
AS THE OVERVIEW OF THE SUMMIT
THAT WE RECENTLY HAD.
SO BRIEFLY, THE GEROSCIENCE
HYPOTHESIS ASSERTS THAT ANY
INTERVENTIONS THAT SLOW THE
AGING PROCESS WILL DELAY THE
ONSET OF MULTIPLE AGE RELATED
DISEASES AND FUNCTIONAL
DECLINES.
HOWEVER, TESTING HYPOTHESIS AND
APPLYING THE KNOWLEDGE GAINED
ARE COMPLICATED BY A MULTITUDE
OF FACTORS.
THE CROSS-SCALES OF RESEARCH
FROM MOLECULAR TO POPULATIONS
RANGING FROM DIFFERENCES IN
MULTIMORBIDITIES RELATED TO AGE,
SEX, ETHNICITY, TO A COMPLEX
INTERPLAY AMONG MOLECULAR
DRIVERS OF AGING.
THE GOALS OF USING A GEROSCIENCE
APPROACH INCLUDE TO SEEK OUT
INTERVENTIONS THAT SLOW OR
REVERSE CELLULAR MOLECULAR AGE
RELATED CHANGES, TO VALIDATE
NOVEL INTERVENTIONS THAT ENGAGE
THE HALLMARKS OF AGING, AND TO
DETERMINE THEIR IMPACT ON
AGE-RELATED DISEASES AND OVERALL
FUNCTION, AS WELL AS TO SUPPORT
THE SPECTRUM OF TRANSLATIONAL
RESEARCH NEEDED TO VALIDATE
GEROSCIENCE INTERVENTIONS INTO
CLINICAL PRACTICE.
ONE OF THE MAJOR ACTIVITIES FOR
GEROSCIENCE AT NIH IS THE GSIG.
IN 2012 DOCTORS SIERRA AND RON
KOHANSKI, BOTH FORMER DIRECTORS
OF DWIFTION AGE -- DIVISION OF
AGING BIOLOGY ESTABLISHED GSIG,
GEROSCIENCE INTEREST GROUP.
THE OBJECTIVES OF THE GROUP ARE
TO STIMULATE INTEREST IN THE
BASIC SCIENCE OF AGING ACROSS
INSTITUTES, CENTERS AND OFFICES
AT NI H AND TO FACILITATE
EDUCATION, COMMUNICATION AND
COLLABORATION.
THE GROUP WHICH NOW INCLUDES
ABOUT 19 OF THE 27 INSTITUTES
AND CENTERS AT NIH MEETS
REGULARLY AND PROVIDES
EDUCATIONAL WEBINARS FOR NIH
STAFF ON TOPICS IN GEROSCIENCE,
CONTRIBUTES TO CONCEPTS AND
FUNDING OPPORTUNITIES AND
PUBLISHES PERSPECTIVE PAPERS ON
AREAS OF INTEREST TO THE
GEROSCIENCE COMMUNITY.
IN ADDITION, THE GSIG HOAS THE
GEROSCIENCE -- HOSTS THE
GEROSCIENCE SUMMITS THAT OCCUR
APPROXIMATELY EVERY THREE YEARS.
THERE HAVE BEEN FOUR SUMMITS SO
FAR SINCE 2013, WITH THE FOURTH
SUMMIT TAKING PLACE IN 2023.
SO NIA IN PARTNERSHIP WITH THE
GSIG CONVENED THE FOURTH
GEROSCIENCE SUMMIT ON APRIL 24
THROUGH THE 26 OF 2023.
AND THE GOAL OF THE SUMMIT WAS
TO EXPLORE TOPICS AT THE
FOREFRONT OF THE GEROSCIENCE
FIELD AND TO CONSIDER NOVEL WAYS
TO ADVANCE THIS RAPIDLY EVOLVING
AREA OF RESEARCH.
THE EVENT HIGHLIGHTED THE NEED
TO FURTHER DEVELOP THE FIELD IN
AN EQUITABLE AND INCLUSIVE WAY
AND HEALTH DISPARITIES IN AGING
WAS A CENTRAL THEME CARRIED
THROUGHOUT THE SUMMIT.
THE INTENT OF THE THREE-DAY
WORKSHOP WAS TO ASSESS THE
STATEMENT OF THE SCIENCE AND
GEROSCIENCE, LEARN FROM EARLY
AND MID CAREER RESEARCHERS
WORKING IN THE SPACE, CONVENE A
DIVERSE GROUP OF STAKEHOLDERS TO
FACILITATE NEW COLLABORATIONS
AND TO DETERMINE THE BARRIERS TO
PROGRESS AND EXPLORE POTENTIAL
SOLUTIONS.
THERE WERE ALSO SEVERAL
CHALLENGES THAT ACTUALLY DROVE
THE AGENDA FOR THE SUMMIT, AND
THEY INCLUDED THE NEED TO
DEVELOP AND IMPLEMENT
GEROSCIENCE FOR THE BENEFIT OF
ALL, AND THIS WOULD INCLUDE THE
DISCIPLINES OF PRECISION
MEDICINE CHRKS WE HEARD QUAIT A
BIT -- WHICH WE HEARD QUITE A
BIT ABOUT FROM YOUR SUMMIT,
MINORITY HEALTH AND HEALTH
DISPARITIES AS WELL AS THE NEED
FOR GEROSCIENCE RESEARCH TO
ADDRESS CO-MORE MID TIZ,
MULTIMORBIDITY AND GERIATRIC
SYNDROMES, ADVANCING THE
DEVELOPMENT OF MEASURES
REPORTING HEALTH AND FUNCTION IN
AGING, AND THE IMPORTANCE OF
EVIDENCE-BASED INCLUSIVE
GEROSCIENCE IN MEDICAL PRACTICE
AND FEASIBILITY DESIGN AND
IMPLEMENTATION OF GEROSCIENCE IN
CLINICAL TRIALS.
THEREFORE, THE AGENDA WAS BROKEN
OUT INTO EIGHT SESSION THEMES
THAT WERE DESIGNED TO ADDRESS
CHALLENGES IN THE FIELD.
ON DAY ONE, SESSIONS INCLUDED
THE BIOLOGICAL DETERMINANTS OF
HEALTH AND DISPARITIES IN AGING,
WHICH PROVIDED AN INTRODUCTION
AND OVERVIEW OF THE NIH DEATH
DISPARITIES FRAMEWORK FOR
RESEARCH -- HEALTH DISPARITIES
FRAMEWORK FOR RESEARCH AND
IMPACTS ON AGING RELATED HEALTH
OUTCOMES AND OVERVIEW OF BASIC
AND TRANSLATIONAL CANCER BIOLOGY
RESEARCH, UNDERSTANDING AND
REDUCING CANCER HEALTH
DISPARITIES WAS ALSO PRESENTED,
AND PERSPECTIVES ON FRAMING
FUNDAMENTAL BIOLOGICAL RESEARCH
TO EXPAND PROGRESS IN ADDRESS
HEALTH DISPARITIES OF THE AGING
WAS ALSO DISCUSSED.
THE SECOND SESSION IN DAY ONE
FOLK TUSKED ON POPULATIONS FOR
GEROSCIENCE RESEARCH -- FOCUSED
ON.
THIS FOCUSED ON STUDIES THAT
REVEALED DIFFERENCES RELATED TO
CHARACTERISTICS, DIFFERENCES IN
RATES OF AGING RELATED TO
CHARACTERISTICS SUCH AS FAMILIAL
LIFE SPAN, EARLY DISEASE OR
CHRONIC INFECTION, AS WELL AS
WITHIN POPULATION HETEROGENEITY
AND RATES OF AGING.
THERE WERE REPORTS FROM SEVERAL
MAJOR FINDINGS FROM THESE WELL
STUDIED POPULATIONS THAT WERE
PRESENTED DURING THE SESSION IN
ORDER TO EXPLORE HOW THESE
STUDIES MIGHT BE FORMED -- MIGHT
INFORM BIOLOGICAL RESEARCH AND
HEALTH DISPARITIES.
AND FINALLY, ON DAY ONE, OH,
SORRY, I'LL TRY AND GO BACK.
MULTIMORBIDITIES AND GERIATRIC
SYNDROMES TO EXPLORE THE IDEA
THAT BOTH MULTIMORBIDITY AND
GERIATRIC SYNDROMES ARE EMERGENT
PROPERTIES OF UNDERLYING GLOBAL
INSTABILITY.
THAT IS INTRINSICALLY CEKED WITH
THE BIOLOGY OF THE AGING.
AND ONE OF THE CRITICAL
QUESTIONS THAT WAS ADDRESSED IN
THIS SESSION WAS HOW WE CAN USE
OTHER MORE RELEVANT ANIMAL
MODELS FOR GEROSCIENCE RESEARCH
ON MULTIMORBIDITIES AND
GERIATRIC SYNDROMES.
DAY TWO SESSIONS INCLUDED
METHODS FOR MEASURING HEALTH,
THE SESSION EXPLORED DIFFERENT
METHODS FOR MEASURING HEALTH
ACROSS THE LIFE SPAN INCLUDING
DEFICIT ACCUMULATION AND FRAILTY
IN DISEASE, AS WELL AS GERIATRIC
MOBILITY ASSESSMENTS.
MATHEMATICAL MODELING OF AGING
AND HEALTH FOR GEROSCIENCE.
THIS SESSION FOCUSED ON MODELING
TO ASSESS WHICH LIFE CONDITIONS
OR INTERVENTIONS SLOW OR
ACCELERATE AGING.
ESPECIALLY IN THE CONTEXT OF
CLINICAL OUTCOMES, WITH THE GOAL
OF IDENTIFYING PARAMETERS TO
MEASURE RATES OF AGING AS WELL
AS TO INDICATE WHICH TYPES OF
INTERVENTIONS MAY BE MOST
EFFECTIVE IN CHANGING RATES OF
AGING.
AND THE FINAL SESSION ON DAY TWO
FOCUSED ON CHALLENGES IN THE
DEVELOPMENT OF BIOMARKERS FOR
AGING AND GEROSCIENCE.
THESE CHALLENGES INCLUDE A
COMPLEX HETEROGENEITY AND ANY
HEALTH METRIC WHEN MEASURED
AGAINST AGE.
VARIATION IN ORGAN AND TISSUE
FUNCTION COMPARED BETWEEN
INDIVIDUALS AND VARIATIONS IN
LIFE HISTORIES THAT IMPACT
HEALTH AT ANY AGE.
THESE MAY IMPACT HEALTH IN WAYS
THAT MAY BE ADAPTIVE OR
MALADAPTIVE.
WE FINISHED ON DAY THREE WITH
TWO SESSIONS.
ONE ON GEROSCIENCE AS MEDICINE
IN THE CLINIC AND THE COMMUNITY,
WHICH HAD PRESENTATIONS THAT
DISCUSSED AREAS IN WHICH
GEROSCIENCE COULD ADVANCE CARE
OF OLDER ADULTS WITH THE GOAL TO
FACILITATE COMMUNICATION AMONG
RESEARCHERS AND PROVIDERS AND
THEIR PATIENTS, AS WELL AS TO
IMPROVE OUR UNDERSTANDING AND
INTEGRATION OF GEROSCIENCE IN
CLINICAL PRACTICE OR PATIENT
CARE.
THE FINAL SESSION ON DAY THREE
WAS ON GEROSCIENCE CLINICAL
TRIALS.
THIS SESSION TIMED ADDRESS THE
CHALLENGES ASSOCIATED WITH
DEVELOPING AND CARRYING OUT
GEROSCIENCE BASED CLINICAL
TRIALS THAT ARE INCLUSIVE AND
INCORPORATE SOCIAL DETERMINANTS
OF HEALTH, IN ORDER TO TEST
INTERVENTION THAT IS CAN AFFECT
MULTIPLE CONDITIONS OF AGING.
SO OVERALL, THE SPEAKERS AND
PANELISTS RECOMMENDED SEVERAL
THINGS TO KEEP IN MIND AND TO
AIM FOR IN THE FUTURE AND SOME
OF THESE WILL PROBABLY BE VERY
FAMILIAR TO YOU ALL.
I'VE HEARD ABOUT THIS SEVERAL
TIMES OVER THE COURSE OF THE AD
SUMMIT.
AND THAT IS, GIVEN HETEROGENEITY
IN AGING, INCLUDING DIFFERENT
LIFE CONTEXTS, PANELISTS AND
SPEAKERS THOUGHT PRECISION
MEDICINE WOULD BETTER TAILOR
THERAPEUTIC INTERVENTIONS THAT
WOULD BE APPLICABLE TO A LARGE
PROPORTION OF THE POPULATION.
THEY ALSO RECOMMENDED MOVING WAY
FROM SINGLE DISEASE RESPONSES
AND MORE TOWARDS STRUCTURAL
CHANGE, MULTILEVEL
INTERVENTIONS, AND
INTERDISCIPLINARY APPROACHES.
THEY ALSO STRESSED THE
IMPORTANCE OF DEVELOPING ACROSS
SPEE -- A CROSS-SPECIES
FRAMEWORK TO TRANSLATE INSIGHTS
GAINED FROM ANIMAL MODELS TO THE
CLINIC.
PRESENTERS ALSO MENTIONED AGING
BEING A SERIES OF OUTCOMES WITH
DIVERSE CONTRIBUTING FACTORS.
RATHER THAN A SET OF OUTCOMES
ARISE FRG A SMALL SET OF
PROCESSES, AGING OUTCOMES ARE
LIKELY SHAPED IN COMPLEX WAYS BY
A LARGE NUMBER OF FACTORS AND
MORE ACCURATELY MODELING OF
AGING WILL BE IMPORTANT TO
ADVANCE GEROSCIENCE.
FINALLY, BIOMARKERS WERE ALSO
DISCUSSED QUITE A BIT AND
PRESENTERS INDICATED THAT
BIOMARKERS SHOULD BE
MULTIFACTORIAL AND HAVE MEASURED
THAT ARE SHORT -- HAVE MEASURES
THAT SHORT-TERM FOR CLINICAL
TRIALS, BE PREDICTORS OF
DISEASE, SO BEFORE THE ONSET OF
DISEASE, INDICATE CURRENT HEALTH
VERSUS FUTURE HEALTH, VERSUS
TRAJECTORIES OF AGING,
BIOMARKERS SHOULD IDENTIFY
ORGANISM HEALTH VERSUS
CRECIALTION ORGAN OR DISEASE
SPECIFIC -- CRECIALTION ORGAN OR
DISEASE SPECIFIC, DISEASE
SPECIFIC VERSUS HALLMARK
SPECIFIC FACTORS, AND ALSO THE
PANELISTS AND SPEAKERS OF THE
SUMMIT STRESSED THE NEED TO MORE
CAREFULLY CONSIDER THE
STRATIFICATION OF PATIENTS FOR
INTERVENTIONS IN THE TRACKING OF
RESPONSES TO INTERVENTIONS.
SO THERE WERE SEVERAL
OPPORTUNITIES THAT WERE ALSO
IDENTIFIED FOR GEROSCIENCE
RESEARCH, INCLUDING DESIGNING
MULTILEVEL AFROACHES ADDRESS AGE
RELATED -- TO ADDRESS -- MURLT
LEVEL APPROACHES TO ADDRESS AGE
RELATED HEALTH DISSPARES,
EXPLORING AND TESTING
GEROSCIENCE BASED INTERVENTIONS
FOR CHRONIC DISEASE PATIENTS AND
SURVIVORS, DEVELOPING RESEARCH
MODELS TO STUDY AND TREAT
MULTIMORBIDITY, IDENTIFYING AND
IMPLEMENTING AGE RELATED HEALTH
OUTCOME MEASURES, DEVELOPING AND
VALIDATE PREDICTIVE BIOMARKERS
OF AGING, AND QUITE IMPORTANT
AND SOMETHING I THINK THAT WE
DON'T DO ENOUGH OF IS TO IMPROVE
OUR COMMUNICATION AND TRAINING
IN THE GEROSCIENCE SPACE.
FINALLY, I WANTED TO CALL YOUR
ATTENTION TO A SPECIAL ISSUE OF
THE JOURNAL OF GERONTOLOGY.
IT CONTAINS SEVERAL ARTICLES
FROM PARTICIPANTS OF THE FOURTH
SUMMIT AND IT WAS RECENTLY
RELEASED ABOUT A WEEK OR TWO
AGO, AND IT CAN BE ACCESSED
USING THE QR CODE ON THE SCREEN.
I WANT TO AGAIN THANK YOU FOR
YOUR TIME AND ATTENTION, I'M
HAPPY TO ANSWER ANY QUESTIONS.
>> THANK YOU, STACY, THANK YOU
VERY MUCH.
NOW IT'S MY PLEASURE TO INVITE
ERIN HARRELL TO PRESENT THE
HIGHLIGHTS FROM THE COGNITIVE
AGING SUMMIT.
>> GOOD AFTERNOON, EVERYONE.
IT'S A PLEASURE TO BE HERE TODAY
TO PRESENT SOME OF THE KEY TAKE
AWAYS FROM THE COGNITIVE AGING
SUMMIT.
I AM DR. ERIN HARRELL FROM THE
DIVISION OF BEHAVIORAL AND
SOCIAL RESEARCH, AND I WOULD
LIKE TO START BY JUST GIVING A
LITTLE BIT OF BACKGROUND ABOUT
THE COGNITIVE AGING SUMMIT.
SO THE COGNITIVE AGING SUMMITS
ARE MADE POSSIBLE DUE TO THE
McKNIGHT BRAIN RESEARCH
FOUNDATION'S DECADE LONG
PARTNERSHIP WITH THE FOUNDATION
FOR THE NATIONAL INSTITUTES OF
HEALTH.
THE MISSION OF THE McKNIGHT
BRAIN RESEARCH FOUNDATION IS TO
BETTER UNDERSTAND AND ALLEVIATE
AGE-RELATED COGNITIVE DECLINE
AND MEMORY LOSS, AND THIS
MISSION HAS LED TO FOUR
COGNITIVE AGING SUMMITS WITH
JOINT COLLABORATIONS BETWEEN THE
DIVISION OF NEUROSCIENCE AND THE
DIVISION OF BEHAVIORAL AND
SOCIAL RESEARCH.
UNLIKE CONFERENCES THAT
GENERALLY TAKE PLACE EVERY YEAR,
EVEN THE GEROSCIENCE SUMMITS
THAT TAKE PLACE GENERALLY EVERY
THREE YEARS, THE COGNITIVE AGING
SUMMITS DO NOT OCCUR EVERY YEAR
EVEN ON A REGULAR BASIS.
IN FACT, THE LAST SUMMIT TOOK
PLACE SEVEN YEARS AGO IN 2017
AND WAS FOCUSED ON COGNITIVE
RESILIENCE AND RESERVE.
AS WITH THE FIRST AND SECOND
SUMMITS, OUTCOMES FROM SUMMIT
THREE INCLUDED A SPECIAL ISSUE
IN NEUROBIOLOGY OF AGING WITH
PAPERS RELATED TO EACH SESSION
OF THE SUMMIT AND ALSO THE RFA
WHICH YOU MIGHT RECALL HAVING
BEEN MENTIONED DURING SESSION
ONE WHEN SOMEONE WAS TALKING
ABOUT THE COGNITIVE SUPER AGERS.
CO-SPONSORED BY THE McKNIGHT
BRAIN RESEARCH FOUNDATION, THE
RFA WAS AN OUTGROWTH OF THE
SUMMIT AND FOCUSED ON RESERVE
AND RESILIENCE.
TITLED NETWORK FOR
IDENTIFICATION, EVALUATION AND
TRACKING OF OLDER PERSONS WITH
SUPERIOR COGNITIVE PERFORMANCE
FOR THEIR CHRONOLOGICAL AGE,
THIS INITIAL TIFER SUPPORTS TWO
NETWORKS TO IDENTIFY AND FOLLOW
COGNITIVE SUPER AGERS AND
CONDUCT RESEARCH ACROSS MULTIPLE
SITES ON ADULTS 85 YEARS AND
OLDER WITH COGNITIVE PERFORMANCE
SIMILAR TO THOSE 20 TO 30 YEARS
YOUNGER THAN THEM.
ALTHOUGH THESE COGNITIVE SUPER
AGERS ARE BELIEVED TO CONSTITUTE
A VERY SMALL MINORITY OF THE
POPULATION, THEY REPRESENT AN
UNPARALLELED RESOURCE FOR US TO
BE ABLE TO STUDY THE BEHAVIORAL,
ENVIRONMENTAL, HEALTH, NEURAL
AND GENETIC PROFILES OF OLDER
INDIVIDUALS THAT LEAD TO
SUPERIOR COGNITIVE AND BRAIN
FUNCTION IN ADVANCED AGE.
SO LET'S TAKE A LOOK AT THIS
YEAR'S SUMMIT.
SO SUMMIT FOUR TOOK PLACE IN
MARCH OF THIS YEAR, AND FFS
FOCUSED ON PRECISION DAIRK AND
IT WAS FOCUSED ON PRECISION
AGING AND BRAIN HEALTH, EXPLORED
AGE RELATED COGNITIVE CHANGE,
FOIKSING ON INDIVIDUAL
DIFFERENCES AND THE DEVELOPMENT
OF PERSONAL BIASED APPROACHES
FOR NEW YORK STOCK EXCHANGE OR
GAINING COGNITIVE HEALTH.
THE SUMMIT WAS COMPRISED OF SIX
SESSIONS WHICH I WILL BRIEFLY
DISCUSS AND HIGHLIGHT SHORTLY.
BUT THERE WILL ALSO BE A SPECIAL
ISSUE WITH MORE IN DEPTH
ARTICLES RELATED TO EACH SESSION
THAT WILL BE PUBLISHED IN THE
NAWR OH BIOLOGY OF AGING.
IN THE INTERIM, I DO ENCOURAGE
YOU TO VISIT OUR WEBSITE AND
REVIEW OUR EXECUTIVE SUMMARY AND
SESSION VIDEO RECORDINGS FOR
MORE DETAILED INFORMATION.
AND THERE IS A QR CODE THERE
THAT WILL TAKE YOU TO OUR SITE.
SO NOW I'LL JUST START BY GIVING
SOME BRIEF HIGHLIGHTS FROM EACH
SESSION, STARTING WITH SESSION
ONE, WHICH WAS THE BLOOD,
METABOLISM AND SYSTEMIC
ENVIRONMENT.
IN THIS SESSION, SPEAKERS
EMPHASIZED THAT BECAUSE BRAIN
HEALTH AND BODY HEALTH ARE
INTRICATELY LINKED, IMPROVEMENTS
IN LIFESTYLE FACTORS ALSO MAY
BENEFITED COGNITION AS
INDIVIDUALS AGE.
HIGHLIGHTS FROM THIS SESSION
INCLUDED RESEARCH THAT SHOWED
LEVELS OF SEVERAL INFLAMMATORY
PROTEINS INCREASE IN THE BRAIN
WITH AGE AND THAT HIGHER
ESTROGEN LEVELS DURING PREGNANCY
CAN LEAD TO INCREASED BRAIN
FUNCTIONAL CONNECTIVITY.
SAY KEY TAKE AWAY FOR THIS
SESSION IS THAT FUTURE RESEARCH
INTO SPECIFIC MECHANISMS BY
WHICH PLASMA PROTEIN AND HORMONE
LEVELS AFFECT BRAIN FUNCTION MAY
HELP INFORM INDIVIDUALIZED
THERAPEUTIC INTERVENTIONS.
SESSION TWO WAS THE STRUCTURAL
AND SOCIAL ENVIRONMENT.
IN THIS SESSION, SPEAKERS
ADDRESSED THE COGNITIVE EFFECTS
OF SOCIODEMOGRAPHIC FACTORS, THE
BUILT ENVIRONMENT AND
INTERPERSONAL SOCIAL
DETERMINANTS OF HEALTH, ALL OF
WHICH MAY CONTRIBUTE TO
INDIVIDUAL DIFFERENCES ACROSS
THE LIFE COURSE.
THE STETION HIGHLIGHTED THE NEED
FOR -- THE SESSION HIGHLIGHTED
THE NEED FOR FURTHER RESEARCH TO
DISENTANGLE THE IMASKTS
FREQUENTLY INTERSECTING SOCIAL
AND EXPERIENTIAL FACTORS ON
INDIVIDUAL COGNITIVE HEALTH
OUTCOMES, SHOWING HOW STRESSORS
LIKE PERCEIVED DISCRIMINATION
AND LACK OF EQUITABLE ACCESS TO
EDUCATION CORRELATE WITH
INFLAMMATION IN THE BRAIN AS
WELL AS INCREASED DEPRESSIVE
SYMPTOMS.
AND WHILE RESILIENCE PATHWAYS
APPEAR TO BE PROTECTIVE OF
MEMORY FUNCTION IN CONTEXT TO
THESE STRESSORS.
KEY TAKE AWAYS WERE THAT
IMPROVING OUR UNDERSTANDING OF
THESE FACTORS CAN INFORM POLICY
AS WELL AS NEIGHBORHOOD LEVEL
INTERVENTIONS.
SESSION THREE WAS THE GENETIC
ENVIRONMENT.
THIS SESSION FOCUSED ON THE ROLE
OF SPECIFIC CHROMOSOMES, GENES,
AND PROTEINS IN SHAPING
COGNITIVE AGING AND DISEASE.
RESEARCH PRESENTED HIGHLIGHTED
CORRELATIONS BETWEEN COGNITIVE
DECLINE AND GENE EXPRESSION
THROUGHOUT NEURONAL CELLS AND ON
THE X CHROMOSOME.
THE KEY TAKE AWAY BEING THAT
FURTHER RESEARCH ON SEX AND GENE
INTERACTIONS MAY CONTRIBUTE TO
THE DEVELOPMENT OF TARGETED AND
PERSONALIZED INTERVENTIONS TO
IMPROVE COGNITIVE HEALTH.
SESSION FOUR WAS THE CIRCUIT
ENVIRONMENT.
THIS SESSION EXAMINED HOW GENE
EXPRESSION, CELLULAR ACTIVITIES
AND BRAIN MORPHOLOGY CAN AFFECT
LEARNING, MEMORY AND NAVIGATION.
RESEARCH PRESENTED SHOWED HOW
AGING RESULTS IN LOSS OF
SYNAPTIC DENSITY AND
INCONSISTENCY IN SPATIAL FIRING
PATTERNS.
AND THAT IN BOTH HUMAN AND
ANIMAL EXPERIMENTS, UPREGULATION
OF THE PER 1 GENE, HIGHER LEVELS
OF ESTROGENS, AND CONSISTENCY IN
NEURONAL FIRING CORRESPOND WITH
BETTER ABILITY TO LEARN AND
REMEMBER SPATIAL ENVIRONMENTS IN
YOUNG INDIVIDUALS.
THE KEY TAKE AWAY IS THAT
FURTHER STUDIES CAN HELP
IDENTIFY OTHER GENES, THEIR
MECHANISM OF ACTION, AND
POSSIBLE INTERVENTIONS TO
PROTECT AGAINST AGE-RELATED
DECLINE.
SESSION FIVE WAS COMORBIDITIES
AND THE SLEEP ENVIRONMENT, AND
THIS SESSION SPEAKERS EXPLORED
THE IMPORTANCE OF SLEEP,
CARDIOVASCULAR DISEASE AND
DEPRESSION AND RISK FOR
COGNITIVE DECLINE AND DEMENTIA,
HIGHLIGHTING THE CENTRALLY ROLE
THAT SLEEP PLAYS IN LEARNING AND
MEMORY BY HELPING CLEAR THE
BRAIN OF MISS FOLDED PROTEINS
AND OTHER DEBRIS THAT COULD LEAD
TO NEURODEGENERATION.
THE KEY TAKE AWAY FROM THIS
SESSION IS THAT FUTURE STUDIES
THAT PROBE HOW COMORBIDITIES AND
SLEEP AFFECT RISK FOR COGNITIVE
DECLINE NEED TO TAKE PLACE IN
EARLY AND MIDLIFE.
AND THE FINAL AND SIXTH SESSION,
STUDY DESIGN AND INTERVENTION
ENVIRONMENT, PRESENTERS DELVED
INTO NOVEL METHODS FOR DELAYING
COGNITIVE DECLINE AND REVIEWED
THE RESULTS FROM SEVERAL RECENT
INTERVENTION TRIALS,
HIGHLIGHTING THAT TREATMENT
RESPONSES WITHIN INTERVENTIONS
ARE COMPLEX.
I THINK WE'VE SEEN THAT
HIGHLIGHTED IN THE AD SUMMIT.
A KEY TAKE AWAY IS THAT THE USE
OF METHODOLOGICAL DESIGNS LIKE
DIGITAL TWINS AND OTHER AI BASED
METHODS MAY HELP RESEARCHERS
DESIGN MULTIFACTOR INTERVENTIONS
THAT TARGET INDIVIDUALS BASED ON
GENETIC AND LIFESTYLE RISK
FACTORS.
AGAIN, I THANK YOU FOR THE
OPPORTUNITY TO BE ABLE TO SHARE
SOME OF THE KEY TAKE AWAYS AND
HIGHLIGHTS FROM OUR COGNITIVE
AGING SUMMIT FOUR THAT TOOK
PLACE IN MARCH OF THIS IMREER,
AND AGAIN -- OF THIS YEAR, AND
AGAIN, I ENCOURAGE YOU TO VISIT
OUR WEBSITE WHICH YOU CAN SEE
TALKS FROM THE SESSIONS AND ALSO
SEE UPDATES ONCE THE SPECIAL
ISSUE IN NEUROBIOLOGY OF AGING
HAS BEEN RELEASED.
>> THANK YOU, ERIN.
WELL, AND FINALLY, I AM AT A
LOSS FOR WORDS.
THAT DOESN'T HAPPEN VERY OFTEN,
AS YOU KNOW.
BUT FROM ALL OF US AT THE NIA,
FROM ALL OF MY COLLEAGUES WHO
HAVE CONTRIBUTED AND MADE THE
SUMMIT POSSIBLE, NOT JUST THE
SUMMIT POSSIBLE, FOR ALL OF US
AT THE NIA, PARTICULARLY MY
COLLEAGUES WHO DEVELOPED THE
INITIATIVES THAT LED TO THE
PROGRAMS, THAT LED TO THE
PROGRESS YOU HEARD ABOUT IN THE
LAST THREE DAYS, AN ENORMOUS
GRATITUDE TO ALL OF YOU.
ALL OF THE SUMMIT SPEAKERS,
PANELISTS, CO-CHAIRS, WHO ARE
GOING TO CONTINUE TO WORK OVER
THE NEXT FEW WEEKS TO CONTINUE
TO REFINE THE GAPS AND
OPPORTUNITIES AND FINALIZE THE
PRODUCT FROM THIS SUMMIT THAT WE
WILL THEN TAKE AND TRANSLATE
INTO TACTICAL STEPS AND BUILD IT
AND REFRESH THE RESEARCH
FRAMEWORK FOR ADRD THAT WILL BE
POINTED TO THE CONTINUED
EVOLUTION OF PRECISION MEDICINE
RESEARCH ENTERPRISE WITH THE
PARTICIPANTS, PATIENTS AND THEIR
FAMILIES AND ITS EPICENTER.
A SPECIAL DEBT OF GRATITUDE TO
THE PARTICIPANTS IN THE PANEL,
PARTICIPANTS AS DIRECT PARTNERS
OF THE RESEARCH.
THAT FOR ME WAS THE SUMMIT OF
THE SUMMIT, IF I CAN PICK A
FAVORITE.
AND AGAIN, THANK YOU ALL.
SAFE TRAVEL HOME.
WE REST TONIGHT, BUT TOMORROW,
WE CONTINUE.
THANK YOU.
[3:32 P.M. EST]
RESISTENT MOUSE
AND START TO SEE INCREASE IN
MICE IN ALLERGEN ABSORPTION
NAÏVE NOT ALLERGIC MICE AND IS
STEADY STATE AND WHAT IS
INTERESTING IS IF YOU TAKE
SUSCEPTIBLE MICE HERE WITH SILO
STATIN AND WE HAVE IMPAIRED
FUNCTION AND SILO STATIN DIDN'T
DO MUCH AND IS CONSISTENT ADDING
UP TO THIS WORKING MODEL THAT
SENSITIZED TOLERANT AND
RESISTENT GROUP OVER HERE IN RED
HAD AN OVERACTIVE OR HIGHLY
ACTIVE D PEP 1 THAT IS CLEARING
ACTIVE LEUKO TRYINES BAD ACTORS
IN THE GUT REDUCING ABSORPTION
AND WHAT IS EXCITING IS LEUKO
TRYINES ARE POTENTIALLY PRESENT
NOT AT STEADY STATE AND ALLERGIC
REACTION AND SENSITIZATION AND
PHYSIOLOGY OF THE GUT AND
ALLERGENS GETTING ACROSS AND NEW
WAYS TO THINK ABOUT THESE.
AGAIN THOUGH THIS IS A FAIRLY
DRUGGED PATHWAY IN HUMANS AND
ALSO MEANT WE HAD A BUNCH OF
TOOLS AT DISPOSAL TO MESS WITH
THIS IN MICE AND SEE DO WE ALTAR
WHAT WE THINK WE ARE ALTARING?
ONE DRUG IS THIS WIDELY USED
DRUG IN PATIENTS WITH A-S MA AND
IT HITS ONE OF THE TWO RECEPTORS
OF THE LEUKO TRYINES AND TO OUR
DISMAY WHEN WE USE MONTI LEUKAS
WE DIDN'T CHANGE THE RESPONSE
WHATSOEVER TO ANAFILL AXIS THAT
IS TEMPERATURE DROP AND ANAFILL
AXIS SCORE AND WE ARE TAKING
SUSCEPTIBLE MICE WITH IMPAIRED D
PEP 1 AND HEIGHTENED LEUKO
TRYINES GIVING INHIBITOR DIDN'T
SEEM TO PROTECT AND SCRATCHING
HEADS ABOUT THIS FOR A WHILE AND
REALIZE WHAT WE ARE DOING IS
HITTING ONE OF THE TWO RECEPTORS
AND MAY HAVE REDUNDANCY HERE AND
WHAT WE THINK IS GOING ON AND WE
WENT UPSTREAM AND USED A
DIFFERENT DRUG THAT IS
CLINICALLY USED NOT WIDELY USED
ANYMORE AND WE COULD ACTUALLY
INHIBIT PRODUCTION OF THESE
WHICH IS KNOCK THE WHOLE THING
OUT AND DID THAT AND IT IS
REALLY EXCITING AND COMPLETELY
WIPED OUT RESPONSE AND NO
ANAFILL AXIS IN SUSCEPTIBLE MICE
AND EXCITING WE LOST ALLERGEN
ABSORPTION AND ARGUED PATHWAY
THAT IS REGULATING THE RESPONSE
AND SERUM UPTAKE AND THEREBY
TRIGGERING OF SUBMUCOSAL MASS
CELLS AND ANAFILL AXIS RESPONSE
AND EXCITING PROOF OF PRINCIPLE
TYPE OF EXPERIMENT IF YOU BYPASS
GUT AND GIVE PEANUT TO MICE AND
PRE-TREATED THEM WITH SDIELUTIN
NOW THEY RESPOND IT IS NOT JUST
AN INHIBITOR OF ANAFILL AXIS
RESPONSE AND WHAT IT IS REALLY
DOING IS REGULATING HOW MUCH
ALLERGEN GETS ACROSS TO MASS
CELLS AND IS EXCITING AND WANT
TO UNDERSTAND IS THIS TRUE IN
HUMANS?
I WILL LEAVE YOU WITH KIND OF
TANTALIZING LEADS AND ARE
WORKING ON THIS NOW AND WHERE WE
I THINK NEED TO GO AND THERE HAS
ACTUALLY BEEN DATA OUT THERE FOR
A LONG TIME AND KEPT SEEING
ALLERGEN ABSORPTION DIFFERENCES
IN MICE LOOKED BACK THIS SEEMS
WEIRD WHY DO YOU WANT ALLERGENS
IN TACT WHEN MEASURING IN SERUM
WE ARE MEASURING IN TACT
ALLERGENS NOT DIGESTING UP FOR
NUTRIENTS YOU ARE DOING SOME OF
THAT AND GETTING ATTACKED
ALLERGENS ACROSS AND MASS CELL
AND IGE HAS TO RECOGNIZE THAT
STRUCTURE AND IF YOU LOOK BACK
EVEN IN THE 20S AND 30S THAT
PEOPLE HAVE BEEN DESCRIBING THIS
PATHWAY IN HUMANS USING ALL
SORTS OF WEIRD THINGS IF YOU
WANT A FUN AND INTERESTING
BIZARRE READ I HIGHLY RECOMMEND
READING THIS ONE AND WHERE
AUTHORS THAT ACTUALLY HAVE A
STRIKING SIMILARITY TO PATIENTS
ALSO TESTED IN THE STUDY AND
INGESTED TISSUE FIBRINO GIN AND
CLOTTING FACTOR AND MEASURED
CLOTTING TIME AND SHOWED IT
CHANGES IN A SLIGHTLY
FRIGHTENING WAY AND YOU CAN DO
THIS WITH OVALBUMI AND WITH
PEANUT AND DONE ALL SORTS OF
THINGS AND ARGUES PATHWAY IS
OPERATIONAL IN HUMANS AS WELL
AND FUN TO SPECULATE AS TO WHY
AND HAVE THOUGHTS IF ANYBODY
WANTS TO TALK ABOUT IT AT THE
END AND WHAT IS EXCITING IS
TAKING D PEP 1 WE DESCRIBED IN
THE MICE AND LINE IT UP WITH
HUMANS AND ACTUALLY THE HUMANS
HAVE THE VERSION THAT MATCHES
VERY MUCH THE SENSITIVE GROUP
AND ACTUALLY IN MOST OF THE
STUDIES, MOST PATIENTS --
ACTUALLY THESE ARE HEALTHY
VOLUNTEERS NO THE JUST ALLERGIC
PATIENTS ABSORB ALLERGENS AND
THIS IS NORMAL STEADY STATE AND
B6 MICE ARE WEIRD MICE HERE
POINT MUTATION RESULTING IN
CHANGE IN D PEP 1 ACTIVITY.
THERE IS ACTUALLY A PRETTY
STRIKING HOMOLOGY HERE.
THIS IS THE MODEL I WILL SUM UP
HERE.
I WOULD LOVE TO HAVE A
DISCUSSION AND QUESTIONS.
SO WE THINK WHAT IS HAPPENING IN
SENSITIZED TOLERANCE STATE IS
POTENTIALLY THERE IS A LOW LEVEL
OF LEUKO TRINES; RIGHT?
A LITTLE C AND A LITTLE D AND
NOT A LOT AND REGULATING HOW
MUCH ALEARTHINS GET ACROSS AND
HAVING IGE LOADED ON A MASS CELL
ALEARTHINS CAN'T GET ACROSS AND
TAKEN UP IN TACT AND IN TACT
PART OF THIS IS IMPORTANT AS A
WHOLE PEANUT AND PROTEIN
EPITOPES NEEDING TO BE
RECOGNIZED BY ANTIBODIES AND
WHAT HAPPENS IS THEY HAVE BEEN
SENSITIZED AND NOW HAVE A LOT
MORE ASIS ENNO LEUKO TRYINES
WHETHER D PEP 1 OR IN MICE AND
PART OF THE PATHWAY AND NOT JUST
D PEP 1 AND ALLERGENS GET ACROSS
AND MAGIC ARROW HERE AND
FIGURING OUT CELLULAR MECHANISM
FOR THIS DON'T THINK IT IS A
LEAKY GUT BUT ACTIVE PROCESS AND
NOW PEANUT GETS ACROSS AND
ALLERGEN GET AS CROSS
DEREGULATING MASS CELLS ENDING
UP WITH ANAPHYLACTIC RESPONSE
AND MEASURE PROCESS AND ARROW
MEASURING WHAT IS IN THE BLOOD
STREAM AND ONE OF THE MOST
EXCITING THINGS I HAVE BEEN ABLE
TO DO BY MOVING TO MORJ WESTERN
WHICH I'M EXCITED ABOUT IS PROOF
OF CONCEPT TRIAL THAT IS
STARTING HOPEFULLY IN THE FALL
AND DO A PROOF OF CONCEPT TRIAL
IN HUMANS ASKING CAN WE MODULATE
ALLERGEN ABSORPTION IN SOMEONE
WHO MAYBE HAS A FOOD ALEARTHY
AND WON'T GET ALLERGEN AND DO
REAL DEAL TEST CAN WE BLOCK
ANAFILL AXIS UPTAKE INTO THE
BLOOD STREAM. PEOPLE HAVE BEEN
DOING THIS IN HEALTHY VOLUNTEERS
AND IS A TIME COURSE FROM A
REALLY ELEGANT STUDY LOOKING AT
ABSORPTION OF PEANUT ALLERGENS
INTO THE BLOOD STREAM IN
PATIENTS YOU CAN SEE HOW FAST IT
HAPPENS THIS IS 10 MINUTES HERE
AND TWO DAYS OUT HERE AND MOST
PEOPLE DO THIS AND CAN THEY
ABSORB ALLERGENS INTO THE BLOOD
STREAM AND DO THIS WITH OR
WITHOUT TREATMENT AND GIVES
ANGLE FOR THERAPEUTICALLY
INTERVENING AND PREVENTING
ANAFILL AXIS AND WITH THAT I
WANT TO STOP AND THANK AMAZING
GROUP THAT IS LAB PARTY STILL AT
YALE AND NORTHWESTERN AND IS THE
GROUP THAT GETS TOGETHER EVERY
SUMMER IN CHICAGO IN BOTH SITES
AND WORK TOGETHER AS A TEAM AND
LAURA AND ELYSE IS AT YALE AND
LAURA IS INCREDIBLE DEDICATED
PHD WILLING TO TAKE ON THAT FOR
GENETIC TEAM AND STUDIES AND
DOING STUDIES AT TWO DIFFERENT
INSTITUTIONS ALL HIGHLIGHTED
HERE IN RED AND ARE AN
INCREDIBLE GROUP AND WE HAVE HAD
HELP FROM A NUMBER OF DIFFERENT
LABS AND WYLAN LAB AMAZING DOING
BEAUTIFUL WORK AT YALE LOOKING
AT GUT IMMUNE SYSTEM TELLING US
A LOT AND HELPED WITH A BIT OF
STUDIES AND POINTING OUT THIS IS
HUSBAND ADAM MOVING TO
NORTHWESTERN AND TOLD TRAINEES
TODAY WE ARE ABLE TO HAVE A
JOINT LAB SUPER FUN AND NEW
SPACE WE MOVED INTO NOW MORE
THAN A YEAR AGO AND IS A JOY TO
REALLY BE ABLE TO DO THIS WORK
WITH HIM.
WE HAVE A NUMBER OF GREAT
FUNDERS THAT REALLY HAVE STUCK
WITH US WHILE DOING -- YOU KNOW,
WE WERE REALLY WRONG ABOUT IGA
AT BEGINNING I THINK AND HAD TO
COME BACK TO BASELINE SAYING
WHAT ELSE COULD IT BE AND STUCK
WITH US THROUGH ALL OF THAT AND
INTERESTED IN THE NEW CENTER
STARTING AT NORTHWESTERN Q.R.
CODE CAN LEARN ABOUT WHO IS IN
IT AND WHAT WE ARE DOG AND
SHOUTOUT TO [INDISCERNIBLE] AT
YALE AND CLASSMATE OF LAURA'S
FROM DIFFERENT VANTAGE POINT
STUMBLED ON SAME EXACT PATHWAY
ALLERGEN ABSORPTION FROM
DIFFERENT VANTAGE POINTS
REGULATING ASPECTS OF ALLERGY
AND COSIGNED PAPERS TOGETHER AND
FUN AND WONDERFUL SYNERGISTIC
COLLABORATION BETWEEN OUR LAB
AND THEIR LAB AND WITH THAT
WOULD LOVE TO TAKE QUESTIONS.
>> GREAT TALK. IT IS REALLY
STRIKING HOW QUICKLY ALL OF THIS
HAPPENS AS YOU POINTED OUT A
COUPLE TIMES.
>> YEAH.
>> HAS THAT MADE YOU WONDER
WHETHER EXPOSURE THAT HAPPENS IS
HAPPENING IN THE ORAL MUCOSA OR
ES AFTER GAUS BEFORE IT GETS TO
GUT AND LOOKING AT IT IN SALIVA
OR TISSUES THERE.
>> IT IS ABSOLUTELY A PERFECT
QUESTION AND IF YOU DON'T THINK
ABOUT ALLERGY PEOPLE WITH FOOD
ALLERGY CAN RESPOND SOMETIMES
WITHIN MINUTES BEING EXPOSED TO
AN ALLERGEN AND WHAT THAT HAS
ARGUED IN THE FIELD; RIGHT?
NOT JUST OUR LAB THINKING ABOUT
THIS AND MAYBE ALLERGENS ARE
GETTING ABSORBED THROUGH ORAL
MUCOSA AND HOW IT IS GETTING IN
AND ONE THING I WILL SAY IS MOST
OF THE MOUSE STUDIES WE BYPASS
MOUSE AND LIKE PEANUTS AND IF
YOU FEED THEM THEY ARE HAPPY AND
WILL EAT THEM AND STUDIES AND
TIMING AND EVERYTHING TO DO
ORALLY GAF AUJ IT AND NOT GOING
THROUGH MOUTH BUT GETTING
THROUGH AND ADMINISTERED TO THE
STOMACH AND THEN INTO THE GUT.
WE CAN REALLY FIND THE ALLERGEN
IN THE BLOOD WITHIN 30 MINUTES
TO AN HOUR AND IS DETECTING IT
IN THE SERUM AND WHATEVER IS
HAPPENING IS HAPPENING QUICKLY
NO MATTER WHERE IT IS IN MUCOSA.
>> MAY BE STOMACH TOO AND
EVERYONE THINKS OF GUT AS
DOWNSTREAM OF THAT.
>> ABSOLUTELY. GOOD THOUGHT.
>> REALLY INTERESTING.
>> GREAT TALK. I HAD A COUPLE
QUESTIONS AND FIRST ONE IS
SENSITIZED TOLERANT GROUP AND
LOOKING AT SYSTEMIC AND GUT IGA
AND DID YOU LOOK AT OTHER
SYSTEMIC ANTIBODIES LIKE
CIRCULATING IGA.
>> WE DID.
>> YOU MENTIONED IGG AND ANY
PATTERN TO BE ABSORBING AND
PREVENTING.
>> NO. MOST OF THE WORK TO DATE
IS DONE USING BLOOD SAMPLES IS
EASIER AND LESS SMELLY THAN
STOOL AND MOST LOOKED AT IGA AND
IT MATCHED THE SAME AND WAS SAME
AS STOOL AND IF ANYTHING IS
HIGHER IN ALLERGICS.
>> THAT IS INTERESTING AND
SECOND QUESTION QUICKLY IF NOT
COMING THROUGH ESOPHAGUS OR
STOMACH IS A BIG BARRIER IN THE
GUT AND MUCUS AND TIGHT
JUNCTIONS.
>> YEAH.
>> IMMUNE RESPONSES CAN EFFECT
DIFFERENT JUNCTIONS.
>> YEAH.
>> PORES OR BIGGER PORES AND
EPITHELIAL CELLS AND LOOKING AT
THOSE AND IF CHANGED WITH REGARD
TO LEUKO TRYINES.
>> MY BIAS IS PARACELLULAR
ALLERGEN ABSORPTION OR PASSAGE
OR YOU WANT TO CALL IT IS NOT
MOST COMMON WAY TO GET IT ACROSS
AND LEAKY GUT LOSS OF JUNCTIONS
BETWEEN EPITHILIUM AND IS DATA
TO SUPPORT THAT CERTAINLY.
WHEN WE IMAGE WHAT WE SEE IS
LOTS -- IF YOU FLUORESCENTLY TAG
AN ALLERGEN LIKE OVA WE ARE
USING YOU CAN FIND IT ACTUALLY
TRANCE CELLULARLY BEING
TRANSPORTED THROUGH GUT
EPITHILIUM AND IN PARTICULAR
POPULATION IN THE GUT THAT IS
GOOD AT TAKING UP LARGE POCKETS
OF -- OF NOT JUST ALLERGENS BUT
THINGS IN THE GUT AND GOES
THROUGH CELL BODY AND TRANCE
CELLULAR TO THE OTHER SIDE AND
THINK THAT IT IS HOW IT IS
PROTECTED AND IN TACT AND NOT
ONES TO DESCRIBE THIS WORK FROM
RON NEWBURY.
>> GABBA CELLS.
>> I THINK THAT IS WHERE THIS IS
GOING.
>> UH-HUH.
>> THIS IS ACTUALLY REGULATED BY
PATHWAY WE DESCRIBED AND HOW
MUCH ALLERGEN TRANSPORT
HAPPENING AT THAT LEVEL AND
DON'T UNDERSTAND HOW.
>> DON'T THINK THEY EFFECT GABBA
CELL NUMBERS FOR EXAMPLE.
>> DON'T KNOW.
>> OKAY.
>> THAT IS SOME WHERE THERE IS
CONNECTION THERE WHERE DIRECT OR
INDIRECT AND DON'T KNOW.
>> THANK YOU VERY MUCH.
INTERESTING.
>> HEY. GREAT TALK.
>> [INDISCERNIBLE].
>> YES. SO I HAVE TWO QUESTIONS
AND FIRST IS DO YOU THINK
DIFFERENCE IN ABSORPTION PLAYS
ALSO A ROLE AND NOT ONLY IN
CHALLENGE BUT DURING
SENSITIZATION BREAKDOWN?
SECOND QUESTION IS OTHER
ALLERGEN ABSORPTION CHANGES
THROUGHOUT LIFESPAN.
>> GREAT QUESTIONS AND QUESTIONS
WE WOULD LOVE TO ANSWER.
IF I HAD TO SPECULATE AND WE
HAVE NOT DONE ANYTHING YET AND
WILL START TO DO SOME OF THIS
NOW.
IF PATHWAY IS OPERATIONAL FOR
ORAL TOLERANCE AND BET IT IS
IMPORTANT FOR ORAL TOLERANCE AND
DON'T KNOW HOW AND DON'T KNOW IF
THAT IS EVEN TRUE AND IS MY
GUESS AND WHY I THINK THIS IS A
HOMEO STATIC MECHANISM AND IF
YOU MESS WITH IT DOES IT CHANGE
AND WE ARE TRYING TO FIGURE IT
OUT RIGHT NOW AND HAVEN'T -- WE
DON'T HAVE ANY DATA YET JUST
HYPOTHESES.
IDEA OF IT CHANGING OVER A LIFE
OR ESPECIALLY AT YOUNG AGE
VERSUS IS A GREAT THOUGHT AND WE
HAVE LIKE 8 MILLION EXPERIMENTS
WE ARE TRYING TO DO AND TRYING
TO DO IT WITH PEDIATRIC SAMPLES
TO SEE IF WE CAN LOOK AT THIS.
WE HAVEN'T -- WE ARE STARTING
PROOF OF CONCEPT TRIAL I TOLD
YOU ABOUT WE WILL DO WITH ADULTS
AND FOR SAFETY REASONS AND OTHER
THINGS WE HAVE TO START WITH
ADU
ADULTS.
>> I WOULD LOVE TO DO IT AND
DON'T KNOW TO DO A HUMAN TRIAL
TO TEST THAT YET AND CAN TRY TO
DO IN MICE AND GETS HARDER
TRYING TO GAF AUJ THINGS.
>> SOMETHING NOT RELATED TO THIS
STUDYING INFECTION AND BREAKDOWN
TOLERANCE AND FOUND MICE WITH
INFLUENZA AND GIVE OVA YOU HAVE
RESPONSES IN LYMPH NODE AND
CONTRIBUTES TO BREAKDOWN
TOLERANCE.
>> YEAH.
>> QUESTION IS ANTIGEN ORALLY.
>> YEAH.
>> IN LYMPH NODE.
>> I BET WITH THIS AND HAPPY TO
SHARE PROTOCOL AND OVA ALIZA
FROM BLOOD IS FINICKY AND IF YOU
WANT TO TRY THAT IS MY BET HOW
IT IS GETTING THERE.
>> THANK YOU.
>> WONDERFUL, STEPHANIE.
>> GREAT TO SEE YOU.
>> SORRY I DIDN'T TALK ABOUT
[INDISCERNIBLE].
>> THIS IS BETTER THAN THAT.
I HAVE A QUESTION IF YOU LOOKED
AT D PEP 1 VARIANCE IN YOUR
POPULATION AND PREDICTION IS
LEVEL OF BIOCHEMICAL ACTIVITY
MIGHT CORRELATE TO HOW SEVERE
ALLERGEN OR ALLERGIC RESPONSE
MIGHT BE.
HUGE QUESTION THAT WE HAVE BEEN
TRYING TO TACKLE AND FAILED.
GWAS STUDIES NOT PULLING THEM
OUT D PEP 1 ITSELF AND DOESN'T
HAVE TO BE IT AND COULD BE
ANYTHING ALONG THE PATHWAY AND
SCOURING GWAS DATA BASE AND
PROBLEM FOR US IS WHERE WOULD WE
-- WE WOULD PREDICT TO SEE
BIGGEST DIFFERENCE BETWEEN
PATIENTS WHO HAVE IGE AND PASS
ORAL FOOD CHALLENGE VERSUS THOSE
THAT HAVE IGE AND FAIL AT ORAL
FOOD CHALLENGE AND PROBLEM NOT
HEALTHY VERSUS ALLERGIC
POPULATION WHICH IS WHERE GWAS
DATA IS AND SECOND PROBLEM TO
THAT IS IF YOU PASS ORAL FOOD
CHALLENGE IF SENSITIZED YOU ARE
-- YOU ARE NOT FOOD ALLERGIC AND
TRYING TO GET RIGHT DATA BASE OR
SAMPLES TO DO A PROOF OF CONCEPT
TRIAL THERE AS WELL AND IS A
LITTLE HARD AND THINK WE MIGHT
HAVE IDENTIFIED A GROUP TO DO
THIS AND HAVE TO -- IT WILL TAKE
A LITTLE WHILE.
>> VERY EXCITING. THANKS.
>> IF YOU THINK ABOUT THE
STUDIES LIKE NOW THE IDEA IS WE
SHOULD GIVE FOOD OR THIS TYPE OF
FOOD TO CHILDREN.
>> YEAH.
>> SO LIKE TO SENSITIZE THEM AND
NOW YOU ARE SAYING THERE IS
SOMETHING THAT ALLOWS THE FOOD
PASSAGE AND IS REGULATED ABOUT I
THIS MOLECULE.
HOW COME ONES WHICH HAVE THIS OR
B6 OR ONES WHICH ALLOW FOOD OR
ABT R- ANTIGEN PASSAGE AND
DEVELOPING ALLERGY REACTIONS
THAT ANYTHING POTENTIALLY GOING
THROUGH INTESTINE AND OTHER SIDE
HOW IS IT POSSIBLE WE CAN
DESENSITIZE BY FEEDING.
>> RIGHT. YOU HAVE MULTIPLE
QUESTIONS IMBEDDED IN THAT.
>> I KNOW.
>> LEAP TRIAL AND ORAL TOLERANCE
AND WHAT I WOULD CALL REAL ORAL
TOLERANCE THAT I THINK IS THE
BASIS OF TRIALS SHOWING EARLY
EXPOSURE BEING IMPORTANT WHAT
YOU ARE DOING IS INDUCING T
REGULARS AND NOT INDUCING IGE
AND NEVER GETTING TO SENSITIZED
PHASE AND THINK THAT IS BECAUSE
THE -- THE QUOTE ON QUOTE
NATURAL RESPONSE IN THE GUT IS
TO TOLERATE WHATEVER IS COMING
IN.
RIGHT?
>> YEAH.
>> BUT THEN HOW CAN YOU LIKE IF
YOU HAVE OVA PASSING THROUGH,
HOW DO YOU DEVELOP ALSO AN
ALLERGIC REACTION TO OVA BUT
DEVELOP RESPONSE, IG RESPONSES
AGAINST PEANUT WHICH GOES
THROUGH.
>> I WOULD ARGUE THEY WILL BE
IDENTICAL IF YOU MAKE IGE
RESPONSE AND PUT ALL THEM
THROUGH YOU HAVE ALLERGIC
REACTION TO EITHER IN GROUP THAT
PASSAGES THEM AND COMPLICATION
HERE IS I DON'T -- WE HAVE TO BE
CAREFUL IN THINKING ABOUT WHERAL
EARTH JI AND WE ARE MEASURING IN
BLOOD AND NICE SURROGATE READ
OUT GOTTEN ACROSS GUT AND DON'T
THINK ALLERGEN IN THE BLOOD IS
RELEVANT SITE FOR TOLERANCE AND
IS A READ OUT FOR US AND WHERE
ALL OF THE ACTION IS, IS IN THE
GUT ITSELF AND SURROGATE FOR
ALLEN TO GET ACROSS AND BAE NEEJ
IN THE GUT ITSELF THOUGH IS THAT
KIND OF -- WE CAN TALK MORE AT
DINNER.
>> REALLY INTERESTING TALK.
I HAVE A QUESTION ABOUT
SOMETHING YOU MENTIONED IN
BEGINNING OF TALK THAT IS
QUESTION OF WHAT MAKES ALLERGEN
AN ALLERGEN AND WRITTEN ABOUT IT
AND IN PARTICULAR SOMETHING THAT
STRUCK ME WHEN RESEARCHING THEM
IS LOTS ARE STORAGE PROTEINS IN
TET PRO MERS OR HEXO MERS AND
MORE STABLE FORMATIONS GETTING
DIGESTED LESS IN THE STOMACH AND
ABLE TO BE MORE IN INTACT FORM
WHEN POTENTIALLY CROSS A
BARRIER.
>> WHY HE.
>> HAVE PEOPLE COMPARED
DIFFERENT PROTEINS, PROTEINS
NONALLERGENS FOR WHAT PROPORTION
OF THE PROTEIN MAKES IT THROUGH
FOR EXAMPLE INTO THE
BLOODSTREAM?
>> WE CAN HAND WAVE A LOT ABOUT
THIS AND YOU NAILED A COUPLE OF
THEM ALREADY THAT IS PERFECT AND
ALLERGENS ARE SEED STORAGE
PROTEINS AND YOU ARE RIGHT AND
THEY ARE MORE STABLE AND THOUGHT
IS THEY ARE SMALL AND STABLE AND
MEANS THEY CAN PASS THROUGH
ACIDIC ENVIRONMENT OF STOMACH
AND STILL IN TACT THAT IS
IMPORTANT FOR TRIGGERING
RESPONSE AND PEOPLE HAVE LOOKED
AND ARGUED THAT YES THESE ARE
MORE LIKELY TO MAKE IT INTO THE
INTESTINE.
I DON'T KNOW OF ANYBODY WHO HAS
ARGUED FOR -- MOST PEOPLE DON'T
LOOK IN THE BLOOD.
IT IS A LITTLE PAIN TO DO AND I
CAN -- I DON'T -- IF YOU ASKED
ME A COUPLE YEARS AGO WOULD I
ANTICIPATE SEEING IN TACT
ALLERGENS IN THE BLOOD I WOULD
SAY NO AND DESPITE LITERATURE ON
HUMANS FOR THIS IN 80 YEARS AND
NOT SOMETHING WE THINK ABOUT AND
THEY ARE MOSTLY BROKEN UP IN THE
GUT; RIGHT?
ANSWER TO THAT LAST PART IS NO
AND SOMETHING WE SHOULD THINK
ABOUT IN TERMS WHAT MAKES
ALEARTH JEN ALEARTH JEN AND
AGREE WITH YOU.
>> RELATEBLY I HAVE A FOLLOW-UP
QUESTION AND WHEN LOOKING FOR
OVA IN THE BLOOD YOU USE
PRESUMABLY ANTIBODY AGAINST OVA.
>> WHY HE.
>> IT RECOGNIZES IN TACT.
>> YES.
>> YOU DON'T NECESSARILY KNOW
IFFA OVA FRAGMENTS ARE IN THE
BLOOD.
>> THAT IS RIGHT.
>> IT WOULD BE INTERESTING FOR A
COMPLICATED EXPERIENCE TO SEE IF
ACTUALLY IT IS A DIFFERENCE IN
ABSORPTION OR NOT ABSORPTION AND
DIFFERENCE IN IN TACT VERSUS NOT
IN TACT AND FRAGMENTED.
>> WE THOUGHT ABOUT THIS BY
NONINTACT DO YOU MEAN AMINO
ACIDS OR FRAGMENTS?
>> I GUESS BOTH.
>> YEAH. AMINO ACIDS I THINK
ARE VERY CLEARLY REGULATED FOR
NUTRIENT REASONS IN A DIFFERENT
WAY AND DON'T THINK AND THINK WE
ARE