THEY MAYBE AT LEAST A FRAMEWORK OR A BEGINNING FOR, FOR WHAT WE
WANT TO TALK ABOUT.
OK.
AND THIS IS BASICALLY A SUMMARY OF OF WHAT HAS BEEN OUR
DISCUSSIONS OVER THE LAST FEW MONTHS THROUGH THE BIOMARKERS
WORKING GROUP AND ALSO THE DISCUSSION THAT TOOK PLACE
EARLIER TODAY AND REALLY OVER THE LAST COUPLE OF DAYS.
AND WHAT I WOULD LIKE, I THINK MANY OF US WOULD LIKE, BUT I
WOULD LIKE OUT OF SESSION IS THAT IT, IT CREATES THE
ENTHUSIASM THAT OVER THE NEXT FEW WEEKS, THE NEXT FEW MONTHS,
WE HAVE SOME DISCREET PROJECTS THAT PEOPLE DECIDE TO WORK
TOGETHER ON.
AND THAT INCLUDES GRANT PROPOSALS THAT PEOPLE WANT TO
PUT IN PAPERS THAT THEY WANT TO WORK TOGETHER ON KNOWLEDGE OF
THE PROJECTS THAT ARE ONGOING BUT THAT NEED ADDITIONAL EFFORT,
THAT NEED ADDITIONAL PEOPLE TO PUT THEIR SHOULDER TO THE WHEEL
AND CRANK THINGS FORWARD AND THAT NEED ADDITIONAL EXPERTISE
THAT MAY NOT BE READILY AVAILABLE OR MAY BE OPEN TO
PEOPLE IN THE ROOM.
SO.
SO THAT'S GREAT.
BEFORE WE GET GOING, ANY ANY PRESSING COMMENTS FROM ANYONE IN
THE ROOM AS TO WHAT YOU WOULD FEEL IS A GAP YOU WOULD FEEL IS
PARTICULARLY IMPORTANT THAT WE HAVE MISSED THAT IS OF BURNING
IMPORTANCE TO YOU.
YOU DON'T FEEL SHY AND THERE'S A MICROPHONE HERE IF YOU'RE GOING
TO USE IT.
OK, WELL, WE HAVE SOME SLIDES FROM CHERYL WELLINGTON TALKING
ABOUT THE ISSUE OF REFERENCE INTERVALS AND AND AND CHERYL
THIS IS YOUR DATA, I DON'T WANT TO TOO MUCH EXPLAIN HERE, BUT I
JUST TO PUT EVERYBODY INTO THE SAME PERSPECTIVE.
SO.
SO CHERYL IS A COLLABORATOR ON AUO 1 THAT I RECEIVED THROUGH
THE UNIVERSITY OF PENNSYLVANIA BACK I ACTUALLY THE PROJECT
STARTED IN MARCH 1 OF 2020, SO JUST A FEW WEEKS BEFORE THE
COVID SHUTDOWN STARTED AND AND AND THROUGH THAT PROJECT, CHERYL
STARTED QUITE A BIT OF WORK INCLUDING A PAPER THAT WAS
PUBLISHED A FEW MONTHS AGO ENROLLING ABOUT 900 OR OR
ANALYZING DATA FROM 900 PARTICIPANTS IN THE CANADIAN
HEALTH SPECIAL SURVEY.
CHERYL, DO YOU WANT TO TAKE THE MICROPHONE AND INTRODUCE PEOPLE,
MAKE SURE EVERYONE KNOWS WHAT THIS IS, WHAT YOU FURTHER WANT
TO DO WITH THIS PROJECT, WHAT WHAT THE OTHER POSSIBILITIES
ARE?
SURE.
SO FOR BASICALLY, YOU KNOW, YEAH, WHY DON'T YOU COME UP
HERE.
SO, SO BASICALLY WHAT WE'RE DOING HERE IS TO TRY TO BRING A
LITTLE BIT OF THE FIELD OF LABORATORY MEDICINE TO TO TBI
AND KIND OF BREAK THINGS DOWN FOR CLINICIANS TO BE ABLE TO
EVENTUALLY ORDER AND INTERPRET WHAT A BLOOD TEST OR ACSF TEST
MIGHT MEAN.
PART OF THIS IS TO DETERMINE WHAT THE NORMAL RANGE IS IN A
PARTICULAR RELEVANT POPULATION TO THE ONE THAT YOU'RE STUDYING.
SO FOR THIS EFFORT WE WERE ABLE TO LEVERAGE AN EPIDEMIOLOGICAL
STUDY OF OF CANADIANS THAT SPAN AGES 3 TO 79 THAT IS RUN BY
STATISTICS CANADA AND THEY COLLECT IN A CROSS-SECTIONAL
MANNER ABOUT SPLIT SPECIMENS FROM AROUND 6000 PEOPLE EVERY
TWO YEARS.
SO WE GOT A FULL CYCLE OF THOSE SPECIMENS AND WE HAVE RUN NOW
REFERENCE INTERVAL STUDIES THAT MEET CLINICAL AND LABORATORY
STANDARDS INSTITUTE RIGOR FOR NEUROFILAMENT LIGHT, GFAP A BETA
40A BETA 42P TAU 181 AND WE PUBLISHED THAT THAT WORK AND NOW
GOING FORWARD, OK, SO BASICALLY WHAT WE THE THE DATA USUALLY IF
YOU ORDER A BLOOD TEST OR ANY SORT OF LABORATORY TEST YOU'LL
YOU'LL HAVE A CUT OFF WHERE YOU KNOW YOU CAN INTERPRET THIS AS
NORMAL OR ABNORMAL.
THERE ARE NEWER METHODOLOGIES NOW THAT ARE MUCH MORE GRANULAR
THAT CAN BREAK THE THE CUT OFFS DOWN IN A CONTINUOUS WAY USING A
QUANTILE REGRESSION METHODOLOGIES.
SO THIS WAS THE CANADIAN HEALTH MEASURES SURVEY SAMPLES THAT WE
HAVE LEVERAGED.
THIS IS VERY SIMILAR TO THE N HAYNES STUDY IN THE UNITED
STATES FOR THOSE OF YOU WHO MIGHT HAVE HEARD OF N OF OF N
HAYNES, THERE ARE A LOT OF OTHER VARIABLES COLLECTED ON THESE ON
THESE PARTICIPANTS AND AND WE HAVE NOW COMPLETED, SO WE
PUBLISHED ON THE 900 AND NOW THAT WE HAVE COMPLETED 2500, SO
THAT'S 50% OF THE TOTAL CYCLE.
WE WILL NOW HAVE ACCESS TO ALL OF THESE OTHER VARIABLES AND
THEN BE ABLE TO DELIVER MUCH MORE GRANULAR LIKE EACH
PERCENTILE AS A FUNCTION OF AGE PLUS DEVELOP A TOOL SO THAT IF
YOU ORDER A TEST ON A SPECIFIC PLATFORM AND IT GIVES YOU A
NUMBER, YOU WILL THEN HAVE THE INTERPRETATION OF WHAT
PERCENTILE OR WHETHER YOU'RE OUTSIDE THE NORMAL RANGE FOR
THAT.
FOR THAT ANALYTE, WE'VE ALSO WORKED WITH KOSRO DELI.
HE WAS INSTRUMENTAL IN INITIATING A WORLDWIDE OR OR
CANADIAN STUDY CALLED CALIPER THAT REALLY LOOKS AT PEDIATRIC
REFERENCE INTERVALS BECAUSE CHILDREN, ESPECIALLY YOUNG
CHILDREN, ARE QUITE DIFFERENT THAN ADULTS.
AND HE'S RECRUITED ABOUT 13,000 CHILDREN FROM BIRTH ALL THE WAY
UP TO AGE 19.
AND HE HAS IMPLEMENTED PEDIATRIC BLOOD TESTS AND AND LABORATORY
TESTS, CLINICAL CHEMISTRY TESTS IN HOSPITAL LABORATORIES
WORLDWIDE.
AND SO FOR FOR THESE DATA, THIS IS AN EXAMPLE OF WHAT WE HAVE
JUST ALSO PUBLISHED FROM THE FROM THE CALIPER COHORT YOU CAN
SEE HERE IN THE LEFT ARE THE ARE THE ACTUAL RAW DATA WITH MALE
AND FEMALE PARTICIPANTS LISTED AND THEN THE CONTINUOUS AND
DISCRETE REFERENCE INTERVALS.
SO WHAT YOU CAN SEE IS A PATTERN WHERE KIDS UNDER 4 HAVE ACTUALLY
VERY HIGH CIRCULATING LEVELS OF GFAP JUST NATURALLY THESE ARE
NOT INJURED CHILDREN.
AND THE PATTERN FOR P TAU AND TO A SLIGHTLY LESSER EXTENT NFL
LOOKS QUITE SIMILAR TO THIS.
SO I THINK WHAT THIS IS TELLING US IS THAT FOR EXAMPLE ELEVATED
GFAP WILL BE HARD TO DETECT IN VERY YOUNG CHILDREN, BUT BY THE
TIME YOU GET TO SCHOOL AGE THE THE, THE, THE NORMAL VALUES KIND
OF CONDENSE DOWN TO WHERE WE SEE IT VERY SIMILAR TO ADULTS.
THIS IS IMPLICATIONS POTENTIALLY FOR HOW WE MIGHT BE ABLE TO
EXTEND THE AGE AT WHICH SAY TESTS LIKE THE ABBOTT I STAT
GFAB AND UCHL ONE TEST IT COULD BE POTENTIALLY MOVED DOWN TO
SCHOOL AGE CHILDREN BUT PROBABLY NOT BELOW THAT.
SO WHAT WE'RE TRYING TO DO IS ENABLE THE THE THE FIELD HERE IS
TO USE AGE ADJUSTED REFERENCE INTERVALS AND ONCE WE HAVE OTHER
VARIABLES THAT WE CAN TRY TO UNDERSTAND SOME OF THE NOISE
HERE, CONTINUE TO REFINE HOW WE CAN USE AND INTERPRET BLOOD
TESTS FOR WHATEVER POPULATION THAT WE'RE LOOKING.
AD THESE ARE THE NFL DATA.
AGAIN THE PATTERN IS THAT IT'S IT'S IT'S IT'S FAIRLY HIGH IN
KIDS UNDER 4 AND SO ON AND SO FORTH.
SO WHAT'S NICE HERE IS WE ALSO HAVE FAIRLY GOOD CONGRUENCY
BETWEEN CALIPER AND CHMS DATA.
EVEN THOUGH WE'RE USING DIFFERENT MATRICES, THEY'RE NOT
TOO FAR OFF AND HAVING THESE DATA NOW THIS IS ALL DONE ON THE
QUANTERICS PLATFORM.
BY DOING CROSSOVER STUDIES, WE CAN THEN DETERMINE HOW A TEST
RUN ON A QUANTARIS PLATFORM COMPARES TO ROCHE OR ABBOTT OR
SIEMENS OR ANY OTHER OF THE UP AND COMING ANALYTICAL PLATFORMS
THAT MIGHT BE MORE WELL PLACED WITHIN HOSPITAL LABORATORY
SETTINGS TO DO THESE CLINICALLY.
SO ANY QUESTIONS FOR CHERYL, I THINK THIS IS IMPORTANT STUFF
THAT CAN ACTUALLY ULTIMATELY HAVE A LOT OF REGULATORY
SIGNIFICANCE.
YEAH.
SO.
SO DO YOU THINK THAT IN THESE SMALL CHILDREN THIS IS A
CONSEQUENCE OF A IDIOSYNCRATIC BEHAVIOUR OF A SINGLE ANALYTE OR
ARE YOU ACTUALLY SEEING A MARKER OF CHANGE GLIAL DYNAMICS.
IF YOU TAKE ANOTHER GLIAL MARKER S 100 OR SOMETHING LIKE THAT,
WHAT HAPPENS IT'S IT'S ACTUALLY NOT UNCOMMON.
THE CARDIAC MARKERS ARE LIKE THIS AS WELL LIKE THE SO KIDS
UNDER 4 ARE JUST UNIQUE SPECIES.
AND SO WE THINK THAT THERE'S A, THERE'S A, THERE'S SEVERAL
THINGS AT PLAY.
ONE IS NEURODEVELOPMENT OF COURSE THAT IS THAT IS
HAPPENING.
ANOTHER THAT WE HYPOTHESIZE MIGHT BE HAPPENING IS JUST
MATURATION OF THE BRAIN CLEARANCE PATHWAYS THAT WE DON'T
KNOW IN IN PEOPLE.
HOW LONG THAT TAKES TO REALLY ESTABLISH BLOOD BRAIN BARRIER IS
ONE THING, BUT ALL THE DRAINAGE PATHWAYS MAYBE ANOTHER.
THERE'S ALSO, YOU KNOW LITTLE KIDS NEWBORNS ARE ALMOST ALL
HEAD AND VERY LITTLE BODY.
SO YOU HAVE THAT SORT OF ANATOMICAL SCALE TO TO, TO MODEL
AS WELL.
WE DON'T KNOW THINGS LIKE, YOU KNOW, KIDNEY FUNCTION CLEARANCE,
YOU KNOW HOW THEY TACKLE THESE ANALYTES.
SO THERE'S A MULTITUDE OF THINGS THAT HAPPEN IN SMALL CHILDREN
THAT WE HAVE YET TO UNDERSTAND.
YEAH, HI.
SO WE'RE, WE'RE HAVING NICE DATA.
I'M JUST WONDERING ABOUT UCHL ONE, DO YOU SEE THE SAME
ELEVATION IN THE VERY YOUNG?
WE DID NOT DO UCHL ONE IN IN THIS STUDY BECAUSE THE AT LEAST
ON THE QUANTERICS PLATFORM WE GET A LOT OF READS THAT ARE
BELOW LIMIT OF OF DETECTION.
SO WE DID NOT CARRY THROUGH.
YEAH.
I'M BRINGING UP.
HOW DO YOU HANDLE SEX?
DO YOU.
YEAH.
SO SEX IS WAS FOUND NOT TO BE A VARIABLE.
MALES AND FEMALES WERE EXACTLY OVERLAID.
WE WILL DETERMINE IF THAT STILL REMAINS ONCE WE GO FROM 900 TO
2500 SPECIMENS.
BUT SEX WAS NOT FOUND TO BE A VARIABLE IN ANY OF THE COHORTS
THAT WE'VE TESTED.
PLUS OTHER LARGE REFERENCE INTERVAL STUDIES FOR NFL AT
LEAST.
YEP.
BEAUTIFUL STUDY CHERYL.
DON'T RUN AWAY YET.
SO THE FDA MAKES US WHEN WE DO UPPER REFERENCE RANGE TRIALS
DICHOTOMIZE OR TRY SPLIT THE POPULATION UP TO BEING WHAT
PERCENT AFRICAN AMERICANS GOT TO BE 15% FIFTEEN OR PROBABLY
HIGHER PERCENT HISPANIC 10% ASIAN AND WE HAVE TO REPORT
RESULTS AND THEY WON'T LET US USE OTHER COUNTRIES SPECIMENS
UNLESS IT'S LESS THAN 20 OR 30% DEPENDING ON THE ON THE STUDY
HOW MANY HISPANICS YOU HAVE IN CANADA BUT DID YOU LOOK AT
VARIATIONS IN RACE.
THIS IS A GREAT QUESTION FRANK.
WE WE DO HAVE, WE DON'T HAVE ACCESS YET BY STATS CANADA TO
ALL OF THOSE ETHNIC AND RACIAL VARIABLES, BUT THE COMPOSITION
OF THE CANADIAN POPULATION IS VERY DIFFERENT.
WE DO HAVE AFRICAN AMERICANS, OUR HISPANIC POPULATION IS VERY
LOW, BUT WE HAVE A HIGH PROPORTION OF SOUTH ASIAN AND
EAST ASIAN PEOPLES AS WELL.
SO I THINK FROM A GLOBAL SCALE OTHER REFERENCE INTERVAL STUDIES
THAT I KNOW THAT ARE HAPPENING IN ANHENES THAT IS US BASED SOME
OF THE EUROPEAN POPULATIONS TOGETHER THEN WE CAN KIND OF
DRILL DOWN AND AND YOU KNOW AND TRY TO UNDERSTAND HOW TO MAKE IF
WE DO NEED TO ADJUST FOR ANY DIFFERENCES IN RACE OR RACE OR
ETHNICITY FOR A REFERENCE INTERVAL CUT OFFS.
SO IT'S COMING.
I WONDER IS IS BETH IN THE ROOM BETH WAS UPSTAIRS.
OK, HERE'S YES BETH, THIS IS SOMETHING THAT FDA BROUGHT UP
WITH YOU GUYS IN ANY OF YOUR DISCUSSIONS WHEN IT'S THE GFAP
AND UC AND JILL ONE TEST ARE BEING CLEARED REFERENCE
INTERVALS BY AGE.
IN FACT THE PRODUCT IS CLEAR.
THEY LOOKED AT ALL OF THOSE DATA AND THEY LOOKED AT IT IN HTTP
FOR THOSE THAT ENTIRE.
SO THEY LOOK BIG FORWARD THROUGH AND WE SEND IN AN FDA SUBMISSION
OF STACK DATAS.
NO, THEY TURNED IT ALL OUT.
NO MY EXACTLY HEARD LIKE THIS A LITTLE BIT.
SO THEY LOOKED AT ALL OF THAT QUITE POTENTIALLY FOR NOT JUST
THE CARE DEVICE FOR THAT DEVICE FOR THIS PARTICULAR CUT OFF FOR
THAT PARTICULAR CERTIFICATE SPECIMEN STATED THEY WERE ALL IN
AN AGE OF 18 TO 92 FOR OUR ESSAY.
NOW, YOU KNOW, WE LOOK AT OTHER PEOPLE'S ESSAYS AND IT'S NOT
LIKE AN ANALOGY WOULD BE AT A DOLLAR BILL, RIGHT.
A DOLLAR IN THE UNITED STATES VERSUS A DOLLAR IN CANADA VERSUS
A DOLLAR AND A RIGHT.
AND THEY'RE NOT EXACT.
WHEN YOU LOOK AT THE ESSAYS, YOU HAVE TO LOOK AT WHO MADE THE
ESSAY BECAUSE G BAP IS NOT GBAP IS NOT GBAP, CHO ONE IS NOT CHO,
ONE IS NOT CHO.
ONE HAS TO LOOK AT WHERE MANUFACTURING AND YEAH, FOR
SURE.
THANK YOU.
THANK YOU, BETH.
I MEAN CERTAINLY WHAT OUR PLAN GOING FORWARD IS TO DO A LOT OF
PLATFORM COMPARISON AND ASSAY COMPARISON FOR TO DETERMINE WE
DO SEE A RAISE OF GFAP BY AGE AND OLDER POPULATION, YOU KNOW,
NO MAN, IT RAISES A VERY IMPORTANT POINT, YOU KNOW IN
ORDER.
SO, SO AT OUR HOSPITAL, I MEAN I REACHED OUT TO OUR CLINICAL
CHEMISTRY DEPARTMENT AT UNIVERSITY OF PENNSYLVANIA
HEALTH SYSTEM TO SAY GEE, WE HAVE THIS FDA CLEARED TEST FOR
GFAP AND NEW GHL ONE, LET'S START USING IT AND AND THEY TOLD
ME WE'RE NOT AN ABBOTT SHOP, THEY SAID WE DON'T HAVE ABBOTT
EQUIPMENT, WE'RE NOT GOING TO PURCHASE AN UNLIMITED JUST FOR
YOU, RIGHT.
SO, SO THAT THAT'S DISAPPOINTING ACTUALLY VERY DISAPPOINTING.
YES, RIGHT, RIGHT.
THEY ALSO THEY ALSO DIDN'T LIKE THE HANDHELDS EITHER IT'S IT
WAS, IT WAS A BARRIER RIGHT NOW I I I THINK EVERYONE KNOWS.
SO BIO MERU HAS CE MART CLEARANCE FOR A JFAPUC HO1 TEST
IN EUROPE.
ABBOTT HAS YOUR CE MART CLEARANCE AS WELL AS I
UNDERSTAND IT, THIS IS THE DEVICE, RIGHT.
AND THEN YOU HAVE, LIKE, A PARTRIDGE THAT YOU JUST, YOU
KNOW, IF YOU WANTED TO CREATE, OH, OH, BETH, I'M REMINDED THAT
YOU NEED TO USE THE MICROPHONE SO PEOPLE ONLINE CAN HEAR YOU.
YEAH.
BUT ONLINE'S A DIFFERENT DEAL.
YEAH.
COME UP.
COME UP HERE.
SO YOU CAN SHOW IT FROM THE CAMERA.
OH, OK.
THAT'S RIGHT.
I HAVE A NEW ANSWER.
MOM.
THANK YOU FOR ASKING.
SO THE ONE DEVICE, HI EVERYONE.
NOW THAT YOU CAN HEAR ME AND BETH MCQUISTON, I'VE MET A LOT
OF YOU GUYS BEFORE AND ALSO VERY INTERESTED IN MEETING ANYONE
NEW.
SO PLEASE REACH OUT TO ME AND IT'S NICE TO SEE YOU AGAIN,
CHERYL.
AND WE HAVE, THIS IS ONE OF OUR DEVICES.
WE DEVELOPED THIS IN CONJUNCTION WITH THE UNITED STATES
DEPARTMENT OF DEFENSE, SO KUDOS TO THEM.
THEY ACTUALLY USE OUR DEVICES IN THE FIELD AND THEY CAME TO
ABBOTT IN 2011 AND THEY ASKED US IF WE COULD MAKE THESE
BIOMARKERS ON A HANDHELD DEVICE DOWN, MEASURED DOWN TO THE
PICOGRAM LEVEL AT THE SAME TIME WITH TWO DROPS OF BLOOD IN 15
MINUTES.
SO WE WORKED DILIGENTLY WITH THEM FOR YEARS AND WE WERE FDA
CLEARED.
WHAT WAS IT ABOUT A YEAR AND A HALF AGO, TWO YEARS AGO ON THE
POINT OF CARE DEVICE, THE HANDHELD DEVICE WITH THIS
CARTRIDGE AND THEN IT'S ALSO ON THE CORE LAB PLATFORM.
AND WE ALSO WANT TO DO A SHOUT OUT TO TRACK TBI BECAUSE THEY
HELPED US WITH OUR TRAINING SET AND WITHOUT EVERYBODY IN THIS
ROOM AND WITHOUT THE DEPARTMENT OF DEFENSE AND WITHOUT THE
PARTNERSHIP WITH ACADEMIA AND WITHOUT THE BRILLIANT SCIENTISTS
AT ABBOTT, WE WOULDN'T HAVE THIS.
SO KUDOS TO EVERYONE IN THE ROOM, FDA CLEARED, CE MARK, TGA
REGISTERED, ETCETERA, SO FORTH.
SO ON ANY OTHER QUESTIONS, NO THANKS FOR THAT.
AND REALLY BETH, THANKS FOR ALL THE SUPPORT TO THE FIELD.
I THINK BETH PERSONALLY AND ABBOTT MORE GENERALLY DESERVES A
LOT OF CREDIT WHERE WE ARE NOW I MUST SAY THIS WORKS AS AS WE'VE
HEARD AND AND IT'S GOING TO ATTRACT A LOT OF COMPETITION,
RIGHT.
SO THERE ARE, I'M I'M AWARE OF AT LEAST THREE OR FOUR COMPANIES
THAT ARE WORKING HARD ON GFAP ASSAYS THAT ARE TRYING TO GET
INTO THE MARKET, WHICH IS I THINK ULTIMATELY WHAT WE'LL
NEED.
I THINK IN ORDER FOR ME TO USE THIS AT PENN, WE'RE GOING TO
HAVE TO REQUIRE BECKMAN TO DEVELOP SUCH AN ASSAY, WHICH I
KNOW THEY'RE WORKING ON IT AT SOME POINT IT MAY MAY COME
THROUGH, BUT BUT THERE ARE SEVERAL OTHER COMPANIES THAT ARE
CLEARLY WORKING ON THIS AS WELL.
SO ONE THING WE AGAIN GOING BACK TO THE ISSUE THAT FRANK BROUGHT
UP RIGHT, THAT THE UNDER REPRESENTATION OF AFRICAN
AMERICANS IN THE CHMS COHORT.
NO, ONE OF THE THINGS THAT WE HAD TALKED ABOUT, I THINK WE PUT
IT ON OUR GRANT IS THAT WE WERE GOING TO TRY AND GET SAMPLES
FROM THE FRAMINGHAM OFFSPRING STUDY WHERE THE FRAMINGHAM
CONTROL STUDY.
SO I BELIEVE THAT IS HAPPENING OR IT'S IT'S EITHER IT'S BEEN
DONE OR WILL WILL SOON BE DONE.
THERE ARE A LOT OF ESSAY, THERE ARE A LOT OF PROSPECTIVE STUDIES
LIKE FRAMINGHAM, ERIC, IF WE HAVE ANDREA HERE, MAYBE SHE CAN
COMMENT ON THAT.
ERIC HAS OBTAINED NFL AS WELL AS TAO AND P TAO ON THE EQUINTERI
PLATFORM.
IS ANDREA HERE?
MAYBE SHE'S NOT.
SHE MUST HAVE BEEN ON THE OTHER SESSION, RIGHT, AND THAT'S
THAT'S GOING TO BE AVAILABLE.
THAT WAS ALSO RUN IN THE QUINTERIX PLATFORM IN IN BAYLOR
BY CHRISTY BALENTINE'S GROUP, WHICH IS THAT ALSO BEEN BEEN
VERY ACTIVE IN THIS FIELD.
SO THERE'S A LOT OF THIS DATA THAT'S GOING TO BE COMING.
IT'S CLEARLY GOING TO HAVE AN IMPACT IN OUR FIELD AS WELL AS
MANY OTHER AREAS OF NEUROSCIENCE AS WELL.
ANY OTHER COMMENTS ON THIS WHOLE ISSUE OF OF REFERENCE INTERVALS
WHICH I I DO THINK IT'S GOING TO BE IMPORTANT TO GET WIDE
APPLICABILITY.
CHERYL, MICROPHONE, I'M, I'M SORRY, MICROPHONE, DO YOU WANT
TO TALK ABOUT MATERIALS, REFERENCE MATERIALS SO THAT LABS
CAN CALIBRATE WORSE?
YES, I DIDN'T HAVE SLIDES FOR THAT, BUT BUT ONE OF THE THINGS
THAT ARE ALSO GOING TO BE NEEDED ARE REFERENCE MATERIALS THAT ARE
INTERNATIONALLY RECOGNIZED, DEVELOPED UNDER VERY ROBUST
CONDITIONS THAT CAN BE SHARED INTERNATIONALLY.
THIS, THIS WAS PIONEERED BY KAI BLANOW AND HENRY ZETTERBERG FOR
A BETA AND THAT MADE AN ENORMOUS DIFFERENCE IN THE ALZHEIMER'S
FIELD MANY YEARS AGO.
AND I YOU KNOW WE CLEARLY NEED TO DO THAT IN THE IN THE TBI
FIELD AND KEVIN WHO WAS HERE IS SORT OF GOING TO BE LEADING THAT
EFFORT HAS ALREADY BEEN WORKING ON THAT AND WILL WILL DEVELOP
SOME MORE OF THESE REFERENCE MATERIALS AND THESE ARE
RECOMBINANT PROTEINS THAT CAN BE QUALIFIED AND AND CALIBRATED.
IT CAN BE SHARED BROADLY.
I THINK THE OTHER THING THAT WILL BE NEEDED AND WE'RE
PROBABLY A LITTLE LESS FAR ALONG IN DOING THIS IS TO DEVELOP
MATRIX SPECIFIC REFERENCE MATERIALS MEANING PLASMA AND
SERUM AND POTENTIALLY CSF BUT AT LEAST PLASMA AND SERUM THAT FROM
FROM LARGE POOLS WHERE THE VALUE IS IS WELL RECOGNIZED AND KEPT
CALIBRATED.
KEVIN, YEAH, I KNOW JUST TO PEGGY BACK ON THAT, YOU KNOW THE
OBVIOUSLY THE NORMATIVE CONTROL HUGELY USEFUL AND THEN THE,
YEAH, WE'RE TRYING TO DEVELOP THE RECOMBINANT PROTEIN.
SO WE'RE FINDING OUT THAT WHEN YOU SPIKE IN THIS PROTEIN INTO
NAIVE YOU KNOW CONTROL PLASMA, A LOT OF IT DISAPPEARS.
SO.
SO IT'S NOT TO SAY THEY'RE NOT USEFUL, BUT THEN IT'S A LOT OF
GETTING ABSORBED BASICALLY.
SO THAT REALLY ARGUES FOR HAVING A POOL OF TBI OR YOU KNOW,
DISEASE, PATIENT SERUM AND PLASMA FOR THAT PARTICULAR
INDICATION AS A POSITIVE CONTROL, AS MUCH AS THE NEGATIVE
CONTROL, IMPORTANT, POSITIVE CONTROL, HUGELY IMPORTANT.
SO I'M CURIOUS WE WE HAVE A PRETTY GOOD TURN OUT HERE AND AS
WELL AS PEOPLE ONLINE AND AND HOW MANY OF YOU IS IN YOUR
HOSPITAL USING GFAP FOR CLINICAL INDICATIONS NOT RESEARCH OR OR
AT LEAST THINKING ABOUT IT OR OR MAKING THE THE STEPS TO TO GET
IT, GET IT ONLINE AT YOUR HOSPITAL IT'S FASCINATING.
SO, SO NO ONE AT LEAST IN THIS ROOM PEOPLE ARE VERY INTERESTED
IN TBI IS YET USING GFAP AND NEW CHL ONE AS A CLINICAL TOOL.
I AM AWARE THAT THERE ARE A COUPLE OF HOSPITALS THAT ARE
DOING THIS BUT BUT NOT VERY MANY.
THERE'S THIS HAS BEEN A CHALLENGE IN BEEN IN
DISSEMINATING AND GETTING THE THE ADOPTION.
I THINK THERE ARE A NUMBER OF REASONS WHY THAT COULD BE.
OBVIOUSLY THINGS ARE SLOWING AND AND GETTING ADOPTED.
YOU KNOW THOSE OF YOU WHO WERE HERE FOR THE LAST COUPLE OF DAYS
SINCE THE INTEREST AND ENTHUSIASM TO FEEL AS A WHOLE
FOR BIOMARKERS TO HELP CLASSIFY TRAUMATIC BRAIN INJURY.
AND IT'S SOMETHING THAT AT LEAST THE YOU KNOW, FDA CLEARED THE
ABBOTT TESTS COUPLE OF YEARS AGO, ALMOST TWO YEARS AGO AND
AND WE'RE WE'RE NOT DOING IT YET AND THEY'RE GOING TO BE SOME
BARRIERS AND I HOPE THAT SOME OF THE WORK WE CAN DO CAN CAN HELP
ALLEVIATE SOME OF THOSE BARRIERS.
I THINK A A MAJOR INTERNATIONAL QUESTION WILL BE WHAT'S THE
FUNDING MODEL TO BRING IN THESE NEW LABORATORY TESTS.
AND IN SOME PLACES IT MIGHT BE POSSIBLE TO SAY WELL, WE COULD
REDUCE MRI BURDEN OR INCREASE, YOU KNOW, AND THAT SAVINGS COULD
GO TO THAT AND OTHER PLACES LIKE IN BRITISH COLUMBIA, THAT'S NOT
POSSIBLE.
YOU CAN'T PUT ONE MONEY LIKE ONE SOURCE OF FUNDING INTO.
I MEAN THAT'S THAT'S GOING TO BE THE OTHER BARRIER.
SO NOT ONLY DO WE HAVE THE INFRASTRUCTURE, DO WE HAVE A
QUALITY PROGRAM THAT WE CAN MONITOR HOW WELL THESE ASSAYS
ARE BEING PERFORMED AND DO WE HAVE THE PERSONNEL TRAINED IN IN
DOING THEM.
ALL OF THIS NEEDS TO BE BUILT UP PLUS THE FUNDING MECHANISM A, A
RELATED ISSUE.
SO OBVIOUSLY S 100 BETA HAS BEEN PART OF THE SCANDINAVIAN
GUIDELINES FOR FOR REALLY QUITE A WHILE, OVER A DECADE.
AND I'M CURIOUS, I KNOW I SEE WE HAVE ERIC FILENE REMOTELY.
ERIC, I WONDER IF YOU WOULD COMMENT AT THE CAROLINE SCOUT,
RIGHT, HOW, HOW OFTEN OR OR WHAT BARRIERS HAVE YOU FOUND TO USING
S 100 BETA SORT OF ACCORDING TO THE SCANDINAVIAN GUIDELINES.
SO WE HAVE QUITE A, WE HAVEN'T REALLY HAD THAT MANY BARRIERS.
I WOULD SAY AFTER THE IMPLEMENTATION OF THE
SCANDINAVIAN GUIDELINES IN 2013, THEY BECAME QUITE WIDESPREAD IN
TERMS OF SCREENING FOR MILD TBI.
THERE'S SCREENING FOR WHO TO DO ACT SCAN ON IN MILD TBI FOR SORT
OF A COST SAVING PURPOSE.
SO I I THINK THAT I DON'T NECESSARILY THINK THAT YOU IF
YOU HAVE APPROVAL AND YOU HAVE SOMEWHAT SOLID MORE ROBUST
EVIDENCE THAT IS GOING TO BE THAT PROBLEMATIC.
KARLINSKA IS A VERY BIOMARKER HEAVY INSTITUTION IN TERMS OF
THE SEVERE TBI WHERE WE USE S100B FOR SERIAL MONITORING IN
UNCONSCIOUS TBI AND SCH PATIENTS TWICE PER DAY.
SO I I THINK THAT WE'RE SOMEWHAT BIASED, BUT I I ALSO THINK THAT
WE MIGHT BE ABLE TO SHARE SOME OF OUR EXPERIENCE IN A FEW
UPCOMING PAPERS THAT WE HAVE NOW THAT WE WE REALLY CAN SHOW THAT
THIS HELPS US IN OUR CLINICAL ASSESSMENTS OF OUR PATIENTS
WELL.
SO IT'S GOOD TO KNOW THAT AT LEAST IN, IN IN SOME HOSPITALS
IN IN SWEDEN AND OTHER AREAS IN SCANDINAVIA THAT THAT THIS IS
ACTUALLY HAPPENING BECAUSE WE'RE ALL VERY EXCITED TO BE ABLE TO
USE IT HERE.
THERE'S A QUESTION IN THE CHAT.
HOW CAN I SEE THE CHAT?
OH, HERE WE GO.
ALL RIGHT.
THIS IS A QUESTION FROM JONATHAN.
DO EVERYONE CLINICIANS LOVE A NEW GADGET, BUT WHAT IS THE
BUSINESS CASE FOR BIOMARKERS AND TBI, ADDITIONAL COSTS VERSUS
BENEFITS?
SO THAT'S A GREAT QUESTION.
THAT'S EXACTLY WHAT WHAT WE'RE TALKING ABOUT RIGHT NOW.
I CAN GIVE MY ANSWER, ANYONE CARE TO ANSWER BUT OBVIOUSLY THE
THE CONTEXT OF USE THAT IN THE US IS FDA CLEARED IS TO REDUCE
THE NUMBER OF UNNECESSARY CT SCANS AND THE ESTIMATES FROM THE
ALERT STUDY IS THAT APPROXIMATELY 35% OF THE CTS
THAT WE DO IN THE UNITED STATES COULD BE SKIPPED IF WE WERE TO
USE THIS TEST AND AND THAT IS OBVIOUSLY A SUBSTANTIAL SAVING.
NOW WHETHER WHETHER EMERGENCY MEDICINE PHYSICIANS WILL WILL IN
FACT DO THIS, IT'S A QUESTION OR TIMING IT'S A QUESTION OR A
NUMBER OF OTHER THINGS.
I THINK THAT THAT REMAINS TO BE SHOWN IT IT LIKELY WOULD, WOULD
TAKE A WHILE, RIGHT.
I I MEAN I SAY I I THINK AS A NEUROLOGIST AND YOU KNOW SOMEONE
WHO'S WORKING THE ICU AND ALSO IN THE OUTPATIENT SETTING, I
THINK IT WOULD BE VERY VALUABLE.
IT WOULD BE INFORMATIVE TO ME AND CERTAINLY INFORMATIVE TO
PATIENTS AND THEIR FAMILIES IF WE HAD THIS DATA RIGHT, EVEN IF
IT IT CAN HELP DIAGNOSTICALLY.
YOU KNOW MANY PEOPLE THAT HAVE A NEGATIVE CT NONETHELESS HAVE
ATBI AND IF THEY THEY HAD PROOF THAT THEY HAD HAD A TB, A
SIGNIFICANT BRAIN INJURY THAT COULD POTENTIALLY HAVE
IMPLICATIONS FOR THEIR DISABILITY ASSESSMENTS OR
WORKMAN'S COMPENSATION OR MANY OTHER THINGS LIKE THIS.
WE HEARD THIS OVER THE LAST COUPLE OF DAYS FROM THE LIVED
EXPERIENCE CONSULTANTS THAT THIS WOULD BE A VERY VALUABLE THING
FOR HIM TO HAVE EVEN IF IT DIDN'T NECESSARILY LEAD TO
SKIPPING ACT SCAN.
DOUG YEAH.
SO I I ONE EXAMPLE OF OF I MEAN THIS BEING REALLY USEFUL IS LIKE
IN PEDIATRICS WHERE OUR HOSPITAL CHOPPED DOESN'T LIKE TO USE CTS
AND SO YOU CAN SEE THE ALTERNATIVE.
BUT THEN I SAW CHERYL'S DATA AND I'M LIKE OH YEAH, SO IT'S
PROBLEMATIC, BUT THERE ARE MANY, YOU KNOW, AUSTERE ENVIRONMENTS
AND WHATNOT AND MAYBE PEDIATRICS OF A CERTAIN AGE OR WHATEVER
THAT THAT THAT WOULD BE STANDARD FOR CARE MAYBE EVENTUALLY AND
OBVIOUSLY WE HEARD THIS MORNING FROM FROM NEIL GRAHAM.
AND THEN THERE'S OTHER DATA ON THIS THAT GFAP MAY BE USEFUL FOR
ASSESSING THE LONG TERM EFFECTS OF TBI AS WELL.
SO THIS COULD COULD HAVE A ROLE IN THE OUTPATIENT CLINIC, FRANK.
YEAH.
SO IN THE UNITED STATES WHERE MOST OF US CAN GET IT AT ACT IN
A FEW MINUTES, IF YOU WORK IN A TRAUMA PLACE, YOU CAN GET IT IN
10.
AND THAT'S EVER SINCE WE MOVED INTO THE STROKE WORLD WHERE WE
HAVE TO GET A CAT SCAN TO DECIDE IF YOU CAN GET A LYTIC.
OUR ABILITY TO GET CTS RAMPED RIGHT UP BECAUSE NOW IT'S GOT TO
BE WITHIN 10 MINUTES.
SO WE CAN DO THAT IF WE IF WE NEED TO.
NOW NOBODY WANTS TO DO EXTRA CTS AND IT WOULD BE LOVELY IF I
DIDN'T HAVE TO DO THEM.
THE CHALLENGE IS, IS THE CURRENT FORMAT OF THAT ESSAY IS IS NOT
IN WHOLE BLOOD, IT'S IN SERUM.
SO IT'S GOT TO SIT AROUND FOR HALF AN HOUR AND GO TO THE LAB
AND ANYTHING GOES TO THE LAB TAKES AN HOUR.
AND THAT'S JUST THE REALITY.
I KNOW YOU'RE BEST ABOUT TO SAY IT'S GOING TO BE IN WHOLE BLOOD
AND WE WILL HAVE A PARTY THE DAY THAT IT IS BECAUSE THEN I CAN
USE IT.
THE OTHER PART OF THIS COMES, AND I JUST HAD THIS CONVERSATION
WITH DAVID AQUANCO A FEW MINUTES AGO, IS THAT IF THERE'S A NUMBER
THAT TRIGGERS THE CALL OF A NEUROLOGIST OR A NEUROSURGEON,
WE WILL ALL DANCE BECAUSE WE LIKE ONE OF THE REASONS THE
EMERGENCY DOCS LIKE TROPONIN, BECAUSE IF IT'S A CERTAIN
NUMBER, I CALL A CARDIOLOGIST AND THAT PATIENT GETS OFF OF MY
PLATE.
SO THERE'S THE CLEANING THE PLATE ROUTINE, WHICH IS REALLY
IMPORTANT IN A CROWDED EMERGENCY DEPARTMENT.
IF I CAN DUMP SOMEBODY ON TO SOMEBODY ELSE AND SAY GO NOW, I
CAN TAKE THE NEXT GUY, THAT'S HELPFUL.
SO THERE'S A NUMBER.
NOBODY CAN TELL ME WHAT THE NUMBER IS, BUT I'M GOING TO BE
CALLING NEUROSURGEONS AND NEUROLOGISTS IF IT'S ABOVE 400
OR 600 OR WHATEVER THAT MAGIC IS.
BUT WE NEED THAT DATA.
AND THE REASON WE NEED THAT DATA UP FRONT IS BECAUSE THERE ARE
OTHER, IT'S NOT JUST TRAUMA THAT COMES IN THERE.
EVERY DIRTY PATIENT COMES IN AND IF YOU'VE GOT SOME KIND OF
CHRONIC DEMENTIA AND YOUR G FAB IS NORMALLY 700 AND I CALL THE
NEUROSURGEON, EVERY TIME THIS GUY COMES IN, THE NEUROSURGEON'S
GOING TO TAKE A CRAP ON ME BECAUSE THEY DON'T LIKE THAT AT
ALL.
AND SO WE THERE'S GOT TO BE A STUDY WHICH LOOKS AT IN THE
DIRTY EMERGENCY MEDICINE POPULATION, HOW MANY THESE
PEOPLE HAVE ELEVATED G FAPS THAT ARE NOT TRAUMA RELATED AND DON'T
NEED TO BE CALLED.
AND IF I KNEW THEIR BASELINE AND IT THEN IT'S GOT TO BE A 20% UP
FROM THEIR BASELINE 'CAUSE WE HAVE THOSE NUMBERS FOR TROMBONE
AND I HAVE THOSE NUMBERS FOR BNP.
IF YOU'RE ABOVE YOUR BASELINE, THEN I CALL THE CARDIOLOGIST.
BUT IF YOUR PHONE IS THE SAME OLD NUMBERED EYES IS EVEN THOUGH
IT'S ELEVATED, WE CAN IGNORE IT.
I NEED TO KNOW THOSE DATA FOR G FAP.
I MEAN THAT'S A REALLY IMPORTANT POINT, THE ISSUE OF OF STUDYING
THESE BIOMARKERS AND THE ELDERLY BEST.
SO NICE TO SEE YOU, FRANK.
HELLO, IT'S BEEN A WHILE.
THANK YOU FOR YOUR COMMENTS.
I WANTED TO SAY FOR THE ABBOTT POINT OF CARE TEST AND FOR THE
ABBOTT CORE LAB, IT IS NOT SERUM IMPORTANTLY.
WELL, YOU CAN RUN IN SERUM, BUT IT'S PLASMA.
SO SERUM ADDS AN EXTRA HALF AN HOUR, 45 MINUTES.
SO IT'S IN PLASMA.
AND THE OTHER POINT I WANTED TO MAKE IS THAT THE VAST MAJORITY
OF LABS THAT ARE RUN IN THE CORE LAB INCLUDING HIGH SENSE
TROPONIN AND THEY'RE USED TO RULE OUT MI'S AND SO FORTH.
AND EVEN IN THE UNITED STATES, AT LEAST HALF THE HOSPITALS IN
THE UNITED STATES WILL NOT ALLOW POINT OF CARE TESTING.
THAT'S WHY WE HAVE IT ON CORE AND POINT OF CARE BECAUSE THE
LAB SAYS IT HAS TO GO THROUGH THE LAB SO YOU CAN RUN IT
CERTAINLY STATS ON YOUR PLASMA BLOOD TUBE ALONG WITH ALL THE
REST OF YOUR ASSAYS AND SO FORTH THAT YOU'RE INTERESTED IN
RUNNING.
SO I WANTED TO MAKE THAT POINT AND YOU CAN GET IT WITH THE
RESULTS CERTAINLY WITHIN AN HOUR WHEN YOU RUN IT STAT.
SO VERY IMPORTANT TO HIGHLIGHT THAT AND OF COURSE WHOLE BLOOD
IS ALSO SOMETHING.
SO WE LIKE TO HAVE A LITTLE BIT OF EVERYTHING WHEN YOU WORK FOR
A LARGE DIAGNOSTIC COMPANY.
SO WE'LL HAVE THE SERUM IF YOU WANTED IT, BUT ALSO PLASMA AND
ON A POINTED CARE DEVICE AND ON A CORE LAB DEVICE AND WHOLE
BLOOD IS COMING.
SO WHOLE BLOOD, FINGERS CROSSED.
STAY TUNED.
WE'VE BEEN WORKING VERY CLOSELY WITH THE DEPARTMENT OF DEFENSE
ON THAT.
BUT THANK YOU FOR YOUR POINTS.
JUST WANTED TO HIGHLIGHT THAT THE CORE LAB IS INDEED THE
CORNERSTONE OF ALL OF THE, THE VAST MAJORITY OF THE BLOOD WORK
GLOBALLY.
MEET YOU, JAMIE JAMIE HUTCHISON FROM SICK KIDS IN TORONTO.
YEAH, I JUST WANTED TO.
IT WAS VERY INTERESTING, RAMON, TO SEE THAT NOBODY IN THE ROOM
HAD IMPLEMENTED THE USE OF BIOMARKERS CLINICALLY.
AND I JUST WANTED TO MAKE A COUPLE COMMENTS ABOUT THAT TO
ADDRESS THIS ISSUE AND MAYBE ASK A QUESTION OF THE ROOM.
SO I THINK WHAT'S MISSING MY TAKE IS THAT WHAT'S MISSING IS
THAT THERE'S NO CLINICAL, THERE'S A LACK OF PAUCITY OF
CLINICAL IMPLEMENTATION STUDIES TO SHOW THAT THESE BIOMARKERS
ARE CLINICALLY VALUABLE IN SAY 6.
WE CAN LIST 6 OR MAYBE MORE CONTEXT OF USE.
AND SO THAT WAS INTERESTING TO HEAR THAT THE CAROLINA INSTITUTE
HAS IMPLEMENTED S100B AND THAT THEY HAVE SOME DATA THAT I THINK
THEY'RE ABOUT TO PUBLISH.
SO MY MY QUESTION IS, ARE THERE OTHER PEOPLE DOING CLINICAL
IMPLEMENTATION STUDIES LIKE A KNOWLEDGE TRANSLATION TYPE STUDY
THAT'S IN PROGRESS RIGHT NOW?
IS THERE ANYBODY IN THE ROOM DOING, DOING THOSE TYPES OF
STUDIES 'CAUSE I THINK BESIDES THE ANALYTICAL VALIDATION
STUDIES THAT ARE IN PROGRESS, THIS IS THE NEXT STEP TO FOR US
TO PROVE TO CLINICIANS, RIGHT, THAT THERE'S A, THERE'S AN
IMPORTANT CONTEXT OF USE, RETEST ODDS.
YEAH.
GREAT.
CHRISTIAN, I MEAN I'M NOT AWARE OF ANY OF THESE IMPLEMENTATIONS
THAT ARE GOING.
FRED CORLEY ISN'T HERE, BUT I KNOW FRED WAS INTERESTED IN
LAUNCHING SOMETHING LIKE THAT IN THE ED AT THE UNIVERSITY OF
MICHIGAN.
WE SHOULD MAYBE REACH OUT TO FRED WITH THAT QUESTION.
AND RUSH.
YES.
ON THE SCANDINAVIAN PERSPECTIVE, YES.
SO BASICALLY I THINK THAT THE THE BIOMARKER TO BE A GAME
CHANGER SHOULD BE LIKE THE ISAT AT THE SITE.
SO POINT POINT OF CARE DEVICE, IF YOU SEND THE PROOF TO THE TO
THE SAMPLE TO THE TO THE LAB, THE B PLASMA, B SERUM, IT WILL
TAKE TIME AND THE OTHER.
THE MOST IMPORTANT THING WOULD BE BESIDES HAVING THIS POINT OF
CARE DEVICE EVERYWHERE TO KNOW THE PRICE OF OF THE INDIVIDUAL
TEST, BECAUSE THAT WILL DEFINITELY DEFINE DEFINE IF WE
CAN USE IT WORLDWIDE TO FIGHT A GLOBAL PROBLEM GLOBALLY.
THE OTHER PROBLEM IS OR A PROBLEM TO BE SOLVED PROBABLY TO
IF I RECOLLECTED WELL.
THE EYE STAT WILL GIVE YOU A NUMBER IF YOU HAVE, IF YOU'RE
OVER THE THE LIMIT.
SO IF IF THERE IS A A TEST CT IS NEEDED OR SO.
SO OVER THE THE THRESHOLD BUT UNDER THE THRESHOLD YOU WILL NOT
GET THE NUMBER IF I'M CORRECT THAT MEANS THAT BASICALLY WHAT
WE WHAT WE DEFINITELY WILL USE OUR BIOMARKERS TO HAVE THESE
THESE A LITTLE BIT CONTINUOUS CATEGORIZATIONS FOR FOR CT
NEGATIVE PROBABLY CT NEGATIVE PROBABLY MR.
POSITIVE PATIENTS WHO CAN BE IN HARM'S WAY AND THE LONG TERM CAN
BE APPLIED OR NOT.
BUT IF I HAVE TO DO A NICE STEP FOR EXCLUDING CT POSITIVITY AND
THEN A A LABORATORY TEST TO EXCLUDE THE POSSIBILITY OF OF
NON MR.
POSITIVITY SO THAT THAT CAN COMPLICATE.
SO BETH BETH IS AGAIN PROBABLY IN THE BEST POSITION TO ANSWER
THAT QUESTION.
YEAH, ACTUALLY I WANTED I HAD ONE OF MY COLLEAGUES DR.
CASSINI, HELLO, WHO'S LISTENING ONLINE AND SHE REMINDED ME SHE'S
BASED IN EUROPE THAT THESE THESE TESTS ARE NOW BEING USED
ROUTINELY IN SPAIN.
THE CONSENSUS STATEMENTS IT ALSO IN GERMANY.
AND REGARDING FRANK'S, ONE OF HIS QUESTIONS THERE WAS THE MIND
STUDY THAT WAS DONE BY PROFESSOR BIEBENTHALER LOOKING AT THE
LEVELS THEY INCLUDED DEMANDED DEMENTIA PATIENTS AND SO FORTH
AND THEY WORKED VERY WELL.
SO I JUST WANTED TO CIRCLE BACK TO THAT AND THANK YOU DOCTOR
CASSINIA FOR YOUR INPUT REMOTELY.
ERIC HAS A STAND UP FROM STOCKHOLM LOWER DETECTABLE
LIMIT.
IT ACTUALLY DEPENDS ON THE PLATFORM, BUT FOR THE CORE LAB
IT'S 3 PICOGRAMS WHICH IS VERY VERY LOW.
AND THEN FOR GFAP IT MEASURES ALL THE WAY UP TO 42,000.
IT DOES THAT IN 18 MINUTES AND FOR USE HL ONE IT MEASURES VERY
VERY LOW, UP TO 25,000 PICOGRAMS.
SO IT MEASURES MANY, MANY FOLD LOWER THAN NORMALS AND MANY,
MANY FOLD LOWER OR HIGHER THAN WHAT IS TYPICALLY SURVIVABLE.
THANK YOU.
SO, ERIC, YES, ALL RIGHT, THANKS.
SO WE PAY ABOUT 30 U.S.
DOLLARS FOR SS100B SAMPLE AND IN TERMS OF CD SCAN, SINCE WE
DIDN'T, IT'S ABOUT 100, ONE $150.00, MAYBE UP TO $200 IF
IT'S A WEEKEND OR AN EVENING, BUT SO IT'S IF IT COMES DOWN TO
PRICE.
AND THESE VALIDATION STUDIES THAT HAVE BEEN DONE ON THE
SCANDINAVIAN GUIDELINES SHOWS THAT ABOUT 20% IN THE REAL LIFE
STUDIES CAN BE YOU, YOU CAN SORT OF SKIP ABOUT 20% OF THE CT
SCANS.
BUT IN IN TERMS OF THE MORE SEVERE TBI PATIENTS, I THINK IT
ADDS AS AN ADDITIONAL MONITORING TOOL ESPECIALLY MAYBE IN A LOW
COST SETTING WHERE YOU CAN'T DO ICP MONITORING OR IF YOU CAN'T,
IF YOU HAVE LIKE PROBLEM WITH MULTIMODAL MONITORING THAT YOU
CANNOT ADD THESE IT IT'S ACTUALLY A VERY GOOD SORT OF NON
INVASIVE GLOBAL MONITORING TOOL THAT WE USE.
SO I I THINK IT ALL DEPENDS WHAT YOU WANT AND IF YOU COMPARE IT
TO A LOT OF OTHER THINGS THAT YOU DO IN THE YOUR INTENSIVE K
UNIT, IT IS ACTUALLY NOT THAT EXPENSIVE.
IF YOU THINK LIKE SERIAL SAMPLING, I DON'T KNOW WHAT IT
COSTS FOR THE GFAP COST, BUT I MEAN IF IT'S ABOUT 30 DOLLARS, I
THINK IT'S IT'S PROBABLY PROBABLY LESS EXPENSIVE THAN
SOME OF THE OTHER TOOLS THAT WE USE.
YOU KNOW, OBVIOUSLY HEALTH ECONOMICS ARE A WHOLE DIFFERENT
ISSUE AND AND SO, SO THE RAMON, LET ME ADDRESS REIMBURSEMENT
SYSTEMS IN IN EUROPEAN EUROPE AND OTHER COUNTRIES IS VERY
DIFFERENT FROM WHAT WE HAVE IN THE US FRANK.
I LOOKED UP MY CHARGE FOR RESEARCH CATEGORY CT, WHICH IS
BY FAR A FACTOR OF 5 LOWER THAN WHAT WE REALLY CHARGE BECAUSE I
GET A DEAL FOR RESEARCH, IT'S $355 FOR A CAT SCAN.
SO IF YOU CAN GET A S 100 BETA FOR 30 BUCKS, IT'S A HELL OF A
DEAL.
AND WHAT WE CHARGE FOR A PATIENT IS 18156.
SO THESE ARE CHARGES, THESE NOT COSTS.
COSTS ARE PROBABLY 100 BUCKS BECAUSE IT'S.
I'VE GOT ACT MACHINE.
I'D APPRECIATE IT IN THE LAST DECADE.
I HAVE TO PAY THE RADIOLOGIST TO READ IT AND THAT'S ABOUT IT AND
A FEW ELECTRONS TO MAKE IT RUN.
SO COSTS AREN'T REALLY THE PICTURE BUT $1800 FOR ACT.
SO THERE'S A HUGE MARGIN IF YOU CAN AVOID ACT.
BUT BETH, I WANT TO POINT OUT IT'S NOT JUST DEMENTIA.
IT IS EVERY OLD PERSON WHO JUST HAD IT.
BETH LISTEN HERE, BETH MCQUISTON, IT'S EVERY OLD PERSON
WHO'S GOT NOT JUST DEMENTIA, BUT SOMEBODY WHO JUST HAD A SEIZURE
5 MINUTES AGO AND THEY BRING THEM IN NOW.
AND I DON'T KNOW, HE'S SORT OF UNCONSCIOUS AND HE FELL DOWN AND
HE'S GOT A BIG OLD THING ON THE SIDE OF HIS HEAD IS IT IS A
TRAUMATIC BRAIN INJURY.
I DON'T KNOW.
AND WHAT IF HE HAS MENINGITIS?
WHAT IF HE'S GOT COVID THAT SOMETIMES EATS YOUR BRAIN.
AND THE LIST OF THINGS THAT EATS YOUR BRAIN IS ABOUT 200 THINGS
LONG, JUST LIKE THE LIST OF THINGS THAT EATS YOUR HEART.
AND SO WE HAVE TO IT'S A IT'S REALLY NICE WHEN YOU'RE A
NEUROSURGERY, CAN YOU GET A PATIENT?
BECAUSE THEY PROBABLY REALLY HAD TRAUMA, BECAUSE SOMEBODY SORTED
IT OUT AND CALLED THE NEUROSURGEON.
BUT FOR THE ER DOC, IT'S EVERY FREAKING FOOL WHO WALKS IN THE
ROOM, NO MATTER WHAT'S WRONG WITH HIM, WITH A BEER IN HIS
HAND.
AND THAT'S MY POPULATION.
AND SO IT'S GOT TO BE SHOWN IN THE DIRTY REALITY OF MY WORLD
WHAT THE PERFORMANCE OF A POSITIVE MEANS, BECAUSE I DON'T
KNOW RIGHT NOW.
THAT'S, THAT'S THE CHALLENGE.
AND UNTIL WE GET A REGISTRY AND WE LOOK AT THIS IN 2000,
PATIENTS PROSPECTIVELY OF ALL COMERS, NOT JUST THE ONES WHO
LOOK LIKE THEY HAVE TBI, BUT EVERYBODY YOU MIGHT ACTUALLY
DRAW A LEVEL ON.
WE'RE GOING TO BE SITTING THERE LOOKING THESE NUMBERS GOING, IS
IT HIGH?
I DON'T KNOW, DAVID.
SO IN THE COURSE OF THE RECHARACTERIZATION AND
CLASSIFICATION MEETING, ONE OF THE SUGGESTIONS TOWARDS THE END
WHICH I MADE, WELL, THERE'S A PREAMBLE TO THAT.
IF THIS GETS RELEASED INTO THE WIRE, IT'S GOING TO BE USED FOR
MORE THAN THE PRECISE INDICATIONS THAT THE FDA HAS HAS
PRESCRIBED.
BUT IF IT'S USED MORE WIDELY, I CAN'T SEE ANYONE FUNDING THE
SORT OF STUDY THAT FRANK WANTS EVEN THOUGH I THINK IT'S
ABSOLUTELY, ABSOLUTELY ESSENTIAL.
AND BECAUSE WE'VE GOT SOME FRIENDS FROM INDUSTRY HERE.
THE QUESTION I'D LIKE I'D LIKE TO ASK THEM IS HOW WOULD THEY
FEEL ABOUT FUNDING A REGISTRY.
NOT SO MUCH TO GIVE ANYONE ANY MONEY, BUT YOU SAY TO THE
CENTERS THAT ARE USING IT THAT IF YOU DO CONTRIBUTE SOME
COVARIANCE AS THE PATIENT COMES IN AND A SIX MONTH OUTCOME WHICH
YOU RING UP FOR, WE'LL GIVE IT TO YOU 20% LESS FOR THE 1ST
10,020 THOUSAND PATIENTS.
AND BE INTERESTING TO HEAR WHAT THEY HAVE TO SAY TO THAT.
SO I'VE DONE REGISTRIES WHERE WE PAY $100 FOR EVERY BLOOD SAMPLE
DRAWN AND WE PAY THAT TO THE ER SECRETARY WHO THEN GETS THE
PATIENT'S CHART AND LOOKS AT THE FINAL DIAGNOSIS AND RECORDS
THAT.
AND IT'S THE CHEAPEST STUDY YOU'VE EVER DONE IN YOUR LIFE
AND YOU CAN DO IT FOR $100 A PATIENT.
SO THAT THE COST TO A COMPANY THAT'S GOING TO MAKE A BILLION
DOLLARS FROM THEIR MARKER IS NEGLIGIBLE.
SO FOR FOR 10 GRAND YOU CAN ENROLL 1000 PATIENTS AND THAT
PROVIDES ALL THE ANSWERS YOU NEED.
BETH IS NOT ON THE BUSINESS SIDE AT ABBOTTAS.
SHE STOLE THOSE MANY, MANY TIMES.
YEAH, BUT BUT I MEAN THESE, THESE ARE ALL, THESE ARE ALL
CRITICALLY IMPORTANT ISSUES.
YOU KNOW, I THINK WE'VE IDENTIFIED SOME PRETTY
SIGNIFICANT BARRIERS, A LOT OF EXCITEMENT HERE, BUT THERE'S
ALSO SOME BARRIERS THAT WE'RE GOING TO HAVE TO OVERCOME AND I
THINK WE CAN OVERCOME.
LISTEN, I DON'T DO NOT SPEND ALL OUR TIME ON THIS.
I DO WANT TO MOVE ON TO AND AND ANOTHER THING THAT IS THAT I
REALIZED I'VE MISSPELLED CANDIDATE APOLOGIZE FOR THAT TO
TO PART OF WHAT WE WE BELIEVE IS GOING TO BE A AN IMPORTANT
PAYOFF IN THE FIELD WHICH IS TO UNDERSTAND THE EFFECTS OF
GENETIC VARIATION IN IN OUTCOMES FROM TBI AND YOU KNOW WE DON'T
REALLY KNOW BUT I THINK THE BEST ESTIMATES ARE PROBABLY THAT'S
SOMEWHERE AROUND 25% OF THE VARIANTS IN OUTCOMES FROM TBI
AND THAT MAY BE AN UNDERESTIMATE IS IS GOING TO BE DUE TO TO HOST
DIFFERENCES IN IN GENETIC VARIANTS.
SO RUCHI JHA WHO'S NOT IN THIS CALL BUT I THINK THIS IS AN AREA
WHERE SOME EXPERTISE WITHIN WITHIN THIS GROUP ACTUALLY COULD
COULD GO A LONG WAY TOWARDS MAKING SOME SOME REAL ADVANCES.
AND SO EVERY AREA OF HUMAN MEDICINE ALMOST ALL AREAS OF
HUMAN MEDICINE DID LARGE GUI STUDIES OVER A DECADE AGO AND
THEN THEY HAVE HAD SOME SOME VARIABLE IMPACT CERTAINLY IN THE
DEMENTIA WORLD AND AND OTHER OTHER FIELDS AS WELL.
WE'RE WE'RE PROBABLY THE TBI FIELD IS PROBABLY A LAGGING AREA
LAGGING DISEASE IN IN HAVING G US HAVE AN IMPACT.
WE DID DO AG US OR ABOUT 6000 SUBJECTS WHICH WE ALL RECOGNIZE
AS SMALL BUT I I DO WANT TO REACH OUT TO EVERYONE IN THIS
ROOM AND EVERYONE ON THE CALL.
YOU KNOW WE ALL HAVE OUR SMALL LITTLE COHORTS OF A COUPLE OF
100 PATIENTS EVEN MAYBE UP 1000 OR MORE.
I I I DO THINK THAT THE HISTORY OF GENETIC ASSOCIATION STUDIES
IS THAT IT TAKES MANY, MANY GROUPS OFTEN THESE PAPERS HAVE
100 AUTHORS OR MORE THAT IT TAKES MANY GROUPS CONTRIBUTING
THEIR DATA SHARING THEIR DATA COOLING ANALYTICAL RESOURCES AND
THAT IS WHERE THE ULTIMATE THE REAL ADVANCES COME FROM RIGHT.
OBVIOUSLY TAKE SOME FUNDING BUT IT'S MUCH LESS THAN IT USED TO
THE THE COSTS OF THESE ANALYTICAL STRATEGIES ARE ARE
MUCH LOWER THAN THAN THEY USED TO AND I THINK IT'S SOMETHING
THAT WE JUST HAVE TO DO AND AND AND PIERRE I THINK IT'S A
PERFECT FORUM IN WHICH TO DO IT.
DAVID, I KNOW YOU'VE BEEN VERY PASSIONATE WITH THIS FOR MANY,
MANY YEARS.
IN FACT, WHEN I FIRST MET DAVID, AND THIS IS ALMOST TWO DECADES
AGO, THAT WAS OUR FIRST TOPIC OF DISCUSSION.
AND BOTH OF US RECALLED HOW WHEN WE TOLD OUR COLLEAGUES THAT WE
WERE INTERESTED IN GENETICS OF TBI, WE WERE TOLD YOU'RE
ABSOLUTELY CRAZY.
TBI HAS NOTHING TO DO WITH GENETICS.
SO THIS IS SUCH A BIG ELEPHANT THAT I THINK WE HAVE TO EAT IT
IN VERY SMALL BITES.
AS AS RAMON SAID, WE'RE GOING TO NEED 10S OF THOUSANDS OF
PATIENTS TO REALLY HAVE ROBUST CONCLUSIONS BECAUSE THE EFFECT
SIZES ARE GOING TO BE GENERALLY SMALL, BUT THEY'RE GOING TO TELL
US QUITE A LOT ABOUT WHAT THE UNDERLYING BIOLOGY IS.
THERE WILL OCCASIONALLY BE PATIENTS WHO TELL US A LOT
BECAUSE OF OF A SINGLE MUTATION.
BUT THE THE ASK THAT WE'VE DONE FOR MOST UK STUDIES AND WE HAVE
A BIG COLLABORATIVE PLATFORM NOW IN THE UK CALLED TBR REPORTER ON
WHICH MY GOOD FRIEND HERE WILLIE STEWART AND PETE HUTCHISON WHO
IS IN THE BACK ARE ALSO ALONG WITH DAVE SHARP AND FIONA LECKY
EXECUTIVE COMPANY MEMBERS AND AND THE CONTACT PI AND THE
FORMULA THERE IS THAT WHATEVER STUDY YOU DO WE'RE GOING TO GET
THE THE CLINICAL CHARACTERIZATION AND OUTCOME FOR
FREE.
ALL WE WANT YOU TO DO IS TO STORE ONE EDTA SAMPLE SOMEWHERE
AND ONCE WE'VE GOT UP TO 20,000 OR 30,000 SAMPLES, WE'LL RUN
AGVAS ON IT OR EXOME SEQUENCING OR HOLD GENOME SEQUENCING.
IT'LL DEPEND ON MONEY THEN AND WE WILL HAVE THE PHENOTYPE AND
THE OUTCOME AND WE'LL BE ABLE TO DO REALLY, REALLY GOOD SCIENCE.
SO WHAT I WOULD ENCOURAGE IS ANYONE DOING A CLINICAL STUDY,
FIND A WAY TO BANK 5 MILS VDTA BLOOD.
IT'S TRIVIAL TO BANK AND KEEP AND WHEN ONCE YOU HAVE 20,000
SAMPLES, IT'S RELATIVELY EASY TO GET THE MONEY TO DO THE
GENOTYPING RELATIVELY I SAY.
SO YOU KNOW WE MAY NOT BE THAT FAR FROM 20,000 SAMPLES NOW.
I MEAN OBVIOUSLY WE'VE TALKED TO, YOU KNOW TALKED TO JAMIE
HUTCHISON THIS MORNING AND TALKED TO VALI TENUVU.
YOU KNOW, YOU KNOW PEOPLE HAVE A COUPLE OF 100 HERE, 500 THERE
AND IT KIND OF ADDS UP.
AND I THINK ONE OF THE THINGS THAT WE NEED TO DO, AND I THINK
THIS WORKING GROUP IS, IS THE PERFECT GROUP TO DO IT IS SORT
OF HAVE A CLEARING HOUSE AND YOU KNOW WHAT, WHAT, WHAT SAMPLES
ARE OUT THERE SITTING IN PEOPLE'S FREEZERS, WHAT IS THE
DATA THAT IS LINKED WITH IT?
OBVIOUSLY, IT'S GOING TO BE VARIABLE AMOUNTS OF DATA.
THERE'S GOING TO BE A CERTAIN AMOUNT OF MISSING THIS THAT'S
INEVITABLE.
BUT I I SUSPECT WE'RE NOT THAT FAR AND SO SO THAT'S THAT'S
SOMETHING THAT WE CLEARLY HAVE TO DO AND AND PERHAPS IF THERE'S
SOME OF THE THE MORE JUNIOR PEOPLE IN THIS ROOM WILL WANT TO
RAISE THEIR HAND AND WANT TO TAKE ON A A LEADERSHIP ROLE IN
THIS IS TO BE FANTASTIC YOU YOU WILL CERTAINLY GET A LOT OF
SUPPORT A LOT OF HELP BUT IT'S IT'S ALWAYS GOOD IF SOMEONE
DECIDES TO TAKE THE POINT ON THIS.
THE OTHER, THE OTHER ISSUE AND I'VE LEARNED MORE AND MORE ABOUT
THIS OVER THE LAST SEVERAL YEARS IS IS THIS ISSUE OF POLYGENIC
RISK SCORES, RIGHT.
SO ALTHOUGH FOR COMMON ALLELES, WHICH IS WHAT WE'RE GETTING IN
AG WAS CHIP, IT'S IT'S ALMOST ALL COMMON ALLELES EVEN IF
THEY'RE HIGHLY, SIGNIFICANTLY ASSOCIATED WITH A VERY, VERY LOW
P VALUE WITH A PARTICULAR DISEASE OUTCOME.
THE EFFECT SIZE OF THESE COMMON ALLELES ON THE ON THE DISEASE
PATHOLOGY AND THE DISEASE MANIFESTATION IS USUALLY TINY,
WELL BELOW THE LEVEL WILL BE CLINICALLY ACTIONABLE.
ON THE OTHER HAND IT IS BECOMING MORE APPARENT THAT IF YOU LOOK
AT HUNDREDS OR EVEN THOUSANDS OF THESE COMMON ALLELES AND LOOK AT
THE INHERITANCE ALONG THESE HUNDREDS OF THOUSANDS OF ALLELES
THAT YOU ACTUALLY CAN GET EFFECT SIZES THAT ARE SIGNIFICANT.
SO THIS IS LIKE THAT ARE BORROWED FROM COLIN ELLIS WHO'S
AT PENN WHO IS INTERESTED IN GENETICS OF EPILEPSY.
BUT THIS IS A STUDY FROM THE UK BRAIN BANK THAT IS LOOKING AT AT
POLYGENIC RISK COURSE AND MULTIPLE SCLEROSIS AND AND THE
POINT AND THIS IS THE RELEVANT, THIS IS THE RELEVANT SLIDE HERE
IF YOU GUYS CAN SEE IT AND PARTICULARLY THIS ONE, YOU KNOW
THAT THAT THAT ONCE YOU GET TO THE UPPER DECILE OF THE OF THE
POLYGENIC RISK CORPS YOU ACTUALLY ARE ABLE TO ACCOUNT FOR
SIGNIFICANT ODDS RATIOS FOR THE MANIFESTATION OF THAT DISEASE.
YOU KNOW ODDS RATIOS TO THREE TO FIVE OR IN SOME CASES EVEN EVEN
FURTHER.
NOW THERE ARE IN ORDER TO GET APOLOGENIC RISK AURA THAT IS
RELIABLE, YOU OBVIOUSLY NEED A VERY ROBUST GY STUDY THAT HAS
BEEN DONE.
BUT THESE NOW EXIST FOR MOST COMMON DISEASES, CERTAINLY ONES
FOR ALZHEIMER'S DISEASE, FRONTOTEMPORAL DEMENTIA,
PARKINSON'S DISEASE, STROKE, MULTIPLE SCLEROSIS, CERTAINLY
CARDIOVASCULAR DISEASE.
AND GIVEN THAT WE ALREADY HAVE G WAS DATA ON ALMOST 6000 TBI
PATIENTS.
THIS IS, THIS IS SOMETHING THAT IS A A VERY TRACTABLE STUDY.
AND YOU KNOW THAT AGAIN IT'D BE TERRIFIC IF SOMEONE IN THIS ROOM
WHO HAD THE EXPERTISE OR THE BACKGROUND OR OR IN FACT I HAD
MAYBE A LITTLE BIT OF EXPERTISE IN BACKGROUND AND WANTED TO TAKE
THAT ON AND WANTED TO TRAIN THIS.
THIS WOULD BE A VERY COOL STUDY TO DO WHICH THIS NETWORK WOULD
BE OR OR THIS GROUP WOULD BE VERY PERHAPS A VERY GOOD
PLATFORM TO TO TO GET AT THAT DATA.
SO AGAIN IT'S JUST ONE OF ONE OF THE THINGS THAT THAT MY SENSE IS
THAT WE'RE PARTICULARLY IN A GOOD POSITION TO TRY AND PROMOTE
THAT KIND OF STUDY WHICH WHICH CERTAINLY HAS THE POTENTIAL TO
OPEN UP PREVIOUSLY UNEXPECTED AVENUES OR PREVIOUSLY UNEXPECTED
PATHOLOGIES IN IN IN HUMAN TBI AND CAME AND AND REALLY WHAT
WHAT YOU NEED ARE THE GS SUMMARY STATISTICS WE SORT OF HAVE YOU
KNOW THESE THESE EXIST FOR MANY DISEASES OBVIOUSLY SNIP ARRAY
DATA FROM WE ALREADY HAVE WE NEED ANCESTRY MATCH CONTROLS OF
COURSE AND THIS WOULD BE VERY WORTHWHILE DOING.
I THINK WE ALSO TALKED ABOUT THIS IS ANOTHER OPPORTUNITY AND
THIS IS THE THERE ARE THERE ARE A NUMBER OF OF PROSPECTIVE GOOD
POINT.
SO WE HAVE 10 MINUTES, WE STARTED A LITTLE LATE I WE I CAN
WIND UP IN 10 MINUTES EASILY THIS THIS HAS BEEN A TERRIFIC
DISCUSSION.
I CERTAINLY DIDN'T WANT TO LIMIT THE DISCUSSION HERE BUT AGAIN
JUST JUST AN AREA WHERE THIS IS DATA THAT EXISTS AND
COLLABORATIONS WITHIN OUR GROUP CAN BE PROMOTED THERE.
THERE ARE A NUMBER OF STUDIES, LARGE POPULATION BASED
PROSPECTIVE STUDIES THAT HAVE BEEN GOING ON FOR DECADES AND
THAT'S TRUE FOR THE FRAMINGHAM HEART STUDY.
IT'S TRUE FOR THE ATHEROSCLEROSIS WRITTEN
COMMUNITY STUDIES.
THERE ARE ACTUALLY SEVERAL OTHERS THAT BY THE WAY THEY'VE
ALREADY DONE GYS.
THEY HAVE ALREADY DONE IN SOME CASES PRETTY DENSE BIOMARKER
TESTS.
BUT THE TBI RELATED PHENOTYPING IS VERY MUCH IN ITS INFANCY AND
THERE ARE PEOPLE IN THIS ROOM OR PEOPLE IN OUR GROUP WHO ARE
AMONG THE LEADERS IN ASSESSING THE TBI RELATED PHENOTYPING
THERE.
SO, SO THIS THIS IS AGAIN SOMETHING WHERE THE THE THE
PROPER EXPERTISE AND THE PROPER BACKGROUND CAN ESTABLISH THE
PROPER COLLABORATIONS AND YOU KNOW IT'S IT'S IT'S BASICALLY
LOOKING AT RESULTS WHERE WHERE YOU KNOW CREATIVITY SHOULD NOT
BE THE LIMITING FACTOR IN IN THE QUESTIONS THAT WE WANT TO ANSWER
AND MAKE MAKE SOME PROGRESS IN THE FIELD.
I FINALLY THIS, THIS IS THE LAST SLIDE THAT I WANTED TO SHOW.
THIS IS AGAIN ANOTHER TOPIC THAT THAT WE DISCUSSED AND THIS IS
SOMETHING ELSE THAT IT'S NOT TOTALLY NEW, BUT IT HAS
CERTAINLY GOTTEN ATTENTION RECENTLY, RIGHT, THE ABILITY TO
DO VERY HIGHLY MULTIPLEXED PROTEOMIC PLATFORMS.
AND THIS INITIALLY STARTED AT MASS SPECTROMETRY.
BUT THERE ARE NOW OTHER TOOLS EITHER WITH IMMUNOASSAYS OR EVEN
PROXIMITY EXTENSION ASSAYS WHICH ARE STILL BASICALLY AN IMMUNO
ASSAY WITH A NOVEL WAY OF DETECTING IT OR APTAMER BASED
ASSAYS SUCH AS THE SOMA SCAN.
AND I THINK WE INTRODUCED THIS TO MANY OF OUR GROUP.
SOME OF THESE ARRAYS ALREADY EXIST FOR SOMETHING LIKE ERIC OR
OR FRAMINGHAM.
OBVIOUSLY THE THE TBI RELATED PHENOTYPING THERE IS SOMETHING
THAT WOULD BE THAT WOULD BE NOVEL AND AND WORTHWHILE.
I I KNOW THERE'S THERE'S SOME, I KNOW CHERYL YOU'VE HAVE LOOKED
INTO THE SOMA SCAN AND AND TRYING TO SET THAT UP AT UBC OR
PERHAPS IN YOUR LAB.
OTHERS HAVE WELL OVER HAD THIS DISCUSSION.
YOU WANT TO MAKE SOME COMMENTS, YEAH WE ARE LOOKING AT MOST OF
THESE PLATFORMS.
I THINK OUR MOST ADVANCED DISCUSSIONS ARE WITH ALOMAR
USING THE NEW LIZA.
SO REALLY INVITE ANYBODY THAT WANTS TO COLLABORATE WITH SOME
OF THOSE THOSE STUDIES THAT ARE JUST BEING PLANNED.
EXCELLENT.
OK.
NEIL, JUST TO COMMENT ON, ON THE PLATFORMS AND WE'VE HAD SOME
LIMITED EXPERIENCE WITH THE SOMA SCAN IN PATIENTS WHO'VE ALSO GOT
KIND OF QUANTRIX ASCERTAINMENT OF SOME OF THE BIOMARKERS THAT
WE WE'RE MORE EXPERIENCED WITH.
AND WE WE'VE NOT SEEN ALWAYS A GREAT CORRELATION BETWEEN THE
TWO.
AND I THINK THERE IS SOME WORK ON KIND OF QUANTITATIVE TRAIT
LOCI WHICH MIGHT GIVE YOU AN INDICATION FOR THE FOR THE SOMA
PLATFORM WHICH MARKERS ARE MORE RELIABLE THAN OTHERS.
THAT'S LARGELY BEEN THE EXPERIENCE OF A LOT OF PEOPLE
AND SOMOS CAN IS THOUGHT TO BE OK AS A HYPOTHESIS GENERATING
RATHER THAN A TRUE DEFINITIVE ISSUE.
BUT NONETHELESS THIS IS, THESE ARE QUESTIONS THAT ARE OUT THERE
AND HAVE BEEN LOOKED AT.
OK, THERE'S A QUESTION IN THE CHAT.
OK, THIS IS FROM BRENT WINSTON.
WELL, I AM BIASED.
I BELIEVE THERE WILL BE IMPORTANT INFORMATION THAT COMES
FROM MULTIOMICS, ESPECIALLY METABOLOMICS AND LIPIDOMICS.
IT WOULD BE NICE TO SEE A FOCUS GROUP ON THIS.
AND I THINK THIS IS ACTUALLY AN EXCELLENT POINT.
THIS IS NOT SOMETHING THAT THE FIELD HAS, HAS PUT MUCH EFFORT
ON, BUT I THINK THERE IS A LOT OF VERY EXCITING PROGRESS IN
BOTH LIPIDOMICS AND METABOLOMICS IN IN OTHER AREAS OF MEDICINE
AND THIS IS VERY RIPE FOR TBI AND I I KNOW THERE ARE SEVERAL
FOLKS IN THIS ROOM WHO ARE VERY INTERESTED ALONG THESE LINES.
I WONDER IF ANYONE WANTS TO COMMENT ON ANY WORK THAT THEY
ARE DOING ALONG THOSE LINES OR ANY PARTICULAR TOOLS THAT ARE
PLANNING ON USING BECAUSE I I MEAN I I COMPLETELY AGREE.
I THINK THERE ARE MANY MOLECULES BEYOND PROTEINS THAT ARE GOING
TO HAVE IMPORTANT EFFECTS IN BIOLOGY THAT ARE THAT ARE WORTH
LOOKING AT.
AND IN FACT THE OTHER THE OTHER ISSUE THAT WE HAVEN'T REALLY
EVEN TALKED ABOUT MUCH IS THE POST TRANSLATIONAL MODIFICATION
OF PROTEINS, RIGHT.
SO ALMOST ALL PROTEINS THAT ARE PRESENT IN IN, IN THE BODY AND
CERTAINLY THOSE THAT ARE PRESENT IN THE BLOOD ARE ARE POST
TRANSLATIONALLY MODIFIED PHOSPHORYLATIONS, ACETYLATIONS,
GLYCATIONS AND THEN THEY OFTEN HAVE VERY POWERFUL EFFECTS IN
BIOLOGY AND IT'S SOMETHING WE'VE ONLY STARTED TO TO LOOK AT.
SO JUST BUILDING ON WHERE CAN WE GO FROM HERE 11 AREA THAT IS I
THINK ENTIRELY UNEXPLORED IN THE FIELD OF TBI ARE CIRCULATING
STEM CELLS LIKE ENDOTHELIAL STEM CELLS WHICH WOULD BE REALLY
INTERESTING TO PROBE FOR CAN BE DONE USING FAX ANALYSIS.
BUT IT IT COULD BE THAT THIS MIGHT BE PART OF THE PROGNOSTIC
ABILITY TO HEAL.
YEAH.
AND BY THE WAY, I MEAN THIS IS NOT SOMETHING THAT WE HAVE
ROUTINELY BEEN COLLECTING.
WE USUALLY COLLECT SERUM AND PLASMA AND OCCASIONALLY WHOLE
BLOOD.
BUT COLLECTING CIRCULATING CELLS IS IS SOMETHING THAT'S NOT
ROUTINELY DONE.
I KNOW SOME GROUPS HAVE STARTED DOING THAT.
I'VE CERTAINLY THOUGHT ABOUT IT, HAVEN'T QUITE MADE THE MADE THE
LEAP YET BUT IT CERTAINLY HAS A LOT OF VALUE.
YES.
I JUST WANTED TO MENTION ONE OTHER MODALITY OR OR ANALYTE
THAT WE COULD LOOK INTO.
MY NAME IS NICOLE BJORKLUND.
I'M, I'M NEW HERE FROM FROM CVB, BUT I KNOW INITIALLY THERE WAS A
LOT OF PROMISE IN AUTO ANTIBODIES.
I'M LOOKING AT VERY SPECIFIC AUTO ANTIBODIES THAT THAT DOCTOR
WANG HAD DONE AND I THINK IN SOME OF THE PRECLINICAL WORK
THERE WAS SOME SOME VERY PROMISING RESULTS.
SO I THINK THAT'S AN AREA WHERE YOU COULD HAVE THE NEW
TECHNOLOGIES HAVE WIDE PLATFORMS OR YOU CAN LOOK AT MANY
DIFFERENT AUTO ANTIBODIES AND I THINK THOSE COULD BE USEFUL FOR
LOOKING AT REPETITIVE INJURY AND PERHAPS RETROSPECTIVE.
YEAH, EXCELLENT POINT.
KEVIN IS UP AND I KNOW KEVIN YOU HAD SOME PUBLICATION THIS, BUT
JAMIE, YOU WANT TO MAKE A COMMENT FIRST?
YEAH, I JUST WANTED TO BUILD A LITTLE BIT ON WHAT BRENT BRENT'S
COMMENT AND THEN KIND OF PROMOTE.
HE HAD HIS LAB HAD BEEN LOOKING AT METABOLOMICS WITH THREE
DIFFERENT METHODOLOGIES AND THE PAPERS JUST PUBLISHED IN
CRITICAL CARE USING SAMPLES FROM OUR CANADIAN BIOBANK AND
DATABASE.
AND SO THE BRAIN IS OVER 50% FAT.
WE ALL HAVE FAT FOR FAT BRAINS.
AND SO INTERESTINGLY WHAT HE DID FIND IS THAT THE HE WAS LOOKING
AT THE HYPOTHESIS WAS THAT THERE WOULD BE METABOLITE PROFILES
THAT ARE PREDICTIVE OF GOSE AT SIX AND 12 MONTHS.
AND HE FOUND THAT IT WAS IT DEFINITELY THE HYPOTHESIS WAS
TRUE.
THERE WAS A PATTERNS THAT MOST OF THE PROGNOSTIC METABOLITES
WERE LIPIDS AND THAT THE THERE WAS DAY ONE AND DAY THREE
SAMPLES AND THAT THERE WAS BETTER PROGNOSIS WHEN YOU WENT
ABOUT LONGER AND INCLUDED THOSE DAY THREE SAMPLES.
SO THE LIPIDS APPEARED TO BE EXCELLENT AND YOU CAN READ AND I
THINK THE THE PREDICTIVE VALUE IS VERY HIGH.
IT'S A SMALL SAMPLE SIZE, BUT I JUST WANTED TO PROMOTE THAT.
SO MAYBE FAT IS THE WAY TO GO.
YEAH, I THINK THAT'S IMPORTANT.
SO KEVIN AND THEN DAVID WILL BE THE LAST.
YEAH, THE THE AUTO ANTIBODIES AND SORT OF AN ENIGMA IN THE
SENSE THAT IT'S NOT EVERYONE, IT'S ABOUT YOU KNOW IF YOU COUNT
ALL THE SUBJECT FOR ALL THE ANTIGEN MAYBE AROUND 20% THE
TITLE ARE VERY DIFFERENT FROM PATIENT TO PATIENT.
SO TO REALLY YOU KNOW IN THE IMMUNE, AUTOIMMUNE DISEASE YOU
ACTUALLY HAVE TO DO A TITLE YOU KNOW TO FIND OUT.
AND SO THAT'S VERY TOUGH AND WE HAVE SORT OF ELISA ESSAY, WE
PUBLISH SOME PAPER ON IT.
AND THEN THE OTHER THING IS THERE ARE SO MANY DIFFERENT
ANTIGENS.
SO THEY'RE ALL CREATED EQUAL.
WE KIND OF THINK THAT THE MOTOR ANTIGEN TO CELL SERVICE
RECEPTOR, THEY MIGHT BE THE BAD GUYS, WE HAVE SOME EVIDENCE SOME
ONES IN HYPOTHALAMUS OR THE ANTIBODIES SEEMS TO GO WITH A
BETTER OUTCOME WITH HAVING LOW HYPOGONADISM.
SO, SO IT'S NOT ALWAYS BAD AS WELL AS A COMPLEX STORY.
AND THEN AGAIN IT MAY BE THAT WAY INTO THE CYTOKINE RESPONSES.
SO THE STORY IS NOT COMPLETELY DONE YET, BUT THAT'S A VERY
INTERESTING ANGLE AS WELL.
OK, SO WHAT IS SAYING?
SO, SO WE'VE PUBLISHED A BIT ON AUTO ANTIBODIES OF TRAUMATIC
BRAIN INJURY SHOWN THAT THERE'S AN INITIALLY A VERY BROAD AUTO
ANTIBODY RESPONSE IGN.
IT LOOKS LIKE A VACCINE RESPONSE WITH MATURATION TO IGG.
AND AS KEVIN SAYS THERE'S THERE'S QUITE A LOT OF VARIATION
THAT INNATE INNATE LIKE ADAPTIVE IMMUNE RESPONSE INITIALLY IS
DEFINITELY ASSOCIATED WITH BIRTH OUTCOMES.
SECOND THING TO SAY IS THAT MATTHEW ORASEK WHO WORKS WITH
ANDRAS BOOKIE IN IN SWEDEN HAS PUBLISHED FROM SANTA TBIA LARGE
STUDY OF BOTH METABOLOMICS AND LIPIDOMICS AND THERE'S ANOTHER
PAPER IN IN THE PIPELINE.
SO IF PEOPLE ARE INTERESTED THEY SHOULD GO LOOK AT THAT DATA IT'S
WAITING ON FOR WHAT ABOUT THOUSAND PATIENTS, TERRIFIC,
GREAT TO HEAR.
WELL LISTEN THIS HAS BEEN A VERY LIVELY DISCUSSION AND I I HOPE
NO ONE IS INTIMIDATED BY THE THE LOT OF WORK THAT WE HAVE AHEAD
OF US.
BUT IT'S ALSO A LOT OF OPPORTUNITY THAT WE HAD AHEAD OF
US.
AND AND FRANKLY IT'S JUST GOING TO TAKE A BIG TEAM WORKING
TOGETHER AND AND GROUPS IDENTIFYING THEIR COMMON
INTERESTS AND AND TAKING ADVANTAGE OF THE DATA THAT'S
AVAILABLE AND FRANKLY TAKING ADVANTAGE OF OF THE RESOURCES
THAT LIKELY WILL BECOME AVAILABLE IN THE FUTURE.
SO AND THANKS SO MUCH FOR FOR EVERYBODY'S TIME AND WE WILL
HAVE A SHORT BREAK AND THEN WE'LL RECONVENE IN FOR THE NEXT 1097 01:00:00,530 NEXT BREAKOUT GROUP.