STRAIGHTFORWARD AND PROBABLY THIS STATEMENT THAT WAS DONE
MANY YEARS AGO BY A STATISTICIAN AND TO ACCEPT IT WILL BE
RECORDED.
ALL MODELS ARE WRONG, BUT SOME ARE USEFUL.
PROBABLY TELLS US THAT THERE IS FOR SURE ROOM FOR IMPROVEMENT.
AND SO THE THE IDEA THAT WE WANTED TO DISCUSS ALL TOGETHER
IS WHETHER THERE IS A REASON TO REALLY FOCUS ON BIDIRECTIONAL
TRANSLATION AND ON ONE SIDE TO UNDERSTAND HOW WE CAN BETTER
CALIBRATE ANYONE MODELS.
AND THESE ARE TWO WORDS I JUST LEARNED AND I HOPE I KNEW THEM
PROPERLY.
SO HOW?
BY LOOKING AT A LOT OF PHYSIOLOGY IN PATIENTS AND
DISEASE TRAJECTORIES, WE CAN BETTER ADDRESS WHETHER OR NOT A
SPECIFIC MODEL IS RECAPITULATING THAT SPECIFIC PATTERN OF DISEASE
PROGRESSION AND REFINE THE MODEL ACCORDING TO THE HUMAN
PATHOLOGY.
AND ON THE OTHER SIDE, HAVING ACCESS TO BRAIN SPECIMENS AND
BIOFLUIDS FROM PATIENTS, WE CAN EVENTUALLY CORROBORATE FINDINGS
THAT ARE EMERGING FROM THE BASIC SCIENCE WORK.
SO IN THIS CIRCLE WE IDENTIFIED SOME ASPECTS WE WOULD LIKE TO
DISCUSS TOGETHER.
SO METRICS AND TOOLS AND PARAMETERS WE WOULD LIKE TO
IMPLEMENT IN ORDER TO ADOPT THIS FRAMEWORK AND THEY GO FROM BLOOD
BIOMARKERS TO NEURO IMAGING BIOMARKERS OF COURSE
NEUROLOGICAL OUTCOME AND MORE AND MORE NEUROPATHOLOGY ALSO
INTENDED AS BIOPSY FOR VARIED FINE MOLECULAR PHENOTYPING.
OF COURSE, IN THIS BIO MECHANICS PLAYS A MAJOR ROLE AND SO IN THE
HETEROGENEITY OF TBI.
CAN WE BETTER MODEL DIFFERENT BIO MECHANICS ALSO IN THE
PRECLINICAL SETTING AND PROBABLY OR FOR SURE RODENTS ARE NOT
ENOUGH TO REALLY MIMIC THE COMPLEXITY OF ALSO THE
STRUCTURAL BRAINS BRAIN STRUCTURE AND SO LARGER ANIMAL
WATERS COULD BE ESSENTIAL IN ORDER TO IN IN THE PROCESS OF
TRANSLATING FINDINGS FROM THE CLINICAL SETTING TO THE CLINICAL
SETTING.
SO WITH WITH THIS SLIDE, I THINK WE CAN ALREADY START A
DISCUSSION AND MAYBE DOUG YOU COULD START WITH THIS.
AND YEAH, SO I MEAN I WONDER WHAT PEOPLE THINK ABOUT THIS
FRAMEWORK.
SO THIS IS SOMETHING THAT EVERYBODY'S TALKED ABOUT I
THINK, BUT FEW PEOPLE DO THAT TRUE TRANSLATION PRECLINICAL TO
CLINICAL BY FIRST CALIBRATING WHAT ASPECTS OF THE MODELS ARE
CLINICALLY RELEVANT.
YOU KNOW, HAVE YOU GONE THROUGH THE MOTIONS?
HAVE YOU WORKED WITH SOMEBODY, HAVE YOU TALKED TO A PERSON IN
BIO MECHANICS?
AND JUST ON THE SIDE, WE'RE HOPING TO EXPAND THE BIO
MECHANICS REPRESENTATION HERE, WHICH IS ALMOST ZERO RIGHT NOW.
SO YOU KNOW THAT WE THINK THAT'S GOING TO BE A VERY IMPORTANT
ASPECT.
BUT THEN ON THE OTHER, ON THE FLIP SIDE, YOU HEARD WILLIE
TALKING ABOUT A LITTLE EARLIER THIS MORNING WHEN WE CAN TALK
ABOUT IT MORE LATER.
BUT YOU KNOW, HOW DO YOU CORROBORATE YOUR DATA?
I MEAN YOU KNOW YOUR, YOUR ROTOR MODEL MAY HAVE DIFFERENT
PHYSIOLOGY AND IT MIGHT HAVE DIFFERENT OUTCOMES.
SO HOW DO YOU FIND OUT IF THAT'S GOING TO BE CLINICALLY RELEVANT
AND NOT JUST A MODEL SPECIFIC EVENT?
SO THE IDEA, THE FRAMEWORK IS CAN YOU FIRST, YOU KNOW,
IDENTIFY OR VALIDATE THE CLINICAL RELEVANCE OF YOUR MODEL
AND THEN WHEN YOU GET DETAILS THAT YOU CAN'T POSSIBLY DO IN
CLINIC CLINICAL CIRCUMSTANCES, THEN HOW DO YOU CORROBORATE
THAT.
SO YOU KNOW, WE'RE HAPPY TO, YOU KNOW, HEAR EVERYBODY'S OPINION
ON THAT AND YOU KNOW MAYBE ANY IDEAS OF HOW WE COULD MAKE THIS
HAPPEN MAYBE.
CHERYL, DO YOU HAVE SOME IDEAS?
LET ME GIVE YOU PUT ME ON THE SPOT HERE DOUG.
SO WELL IN TERMS OF SO LET ME START OFF WITH BLOOD BIOMARKERS.
WE'VE SPENT A LOT OF TIME TALKING ABOUT BLOOD BIOMARKERS
AND SOME OF THE ASSAYS THAT HAVE BEEN DEVELOPED FOR HUMANS
ACTUALLY DO WORK IN MOST MODELS, BUT OTHER ONES DO NOT.
SO I DO THINK THAT THERE IS AN OPPORTUNITY FOR US TO MAKE SURE
THAT WE HAVE AT LEAST A PANEL OF OF BIOMARKERS THAT ARE SUITABLE
FOR WORK IN MODEL SYSTEMS.
I THINK UNDERSTANDING THE TEMPORAL AND AND TRAJECTORIES OF
OF BIOMARKER CHANGES WOULD BE A WONDERFUL COMPANION TO THE
CLINICAL STUDIES THAT COULD HELP WITH THAT CALIBRATION.
CERTAINLY NEUROPATHOLOGY, I WOULD CERTAINLY AGREE THAT THIS
IS AN EXCEPTIONALLY IMPORTANT PART OF WHAT WE CAN WHAT WE CAN
DO AND SHOULD BE DOING.
AND THEN I ALSO THINK THAT THERE IS A GREAT WITH WITH THE ADVENT
OF TECHNOLOGIES LIKE SINGLE CELL RNA SEQUENCING AND 3D SPATIAL
METHODS TO BE ABLE TO IN AN UNBIASED WAY KIND OF INTERROGATE
WHAT HAPPENS IN THE INJURED BRAIN FROM A MODEL SYSTEM THAT
HAS THE OPPORTUNITY TO GIVE US A VERY, VERY RICH DATA SET OF
POTENTIAL PATHWAYS, HUBS OF ACTIVITY OR PATHWAYS THAT ARE
AFFECTED BY IN IN VARIOUS MODELS OF TBI.
HOW DO THESE COMPARE WITH CCI, FLUID, PERCUSSION, WEIGHT, DROP
BLAST, ETCETERA.
I THINK THERE'S A LOT OF OF OPPORTUNITY THERE.
WHERE WE STILL NEED, I THINK A LOT OF WORK IS HOW DO WE WORK
WITH THE CLINICAL TEAMS, CAN WE GET SURGICAL RESECTIONS OF OF
HUMAN TISSUE THAT DOESN'T DON'T REQUIRE LONG PERIODS FOR PEOPLE
TO COME TO POSTMORTEM.
WILLIE TALKED ABOUT THIS AS WELL.
FOR ME, THESE ARE THE LOW HANGING FRUIT OF, OF TRYING TO
GET TO MECHANISMS AND BE ABLE TO TEST HYPOTHESES FUNCTIONALLY IN
ANIMAL MODELS, VALIDATING A TARGET AND A PATHWAY TO GO TO
INTERVENTION STUDIES.
THAT'S JUST MY 2 NOTES, YEAH.
AND SO THE, THE IDEA OF THE NEXT SLIDES WERE TO GIVE A FEW
EXAMPLES OF STUDIES TRYING TO COMPARE OR COMBINE PRECLINICAL
AND CLINICAL APPROACHES IN ORDER TO WORK TOWARDS CALIBRATION.
AND THIS IS AN EXAMPLE FROM A STUDY BY VIRGINIA NEWCOMB
SHOWING CLEARLY THAT IN ABOUT 30% OF PATIENTS THERE IS
PROGRESSIVE NEURODEGENERATION THAT CAN BE TACKLED BY MRIDTI
AND THE NUMBER OF TRACKS.
THE DECREASE OVER TIME AND THIS IS LINKED TO FUNCTIONAL
IMPAIRMENT AND WHAT WAS FOUND ALSO IN PRECLINICAL MODELS AND
PARTICULARLY IN THE CONTROL CORTICAL IMPACT TBI MODEL THAT
WAS ORIGINALLY DESCRIBED RATHER AS A VERY FOCAL INJURY WITH
LIMITED DAMAGE BESIDES THE CONTUSIONAL HEMISPHERE.
THE THE CASE IS THAT IF YOU WAIT LONG ENOUGH FOR YOU SEE THAT THE
PATHOLOGY IS PROGRESSING AND THERE IS ALSO A CLEAR DAMAGE IN
SUBCORTICAL AREAS.
AND THIS ALSO INVOLVED CLEARLY WHITE MATTER CHANGES THAT CAN BE
ADDRESSED SIMILAR TO WHAT HAS BEEN DONE IN PATIENTS BY MRI
APPROACHES.
AND WHAT WE OBSERVED IS THAT BY 12 MONTHS THERE IS A DECREASE IN
THE THICKNESS OF THE CORPUS CALLOSUM ALSO IN THE
CONTRALATERAL SIDE.
AND THIS IS ASSOCIATED TO COGNITIVE AND SENSORY MOTOR
FUNCTION.
SO TELLING US THAT POSSIBLY IF YOU ARE WANTING IT, IF IF YOU'RE
AIMING TO TACKLE WHITE MATTER CHANGES EVEN THOUGH THE
PROPORTION OF GREY AND WHITE MATTER IN RODENTS IS OPPOSITE
COMPARED TO HUMAN.
SO IT CAN BE ARGUED THAT IT'S NOT THE IDEAL SETTING IN ORDER
TO DO THIS, BUT AT LEAST IN IN TERMS OF DISEASE PROGRESSION
THAT IS QUITE PARALLEL PROCESS TAKING PART.
AND AND THIS IS ANOTHER EXAMPLES IN THE SETTING OF I MEAN LOOKING
AT PATHOLOGY, IT WAS A VERY PIONEER STUDIES BACK IN 95 BY
DOUG SMITH.
AND WHAT THEY SHOWED WAS IN FACT THAT AGAIN THERE WAS A
PROGRESSIVE ATROPHY AND THIS IS CONSISTENT WITH WHAT OBSERVED IN
PATIENTS MANY YEARS AFTER THE INJURY AND IS UNDERPINNED MOST
LIKELY BY ONGOING NEW INFLAMMATION.
SO THERE IS HERE AN OPPORTUNITY TO GO BACK AGAIN TO THE MODELS
AND SEE WHAT IS AND WHICH IS THE MAIN ROLE OF THE PERSISTENT
INFLAMMATORY INFLAMMATION IN CONTRIBUTING TO INJURY
EVOLUTION.
SO WITH THIS, I I THINK WE SHOULD, WE COULD START
DISCUSSING ABOUT THE NEED TO SHARE DATA AND HAVE ACCESS TO
BRAIN BIOSPECIMENS FOR NEUROPATHOLOGICAL ASSESSMENT AND
FOR DEEPER PHENOTYPING.
AND SO MAYBE REALLY YOU CAN COMMENT ON THIS.
THANK YOU.
LET'S JUST BEFORE WE DO THIS, LET ME JUST FIRST OF ALL ASK FOR
A SHOW OF HANDS OF PEOPLE WHO'VE RESEARCHED OR OR CONDUCTED
RESEARCH IN ANIMAL MODELS OF TBI IN SOME WAY.
OK, NOW KEEP YOUR YOU CAN PUT YOUR HAND UP HIGH.
SORRY, I'M NOT GOING TO PICK AN ENDER YET.
NOW KEEP YOUR HAND UP.
IF YOU'VE ALSO WORKED IN HUMAN TISSUE FOR STUDYING TBI, YOU'D
HAVE TO PUT TWO HANDS UP.
JUST KEEP YOUR HAND DOWN.
OK.
SO THAT'S THAT'S GOOD.
THAT'S GOOD.
FOR THOSE WHO PUT THEIR HAND DOWN AFTER ASHLEY WHO'D WORKED
FOR HUMAN TISSUE.
WHAT WHAT'S WHAT WAS THE BARRIER TO ACTUALLY WORKING WITH HUMAN
TISSUE?
WHY WHY DID WHY DID MY NOT PURSUED STUDIES IN HUMAN TISSUE?
WHY HE WAS STUCK WITH JUST THE ANIMAL MODEL.
YEAH THERE THERE ARE SEVERAL AREAS.
SO AT LEAST GETTING EITHER, YEAH, SO I THINK THERE ARE LACK
OF REALLY ACCESSIBLE REPOSITORIES FOR HUMAN TISSUE
SOMETIMES BARRIERS AND SO OF COURSE, SO WE NEED TO KIND OF
GET AROUND THERE.
HOW CAN WE WORK WITH THOSE ORGANIZATIONS SO THAT THEY CAN
DO THEIR WORK BUT WE CAN STILL GET THE SPECIMENS WE NEED.
YEAH PARDON.
I WORK IN NEUROEMERGING AND TRYING TO RELAY THE
NEUROEMERGING HAS BEEN SO PRE TRANSLATION OF THE CHEMICAL AND
THEY WERE AT LEAST.
I GO NOW TO THE STUDIES.
YEAH.
THESE THESE.
SORRY STUART.
ARE YOU GOING TO SAY SOMETHING?
NO.
YOU COULD YOU COULD.
YEAH.
I'M A I'M A REFORMED RESEARCHER.
I'M NOW JUST A BUREAUCRAT.
IT'S TOO OFTEN FROM THE VA.
YOU KNOW ONE THING IT'S ALWAYS TROUBLED ME WITH GOING FROM THE
ANIMAL TISSUE TO THE HUMAN TISSUE IS THAT BEING.
I KNOW THIS DOESN'T INCLUDE YOU WILLIE.
YOU HAVE MUCH BETTER METHODS BUT BUT YOU KNOW IN THE LAB WE IT
WAS, WE DID THEM IN SQUADS.
IT WAS NICE AND PRECISE.
FIXED THEM IT WAS YOU KNOW EVERYTHING WAS DONE BY A
PROTOCOL.
VERY PRECISE.
WELL HOW LONG DOES THE THE BRAIN STAY IN THE IN THE DECEASED
PERSON'S BODY.
HOW LONG DOES THIS MAYBE GO INTO A BUCKET OF FORMALIN THAT MAY OR
MAY NOT BE AT ROOM TEMPERATURE OR OR A COLD ROOM.
AND THEN HOW LONG IS IT PROCESSED SO IT'S FINALLY IN ITS
FINAL STATE THAT YOU DO YOUR ANALYSIS ON.
SO THERE IS A WHOLE RANGE FROM THE BEST PROBABLY YOUR LAB
REALLY BUT THEN THERE'S OTHER PLACES OR YOUR LOCAL CORONER'S
OFFICE WHERE IT'S MAY NOT BE SO EXACT.
SO HOW CAN YOU DO SCIENCE ON THAT THE THE THE THESE ARE THESE
ARE FANTASTIC POINTS AND AND ALL OF THESE POINTS WHERE WHEN WE
SAT DOWN SOME YEARS AGO AND TRIED TO FIGURE OUT WHAT WHAT
HOW ARE THE WHAT ARE THE SOLUTIONS.
HOW DO WE BRING THE RESOURCES WE HAVE THE THE HUMAN TISSUE
ARCHIVES THE AVAILABILITY FOR RESEARCH TO THE WIDER RESEARCH
COMMUNITY AND ADDRESS SOME OF THESE CHALLENGES AND AND OUR
FIRST RUN AT THIS WAS WAS THIS CONNECT TVI RESOURCE WHERE DOUG
AND I AND OTHERS SET UP A NETWORK A COLLABORATION OF
COLLEAGUES WE KNEW HAD BRAIN TISSUE FOR RESEARCH PURPOSES.
SO SILOS OF EXCELLENT BRAIN TISSUE WHICH IS AVAILABLE FOR
RESEARCH AND AND WOULD ADDRESS MANY OF THE QUESTIONS AND AND
AND CERTAINLY DEALS WITH MANY OF THE CHALLENGES IN TRAUMATIC
BRAIN INJURY BUT THEY WERE THEY WERE IN SILOS THEY WEREN'T SO
EASY TO GET AT.
SO IF YOU HAD A GREAT PROJECT AND YOU'RE YOU'RE AN IDEA YOU
WANTED TO PURSUE HOW HOW HOW WOULD YOU HOW WOULD YOU GET TO
PEOPLE THAT HAD THE TISSUE HOW WOULD YOU FOLLOW UP ON THAT.
SO SO THE IDEA IN CONNECT TBI IS WE WE BROUGHT ALL OF THE
RESEARCH ARCHIVES TOGETHER WE YOU CREATED A A SHOP WINDOW A
WAY IN TO INTERACT WITH WITH THE ARCHIVES THAT ARE THERE THAT
WERE THERE PRESENTLY.
AND THEN WHAT WE'VE DONE IS WE'VE GONE ALONG AS WE WE'VE
WORKED ON STANDARDIZATION OF PROTOCOLS SO THAT THAT WE CAN
SEE THAT THE MATERIALS ARE HANDLED MUCH THE SAME WAY IN THE
DIFFERENT LABORATORIES THAT THE STAINING PROCESSES ARE MUCH THE
SAME.
AND WE DID A BIT OF WORK AT THE BEGINNING TO LOOK AT THE
VARIABILITY AND PROTOCOLS EVEN WITHIN LABS THAT WE'RE JOINING
TOGETHER AND WHAT DIFFERENCE DID THAT MAKE TO THE END RESULTS IN
TERMS OF THE THE IMMUNOSTAINING QUALITY AND AND AND AND IN TRUTH
WE WERE ALL DOING MUCH THE SAME BUT IN SLIGHTLY DIFFERENT WAYS,
BUT THE END RESULTS WERE MUCH THE SAME THAT DIDN'T REALLY
IMPACT THEM.
SO.
SO THAT CREATES A GOOD NETWORK AND FOR THOSE OF YOU WHO'VE NOT
INTERACTED WITH CONNECT TVI, THIS SLIDE IS, IS IS DESIGNED AS
A AS A SUMMARY OF THE THE PROJECT.
THERE'S SEVERAL CORES THAT THAT RUN ALONGSIDE THE BRAIN BANK
CORE BEING THE THE CENTRAL INITIATIVE TO BRING ALL THESE
ARCHIVES TOGETHER AND ALSO TO COORDINATE DONATIONS AND AND THE
THE CENTRES, THE LABS THAT WE HAVE WITH MATERIAL SPREAD
THROUGH NORTH AMERICA, CANADA AND ALSO OUR OWN LAB IN GLASGOW
AND THAT THAT'S NOW THE HOPE IS THAT THE OTHER RESOURCES AND
SOURCES WILL COME TO US AND SAY LOOK CAN WE GET ON BOARD, CAN WE
WORK WITH THIS BUT AND WE'LL WORK WITH THAT WITHIN THE
AVAILABILITY OF THE FUNDS WE HAVE AND RESOURCES WE HAVE.
HAVING SAID THAT WE'RE WE'RE WINDING DOWN AND WE'RE IN A
FINAL YEAR OF THAT PROGRAM.
WE'RE HOPING THAT THERE WILL BE CONTINUANCE FUNDING IN IN
ANOTHER MECHANISM AND I KNOW RAQUEL EARLIER ON MENTIONED THAT
THAT SHE WAS WAITING TO HEAR ABOUT FUNDING AND SUDDENLY GOT
AN E-MAIL WITHIN A MINUTE OF SAYING IT WITH WITH THE FUNDING.
SO I'LL JUST THROW THAT OUT THERE IN CASE THE FUNDING
FAIRIES WANT TO SEND AN E-MAIL RIGHT NOW, ALTHOUGH IT'S SEVERAL
WEEKS AWAY, SO MAYBE NOT.
I MEAN WE WOULD HOPE THAT IT WOULD CONTINUE.
IT'S BEEN, IT'S BEEN HUGELY SUCCESSFUL.
SO, SO WE SET THIS UP WITH AN ASPIRATION TO YOU KNOW BRING THE
ARCHIVES TOGETHER AND ALLOW PEOPLE A CENTRAL POINT OF ACCESS
TO OUR TISSUE SUPPORT AND AND IF NECESSARY SOME RESOURCE TO TO
GET THE PROJECTS RUNNING WITH AN EXPECTATION OF JUST IN THE LAST
SIX MONTHS WE WOULD BE OPEN FOR BUSINESS.
SO INVITING INVESTIGATORS TO GET IN TOUCH AND WE KNOW I THINK
WE'VE HAD 1516 AND WE STARTED EARLY SO WE WE WE WERE IN YEAR
THREE WHEN WE STARTED SUPPORTING PROGRAM AND WE'VE HAD 16
EXTERNAL APPLICATIONS FOR FOR FUNDING.
SO IT'S IT'S WORKING.
IT SEEMS TO HAVE ADDRESSED THAT PROBLEM WITH THE ONE OTHER AREA
IS ALSO WHEN YOU WORK IN YOUR RAT OR MOUSE IN THE LAB BECAME
CHARLES RIVER JACKSON LAB.
YOU KNOW THE WHOLE LIFE HISTORY OF THAT ANIMAL AND YOU DO YOUR
INJURY.
SOME LABS MAY DO MORE THAN ONE BUT YOU GET TO THE HUMAN CASE
AND IT'S LIKE WELL THEY MAY HAVE HAD SOME CHILD ABUSE.
THEY MAY PLAY THE RUGBY OR HOCKEY AND ICE HOCKEY FOOTBALL
AND THEY MAY HAVE A WHOLE SERIES AND MAYBE THEY EVEN SERVED IN
THE MILITARY.
AND SO SO AND AND THESE AGAIN THESE THESE ARE SO SO THE REAL
WORLD OF OF MESSINESS OF OF HUMANITY IS THAT IT IS MESSY AND
NEUROPATHOLOGY IS MESSY WHICH IS WHICH IS A LOT OF THE CHALLENGE
THAT I AND MY COLLEAGUES SPEND OUR TIME AS TRYING TO ARE SO THE
MESSINESS OF OF REAL LIFE AND AND AND THE YEAH SO GETTING TO
YOUR QUESTION HOW CAN WE IT'S NOT ONLY IS IT DIFFICULT TO GET
BUT THERE IS THAT SO THE THE PROS SO THE THE THE
PROSPECTIVELY ACCRUED CASES AMONGST CONNECT OF WHICH WE HAD
AN ASPIRATION TO GET ABOUT 350 I THINK BUT BUT WE WE'VE ACTUALLY
OVER 1000 THAT HAVE BEEN REGISTERED NOW WITHIN THE
ARCHIVE.
THE ASPIRATION IS THAT THEY THEY WILL ALL HAVE STANDARDIZED
CLINICAL INFORMATION CAPTURED, ALBEIT MUCH OF LIKE A
RETROSPECTIVE.
BUT YOU KNOW FROM THE TOP THIS MORNING THE, THE THE NEXT PHASE
OF THIS IS IS WHAT YOU KNOW THE GLOBAL MASTER PLAN I'VE BEEN
WORKING TO FOR THE LAST DECADE OR SO IS THAT WE EVERY SINGLE
CLINICAL TRIAL STUDY THAT'S GOING ON WILL INCLUDE THE, THE,
THE, THE REQUEST OF PARTICIPANTS.
WILL YOU BE WILLING TO DATE YOUR BRAIN AT SOME POINT AND THAT
GIVES US THAT RICH PHENOTYPING THAT WE'RE GETTING IN RESEARCH
CAPACITY TO TAKE FOR.
CAN I JUST FOLLOW UP ON ONE THING THAT STU WAS SAYING?
AND I WORK FOR THE US DEPARTMENT OF DEFENSE, I'M JB PHILLIPS.
AND I SEE HUNDREDS OF HUNDREDS OF THOUSANDS OF PROPOSALS.
SO I KIND OF KNOW WHAT THE LANDSCAPE IS OF WHAT PEOPLE WANT
TO DO TO GET TO SOLUTIONS FOR TBI.
AND MY QUESTION AND SEE IF YOU GUYS ARE AFTER THIS, THE MOST
COMPLEX HUMAN ON EARTH, COMPLEX ANIMAL IS THE HUMAN.
THE MOST COMPLEX ORGAN IN HUMAN IS THE BRAIN.
BUT WE'RE USING STANDARDIZED ANIMALS WITH ONE TYPE OF
CONTUSION AND I BET YOU ANY CONCUSSION IN THIS ROOM IS NEVER
THE SAME AMONGST PEOPLE WHERE YOU'RE HIT, HOW HARD YOU'RE HIT
AND HOW YOU RESPOND.
SO THERE'S SO MUCH VARIABILITY IN PEOPLE AND STILL WE RECRUIT
THEM IN THE TRIALS WITH THE GLASGOW COMA SCALE AND YOU HEARD
THE PROBLEMS WITH THAT EARLIER THIS WEEK.
THAT'S SYMPTOM BASE AND YOU MAY HAVE A LARGER CONTUSION, BUT YOU
JUST YOU'RE FINE WITH IT.
SO HOW DO WE GET AROUND AN ANIMAL MODEL THAT NEEDS TO BE
CONSISTENT WITH A CLOSE CORTICAL IMPACT OR WHATEVER?
AND THAT MAY ALIGN TO MAYBE 1 1/2% OF HUMAN TB IS I DON'T KNOW
HOW WE GET AROUND THIS.
SO THAT THAT'S A REALLY GOOD POINT AND AND AND THAT'S THAT'S
LIKE I THINK THE ASPIRATION OF THIS SESSION IS THAT THE
RECOGNIZING THE THE HUMAN HETEROGENEITY BUT ALSO THAT
MODELS HAVE TO BE RELEVANT TO TO THAT HETEROGENEITY.
SO SO THEY HAVE TO THEY HAVE TO REPLICATE SOMETHING IN THE HUMAN
CONDITION AND THAT'S THAT'S REALLY BEEN THE ASPIRATION FOR
THE ACTIVITY THAT WE'VE BEEN INVOLVED IN FOR FOR THE 20 YEARS
NOW IS TO ENSURE THAT THE MODEL THAT WE'RE WORKING WITH SOME
ASPECT OF IT THAT WE CAN WE CAN SEE WITHIN OUR HUMAN TBI
MATERIALS.
I'M CONSCIOUSLY STUCK ON ON THAT CONNECT TBI.
ONE OTHER THING I JUST I'M I'M DUTY BOUND TO MENTION IS TBI
REPORTER WHICH IF YOU CLICK ON THE LINK IT WILL TELL YOU
EVERYTHING YOU NEED TO KNOW ABOUT IT.
BUT THAT'S GOING TO BECOME A REALLY IMPORTANT PLATFORM FOR
FOR ACCELERATING THIS KIND OF RESEARCH GOING FORWARD.
MAYBE IF I CAN ADD SOMETHING TO TO THIS POINT, SO WHICH IS PART
OF THE PROPOSAL WE ARE WORKING ON AND DISCUSSING, I MEAN IN
ORDER TO EMBRACE HETEROGENEITY IN THE CLINICAL SETTING, BUT
ALSO ENSURE CONSISTENCY OF THE MODEL.
SO ON ONE SIDE WE NEED TO IDENTIFY WHICH MODEL IS
REFLECTING WHICH PART OF THE PATHOLOGY, BUT ON THE OTHER SIDE
WE NEED TO HAVE SOME KIND OF HETEROGENEITY WHICH POSSIBLY
IT'S VERY DIFFICULT TO BE MANAGED WITHIN A SINGLE LAB.
SO ONE POSSIBILITY IS REALLY TO TO CREATE A NETWORK OF LAB, EACH
OF ONE WORKING WITH THEIR ESTABLISHED MODEL.
BUT IN THIS WAY WE WILL CREATE HETEROGENEITY OF DIFFERENT TYPES
OF INJURY AND IN ORDER TO HAVE ACCESS THEN TO THE MATERIAL WE
MAY DEVELOP WHAT WE ARE TRYING TO TO FRAME AS A FEDERATED BIO
REPOSITORY WHERE YOU CAN HAVE, I MEAN WE WE DECENTRALIZED
REGISTRY AND THE CENTRALIZED COORDINATION SO THAT IN
PRINCIPLE WE COULD DECIDE THAT FOR THAT GIVEN, I MEAN
THERAPEUTIC APPROACH OR IN ORDER TO ADDRESS THAT PARTICULAR
DISEASE TRAJECTORY, WE MAY WANT TO ADDRESS IT IN THIS, THIS,
THIS AND THIS MODEL.
AND SO WE CAN CONNECT WITH DIFFERENT LABS AND DO THE WORK
IN A REASONABLE TIME FRAME AND WITH THE LIMITED RESOURCES.
YEAH, I WONDER IF YOU DON'T WANT TO HAVE THE TBI MODEL,
PRECLINICAL MODEL, GESTAPO AFTER EVERYBODY.
BUT YOU KNOW, WE WRITE THE FIRST OR SECOND PARAGRAPH OF OF THE
MANUSCRIPT AND SAY THIS MODEL IS CLINICALLY RELEVANT.
WELL, FORGET ABOUT THAT.
HERE'S ALL THE DATA.
I THINK ALL OF US WOULD REALLY WANT TO SAY LET ME TELL YOU WHY
IT'S CLINICALLY RELEVANT AND AND THEN MOVE ON AND REALLY HAVE
THAT KIND OF UNDERWRITERS LIMITED KIND OF ENDORSEMENT THAT
YES, THIS AT LEAST THAT ASPECT HAS SOME CLINICAL RELEVANCY AND
AND OF COURSE THERE'S HETEROGENEITY CLINICALLY, BUT
THERE ARE SOME VERY COMMON THEMES OF NEUROPATHOLOGIES AND
HUMAN TBI THAT I THINK MOST PEOPLE ARE TRYING TO REPLICATE
WITH THEIR MODELS.
IT'S JUST A MATTER OF THEN THEY MIGHT GET SCIENCY AND LET'S SAY
LOOKING AFTER INFLAMMATION PATHWAYS, WHAT IF THOSE ARE
DIFFERENT BETWEEN THAT SPECIES AND HUMANS THAT WE REALLY NEED
TO KNOW ABOUT.
SO I THINK IT'S IT'S A MATTER OF WE REALLY HAVE TO KIND OF COME
TO TERMS WITH YOU KNOW FOR EXAMPLE 10 YEARS OR SO AGO THE
DOD REFUSED TO FUND RODENT MODELS JUST OUT OF A FEELING
THAT THEY WEREN'T LIKELY RELEVANT.
SO.
SO THIS IS SOME WAY TO KIND OF ADDRESS THAT TO KIND OF OVERCOME
THAT.
WELL RODENTS ARE LIKE FULL TIME BRAINS AND AND HAVE A WAY TO TO
WORK ON THAT.
SO I'D JUST LIKE TO OPEN UP THIS TO THE FLOOR OF PEOPLE WHO USE
PRECLINICAL MODELS AND MAYBE EVEN YOUR OWN EXPERIENCE OF
WHERE YOU, HOW DO YOU HANDLE THAT FIRST OR SECOND PARAGRAPH?
YOU KNOW, MAYBE I CAN, CAN I CALL SOMEBODY OUT, DO YOU THINK
MAYBE, LAURA, SO WHAT IF YOU HAVE A NEUROSURGEON WHO'S USING
A PRECLINICAL MODEL AND KNOWS EXACTLY WHAT THE CLINICAL ASPECT
LOOKS LIKE?
SO DO YOU WANT TO PLEASE.
I DON'T THINK SO.
I'M NOT LYING.
MAYBE THIS ONE ISN'T.
YEAH, I THINK FOR ME I MEAN I DO A LOT OF RESEARCH THAT ALSO IS
LOOKING AT ELECTRICAL PROPERTIES WHICH YOU GUYS DIDN'T HAVE ON
THAT FIRST SLIDE THERE JUST AS A BUT.
BUT I THINK FOR ME AND I WAS TALKING TO SOME PEOPLE ABOUT
THIS I THINK LAST NIGHT, YOU KNOW, WHEN I'M WRITING A GRANT
OR THAT FIRST PARAGRAPH, I I HAVE THE THE BENEFIT OF LIKE THE
SECRET SAUCE OF LIKE I TALK ABOUT LIKE MY CLINICAL STUFF.
BUT IT IS HARD TO ACTUALLY DO THAT TRANSLATION TO SAY WHY MY
MODEL IS, IS, IS YOU KNOW I HAVEN'T DONE THE CALIBRATION
REALLY FOR A LOT OF IT.
SO I CAN TALK ABOUT WHY IT'S IMPORTANT TO ANSWER THE
QUESTIONS AND LIKE THE SPECIFIC QUESTION I'M ANSWERING BASED ON
MY CLINICAL STUFF.
BUT BUT YEAH, I ACTUALLY HAVEN'T DONE A LOT OF THE CALIBRATION.
SO LIKE I STILL HAVE ISSUES WHERE I'LL SAY I'M GOING TO LOOK
AT SOMETHING AT ONE DAY, THREE DAYS AND SEVEN DAYS BECAUSE THIS
IS WHAT I SEE IN MY PATIENTS.
I KNOW THAT'S PROBABLY NOT THE SAME IN A RAT, BUT LIKE I
HAVEN'T DONE THE CALIBRATION CELEBRATION.
SO YEAH, I DON'T HAVE AN ANSWER TO YOUR QUESTION REALLY.
I MEAN BUT LIKE WHEN PEOPLE HERE LIKE THAT.
SO IF WE HAVE THE WHAT WE HAVE FOR THE CONNECT CONNECTED BI IS
REALLY TO HAVE A KIND OF A FEDERATED A CONSENSUS THAT
THERE'S CERTAIN CHRONIC NEUROPATHOLOGIES IN THE CASES.
BUT WITHIN THE UMBRELLA OF THAT THERE ARE ACUTE CASES AND
WHATNOT.
AND THE IDEA WOULD BE THERE CAN'T REALLY BE A SERVICE LIKE I
CAN'T.
IT'S HARD TO IMAGINE THAT YOU KNOW, CENTRAL KIND OF, YOU KNOW,
FISHER SCIENTIFIC RUNNING, YOU KNOW, THESE THESE COORDINATED,
YOU KNOW, COMPARISONS WOULD BE MORE LIKE I I VIEW IT AS SOME
MORE OF A MATCHMAKING CIRCUMSTANCE WHERE THE TYPE OF
PATHOLOGY YOU WANT TO STUDY IS BRINGING YOU TOGETHER WITH
SOMEBODY IN THAT NETWORK.
SO YOU CAN PUT YOUR ANIMAL DATA NEXT TO THE HUMAN DATA.
YEAH, I THINK I MEAN FOR FOR PATHOLOGY IT'S SOMEWHAT EASIER,
RIGHT.
WE CAN LOOK DOWN A MICROSCOPE.
WE CAN SAY, HEY, I CAN SEE INFLAMMATION AND THAT'S GOOD TO
GO.
AND AND SO THE QUESTION WE'RE ASKING HERE IS HOW RELEVANT IS
IT?
SO LIKE TALK ABOUT A BETA OR TAU IN A MOUSE MODEL, WE KNOW
ACUTELY IT HAPPENS IN A HUMAN, WE KNOW ACUTELY IT HAPPENS IN A
RODENT.
SO THAT'S ACTUALLY NOT A BAD MODEL TO UNDERSTAND THE
PATHOPHYSIOLOGY OF WHY THAT'S HAPPENING.
WE KNOW THAT CHRONICALLY IT'S NOT REALLY HAPPENING IN MICE.
AND SO THAT'S A BAD MODEL FOR IT.
AND SO WE ALL USE DIFFERENT MODELS AND TWEAK DIFFERENT
MODELS TO SEE WHAT'S HAPPENING.
I THINK WE CAN YOU KNOW UNDERSTANDING YOUR OWN MODEL AND
AND REALLY LEARNING IT AND NOT TRYING TO OVER PROMISE WHAT IT
CAN DELIVER IS IS IMPORTANT LIKE SAYING WHAT'S CLINICALLY
RELEVANT ABOUT IT.
YOU KNOW THIS MOUSE IS THE SAME PATHOLOGY AND IT HAS MEMORY
DEFICITS.
THEREFORE I CAN DO EVERYTHING IN THIS MODEL ISN'T THE RIGHT WAY
TO GO ABOUT IT.
UNDERSTANDING THE LIMITATIONS AND SAY I'M NOT REALLY GOING TO
STUDY, I'M NOT GOING TO PROMISE TO STUDY SOMETHING AND AND DRAW
OVER CONCLUSIONS FROM IT THAT PROBABLY AREN'T TRUE IS ALSO
IMPORTANT.
BUT LIKE THE THINGS THAT THAT I THINK ARE ALSO REALLY IMPORTANT
WHEN IT COMES TO CLINICAL TRANSLATABILITY ARE THE THINGS
THAT ARE REALLY HARD TO MEASURE.
WHERE WE'VE REALLY RUN INTO TROUBLE WITH ANIMAL MODELS OF
THINGS LIKE POST TRAUMATIC EPILEPSY, SLEEP DISORDERS.
THESE ARE THE THINGS THAT AFFECT HUMANS ON A ON A HUGE SCALE.
AND THEN WE'RE NOT REALLY LOOKING INTO BECAUSE THEY'RE
HARD AND THEY'VE THEY'VE BEEN REALLY DIFFICULT TO DO IN MICE.
AND THERE WAS A GREAT STUDY THAT JUST CAME OUT OF A HIGHER STATE
IN THE LAST COUPLE OF WEEKS WHERE THEY'RE USING THE CC MICE
AND THEY SCREENED A WHOLE BUNCH OF THEM AND THEY SAID, HEY,
THESE COUPLE OF OF OF OF GENETICALLY DIFFERENT MICE ARE
MUCH MORE SUSCEPTIBLE TO EPILEPSY THAN THAN THAN AC 57
MOUSE, WHICH SITS SOMEWHERE IN THE MIDDLE OF THAT SCALE BY THE
WAY, IT WASN'T WASN'T BY FAR THE WORST, BUT IT CERTAINLY WASN'T
THE BEST.
AND SO YOU KNOW WE KEEP RUNNING INTO THESE ISSUES OF, YOU KNOW,
REMEMBER WHEN NIH SAID CAME OUT WITH THE OUTRAGEOUS SUGGESTION
WE HAD TO USE FEMALES IN OUR IN OUR STUDIES AND WE'RE ALL LIKE,
GOD, I CAN'T AFFORD THAT.
LIKE NO, NO HUMAN CAN AFFORD THIS.
AND ALL OF A SUDDEN WE STARTED LOOKING AND GOING, OH CRAP, THAT
IS MASSIVELY DIFFERENT INFLAMMATION BETWEEN A MALE AND
FEMALE RODENT, NEVER MIND ANYTHING ELSE.
AND NOW WE'RE LOOKING AT GOING, DO I HAVE TO SCREEN 32 DIFFERENT
CC MICE TO FIND WHAT'S GOING ON?
AND I THINK THE SAD ANSWER IS WE PROBABLY DO.
AND THE WAY TO DO THAT MIGHT BE TO GET EVERYBODY TOGETHER AND
SAY, OK, CAN WE TAKE THE SAME MODELS, RUN IT ON ALL THESE
DIFFERENT LABS AND SAY, HEY, I FOUND A MASSIVE AMOUNT OF
EPILEPSY IN MY MODEL, WHICH WE SHOULD ALL MOVE FORWARD WITH
THIS BECAUSE HAVING RELYING ON ONE LAB TO DO ALL OF THESE
DIFFERENT SCREENS IS, IS REALLY DIFFICULT.
SO ONE OF THE SHORTCOMINGS OF THE EXPERIMENTAL MODELS IS THAT
COMPARED TO HUMAN TBI, HUMAN TBI IS USUALLY A SERIES OF IMPACTS,
WHETHER WE SPEAK ABOUT TRAFFIC ACCIDENTS OR FALLS OR VIOLENCE.
AND SO THEY ARE A PRODUCT OF SERIES OF IMPACTS.
AND THAT IS SOMETHING THAT TO MY UNDERSTANDING IS NOT CAPTURED IN
EXPERIMENTAL TBI AND THAT MAKES THIS ALSO VERY DIFFERENT.
YEAH, OLLIE, I THINK THERE THERE'S YOU KNOW THERE I THINK
THERE ARE THERE ARE SOME MODELS THAT CAN BE USED FOR TO TO
MIMIC, YOU KNOW THE LESS EXTENSIVE INJURY PARADIGMS.
BUT I I WANT TO COME TO A POINT WHERE I DON'T THINK CALIBRATION
IS GOING TO BE ONE AND DONE.
BECAUSE FOR EXAMPLE THE LIKE THE, THE, THE, THE LIVING
CONDITIONS OF THE ANIMALS CAN RESULT IN VERY, VERY DIFFERENT
INFLAMMATORY TONE IN THE BRAIN EVEN FROM EXACTLY THE SAME
STRAIN.
BUT IN TWO DIFFERENT ANIMAL FACILITIES, THEIR MICROBIOME CAN
BE DIFFERENT AND SO YOU CAN GET COMPLETELY DIFFERENT OUTCOMES OR
TEMPORAL TRAJECTORIES OF SOME OF THE THINGS THAT WE ACTUALLY DO
WANT TO MEASURE.
SO I JUST WANTED TO MAKE THE POINT THAT I THINK CALIBRATION
IS KIND OF A CONSISTENT THING, GOT TO KEEP ON SORT OF TOP OF
IT.
BUT I THINK WE CAN GAIN A LOT BY TRYING TO UNDERSTAND THE FACTORS
THAT MODIFY THESE THESE THESE TRAJECTORIES OR DIFFERENCES IN
PEOPLE LIKE LABS THAT MIGHT BE USING THE SAME STRAIN OR THE
SAME MODEL, YOU KNOW, UNDER UNDER SIMILAR CONDITIONS.
SOMETIMES THE RESULTS ARE NOT GOING TO BE COMPARABLE, BUT I
THINK THERE'S GOING TO BE A LOT OF INFORMATION ON ON ON
UNDERSTANDING THAT AS WELL.
AND HERE'S PROBABLY THE OPPORTUNITY FOR THE THIS NETWORK
IS TO SHARE THESE SAMPLES TO THIS BIO REPOSITORY TO ACTUALLY
EXPLORE SOME OF THESE BASIC MECHANISMS, WHETHER IT BE THE
MICROBIOME OR THE VARIABILITY IN THE MODEL THAT WE CAN ACTUALLY,
YOU KNOW BY HAVING SHARING AND AND DOING WHATEVER TYPE OF
SEQUENCING OR NFL BIOMARKERS, YOU CAN SEE THE VARIABILITY IN
THAT SYSTEM.
SO PERHAPS WE HAVE THE SAMPLES IN OUR FREEZERS ALREADY, IT'S
JUST WE'RE NOT CONNECTING THEM AND AND THAT'S MUCH LIKE CONNECT
TBI, WE NEED TO CONNECT IT FOR THE PRECLINICAL MODELS AS WELL.
SO I THINK THAT THAT'S WHERE THE OPPORTUNITY LIES IN MY, MY MIND
ANYWAY.
YEAH, THIS IS A QUICK POINT, YOU KNOW THE DATA HARMONIZATION,
RIGHT?
YEAH, WE CANNOT MAKE EVERYTHING IDENTICAL.
SO.
SO THERE ARE SOME PROJECTS THAT ARE SHOWING SOME PROMISE LIKE
THE OPTT THAT'S FUNDED BY DOD PED KORANIC IS ANOTHER.
I THINK IT'S FOCUSING ON BIOMARKERS AND AND ALSO
FUNCTIONAL OUTCOME AND ALL THAT.
SO THE MORE RECENT EXAMPLE IS TOP NT THAT YOU KNOW MARK,
MYSELF AND OTHERS.
HIPAA IS A PROGRAM OFFICER.
SO IT'S LIKE 4 DIFFERENT LAB AND THEN WE HAVE A CONSOURCE, YOU
KNOW DATA ANALYSIS LAB, THREE DIFFERENT ANIMAL MODELS, CCI FOR
PERCUSSION AND ALSO CHIMERA.
THEY'RE VERY DIVERSE AND BUT THEY WE WE TRY TO DO IT
REPEATEDLY IN DIFFERENT LABS.
SO WE'RE FOCUSING ON BIOMARKERS INCLUDING BIOMARKER AND ALSO
IMAGING BIOMARKERS.
SO, SO I THINK THAT'S THE WAY TO STANDARDIZE AND AND WE FULLY
EXPECT THAT NOT EVERYTHING WORKS AND NOT EVERYTHING WORK IN ALL
MODELS.
SO WE WANT TO REALLY PUT YOU KNOW SORT OF STRESS TEST AND SEE
WHAT'S ROBUST AND WHAT'S LESS ROBUST.
SO.
SO I THINK THAT'S THAT'S ONE WAY TO I SEE MORE OPPORTUNITY, YOU
KNOW, FOR THIS TYPE OF CONSORTIUM STUDY IN THE P
CLINICAL SETTING.
THANK YOU SO MUCH FOR VALIDATING MY THOUGHT PROCESS HERE.
I'M MY WISH BY THE WAY, I FORGOT TO INTRODUCE MYSELF IN THE
MORNING.
I'M A POSTDOC FELLOW WITH PROFESSOR CHERYL WELLINGTON IN
VANCOUVER, UNIVERSITY OF BRITISH COLUMBIA.
I JUST WANT TO SAY IT LOUD AGAIN ONE MORE TIME.
WHAT HAS BEEN I COULD HEAR IS THE HETEROGENEITY THAT WE SEE IN
HUMAN POPULATIONS AS WELL AS IN ANIMAL POPULATIONS IS ACTUALLY
OUR FRIEND.
IT'S NOT SOMETHING TO KIND OF, YOU KNOW, LET IT BE.
BUT WITH THE ADVENT OF MACHINE LEARNING, BIG DATA ANALYSIS,
DATA HARMONIZATION, DATA MINING, WE COULD ACTUALLY PICK UP
PATTERNS THAT ARE BEYOND OUR DAY-TO-DAY EXCEL SHEET
COMPREHENSIONS AND MAKE US WONDER THAT THINGS ARE SO
DIFFERENT BETWEEN MODELS AND ALL.
AND I PERSONALLY FEEL WE DON'T REALLY NEED TO ALIGN ALL MODELS
ON THE SAME PAGE, RATHER EMPOWER EACH MODEL TO LOOK AT EACH
PATHOLOGY AS IT WAS STATED EARLIER TODAY.
SO I I BELIEVE AS SOON AS WE START PUTTING IN DATA TOGETHER,
WHETHER IT IS ABOUT THE POSTMORTEM TISSUES THAT WE
COLLECT, THE FEATURES, THE ELEMENTS EVEN TO THE POINT HOW
MANY MINUTES WAS IT LEFT IN FORMULA IN 4% ETCETERA.
YOU KNOW THE SUBTLE DETAILS, WE WOULD START PICKING UP THOSE
PATTERNS AND SEEING THOSE CHANGES WITH TEMPORAL
RESOLUTION.
AND AND THAT'S PROBABLY THE WAY TO GO IN MY HUMBLE OPINION.
YEAH, YEAH.
SO YOU ASKED FOR HAVING STANDARD STANDARDIZED MODELS.
THE VA IS FUNDING A INTERAGENCY INITIATIVE CALLED PRECISE.
IT'S THE PI IS IS CANDICE FLOYD AND THAT IS THE GOAL OF THAT IS
TO CATEGORIZE THE TBI MODELS.
YOU MIGHT ACTUALLY HAVE SEEN THEM AT AT SOCIETY FOR NEURO
DRAMA MEETINGS AND THEY'RE CATEGORIZING THE MODELS.
THEY'RE GOING TO BE DOING A A DETAILED PROCESS OF
STANDARDIZING OR WHAT ARE THE STANDARDS FOR THAT MODEL, HOW IT
RELATES TO THE HUMAN INJURY.
AND THAT'S ALL GOING TO BE OPEN TO THE TO THE PUBLIC.
SO THAT THAT INFORMATION ON HOW TO DO THAT MODEL NOT WHAT'S THE
CULTURE IN YOUR LAB BECAUSE I, I, I WAS IN THAT AREA FOR A
WHILE.
I KNOW WE DID OUR INJURY THE WAY THAT WE DID IT IN OUR LAB WHICH
WAS NOT NECESSARILY SAME WAY YOU DID CCI IN ANOTHER LAB.
SO WE'RE WE'RE TRYING TO GET THAT TOGETHER SO AT LEAST YOU
CAN CHOOSE YOUR MODEL AND CHOOSE THE PROTOCOL TO FOLLOW.
SO IT IT WOULD BE SOME SORT OF STANDARDIZATION TO THAT IN
UNIFICATION.
BUT THE THE FEAR IS THAT SO THE SPINAL CORD INJURY FOLKS DID
THIS YEARS AGO OF ASCUS AND THEY DISCOVERED THAT THERE WAS THE
SAME MODEL, THE SAME PARAMETERS AND A COMPLETELY DIFFERENT
OUTCOME AT AT EACH LABORATORY.
BUT I DON'T THINK WE'RE WE'RE AT A PLACE WHERE WE CAN HAVE
REPLICATION OF MODELS.
I THINK WE HAVE A TYPE OF MODEL, YEAH.
AND SO, AND BUT I STILL THINK THAT IT'D BE IMPORTANT FOR EACH
GROUP TO FIND A WAY TO CALIBRATE THE CLINICAL RELEVANCE OF THAT
TYPE OF MODEL, WHATEVER IT IS.
YEAH.
SO YEAH, I MEAN YOU REALIZE THAT IT'S NOT A PERFECT WORLD THAT
THERE'S GOING TO BE DIFFERENCES.
YOU MIGHT HAVE A UNDETECTED OUTBREAK OF ARVO IN YOUR IN YOUR
RODENT COLONY THAT'S GOING TO THROW OFF YOUR, YOUR
INFLAMMATORY BIOMARKERS.
BUT NOW YOU GOT TO START SOMEWHERE.
SO SINCE THE DISCUSSION WAS DIRECTED TOWARDS HOW WE CAN
SHARE MATERIALS EMBRACE HETEROGENEITY.
SO HERE IS SOMETHING WE WE DISCUSSED LATELY AND HOW TO TO
TO BUILD ON EXISTING WORK IN IN IN LARGER COLLABORATIVE
CONSORTIA AND IT HAS BEEN DONE VERY MUCH IN THE CLINICAL
SETTING.
AND HERE ARE JUST EXAMPLES OF HOW THERE ARE EXISTING NETWORKS
AND PLATFORM THAT CAN ACCELERATE DISCOVERING BY SHARING NOT ONLY
KNOWLEDGE AND AND METADATA BUT ALSO BIOMATERIALS AND HOW THE
THE FIELD IS IS MOVING TOWARDS THE IDEA THAT ALSO PHASE TWO
STUDY SHOULD BE DESIGNED IN ORDER TO ADDRESS A PARTICULAR
PART OF PHYSIOLOGICAL ASPECT.
AND I MEAN ADD ON TOP OF CLINICAL OUTCOMES THAT WE HAVE
ALWAYS RELIED ON SURROGATE BIOMARKERS THAT CAN INFORM ON
BATTLE PHYSIOLOGICAL CHANGES AND SO PROVIDE A PLATFORM TO COLLECT
DATA, CLINICAL DATA, RADIOLOGICAL DATA, GENETIC AND
SO ON AND ALLOW RESEARCHERS TO TO EXPLORE THE BIOLOGICAL IMPACT
OF INTERVENTION AND UNDERLYING MECHANISM.
AND IN THESE SLIDES THAT WAS PROVIDED BY ADEL AND ME, HE MADE
A STATEMENT THAT THIS MAY A WAY TO FAIL FAST AND PROGRESS SOON
IN ORDER TO SEE IF WE ARE TARGETING THE SPECIFIC
TRAJECTORY OR OR NOT.
SO AND AND TO BUILD ON ON THAT IN THE PRECLINICAL SETTING AS
WAS JUST MENTIONED THERE ARE ALSO VERY IMPORTANT EXAMPLES OF
PLATFORMS THAT ARE LOOKING TOWARDS SHARING DATA AND REFINE
HOW WE PERFORM THE MODELS IN TERMS OF A GOOD LABORATORY
PRACTICE, COMMON DATA ELEMENTS AND MAYBE CAN SET THE BASIS FOR
MULTI CENTRE STUDIES.
AND AND WHAT WE THOUGHT THAT ON TOP OF THIS WHAT IS PROBABLY
MISSING IN THE PRECLINICAL SETTING COULD BE ROOM FOR
SHARING NOT ONLY DATA BUT ALSO BIOSPECIMENS AND BIOFLUIDS.
SO WITH THIS IDEA OF A FEDERATED PRECLINICAL BIO REPOSITORY AND
ONE POSSIBILITY COULD BE TO START WITH THE LIVING REGISTRY
IN THE PRECLINICAL TBI ARENA TO SEE WHICH ARE THE LABORATORY
THAT WANT TO TO SHARE EXPERTISE, MATERIALS AND METADATA AND REACH
AND AND DEVELOP A GLOBAL NETWORK.
AND OF COURSE WE NEED TO ENSURE THAT ALL THIS IS HAS BEEN WILL
BE DONE IN THE HIGHEST LEVEL AS POSSIBLE.
SO THE IDEA IS TO CONNECT WITH THE ALREADY ESTABLISHED NETWORK
THAT HAVE DEVELOPED A GOOD LABORATORY PRACTICE, STANDARD
OPERATOR PROCEDURES AND TO COME TO BE COMPLIANT TO COMMON DATA
ELEMENTS.
SO THIS CAN ONLY BE DONE BY COLLABORATING WITH WITH ALREADY
EXISTING ACTIVITIES AS MENTIONED PRECISE, TBI, TOP AND TOBTT AND
SO ON AND SO ON.
BUT THIS COULD BE THE BASIS TO DEVELOP WITHIN INTERVIEW THAT
MERGES CLINICAL AND PRECLINICAL EXPERIENCE A COMMON STRATEGY TO
INTEGRATE PRECLINICAL AND CLINICAL DATA.
SO IN THIS IDEA OF A CENTRE WITH NO WORDS BUT BUT PILLARS, WHAT
WE WOULD NEED TO SEEK WOULD BE RESOURCES FOR A CENTRALIZED
COORDINATION.
SO TO ENSURE OF COURSE THAT WHO WANTS TO CONTRIBUTE CAN SEE HIS
INTELLECTUAL PROPERTIES INSURED AND DATA PRIVACY AND SO ON.
BUT ALSO HAVE THE POSSIBILITY TO HAVE THE MANAGEMENT OF LOGISTIC
AND DISTRIBUTION ROLES SET UP AND A SORT OF A PRECLINICAL
MONITOR THAT WILL VISIT THE DIFFERENT CENTRES IN ORDER TO BE
SURE THAT ALL THE PROCEDURE ARE HARMONIZED WITHIN DIFFERENT
LABORATORIES.
AND IDEALLY THIS COULD REALLY CONTRIBUTE TO OF COURSE WE WITH
WHAT IS ALREADY EXISTING TO TO PROVIDE ADDITIONAL METADATA AND
BIG DATA ANALYSIS AND TO BE THE BASIS FOR CONDUCTING WHAT WE
DISCUSSED BEFORE LIKE MULTI SIDE PRECLINICAL STUDIES TO TAKE INTO
ACCOUNT DIFFERENT MODELS, DIFFERENT SETTING TO INVESTIGATE
THE PARTICULAR APPROACH.
THIS WAS GETTING INTO SOMETHING THAT I WAS THINKING ABOUT, BUT
AGAIN I'M NOT AT YOU GUYS ARE THE EXPERTS.
AND SO MY POINT IS USUALLY IN A QUESTION IF YOU'RE GETTING THE
CLINICAL DATA, I WAS THINKING EARLIER ABOUT ALL THE CLINICAL
NETWORKS, YOU GUYS KNOW THEM FROM TRACK TO CARE TO THE
LIGHTS, TRAUMA NETWORK TO CONNECTING ALL OF THESE, IF YOU
COULD GET SOME TYPE OF.
AI, MACHINE LEARNING OR SOMETHING TO TELL YOU THAT 20%
OF 10,000 OF THESE TB IS ARE SIMILAR, 20% OF THEN YOU CAN
BUILD AN ANIMAL MODEL TO MEET THAT 20% CAUSE.
THE REST OF THEM ARE NOT REALLY, THEY'RE KIND OF ALL OVER THE
PLACE.
BUT IF YOU CAN GET SOME HUMAN DATA THAT IT'S SOMEWHAT SIMILAR
TO SOME STANDARDS THAT YOU DECIDE AND IT'S 20% OF THE
POPULATION OR WHATEVER, THEN THAT ANIMAL MODEL COULD ADDRESS
20% OF THOSE OF THAT BECAUSE I DON'T THINK WE'RE GOING TO GET
ALL TB IS WITH ONE MODEL.
YOU KNOW, I'M JUST TRYING TO RELATE IT TO, BUT THAT'S
PROBABLY EASIER SAID THAN DONE TO GET ALL THAT CLINICAL DATA
OUT.
ALL RIGHT EVERYBODY.
WELL THIS IS A PRETTY INTERESTING AND THEN I THINK AND
SOMEBODY'S INSPIRING BUT I THINK IT BRINGS QUESTIONS TO A LOT OF
US TO KIND OF HELP KIND OF YOU KNOW YOU KNOW REFINE THE THE
APPROACH AND A LOT OF THIS WORK IS DONE THROUGH THE DIFFERENT
WORKING GROUPS WHETHER IT'S NERPATHOLOGY OR OR THE
TRANSLATIONAL.
SO IF YOU WANT TO BE PART OF THAT PLEASE I MEAN IT'S YOUR
EVERYBODY'S WELCOME AND REALLY TRY TO WORK.
I I THINK WE'RE REALLY CLOSE TO BEING ABLE TO HAVE A FIRST START
SOLUTION HERE IN KIND OF, YOU KNOW, GETTING THAT THAT YOU KNOW
WORK TOWARDS CLINICAL RELEVANCY BOTH THE ONE DIRECTION AND THE
OTHER.
THINKING IS YOUR MODEL CLINICALLY RELEVANT AND DO THE
IS THE DATA FROM YOUR MODEL CLINICALLY RELEVANT.
SO I'M I'M AFRAID WE'RE KIND OF RUNNING A LITTLE LATE. 732 00:41:41,799 SO THANK YOU ALL FOR YOUR PARTICIPATION