>> OKAY. SEE WE'RE AT ONE
O'CLOCK. GOOD AFTERNOON,
EVERYONE. HAPPY SUMMER TO ALL OF
YOU. MY NAME IS MARK STEVE STEV.
I'M EXECUTIVE OFFICER NATIONAL
INSTITUTE ON DEAFNESS AND OTHER
COMMUNICATION DISORDERS HERE AT
THE NATIONAL INSTITUTES OF
HEALTH. ON BEHALF OF NIDCD
DIRECTOR DR. DEBRA TUCI WELCOME
TO OUR NIDCD BEYOND THE LAB
SERIES. TODAY'S TALK CAN YOU
SMELL THAT? SMELL IS A BIOMARKER
OF BRAIN HEALTH AND QUALITY OF
LIFE, WILL GIVE US INSIGHT INTO
THIS IMPACT OF SMELL ON GENERAL
HEALTH AND QUALITY OF LIFE AND
THE EMERGING RESEARCH THAT AIMS
TO IMPROVE SYMPTOMS AND THOSE
SUFFERING WITH AN OLFACTORY
DYSFUNCTION. NIDCD'S MISSION IS
TO SUPPORT RESEARCH AND RESEARCH
TRAINING IN THE NORMAL AND
DISORDER PROCESSES OF HEARING,
BALANCE, TASTE, SMELL, VOICE,
SPEECH AND LANGUAGE AND TO
SUPPORT BIOMEDICAL AND
BEHAVIORAL RESEARCH THAT WILL
IMPROVE THE LIVES OF MILLIONS OF
PEOPLE WITH THESE DISORDERS. NOW
FOR TODAY'S SPEAKER SERIES.
BEYOND LAB LECTURE SERIES IS
OPPORTUNITY FOR EVERYONE INSIDE
AND OUTSIDE THE NIH INCLUDING
ADMINISTRATIVE STAFF, SUPPORT
STAFF, SCIENTISTS AND THE PUBLIC
TO LEARN ABOUT NIDCD'S RESEARCH
PLEASE NOTE THAT WE EXPECT TO
HAVE A FEW MINUTES AFTER THE
PRESENTATION FOR OUR SPEAKER,
DR. LEVY, TO ANSWER YOUR
QUESTIONS FOR TODAY. NOW I
WOULD LIKE TO INTRODUCE DR. LISA
CUNNINGHAM NIDCD SCIENTIFIC
DIRECTOR SHE LEADS THE DIVISION
OF INTRAMURAL RESEARCH WHICH
CONDUCTS BASIC AND CLINICAL
RESEARCH AND HUMAN
COMMUNICATION. SHE WILL
INTRODUCE TODAY'S SPEAKER DR.
JOSH LEVY, AND AT THIS MOMENT I
WOULD LIKE TO ASK YOU TO PLEASE
JOIN ME IN WELCOMING DR.
CUNNINGHAM TO THE PODIUM.
[APPLAUSE]
>> THANK YOU, VERY MUCH MARK.
THANK YOU TO EVERYONE FOR
JOINING US TODAY. IT IS MY
PLEASURE TO WELCOME YOU TO
TODAY'S BEYOND THE LAB TALK,
FROM DR. JOSH LEVY IMPACT OF
SMELL ON OUR HEALTH AND OUR
EVERY DAY QUALITY OF LIFE. AS
MARK MENTIONED NIDCD DEVELOPED
THIS SPEAKER SERIESES WITH THE
GOAL OF TAKING WHAT WE ARE
DISCOVERING IN THE LAB OR CLINIC
AND SHARING THAT INFORMATION
WITH BOTH SCIENTIFIC AND
NON-SCIENTIFIC STAFF AT NIH
INTERESTED COMMUNITY MEMBERS,
PATIENTS AND THEIR FAMILIES,
ADVOCATES AND HEALTH
PROFESSIONALS. WE HOPE SHARING
SCIENTIFIC ADVANCES IN OUR
MISSION AREAS HELPS STAFF AND
COMMUNITY COME AWAY WITH A
GREATER UNDERSTANDING OF HOW WE
ARE ADVANCING SCIENCE AND
ULTIMATELY HELPING PEOPLE AND
THEIR FAMILIES. WE ALL PLAY A
ROLE IN PUBLIC HEALTH. NOW I GET
TO TELL YOU ABOUT OUR SPEAKER
TODAY. DR. JOSH LEVY. JOSH IS A
BETHESDA NATIVE AND HIS FIRST
RESEARCH EXPERIENCE WAS RIGHT
HERE AT NIH. SO I WANT OUR
TRAINEES TO NOTICE DR. LEVY'S
FIRST RESEARCH EXPERIENCE AS
SUMMER TRAINEE, HE SPENT THREE
SUMMERS AT THE NIH I BELIEVE IT
WAS TWO SUMMERS IN HIGH SCHOOL,
AND ONE SUMMER AS UNDERGRAD. AND
ADDITIONALLY HE WORKED
AFTERNOONS THROUGHOUT HIS SENIOR
YEAR IN HIGH SCHOOL AND JOSH
TELLS ME HIS RESEARCH EXPERIENCE
HERE AT NIH AND DR. (INAUDIBLE)
LAB SHAPED HIS CAREER AS A
PHYSICIAN SCIENTIST. DR. LEVY
COMPLETED HIS MEDICAL AND PUBLIC
HEALTH TRAINING AT TULANE
UNIVERSITY NEW ORLEANS, WHERE HE
ALSO COMPLETED HIS RESIDENCY IN
OTO LAYER GONG. HE COMPLETED
FELLOWSHIP IN SINUS AND SKULL
BASED SURGERY IN PORTLAND. HE
THEN SERVED ASSOCIATE PROFESSOR
AND ASSOCIATE VICE CHAIR
RESEARCH DEPARTMENT OF OTO
LARYNGOLOGY, HEAD AND NECK
SURGERY EMORY UNIVERSITY
ATLANTA. HE JOINED THE NIDCD AS
CLINICAL DIRECTOR IN APRIL 23
AND HIS RESEARCH FOCUSES ON
ESTABLISHING INNOVATIVE CLINICAL
TRIALS RELATED TO HEARING SMELL
AND OTHER COMMUNICATION
DISORDERS. HE IS THE CO-FOUNDER
ALONG WITH DR. POLY JOSEPH
NATIONAL SMELL AND TASTE CENTER
WHICH OPENED ONE YEAR AGO TODAY
JULY 9. DR. LEVY WILL TELL ABOUT
HIS RESEARCHING ON SMELL WHICH
IS A FOUNDATIONAL SENSE THAT
ALLOWS US TO INTERACT WITH THE
OUTSIDE WORLD. HOWEVER OUR SENSE
OF SMELL DECLINES WITH AGE AND
LOSS OF SMELL IS ASSOCIATED WITH
OVER A HUNDRED UNIQUE MEDICAL
CONDITIONS. SO I LOOK FORWARD TO
LEARNING MORE FROM JOSH ABOUT
THAT TODAY. THANK YOU FOR
JOINING US. I HOPE YOU ENJOY
TODAY'S TALK AND LET'S WELCOME
JOSH.
[APPLAUSE]
>> THANK YOU SO O MUCH, MARK,
LISA. I'M ABSOLUTELY THRILLED TO
BE HERE. A SMALL ANECDOTE IS I
LEARNED EARLY ON AS A SCIENTIST
OUR WORK OUR DISCOVER IS RISK
BEING COMPLETELY USELESS UNLESS
IF WE COMMUNICATE AND WE TEACH
OTHERS NOT ONLY WHAT WE ARE
DISCOVERING BUT WHY WE ARE
DISCOVERING IT. THIS SEMINAR
SERIES IS MY OPPORTUNITY,
SEMINAR TODAY TO SHARE WITH YOU
WHAT AND THE WHY WHY AM I HERE
AND SO DARN PROUD TO BE PART OF
THIS TEAM. TIMS CLOSURES ARE
HERE. THE MOST RELEVANT PART TO
KNOW IS I'M A TRAINED SINUS
SURGEON THAT INFORMS THE CARTOON
AND MY SENSE OF HUMOR. THIS
SHOULD BE AS INTERACTIVE AS
POSSIBLE. I'M HAPPY TO ANSWER
ANY QUESTIONS ALONG THE WAY AT
THE END, ET CETERA. SO I WOULD
LIKE TO START WITH A FEW PATIENT
EXAMPLES TO GIVE YOU SOME
CONTEXT OF THE WHY. WHY DO WE
STUDY SMELL. THIS IS FROM MY
PRIOR PRACTICE IN ATLANTA AND
YOU CAN SEE THE TIME FRAME IS
QUITE MOMENT US FOR ALL OF US.
MARCH 2020, THERE WERE RUMORS
GOING AROUND THE HOSPITAL, GROUP
OF PHYSICIANS JUST RETURNED FROM
INTERNATIONAL WORK IN ASIA, ALL
OF WHICH COMPLAINED OF A
DISTURBANCE OF SMELL AN TASTE.
NO OTHER TYPICAL VIRAL SYMPTOMS
AS WE THOUGHT OF IT AT THE TIME
JUST ONE MONTH LATER I WAS
TAKING CALL FOR OUR EMERGENCY
ROOM, AND THANKFULLY A FRIEND
WORKING IN THE ER AND HE CALLS
ME. SAYS I HAVE AN 18-YEAR-OLD
SITTING OUR IN THE WAITING ROOM.
NOT ISOLATED. SHE'S VERY
HEALTHY, VERY SMART, SAYS SHE
HAS INFECTIOUS LOSS OF SMELL.
WOULD YOU LIKE TO COME SEE HER?
I SAID ABSOLUTELY NO, I WOULD
NOT. I THINK THERE'S SOMETHING
GOING ON AND AS A FIELD WE
HAVEN'T FUNDAMENTALLY CONNECTED
THE DOTS. THE REST OF THAT STORY
IS HISTORY. BUT THERE ARE OTHER
VERY IMPORTANT EXAMPLES THAT
EXTEND WELL BEYOND VIRAL
ILLNESS. THIS WAS A PATIENT I
SAW IN CLINIC. 70-YEAR-OLD MALE,
OTHERWISE HEALTHY, WITH SLOWLY
WORSENING SENSE OF SMELL. THIS
WAS GOING FOR TWO YEARS. ONE OF
THE THINGS TO KEEP IN MANY MIND
WE WILL TALK ABOUT THIS A BIT,
AS WE AGE IT IS EXPECTED THAT
SMELL DECLINES TO A CERTAIN
EXTENT. IT IS A CONFOUNDER THAT
MAKES DIAGNOSIS REALLY
DIFFICULT. HE HAD NO OTHER
FINDINGS. IS THIS AN EARLY
PRESENTATION OF MORE SEVERE
DISEASE? OR IS THIS COMPLETELY
NORMAL? WE DON'T HAVE THE
ANSWERS RIGHT NOW. HOWEVER, I
WAS FORTUNATE ENOUGH TO MAINTAIN
RELATIONSHIP WITH THIS PATIENT
AND FOUR YEARS LATER HE RETURNED
WITH A NEW ONSET TREMOR AN
DIFFICULTY SPEAKING. HIGHLY
SUGGESTIVE OF MORE SEVERE
DISEASE. ANYONE WANT TO TAKE A
SHOT AS TO WHAT WAS GOING ON? SO
THIS IS A SUMMARY, A GRAPHIC OF
PARKINSON'S DISEASE, THE COMMON
SYMPTOMS AND SIGNS. THIS IS NOT
FROM THE MEDICAL LITERATURE,
THIS IS ACTUALLY ADOBE STOCK
IMAGE, SOMETHING USED TO TEAC T.
SMELL ISN'T THERE, NOT LISTED
WHATSOEVER, ALTHOUGH AMONG THE
OVER HUNDRED AS LISA MENTIONED
CONDITIONS, THE CONNECTION
BETWEEN LOSS OF SMELL AND
SUBSEQUENT DEVELOPMENT OF
PARKINSON'S IS EXTREMELY WELL
ESTABLISHED. THERE IS A BIG
DISCONNECT HERE IN HOW WE ARE
COMMUNICATING, HOW WE ARE
TEACHING, BOTH EACH OTHER AS
CLINICIANS AND SCIENTISTS, AND
OUR PATIENTS. WE NEED TO DO
BELTER. SO WHAT IS THE COMMON
THREAD HERE? IN ALL THREE OF
THOSE CASES, THESE ARE SMELL
LOSS, PRESENTING PRIOR TO OTHER
SYMPTOMS. SMELL LOSS IS AN EARLY
INDICATOR OF OTHER DISEASE. THIS
IS BOTHERSOME. THIS IS NOT
SOMETHING MOST PATIENTS BRUSH
OFF. IN ALL THREE OF THESE CASES
THEY ARE PRESENTING TO THE
DOCTOR. OUR PATIENTS ARE ASKING
FOR HELP. THE PROBLEM IS THAT WE
HAVE VERY POOR UNDERSTANDING OF
THE SIGNIFICANCE OF THESE
SYMPTOMS. WE DON'T HAVE
DIAGNOSTIC TOOLS TO SAY THE
SMELL LOSS IS EXPECTED WITH
AGING VERSUS ONE OF THESE OTHER
HUNDRED PLUS CONDITIONS. SO
WHAT IS THE CLINICAL RELEVANCE?
WHY? WHY DO WE CARE? IT IS MORE
THAN A HUNDRED CONDITIONS.
THESE A RECENT REVIEW THAT
DESCRIBED AN ASSOCIATION OF
SMELL LOSS WITH 139 OTHER
DISEASES AND DISORDERS OF THE
HUMAN BODY. I RECOGNIZE THIS
CLIP SHOT ON THE RIGHT IS WAY
TOO SMALL FOR ANYONE TO READ.
BUT THOUGHT IT WAS IMPORTANT TO
INCLUDE A LIST OF THE NUMBER OF
CONDITIONS AND I WILL SHARE WITH
YOU ITS INCREDIBLY BROAD FOR
MULTIPLE FORMS OF
NEURODEGENERATION TO AUTISM, TO
DEPRESSION AND ANXIETY. THERE
ARE A NUMBER OF CLINICAL
CONDITIONS THAT WOULD LIKELY
BENEFIT FROM HAVING A CLEAR
ASSOCIATION, BETTER
UNDERSTANDING OF WHY LOSS OF
SMELL IS DRIVING THIS DISEASE.
WE TALK A LOT ABOUT BIOMARKERS.
BIOMARKERS ARE CRITICAL TOOLS TO
HELP US BRIDGE THIS GAP, TO
UNDERSTAND IF THE LOSS OF SMALL
IS TRULY ASSOCIATED WITH
SOMETHING ELSE. BUT FOR A
CLINICAL BIOMARKER TO BE
RELEVANT, TO BE USEFUL IN THE
CLINIC, IT HAS TO HAVE A FEW
PREREQUISITES. THE BIOMARKER OR
THE LOSS OF SMELL IN THIS CASE
HAS TO PRECEDE OTHER SYMPTOMS OF
IMPROVEMENT. TALKING ABOUT MY
PATIENT WITH PARKINSON'S, ONCE
HE DEVELOPED THE MORE CLASSIC
MOTOR SYMPTOMS, OTHER FINDINGS,
HIS LOSS OF SMELL BECOMES LESS
RELEVANT. WE CAN DIAGNOSE WITH
MORE TRADITIONAL MEANS. DOES THE
DIAGNOSIS, THE BIOMARKER HELP TO
EXPEDITE TREATMENT? THIS IS A
BIG REASON WHY THERE'S NEWBORN
SCREENING FOR HEARING LOSS. BY
IDENTIFYING THE DEFICIENCY EARLY
ON THAT GIVINGS US THE
OPPORTUNITY TO INTERVENE TO HELP
RESTORE HEARING OR PROTECT
WHAT'S THERE. FINALLY, IS THERE
A TREATMENT AT ALL? DOES
IDENTIFYING THE BIOMARKER LEAD
TO NUMBER TWO, A NEW TREATMENT,
AND THEN NUMBER THREE, DOES THAT
TREATMENT IMPROVE DISEASE?
ECONOMISTS ARGUE THAT IF WE
DON'T HAVE THESE THREE, IT IS
NOT WORTH TESTING NOT WORTH
LOOKING FOR A BIOMARKER THAT
DOESN'T HAVE A CLINICAL
RELEVANCE ASSOCIATED WITH IT.
USING POST EARLY VIRAL OLFACTORY
DYSFUNCTION ARE THOSE CASES
PRESENTED AT THE TOP IS MY
ANSWER, WHY SMELL IS A CRITICAL
BIOMARKER AND SOMETHING THAT AS
A FIELD WE SHOULD BE FURTHER
EVALUATING AND TAKING NOTE OF.
WITH POST VIRAL OLFACTORY LOSS,
SELF-REPORTED SCHAPPING IN SMELL
IS NOT ONLY AN EARLY SIGN IT IS
ACTUALLY MORE PREDICTIVE THAN A
FEVER. ALL THOSE YEARS WHERE I
WAS GETTING SCREENED FOR A FEVER
AS I WENT IN THE HOSPITAL, NO
ONE ONCE ASKED HAS YOUR SENSE OF
SMELL CHANGED? WE WOULD HAVE
DONE A BETTER JOB IF WE HAD. WE
ALSO HAVE ANTIVIRAL MEDICATIONS.
IF WE CATCH SOMEONE EARLY STAGES
IS OF ONE OF HE IS VIRAL
ILLNESSES WE CAN TREAT IT,
MINIMIZE THEIR DISEASE, MINIMIZE
THE CHANCE OF SPREADING THE
DISEASE TO OTHERS. THIS IS WHY
WE ARE TALKING SMELL. SMELL IS
MUCH BIGGER THAN JUST A
BIOMARKER. SMELL DRAMATICALLY
IMPACTS OUR QUALITY OF LIFE, OUR
ABILITY TO COMPLETE ACTIVITIES
OF DAILY LIVING. THERE IS
NUTRITIONAL CONCERNS.
PATIENTS WITH SMELL LOSS REPORT
REDUCED FOOD ENJOYMENT WITH
ALTERATIONS IN EATING HABIT HAB.
SOMETIMES QUITE SEVERE AS WE
WILL TALK ABOUT TOWARDS THE END,
AND NUTRITIONAL DEFICIENCIES IN
UP TO HALF THE PATIENTS THAT
REPORT CHANGES TO THEIR SENSE OF
SMELL. WE KNOW CHANGES IN TASTE
CORRELATE WITH SMELL TO THE
EXTENT THAT UP TO 80% OF THE
PATIENTS WE SEE IN CLINIC THAT
COME IN PRIMARILY BECAUSE OF
DIFFICULTY TASTING SOMETHING,
THEIR TASTE BUDS, TASTE SYSTEM
WORKS FINE, IT IS LOSS OF SMELL.
THEY CAN'T DETECT THE FLAVOR OF
FOODS. THERE IS A HUGE SAFETY
COMPONENT AS WELL. SMELL I WOULD
SAY FIRST AN FOREMOST IS A
WARNING SYSTEM FOR OUR BODIES. A
GAS LEAK, FOR EXAMPLE. WE
INTENTIONALLY ADD CHEMICALS THAT
ARE UNIQUE AND DISTINCTIVE TO US
SO THAT WE CAN PICK UP ON THEM
AND UTILIZE THAT AS SAFETY
SIGNAL. THEN THE EMOTIONAL
IMPACT. THIS VARIES BY THE
SPECIFIC TYPE OF SMELL
CONDITION, AND OF COURSE AMONG
EACH PATIENT. BUT IN GENERAL,
OVER HALF OF PATIENTS WITH
CHRONIC SMELL LOSS DEVELOP
SYMPTOMS, CLINICALLY RELEVANT
DEPRESSION AND SOCIAL ISOLATION.
THIS IS A TREMENDOUS ISSUE. THIS
IS AN OLDER STUDY NOW BUT I WANT
TO INCLUDE IT BOTH TO MAKE THE
POINT WE USE OLDER DATA AN SINCE
2020 WORLDS CHANGED SO THIS IS
AN OPPORTUNITY WE HAVE TO UPDATE
OUR FIGURES UPDATE OUR
UNDERSTANDING OF THE IMPACT OF
THIS CONDITION. BUT IF YOU
SURVEY PATIENTS THIS ON X AXIS
HERE 0 TO 100% SURVEYED
RESPONDENTS, THESE ARE PATIENTS
WITH SMELL DISORDERS, EITHER
CAN'T SMELL AT ALL, THEY CAN
SMELL LITTLE OR THERE IS AN
ALTERATION IN WHAT THEY SMELL,
IT IS NOT CORRECT. WE SEE OVER
HALF, IF WE GO UP THIS LINE
HERE, HAVE EATEN SPOILED FOOD,
DIFFICULTIES COOKING, RISK OF
PAIL YOUR TO PERCEIVE LIFE
THREATENING THINGS LIKE A FIRE
OR GAS LEAK. THIS IS INCREDIBLY
CLINICALLY RELEVANT. I MENTION
ANXIETY AND DEPRESSION BEING
ASSOCIATED WITH LOSS OF SMELL.
WE ALSO BELIEVE LOSS OF SMELL
CAUSES THE DEPRESSION, THE
ANXIETY, THIS IS AGAIN, AN OLDER
STUDY, TEN YEARS OLD NOW, BUT IT
TAKES THE VEXED DEPRESSION
INVENTORY, A SCREENING TOOL TO
IDENTIFY PATIENTS LIKELY TO HAVE
CLINICALLY RELEVANT DEPRESSION,
SCALE OF TEN, ANYTHING BELOW IS
CONSIDERED NORMAL. ANYTHING
ABOVE (LOSS OF AUDIO)
O EPITHELIUM. THESE ARE
RECEPTORS THAT BINDS THE
SPECIFIC ODE RANTS THAT
ALLOWS US TO IDENTIFY THIS
IS A ROSE. FROM THERE, THE
SIGNALING MOVES ON TO WHAT
IS CALLED THE OLFACTORY
BULB, THIS WORM STRUCTURE
RIGHT HERE. SO WE ARE
TRANSITIONING FROM THE
OUTSIDE WORLD INSIDE OUR
NOSE, UP NOW TO THE BRAIN TO
THE CENTRAL NERVOUS SYSTEM.
THE OLFACTORY BULB IS ALSO
CALLED CRANIAL NERVE 1,
TAKES THE SIGNAL AND POP
GATES IT CENTRALLY, WHERE IT
GOES TO KEY CENTERS OF THE
BRAIN, THE LIMBIC SYSTEM,
THE HOME OF EMOTION. IS
DIRECTLY CONNECTED THROUGH
OLFACTORY PATHWAYS. IT IS
PART OF THE REASON THERE'S
SUCH STRONG EMOTIONAL SUCH
STRONG MEMORY COMPONENTS
WITH THE SENSE OF SMELL.
OTHER THINGS THAT SENSE OF
SMELL HELPS US WITH IS
EATING AND HUNGER CONTROL
ARE ACTUALLY INSULIN
RECEPTORS ASSOCIATED WITH
THIS SYSTEM. CONNECTING WITH
OTHER PEOPLE, THE SOCIAL
ELEMENT IS TREMENDOUS.
AGAIN, SAFETY. IF WE LOOK A
LITTLE BIT CLOSER AT THIS
KEY REGION OF THE OLFACTORY
EPITHELIUM, THERE IS 6 TO 10
MILLION OLFACTORY RECEPTORS
THAT ARE EXPRESSED IN THIS
AREA. THEY REPLICATE
THROUGHOUT LIFE WHICH IS
SOMEWHAT UNIQUE, EXTREMELY
UNIQUE. AND THEY ARE CAPABLE
OF DETECTING THOUSANDS OF
DIFFERENT ODORANTS. FROM
THERE, THIS PIECE IS
IMPORTANT. IT IS GOING TO
COME UP AGAIN WHEN I TALK
ABOUT PEROSMIIA. EACH NEURON
HAS RECEPTOR FOR ONE
ODORANT. SO THESE THREE
NEURONS HERE ALL GO O THE
SAME STRUCTURE HERE, THE
GLOMERULUS, IT IS A ONE TO
ONE ASSOCIATION. HOW WE CAN
DIFFERENTIATE AN APPLE FROM
AN ORANGE ISN'T BECAUSE WE
HAVE ONE UNIQUE RECEPTOR FOR
EVERY ONE OF THE TENS OF
THOUSANDS OF ODORS THAT WE
SMELL, IT IS BECAUSE EACH
ODORANT ACTIVATES SEVERAL OF
THESE. SO YOU HAVE 10,000
RECEPTOR, 52 ACTIVATED BY A
ROSE AND THOSE 52 TELL OUR
BRAIN THEY ARE SMELLING A
ROSE. THAT'S IMPORTANT
BECAUSE WE BELIEVE ONE TO
ONE RELATIONSHIP IS
DISRUPTED IN OTHER FORMS OF
DISEASE. WE WILL TALK ABOUT
THAT AT END. SO I HAVE
COVERED MOST OF THIS AGAIN
FROM ODOR DETECTION TO A
SINGLE TRANSDUCTIONS FROM
THE NOSE TO THE BRAIN TO
NEURAL PROCESSING TO ALLOW
US TO UNDERSTAND NOT ONLY
THE ODOR YOU ARE SMELLING
BUT THE ASSOCIATED EMOTIONAL
MEMORY COMPONENTS WHICH ALL
TOLD TOGETHER LEAD TO
PERCEPTION. HOWEVER, DESPITE
EVERYTHING THAT I HAVE
SHARED SO FAR TODAY, SENSE
OF SMELL IS OFTEN
UNDERAPPRECIATED, SO WHAT?
IS A VERY COMMON QUESTION
PATIENTS FACE THAT I HAVE
BEEN ASKED, YOU LOSE YOUR
SMELL IT IS NOT GOING TO
KILL YOU. WHY ARE WE
WORRIED? WELL, WE KNOW SMELL
IS DIRECTLY CONNECTED TO
MEMORY AND EMOTION, CRITICAL
FOR DETECTING ENVIRONMENTAL
HAZARDS, ESSENTIAL FOR
FLAVOR PERCEPTION AND
NUTRITION, AND AGAIN, AN
EMERGING BIOMARKER FOR
NEUROLOGIC HEALTH. SO WHY
DOES THIS SENSE NOT GET AS
MUCH ATTENTION AS IT
DESERVES? THERE IS A COUPLE
OF REASONS. I WANT TO CALL
OUT MY PARTNER IN CRIME PAUL
HERE TO HELPED ME PUT
TOGETHER A FEW OF THESE
SLIDES AND MAKE SURE WE WERE
ON THE SAME PAGE. AS I
MENTIONED SMELL IS EXPECTED
TO WORSEN WITH AGE, IT
COMPLICATES QUITE A BIT OUR
ABILITY TO UNDERSTAND WHAT
IS NORMAL AND WHAT IS NOT.
SMELL IS AN EARLY WARNING
SIGN AS I SAID BUT IT CAN BE
A REMOTE EARLY SIGN WHICH IS
WONDERFUL, THAT GIVES US THE
OPPORTUNITY TO TREAT
PARKINSON'S FIVE YEARS
BEFORE NEUROLOGIC SYMPTOMS
DEVELOP BEFORE THE
PATHOLOGIC PLAQUES FORM IN
THE BRAIN BUT THAT ALSO
LEAVES INCREDIBLY LONG
RUNWAY TO FORGET ABOUT
CHANGE IN SMELL OR THINK IT
WAS SOMETHING ELSE. I DIDN'T
HAVE PARKINSON'S UNTIL MY
TREMORS STARTED FIVE YEARS
AFTER I LOST MY SMELL. IT
IS OFTEN IGNORED OUTRIGHT.
IT IS LACK OF TRAINING, LACK
OF UNDERSTANDING IN OUR
MEDICAL COMMUNITY. THE
SECOND PATIENT I SHARED THE
UNDIAGNOSED PARKINSON'S,
WITHIN THE FIRST FOUR YEARS
I WAS SEEING HIM I SENT HIM
TO NEUROLOGY WITH THIS
SPECIFIC CONCERN.
NEUROLOGISTS WROTE ME BACK.
AND SAID YOU ARE WASTING MY
TIME, YOU ARE WASTING YOUR
PATIENT'S TIME. DO NOT SEND
THESE PATIENTS UNLESS THEY
HAVE A FOCAL DEFICIT. SMELL
IS A FOCAL NEUROLOGIC
DEFICIT. BUT TO ME THAT
HIGHLIGHTS THAT WE NEED TO
DO A BETTER JOB OF TEACHING
GIVING SEMINARS LIKE THESE.
SO WITHIN THE 130 PLUS
CONDITIONS WE HAVE
ASSOCIATED WITH LOSS OF
SMELL, WHAT IS MOST COMMON?
VIRAL INFECTION AS WE HAVE
MENTIONED IS RELATIVELY
COMMON WITH A HUGE SPIKE IN
PREVALENCE OVER THE LAST
FIVE YEARS. NEUROLOGIC
DISORDERS AGAIN NOT JUST
PARKINSON'S, TALK ABOUT
ALZHEIMER'S AS WELL AS
OTHERS SUPERNUCLEAR, PALSY,
NUMBER OF NEUROLOGIC
DEGENERATIVE CONDITIONS.
HEAD TRAUMA, AGING AND A
HUGE NUMBER OF MEDICATIONS.
IF YOU ARE DEPRESSED YOU MAY
BE PUT ON AN ANTIDEPRESSANT
BECAUSE OF YOUR SMELL LOSS.
YOUR ANTIDEPRESSANT CAN
CAUSE SMELL LOSS TOO. SO
THERE'S A LOT OF INFORMATION
TO CONSIDER. SO WE MENTION
HOW SMELL LOSS CONNECTS TO
BRAIN DISEASES BEYOND
PARKINSON'S. AS AN EARLY
WARNING SIGN, A NUMBER OF
CONDITIONS INCLUDING
PARKINSON'S THEY LOSE SMELL
FIRST BECAUSE THE PATHOLOGIC
DEPOSITS THE AGGREGATES IN
THE BRAIN ACTUALLY FORM
WITHIN THE OLFACTORY SYSTEM
FIRST. IT CAN EVEN CAPTURE
THEM WITHIN THE NOSE IN THE
OLFACTORY EPITHELIUM,
PATIENTS WITH BOTH
ALZHEIMER'S AND PARKINSON'S
BEFORE ANY OTHER SYMPTOMS.
THOSE ARE THE BRAIN CHANGES.
THEN THE PATTERN OF DECLINE,
THERE'S ACTUALLY A
PREDICTIVE ELEMENT TO THIS
AND A PATIENT WHO HAS
SEVERELY LOST THEIR SENSE OF
SMELL IS MORE LIKELY TO HAVE
MORE ADVANCED SYMPTOMS O
THEIR NEURODEGENERATIVE
DISEASE. AGAIN, ALL OF
THESE THINGS LEAD TO THE
CONCLUSION THAT SMELL LOSS
IS AN IMPORTANT BIOMARKER
SPECIFICALLY FOR
NEURODEGENERATION. I WANT TO
DRIVE THIS POINT HOME WITH
TWO LAST SLIDES, THIS
COVERING PARKINSON'S AND
NEXT ALZHEIMER'S. AS I
MENTION THIS IS THE
STRONGEST KNOWN LINK
ASSOCIATION BETWEEN LOSS OF
SMELL AND NEURODEGENERATIVE
DISEASE. UP TO 90% OF
PARKINSON PATIENT EXPERIENCE
SMELL LOSS OFTEN YEARS PRIOR
TO CLASSIC MOTOR SYMPTOMS.
LEWY BODIES ARE THE
PATHOLOGIC AGGREGATES APPEAR
FIRST IN THE OLFACTORY BULB,
CRANIAL NERVE 1 AND SPREAD
FROM THERE WELL BEFORE IT I
WANT PACTS THE SUBSTANTIA
NIGRA OR ONE OF THE CRITICAL
STRUCTURE WE THINK OF WITH
PARKINSONS. THERE IS A LAND
MARK STUDY THAT SHOWED
AMONGST PATIENTS WITH
UNEXPLAINED SMELL LOSS,
GENTLEMEN THAT PRESENTEDDED
IN THE SECOND SLIDE, THEY
ARE UP TO FIVE TIMES HIGHER
RISK OF DEVELOPING
PARKINSON'S WITHIN THE NEXT
FOUR YEARS. AGAIN
INCREDIBLY IMPORTANT
PREDICTIVE MARKER. IF WE
LOOK AT ALZHEIMER'S AND WE
GO FROM STAGE 1 OR
PRE-CLINICAL STAGE GOING
DOWN WITH ADVANCEMENT OF
SYMPTOMS WE SEE SMELL IS
IMPACTED IN AND PLAYS A ROLE
THROUGHOUT THE COURSE OF
THIS DISEASE. THE
PRE-CLINICAL STAGE BETA
AMYLOID THE PATHOGNOMONIC
STRUCTURE IN ALZHEIMER, THAT
AND TAU APPEAR AGAIN IN THE
OLFACTORY BULB AND THE
INTRARINAL CORTEX FIRST
WEIGH STATION OF THE BRAIN
PROCESSING OLFACTORY SIGNALS
YEARS BEFORE CLINICAL
SYMPTOMS. AS THE PATIENTS
ADVANCE AND NOW DISPLAY MILD
COGNITIVE IMPAIRMENT, 70 TO
80% PATIENTS SHOW IMPAIRED
ODOR IDENTIFICATION. THOSE
WITH MILD COGNITIVE
IMPAIRMENTS AND DECREASE
SENSITIVITY TO SMELLS, THEY
ARE SIGNIFICANTLY MORE
LIKELY TO CONVERT TO FULL
PLEDGE ALZHEIMER'S. YEAH.
YEAH.
(OFF MIC)
>> THAT IS A GREAT QUESTION. SO
HOW DO YOU -- YES, YES. THE
QUESTION IS HOW DO YOU
DIFFERENTIATE IN THIS EXACT
PATIENT THE CAUSE? ARE THEY
HAVING DIFFICULTY IDENTIFYING
THE SENSE OF SMELL THAT THEIR
OLFACTORY SYSTEM IS REGISTERING?
OR IS IT THEY ARE NOT
REGISTERING THAT SENSE OF SMELL?
UNFORTUNATELY IT'S COMPLICATED
AND MY VIEW IS THAT IT REALLY
INVOLVES A THOROUGH EVALUATION
OF THE PATIENT AND A BETTER
UNDERSTANDING OF HOW IMPAIRED
THEY ARE COGNITIVELY. WHAT WE
NEED AND THERE ARE GROUPS
WORKING ON THAT BUT IT IS NOT
CLINICALLY AVAILABLE, IS AN
OBJECTIVE TEST, SOMETHING TO
MEASURE BRAIN WAVES IN RESPONSE
TO ON ODORANT. WE DON'T HAVE
THAT. AMONG PATIENTS WITH
ESTABLISHED ALZHEIMER'S DISEASE,
UP TO 95% SHOW SIGNIFICANT
ALTERATIONS IN THEIR ABILITY TO
SMELL. I MENTION PSYCHIATRIC
CONDITIONS AS WELL, THIS IMPACTS
WELL BEYOND NEURODEGENERATION
AND THERE'S IMPORTANT RESEARCH
AND STUDY LINKING LOSS OF SMELL
WITH MAJOR DEPRESSIVE
DISOFFEDDER, WITH SKITS
FRIENDSIA AND STUDIES LOOKING AT
AUTISM SPECTRUM. VERY BROAD AREA
THAT'S RICH FOR DISCOVERY TO
ADVANCE PATIENT CARE. FROM SO A
GREAT QUESTION THAT LEADS TO THE
SEGUE, HOW DO WE TEST THE SENSE
OF SMELL? I WILL TELL YOU ON THE
FRONT, SELF-REPORT IS NOT A GOOD
TEST. UP TO 40% OF PATIENTS THAT
COME TO YOU AND SAY I THINK I
HAVE LOST MY SENSE OF SMELL,
ACTUALLY HAVEN'T. WE NEED MORE
DEFINITIVE TESTS. PSYCHOPHYSICAL
TESTS ARE TESTS THAT WE
CRUCIALLY RELY ON IN THE CLINIC.
THEY ARE A TEST THAT RELIES ON A
PATIENT'S RESPONSE. THESE ARE
NOT TRULY OBJECTIVE. THERE ARE
OVER 40 OF THESE TESTS ON THE
MARKET TODAY. AND OVERWHELMING
NUMBER WITH AS MUCH VARIATION AS
YOU CAN IMAGINE IN THE STUDY
BEHIND THE TEST, THE APPROPRIATE
INDICATION, THE APPROPRIATE
PATIENT, ET CETERA. IT IS
CONFUSING FOR ANYONE. SEW LIKE
A GOOD RESEARCH TEAM WE SOUGHT A
STRAIGHT FORWARD NARRATIVE
REVIEW GOING THROUGH PEER REVIEW
CURRENTLY, NOT YET PUBLISHED BUT
WE WE LOOKED AT ALL 40 PLUS
TESTS THE HUNDREDS TO THOUSANDS
OF MANUSCRIPTS THAT SUPPORT
THEM. AND THEN WE DEVELOPED THIS
GRAPHICAL ABSTRACT THAT AS FAR
AS I'M AWARE IS THE FIRST EFFORT
TO REALLY TAKE THE DIFFERENT
VARIATIONS, DIFFERENT CAUSES OF
LOSS OF SMELL AND MAKE
RECOMMENDATIONS FOR THE
DIFFERENT SPECIFIC TESTS THAT
CAN BE USED. WHILE I HOPE THIS
IS IMPACTFUL FOR OUR PATIENTS
AND I CERTAINLY AM HOPEFUL THEY
WILL HAVE ACCESS TO THIS AND
WILL READ IT, I THINK IT IS
CRITICAL FOR MY COLLEAGUES IN
OTO LARYNGOLOGY NEUROLOGY FAMILY
PRACTICE THERE IS NO
REIMBURSEMENT FOR SMELL TEST, IT
IS CURRENTLY NOT SUPPORTED. BUT
THEY ARE INEXPENSIVE AND
CLINICALLY IMPORTANT. SO WE VIEW
THIS AS AN OPPORTUNITY FOR
INTERESTED CLINICIAN TO GET
GUIDANCE TO UNDERSTAND WHICH
TESTS AND FOR WHICH PATIENT. I
WANT TO GIVE KUDOS TO NIDCD IN
THAT TWO YEARS AGO WE FUNDED A
GRANT CALLED CHEMO SENSORY
TESTING. THIS IS A REALLY UNIQUE
MULTI-DISCIPLINARY MEETING THAT
BROUGHT TOGETHER BROAD SPECTRUM
OF INDUSTRY, CLINICIANS,
PATIENTS AND THEIR ADVOCACY
GROUPS, TO UNDERSTAND WHY THERE
IS NOT UNIVERSAL TESTING OF THE
SENSE OF SMELL, WHY IS IT NOT
CONSIDERED A VITAL SIGN THAT
SHOULD BE MONITORED JUST LIKE
BLOOD PRESSURE. SURVEY UNRELATE
TOTTED THAT MEETING FOUND 90% OF
PATIENTS APPRECIATE BEING ASKED
TO TEST THEIR SENSE OF SMELL
THESE TESTS ARE NON-INVASIVE,
RELATIVELY QUICK AND GIVES
INSIGHT. 60% OF PEOPLE, 40% OF
PEOPLE THAT HAD THOUGHT THEY
LOST THEIR SENSE OF SMELL
HAVEN'T, FLIP THAT AROUND
PATIENTS THINK THEIR SENSE OF
SMELL IS FINE, YOU IDENTIFY
DEFICIENCY, THIS IS A SOMETHING
THAT SAN EASY ASK IN MY
EXPERIENCE. -- IS AN EASY ASK
IN MY EXPERIENCE. IT SAVES
MONEY. THAT'S THE ECONOMIC
ARGUMENT, IF WE IDENTIFY
DISEASES SOONER, WE CAN TREAT
THEM SOONER, WE CAN SPARE MONEY,
WE CAN SAVE FUNDS FOR OTHER
THINGS, MORE RESEARCH TO ADVANCE
SCIENCE FURTHER. AGAIN AN
AVERAGE OF FIVE TO TEN YEARS OF
EARLIER DIAGNOSIS FOR MANY OF
THESE CONDITIONS. PSYCHOPHYSICAL
TESTING AS I MENTION IS LIMITED
AND THERE IS A NUMBER OF
ADDITIONAL DEVICES APPROACHES TO
OBJECTIVELY MEASURE SENSE OF
SMELSMELL. OLFACTOMETERS A DIGIL
DEVICE TO REDUCE SENSE OF SMELL
IS BEING ACTIVELY DEVELOPED BY
SOME OF THE BIGGEST FORTUNE 500
COMPANIES INTERNATIONALLY. THEY
SEE THE MARKET FOR THIS AND HAVE
REALLY BEEN VERY INTERESTING
PARTNERS, NON-MEDICAL -- I WILL
LEAVE AT THAT BUT INDUSTRY WANTS
TO CONTRIBUTE. AND THEY ARE
LENDING THEIR EXPERTISE TO HELP
TO DEVELOP NEW TOOLS. FUNCTIONAL
NEUROIMAGING, THIS CURRENTLY IS
LIMITED TO THE RESEARCH SETTING,
PARTICULARLY HERE AT THE NIH.
BUT IT ALLOW US TO GET TO THAT
OBJECTIVE QUESTION, CAN WE SEE A
FUNCTIONAL CHANGE IN ACTIVITY
WHEN SOMEONE IS EXPOSED TO AN
ODOR THAT TELLS US THE SYSTEM IS
INTACT? AGAIN, BIOMARKER
INTEGRATION. I MENTION WE CAN
COLLECT TAU PROTEIN IN THE NOSE
OF SOMEONE WITH EARLY
ALZHEIMER'S DISEASE. THESE ARE
CRITICAL ADVANCEMENTS WAITING TO
BE ESTABLISHED AND UTILIZED. SO
WHAT ARE WE GOING TO DO? AS LISA
MENTIONED, A YEAR AGO WE HAVE
OPENED THE NATIONAL SMELL AND
TASTE CENTER. I WILL TELL YOU
ALL THIS WAS THE PUSH FOR ME TO
LEAVE WHAT I ABSOLUTELY LOVED IN
ATLANTA AND TO COME BACK HOME TO
JOIN THE NIH AND TO MAKE A
DIFFERENCE, THAT HAS ALWAYS BEEN
MY DRIVING PRINCIPLE. I IMAGINE
IT IS SOMETHING NEAR AND DEAR TO
Y'ALL AS WELL. WE ARE HERE TO
IMPACT OUR PATIENTS. THE SMELL
AND TASTE CENTER IS A CLINICAL
RESEARCH HOME FOR CHEMO
SENSATION, SMELL AND TASTE
STUDIES AT THE NIH. WE ARE
INTENTIONALLY PATIENT CENTERED,
LOOKING TO LEAD TRANSLATIONAL
SCIENCE TO BRIDGE THE GAP FROM
THE CRITICAL BASIC STUDIES THAT
OUR INVESTIGATORS ARE MAKING TO
THE BEDSIDE. WHERE IT CAN IMPACT
OUR PATIENTS. OUR INAUGURAL
SEMINAR WAS IN BUILDING 35
AROUND THE CORNER AND WE WERE
VERY HONORED TO HAVE PROFESSOR
THOMAS HUMMEL AS OUR INAUGURAL
SPEAKER. THIS IS A GROUP PHOTO
AND SOMETHING I LOVE HANGING IN
MY OFFICE. THIS IS A BIT OF
WHO'S WHO WITHIN THE FIELD AND
REALLY WAS JUST AN AMAZING
OPPORTUNITY TO SHARE ADVANCES
AND AREAS OF INTEREST AND
FURTHER RESEARCH WITH THIS
GROUP. INTENTIONALLY WE ARE NOT
LIMITING OURSELVES TO THE NIH
INTRAMURAL PROGRAM. WE WITH THE
HELP OF OUR CONGRESSIONAL TEAM
WE REACHED OUT TO CONGRESS AND
HAVE RECORDED VIDEOS, THOUGHTFUL
WORDS OF SUPPORT FROM A NUMBER
OF CONGRESSMEN AN WOMEN TO
REALLY TO ME SPEAKS TO THE
IMPORTANCE OF WHAT WE ARE TRYING
TO DO. THE MISSION STATEMENT FOR
THE NATIONAL SMELL AND TASTE
CENTER AT THE NIH IS TO ADVANCE
THE UNDERSTANDING OF CHEMICAL
SENSES, SMELL AND TASTE AND
RELATED DISORDERS THROUGH
COMPREHENSIVE RESEARCH,
EDUCATION, PATIENT CARE. THOSE
ARE OUR BULLETS. OUR PILLAR, IF
YOU WILL. INNOVATIVE RESEARCH,
COMPREHENSIVE CARE, AND
EDUCATION AND OUTREACH. WITHOUT
ALL THREE OF THESE WE WILL NOT
HAVE THE IMPACT THAT OUR
PATIENTS DESERVE. OUR CENTER IS
LED BY PAULY AND I. HOWEVER THIS
TAKES A VILLAGE. AS ALL
RESEARCH DOES. MANY OF YOU IN
THIS ROOM AND I WILL CALL YOU
OUT WITH ACKNOWLEDGMENTS ARE
CRITICAL TO THIS NOT ONLY
YESTERDAY BUT TODAY AND FUTURE.
THIS RESEARCH PROGRAM WILL NOT
SURVIVE WITHOUT DIR AND THE
IMMENSE ADMINISTRATIVE SUPPORT
WE GET ALMOST ON A DAILY BASIS.
I'M LOOK RIGHT AT YOU AS I SAY
THAT. WE HAVE VERY UNIQUE
RESOURCES. THIS IS THE DRIVING
THINGS THAT I POINT TO WHEN
ASKED WHAT IS UNIQUE ABOUT THIS
PROGRAM? IN THE PICTURE ON THE
RIGHT YOU SEE OUR RESEARCH
PARTICIPANT HOOKED UP TO A
MACHINE IN THE BACKGROUND, BUNCH
OF CANISTERS AND TUBES. THIS IS
AN OLFACTOMETER. WHAT WE KNOW
ABOUT SENSE OF SMELL IS STUDYING
IT IS NOT EASY AND IT CHANGES TO
CONCENTRATION OF THE ODORANT,
TEMPERATURE OF THE AIR, THE
RELATIVE HUMIDITY OF THE AIR.
CHANGES PERCEPTION, CHANGES THE
SIGNAL. SO JUST LIKE AN AUDIO
PETRI BOOTH YOU HAVE OBJECTIVE
STRUCTURED SIGNAL TO PRESENT TO
THE PATIENT FOR SMELL WE HAVE
OLFACTOMETERS. WHAT WE HAVE HERE
IS BUILT IN GERMANY. THEY ARE
NOT ASSEMBLED IN THE STATES.
AND FOR ME TO BE TRAINED ON IT,
I ACTUALLY HAD TO FLY AN HOUR
NORTH OF MONTREAL TO THE NEAREST
OLFACTOMETER DEVELOP AND USED
CLINICALLY BY THIS RESEARCH
TEAM. THERE ARE OTHER
OLFACTOMETERS OUT THERE BUT THIS
IS THE MOST ESTABLISHED AND
GIVES US THE GREATEST
OPPORTUNITY TO HAVE A UNIQUE
IMPRINT. OUR CENTER IS NOT
LIMITED TO SMELL. WE ALSO HAVE
A GUTOMETER WHICH IS THE SAME
ANALOGY THAT IS IN AUDIOLOGY
BOOTH FOR TASTE H. WE ARE
ACQUIRING AN EEG TO MEASURE
BRAIN ACTIVITY AND NEURAL
ACTIVATION WITH THESE
STANDARDIZED EXPOSURES. WE WILL
BE USING THIS BOTH IN THE CLINIC
AND IN ASSOCIATION WITH
FUNCTIONAL MRI. SO WE WILL
GENERATE A TON OF DATA AND
INSIGHT TO SEE WHAT IS GOING
WRONG AND HOW WE CAN FIX THESE
ISSUES. THERE ALSO IS A
PARTNERSHIP THAT WE ARE FORMING
WITH NINDS WHERE I THINK IT IS
MY LAST SLIDE, I WILL HIGHLIGHT
INTRACRANIAL RECORDINGS O.
PATIENTS UNDERGOING NEUROSURGE
PROCEDURES AT CLINICAL CENTER
WILL BE EXPOSED TO TESTING
BATTERY AND WILL HAVE THAT MUCH
GREATER DETAIL OF THE NEURAL
ACTIVITY. SO THIS IS A QUICK
SUMMARY OF THE DIFFERENT TYPES
OF SMELL DYSFUNCTION. THERE IS
NOT ONE FORM. I MENTIONED DEPOS
MENTIONA AND ANOSMIA AND I FOX
OUT PEROSMIA A QUALITATIVE SMELL
DISORDER. THIS IS THE FOCUS OF
FIRST PROTOCOL AND I WILL WIND
UP WITH A FEW SLIDES GIVING YOU
GREATER DETAIL ABOUT THIS STUDY
BUT THE REASON WE WANT TO STUDY
QUALITATIVE SMELLS, QUALITATIVE
SMELL DISORDERS, IS THAT THE
PREVALENCE HAS DRAMATICALLY
INCREASED OVER FIVE YEARS. WE
DON'T HAVE THE POPULATION BASED
DATA TO GIVE YOU A FIRM NUMBER,
THIS MANY PARTICIPANTS HAVE
DEVELOPED QUALITATIVE KISS
ORDERS. BUDDIES ORDERS BUT WE
KNOW IT IS SIGNIFICANT. IT IS
RELATIVELY UNDERSTUDIED FOR THAT
REASON. AND IT IS A COMMON AND
DEFINING SYMPTOM OF PATIENTS
WITH LONG COVID. THIS IS A
PREVALENT CONCERNING DISORDER.
BEFORE LAST FIVE YEARS, 2007 THE
POPULATION BASED PREVALENCE WAS
3.9%. NOT RARE DISEASE BY ANY
MEANS BUT THIS NUMBER IS
SEVERELY LOW. GOING TO JUMP
THROUGH A COUPLE FOR THE SAKE OF
TIME. WHAT IS PAAROSMIA IN IT IS
DRAMATIC. PATIENTS THAT DEVELOP
STRONGLY NEGATIVE PERCEPTION
WHEN EXPOSED TO A TRIGGERING
ODOR. THIS CLOUD MAP ON THE TOP
RIGHT ARE THE MOST COMMON
TRIGGERS. YOU CAN SEE THERE ARE
THINGS I PARTICULARLY LIKE.
COFFEE, IMAGINE YOU WAKE UP ONE
MORNING TO HAVE YOUR FAVORITE
CUP OF COFFEE AND IT SMELLS LIKE
SEWAGE. NOT ONLY THAT, IT IS
TRIGGERED A PANIC ATTACK AND YOU
PHYSICALLY HAVE TO REMOVE
YOURSELF FROM THE ROOM. THIS IS
NOT AN EXAGGERATION. THIS IS
VERY TYPICAL FOR THESE PATIENTS.
THEY ARE MORE LIKELY TO AFFECT A
YOUNGER FEMALE PATIENT THAN NOT
THOUGH IT CAN PRESENT THROUGHOUT
THE GENDER AND AGE SPECTRUM.
TYPICALLY THREE TO 12 MONTHS
FOLLOWING A VIRAL ILLNESS IS
WHEN THIS APPEARS. WE NOTICE
SEVERE EMOTIONAL STRAIN AS I
MENTION, THIS CAN LEAD TO FOOD
AVOIDANCE AND WHAT WE CONSIDER
COMPULSIVE EATING DISORDERS.
SASHLY SITTING IN THE BACK --
ASHLEY SITTING IN THE BACK
RECEIVED A GRANT FOR COMPULSIVE
EATING DISORDERS BEHAVIORS TO
STUDY THIS FOR THIS REASON. WE
KNOW ASSOCIATION BUT IT HASN'T
BEEN I STUDIED OR DEFINED. WORST
OF ALL, TREATMENT IS LIMITED.
WHEN I SEE THESE PATIENTS IN
CLINIC I HAVE A SMALL PIT IN MY
STOMACH, ALL I CAN OFFER IS
SUPPORTIVE CARE AND HOPE THAT
THESE SYMPTOMS RESOLVE OVER THE
NEXT FEW YEARS. SO WHAT IS THE
CAUSE OF PAROSMIA? THIS IS OUR
FIRST PROTOCOL. I MENTIONED THE
IMPORTANCE OF THE GLOMERULI AND
THIS ONE TO ONE CONNECTION
BETWEEN OLFACTORY SENSE ARE I
NEURONS TO A SPECIFIC ODORANT IN
THE GLOMERULUS WHERE IT CONNECTS
CENTRALLY. THESE ON THE RIGHT
HIGHLIGHT THAT NORMAL FUNCTION
RECEPTOR ACTIVATES A NERVE,
ACTIVATES A GLOMERULUS. ON THE
RIGHT WHAT WE BELIEVE TO BE A
MISWIRING WHERE THAT ONE
OLFACTORY SENSORY NEURON BECAUSE
OF MAYBE RECOVERY FROM VIRAL
INJURY NO LONGER ATTACHES TO THE
RIGHT GLOMERULUS. THERE IS A
MIX UP MANY THE CODE. AND
BECAUSE OF THAT, THERE IS A MIX
UP IN MANY THE PERCEPTION OF THE
SMELL. WE KNOW THIS IS NOT ONLY
PERIPHERAL, HOWEVER. WE KNOW
THAT THE BRAIN STRUCTURALLY
CHANGES WITH PAROSMIA. THERE IS
REDUCED VOLUME OF THE OLFACTORY
BULB, ATROPHY OF CORTICAL
REGIONS WITHIN THE BRAIN. AND
FUNCTIONALLY, WE KNOW THERE IS
REDUCED CONNECTIVITY, THE
PATHWAYS FOR WHICH OUR BRAIN
INTERPRETS SMELL, IS ALTERED.
AND I HAVE CIRCLED IN RED HERE
(INDISCERNIBLE) NEW RECRUITS NEW
POST-DOCS WITHIN THE NIDCD I
WOULD PARTLY BECAUSE OF THIS
EXACT WORK. SO HERE IS
(INDISCERNIBLE). THE THEMES OF
THE STUDY ARE TO INVESTIGATE
CHANGES IN NEURONAL CONNECTIVITY
THAT ALTERS OLFACTORY PERCEPTION
IN PAROSMIA AND ASSOCIATE NEURAL
INFLAMMATION WITH THESE
FUNCTIONAL CHANGES. I BELIEVE
THE UNDERLYING CAUSE IS
UNRESOLVED INFLAMMATION BOTH
PERIPHERALLY AS WELL AS
CENTRALLY. HERE IS OUR STUDY
DESIGN. WE WILL BE RECRUITING 80
PARTICIPANTS. SO 20 WITHIN FOUR
COHORT, WE WILL FOLLOW THEM OVER
A YEAR. THIS IS A SUMMARY OF
STUDY ACTIVITIES. WE WILL BE
MEASURING QUALITY OF LIFE,
PATIENT SELF-ASSESSMENT, WE WILL
BE DOING PSYCHOMETRIC TESTING.
AND RETRO NASAL TESTING, THE WE
BREATHE IN AN MATERIALLY, HOW IS
SENSE OF SMELL WORKING, IF WE
EAT SOMETHING THE ODOR GOES
BEHIND YOUR PALATE. HOW IS THAT
WORKING? THEN WE WILL
OBJECTIVELY MEASURE WITH EEG
FUNCTIONAL AND STRUCTURAL MRI.
I EXPECT TO FIND A LOT OF
THINGS. THIS IS A PROGRAM
BUILDING STUDY, NOT A SMALL
STUDY THAT I EXPECT TO BE
FINISHED IN THE NEXT SIX MONTHS
SADLY. I EXPECT WE WILL DESCRIBE
ALTER CONNECTIVITY PATTERNS THAT
INVOLVE MOTION CENTERS AND
RESOLVE WITH PATIENT SYMPTOMS
TOWARDS RECOVERY. WILL CORRELATE
CENTRAL FINDINGS WITH NEURAL
INFLAMMATION PATIENT REPORTED
OUTCOMES AND TESTING. ESTABLISH
THE ASSOCIATION OF PAROSMIA WITH
COMPULSIVE EATING DISORDERS AS I
MENTION AND IDENTIFY THERAPEUTIC
TARGETS FOR FUTURE STUDY. THIS
CENTER, THIS PROGRAM, IS
INCREDIBLY UNIQUE TO THE NIH
INTRAMURAL PROGRAM. I AM THE
LUCKIEST PERSON THAT I KNOW. I'M
IN A CENTER, A PLACE WITH Y'ALL
THAT VALUES THIS WORK AND HAS
WORLD-LEADING EXPERTS IN AREAS
THAT DOVE TAIL BEAUTIFULLY.
CENTER FOR ALZHEIMER'S AND
RELATE DEMENTIAS, WE ARE
PARTNERING WITH THEM TO HAVE A
PRESENCE IN THEIR NEW CLINIC IN
THE CLINICAL CENTER, BOTH FOR
HEARING TESTING AS WELL AS SMELL
AND TASTE. THE RESOURCES
UNBELIEVABLE. SAME IS SAID WITH
THE BALTIMORE LONGITUDINAL STUDY
OF AGING, DESPITE THE DISTANCE
IN BALTIMORE WE ARE PARTNERING
AND REALLY LEVERAGING THAT YOU
ARE DATA SET AN INTEREST IN
SMELL AND TASTE. AND THEN
FINALLY, THE FUNCTION PAL
NEUROSURGERY SECTION OF SENIOR
PI IS PRETTY COOL. THIS IS A
STUDY THAT'S VERY SIMILAR TO ONE
THAT WAS JUST PUBLISHED IN
NATURE, THAT USED INTRACRANIAL
ELECTRODES, THIS IS CALLED A
UTAH ARRAY ARRAY. WHICH IS CLIY
USED TO PLACE ON THE SURFACE OF
BRAIN AND IDENTIFY REGIONS OR
FOCI OF EPILEPSY. THESE PATIENTS
COME TO CLINICAL CENTER MONDAY
OR TUESDAY, SPEND THE REST OF
THE WEEK WAITING FOR SOMETHING
TO HAPPEN. CHIP IS ON THEIR
BRAIN, THEY ARE FUNCTIONAL,
AWAKE AND ABOUT, BUT THEY ARE
BORED. WE ARE GOING TO BRING
THEM TO OUR MRI SUITE WE WILL
EXPOSE THEM O ODORS WITH
OLFACTOMETER AND LOOK AT NEURAL
ACTIVITY DOWN TO THE SINGLE
NEURONAL LEVE LEVEL. INCREDIBLY
POWERFUL. Z SOFUL. IN SUMMARY OS
TOP PERIPHERAL MECHANISMS THAT
UNDERLIE THE SENSE OF SMELL AN
DISEASE, FOCUS ON HUMAN SUBJECTS
RESEARCH TO PROMOTE TRANSLATION,
IDENTIFY NOVEL TAUGHTS FOR
THERAPEUTIC STUDY AND
DEVELOPMENT INNOVATIVE TOOLS.
THIS IS THE MOST IMPORTANT
SLIDE. NONE OF THIS WOULD BE
POSSIBLE WITHOUT OUR
ADMINISTRATIVE SCIENTIFIC AND
VISION, THE SUPPORT AND HELP
FROM ALL OF YOU IS CRITICAL AND
I WANT TO MAKE SURE EVERYONE
RECOGNIZES IRAB, AT THE BOTTOM
OF THE DIR WITHOUT SCOTT
BATTERER, JOE I CALLED YOU OUT,
LYNN, SARA, RALPH, NONE OF THIS
WOULD BE POSSIBLE. I'M INC ABLY
GRATEFUL TO OUR ENTIRE TEAM.
THESE ARE MY GIRLS, BUDDING
NEUROSCIENTIST, AND WITH THAT, I
BELIEVE WE HAVE A COUPLE OF
MINUTES FOR QUESTIONS. THANK
YOU.
[APPLAUSE]
>> JOSH, THANK YOU. WHEN YOU
TALKED ABOUT BIOMARKERS YOU SAID
ONE OF THE IMPORTANT THINGS IS
THAT IDENTIFYING THIS EARLY CAN
CHANGE THE TREATMENT. SO I'M
THINKING ABOUT NEUROLOGIST WHO
SAID THAT THEY DIDN'T WANT TO
SEE YOUR PATIENT. I'M TRYING TO
THINK ABOUT THAT NEUROLOGIST
WOULD NEED. IF YOU IDENTIFY
PARKINSON'S DISEASE FOUR OR FIVE
YEARS EARLY, IS THERE ANYTHING
TO BE DONE? ALSO DO PEOPLE WHO
HAVE THOSE PLAQUES IN THEIR
NOSE, DO YOU HAVE A LOT OF
PEOPLE WHO HAVE THOSE PLAQUE'S
YOU SAID THE OLFACTORY BULB,
THAT DON'T GO ON TO GET -- ARE
THEY DEFINITIVE OR SOME PEOPLE
WHO HAVE THOSE DON'T GO ON TO
GET THESE DISORDERS?
>> FANTASTIC QUESTION, LISA. TO
ANSWER THE FIRST ONE FIRST. WE
DON'T KNOW. THE DISCOVERY OR THE
DESCRIPTION OF BEING ABLE TO
CAPTURE THESE PATHOGNOMONIC
PLAQUE THE NOSE, WE KNOW THEY
FORM THE OLFACTORY BULB AS WELL.
BUT WITHOUT PUTTING A PATIENT
THROUGH SURGERY, THIS IS
SOMETHING WE CAN DO IN A CLINIC,
THAT ONE STUDY HAS NOT BEEN
REPLICATED. IT IS ABOUT FOUR OR
FIVE YEARS OLDS NOW AND IT IS
RIPE FOR INVESTIGATION AND
VALIDATION, IT IS JUST TOO EARLY
TO KNOW THESE IMPORTANT
PRACTICAL QUESTIONS. YOUR FIRST
QUESTION, REMIND ME.
(OFF MIC)
>> OH, YES. SO YES. IN THIS CASE
WITH PARKINSON'S THERE ARE
EARLIER MEDICATIONS THAT CAN BE
TRIALED WITH THE THOUGHT OF
SLOWING PROGRESSION OR SEVERITY
OF DISEASE. WHAT IS TRULY NEED
REDIRECT EXAMINATION RANDOMIZED
STUDIES TO DEFINE TIME FRAMES
AND EFFECT AND BECAUSE OF THIS
LACK OF UNDERSTANDING AND
ADOPTION FROM OTHER COMMUNITIES
THAT JUST HASN'T BEEN DONE YET.
IT IS SOMETHING THAT WAS FRONT
OF MIND WHEN PAULE AND I FORMED
THE SMELL AND TASTE CENTER. I
DIDN'T MENTION WE HAVE AN
ADVISERY BOARD OF 25 ADVISORS
FROM ACROSS DISCIPLINE, ACROSS
THE WORLD. WE WERE VERY
THOUGHTFUL IN OUR FIRST MEETING
TO TALK ABOUT THIS AND WHO ARE
THE INFLUENCERS FOR LACK OF
BETTER WORD, WITHIN THE
NEUROLOGY SPACE WHO CAN WE
ELICIT TO PROMOTE THE IMPORTANCE
OF THIS.
>> THANK YOU. THIS WAS VERY
EDUCATIONAL FOR ME. I HAD A
SPECIFIC QUESTION. IS THE -- IN
ALZHEIMER'S OR PARKINSON DO YOU
HAVE GENERALIZED LOSS OF SMELL
OR CAN YOU IDENTIFY PATTERNS OR
DISTINGUISH DISEASE LIKES YOU
SAID DROVES AS 52 URINES LIKE
ROSE JASMINE AND SANDAL WOOD, DO
YOU KNOW SOMETHING IS WRONG?
>> IT IS A QUESTION PAULE AND I
HAVE DISCUSSED A NUMBER OF
TIMES. THE DIVERSITY OF ODORANTS
ARE OVERWHELMING. TENS OF
THOUSANDS OF UNIQUE SIGNALS. AND
WHILE WE STRUCTURALLY YOU
ACTIVATE THIS REGION YOU GET
CITRUS AS A FAMILY, AN ORANGE
WILL HAVE SIMILAR COMPOUNDS TO A
TANGERINE, THAT IS NOT
NECESSARILY TRUE AND FROM A
FUNCTIONAL STANDPOINT WE DON'T
THINK IT IS TRUE. BOB PRESENTED
AT THE WALS LECTURE A FEW WEEKS
AGO WHICH ANYONE HASN'T SEEN ON
VIDEOCAST, IT WAS UNBELIEVABLE,
BUT HE FAILED TO FIND A
STRUCTURAL MAP OR A AORBIATION
OF AREA OF OLFACTORY EPITHELIUM
AND DIFFERENT ODORANTS. SO IT IS
A VERY LONG WAY OF SAYING WE
DON'T KNOW HOW LIKE SIMILAR
SMELLS AR ARE. AND HOW THEY ARE
REPRESENTED IN DISEASE.
>> I BELIEVE THAT'S ALL THE TIME
WE HAVE FOR QUESTIONS.
>> THANK Y'ALL.
[APPLAUSE]
>> THANK YOU SO MUCH, EVERYONE,
FOR YOUR EXCELLENT QUESTIONS,
THANK YOU FOR MODERATING OUR Q&A
SECTION AND MOST IMPORTANTLY,
THANK YOU JOSH FOR A VERY
INFORMATIVE PRESENTATION TODAY.
THANKS TO ALL OF YOU FOR JOINING
US FOR TODAY'S BEYOND THE LAB,
UNDERSTANDING COMMUNICATION
DISORDER SPEAKER SERIES. I HOPE
YOU CERTAINLY ENJOYED JOSH'S
PRESENTATION TODAY, EXCELLENT,
EXCELLENT PRESENTATION. REALLY
LEARNED ABOUT OUR INSTITUTES
RESEARCH EFFORTS TOWARDS
ADDRESSING OLFACTORY
DYSFUNCTION. OUR NEXT BEYOND THE
LAB TALK WILL BE HELD NEXT YEAR
AND OF COURSE WE WILL BE SENDING
OUT MORE INFORMATION AS THE
DETAILS ARE FINALIZED. SO
PLEASE BE ON THE LOOK OUT FOR
THAT. AGAIN, I WANT TO THANK ALL
OF YOU FOR ATTENDING TODAY'S
TALK AND WITH THAT I WILL
CONCLUDE TODAY'S PRESENTATION.
THANK YOU SO MUCH FOR ATTENDING
[APPLAUSE]