progress in scientific and medical research

tourette.org

PROGRESS IN SCIENTIFIC AND MEDICAL RESEARCH

Awareness. Research. Support

Accomplishments, Advances and Impact

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TABLE OF CONTENTS

A: EXECUTIVE SUMMARY .............................................................................................................................................................. 2

B: KEY ACCOMPLISHMENTS AND BREAKTHROUGHS .......................................................................................................... 4-5

C: SCIENTIFIC DISCOVERIES..................................................................................................................................................... 7-9 •InsightsIntoTheCausesofTouretteandTicDisorders •BrainAbnormalitiesUnderlyingTS •DevelopmentofAnimalModelsofTics

D: TREATMENT ADVANCES .................................................................................................................................................... 10-12 •ExistingandEmergingDrugTherapies •BehaviorTherapies(CBIT) •SurgicalTreatment(DBS) •NovelTreatmentResearch(DentalOrthoticDevices,MedicalCannabisandOthers)

E: ESTABLISHING BEST CARE GUIDELINES AND PRACTICES: Centers of Excellence Program ................................. 14-16 •CofEProgramBlueprintandCriteria •TAACofEWorkandImpact •CofELocations •CofEAdvisoryandReviewCommittee

F: ADVANCES AND CONSENSUS IN UNDERSTANDING THE NATURE AND OCCURRENCE OF TIC DISORDERS .... 18-19 •SpectrumDisorders •TicDisordersAreNotRare •Co-morbiditiesandCoprolalia •Impact

G: EDUCATION AND TRAINING ............................................................................................................................................20-22 •BehaviorTherapyInstitute •TouretteHealthandEducationProgram(TAA-CDCPartnership) •1stWorldCongressonTouretteSyndrome&TicDisorders •AuthoritativePublications

H: RESEARCH GRANTS & FELLOWSHIPS PROGRAM ACHIEVEMENTS ..........................................................................24-25

I: DEVELOPMENT OF RESEARCH RESOURCES AND INFRASTRUCTURES ..........................................................................26 •ResearchGrantsandProjectsDatabase •BrainDonorandBankingProgram •PatientRecruitmentProgram •ReferralDatabaseandPublicInquiries

J: FOSTERING COLLABORATIONS BY BUILDING CONSORTIA ....................................................................................... 28-33 •TAAInternationalConsortiumforGenomics •TAANeuroimagingConsortium •TAAInternationalDBSRegistry •TAABehaviorSciencesConsortium

•TAAInternationalConsortiumforMedicalCannabisandRelatedDrugsinTicDisorders

K: CREATING PARTNERSHIPS ..............................................................................................................................................34-35 •FederalInstitutes •FoundationsandInstitutions •PharmaceuticalandMedicalDevicesIndustry

L: GLOBAL NETWORK OF ADVISORS AND THOUGHT LEADERS ................................................................................... 36-37 •ScientificAdvisoryBoard •MedicalAdvisoryBoard •CentersofExcellenceAdvisoryandReviewCommittee •EpidemiologyandPrevalence

•OtherContributors

M: THE FUTURE OF RESEARCH AND DEVELOPMENT IN TOURETTE AND TIC DISORDERS ...........................................38

N: KEY TAA-SUPPORTED PUBLICATIONS AND REFERENCES ....................................................................................... 40-43

O: ACKNOWLEDGEMENTS ......................................................................................................................................................... 44

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A: EXECUTIVE SUMMARY

TheTouretteAssociationofAmericawasfoundedin1972withtheaimofimprovingthelivesofallpeople

affectedbyTouretteandTicDisorders.Today’stherapieshelpsymptomsonlypartially.Therefore,theTAAinvests

inresearchwhichmayleadtotomorrow’sbreakthroughsindiagnosisandtreatment.Towardsthisend,theTAA

hasandcontinuestodevelop,implementandoverseeawiderangeofprogramstodrivescientificandmedical

researchintotheseconditions.Theseeffortshaveledto:

• ScientificdiscoveriesinmanyareasofTouretteandTicDisorders.

• Introductionofmoretreatmentoptionsandexplorationofpromisingtherapeuticstrategies.

• Achievementofbetterpatientoutcomesthroughdevelopmentanddisseminationofbestcareguidelinesand

practices.

• BetterunderstandingsofTicDisordersandtheircauses.

• Educationandtrainingprogramsthatwidenthenetworkofcareproviderswhounderstandandcanbetter

helppatientswithTicDisordersandtheirfamilies.

• Aresearchgrants&fellowshipsprogramwhichhasledtobreakthroughs,andhasattractedsubstantial

funding,expertsandresourcesfromelsewhereforresearch.

• Thedevelopmentofresourcesandinfrastructurestosupporttreatmentdiscoveries,scientificbreakthroughs,

thescientistsstudyingTicDisorders,andsignificantfundingfromthefederalgovernment.

• Fosteringofglobalresearchcollaborationsbybuildingseveralconsortiaforcoordinatedresearch.

• Thecreationofpartnershipstosupportthedevelopmentandtranslationofresearchfindingsintopatentable

andmarketabletherapies.

• Establishmentofglobalnetworksofthoughtleaders,andresearchstrategies,toguidepresentandfuture

advancesinTicDisorders.

Inthisreport,wereviewtheTAA-supportedresearchaccomplishmentsandadvancesoverthepast45years.

Wepresentemergingopportunitiesandhighlightunmetneedswhichrequirefurtherresearchanddevelopment.

Aboveall,wehighlighthowtheTAA’sresearchprogramsarecentraltotheTAA’smissionofimprovingthelivesof

thoseimpactedbyTouretteandTicDisorders.

4

TAA’s research and medical programs over the past 45 years have led to the following 20 key discoveries, advances

and developments in Tourette and Tic Disorders:

1. DiscoverythatTicDisorders(TouretteSyndrome,ChronicMotororVocalTicDisorders,ProvisionalTicDisorder)have

multiplecauseswhicharecomplexinteractionsbetweengenetics1-3,environmental4and/orotherunknownfactors.

2. Findingsofgene,chromosomallociandgeneticvariations(e.g.SLITRK,HDC,NRXN1andCNTN6)thatcauserare

formsofTS,increasetheriskofdevelopingthedisorder,andlinkTSwithotherconditionssuchasOCD5-10.

3. InTS,MRIandotherimagingstudiesshowthatvariousbrainareasarestructurallyandfunctionallyabnormal11-13,and

postmortemstudiesshowthattherearelowernumbersofGABAergicneuronsinthestriatum14-16,suggestingthat

thesebrainsystemsplayaroleinthedevelopmentoftics.

4. Discoverythatthelimbicsystem,aregionofthebrainthat

underliestheexpressionofemotions,couldalsoplayaroleinthe

occurrenceofvocalticsandsomebehavioralfeaturesofTS17.

5. Observationsthatalterationincircadianrhythyms18-19andbrain

excitability20-23maycontributetodifferencesinticsymptomonset,

fluctuationsandvariationsintreatmentresponses.

6. Creationofa‘striataldisinhibition’animalmodelthatcloselyrecapitulatestics,whichcanbeusedforexploring

causes/mechanismsunderlyingTicDisordersandtestingtreatmentsfortheseconditions24-25.

7. EarlyclinicaldemonstrationofeffectivenessandlaterimprovementsintheuseofmanyFDAandnon-FDA-approved

drugs,suchasclonidineandaripiprazole(Abilify),thatarenowusedroutinelytotreatTS26,27.

8. FacilitatedthefirstFDA-approvalofadrug,Abilify(aripiprazole),forTouretteinover30years.

9. Discoverythatanewclassofdrug,ecopipam,interactswithnovelD1dopaminergictargetsinthebrainand

effectivelyreducestics,withlittleadverseeffects,inchildrenandadultswithTS28.

10. DevelopmentofandclinicaldemonstrationthatComprehensiveBehavioralInterventionforTics(CBIT),a

medication-freebehaviortherapy,isaseffectiveasdrugsinsomeindividualswithTS29,30.

11. ShowedthatDeepBrainStimulation(DBS)caneffectivelytreatsevereTSbystimulatingspecificareasinthebrain,

andhavedevelopedandpublishedguidelinesforitsuseinclinicalpractice31-33.

12. FundingandsupportingongoingdevelopmentofnovelandpromisingtreatmentapproachesforTS,suchasmedical

cannabis34,dentalorthoticdevices34,35andhome-basedbehaviortherapies34,someofwhichalreadyhaveobtained

USpatentprotection(US9486419B2)andFederalbusinessgrants(5R44MH096344-03,TicHelper.com),tosupport

developmentandcommercialization.

13. LaunchedaCentersofExcellenceprogram36,with9inauguralCentersatthenation’sleadinghealthcare/academic

institutions,todevelop,implementandmaintainbestpracticeguidelinestoachievethehigheststandardofcarefor

peoplewithTouretteandTicDisorders.

14. FacilitatedtheconsensusthatTicDisorders(TS,CMVT,PTD),representaspectrumofneurodevelopmental

conditionswhicharenotrare37,38.Ticsoccurinasmanyas1in5school-agedchildren39.TSoccursin1in166(0.6%)

school-agedchildren.ThecombinedprevalenceforallTicDisordersisover1%ofschool-agedchildren38,40.

B: KEY ACCOMPLISHMENTS AND BREAKTHROUGHS

$21 Million The amount the TAA has invested in 250 scientists since 1984 to develop new understanding of and treat-ment for Tourette Syndrome

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15. FindingsthatOCDandADHDoccurfrequently(upto80%)inTScasesandmaysharegeneticcauses,but

coprolaliaisrelativelyinfrequent(10%)inpeoplewithTS41.

16. TAAprograms,includingasuccessful13-year/$10millionpartnershipwithCentersforDiseaseControl&

Prevention,havedevelopedanddistributedanimpressivelibraryofauthoritativeinformationonTS,and

haveeducatedandtrainedover350,000individuals,includingover35,000physiciansandothercare

providers,onthedisorder.ThishasledtoincreasedawarenessofTic

Disorders,developmentofagrowingnationalreferralnetworkof1,500

careproviders42,amoreaccurateandshortertimetodiagnoseTicDisor-

ders,andimprovedmanagementofpatientswithbetteroutcomes.

17. Hostedthe1stWorldCongressonTouretteSyndrome&TicDisorders,

whichwasthelargestgatheringofTourettecliniciansandscientistsin

thehistoryofthedisorder,withmorethan430attendeesfrom38coun-

trieson6continents43.

18. TheTAAhasinvestedover$21millioninsmallresearchgrantsandfellow-

shipsthathavefundedapproximately450projectsin13broadareasof

research34.Thesegrantshaveattracted,retained,trainedandsupported

over400establishedandearlycareerresearchers,locatedat150institu-

tionsin16countriesacross5continents,todriveprogressinTS.

19. Between2003-2013,every$1ofTAAresearchgrantfundinghasledtonearly$10ingrantfundingfrom

institutions,suchastheNIH,tosupportTouretteandrelateddisordersresearch.

20. Establishmentofawiderangeofresources,(e.g.ResearchGrantsandProjectsDatabase34,BrainBank44,

PatientRecruitmentProgram45,GeneSampleCollections46),consortia(InternationalConsortiumonGenet-

ics47,48,NeuroimagingConsortium49,InternationalDBSRegistry50andBehavioralSciencesConsortium51)and

partnerships(e.g.NIHandCDC)tofacilitateglobalcollaborationonresearchintoTicandrelateddisorders.

TheaforementionedexamplesandotherTAA-supportedresearchaccomplishmentshaveprovided:insightsinto

thecausesandbrainchangesunderlyingTS;increasedmedical,behavioral,surgicalandothertreatmentoptions;

improvedaccesstoskilledcareproviders,moreaccurate/timelydiagnosesandbettercareoutcomes;abetter

understandingoftheoccurrenceofTicDisorders;andresearchgrantsthathaveledtobreakthroughs,aswellas

attractedmanyexperts,partnerships/collaborations,largefundingandotherresourcesthatareneededtofacilitate

researchanddiscoveryinTS.

TAAresearchprogramshavecreatednewopportunities,suchastheexplorationofnewlyidentifiedand

noveltreatmentstrategies,whichareundergoingfurtherresearchanddevelopment.TheTAA’seffortshavealso

establishedglobalnetworksofthoughtleadersandresearchstrategiestoguidepresentandfutureadvancesin

TicDisorders.

Thus,TAAsupportforresearchoverthepast45yearshashaddemonstrableimpactandpromisestocontinue

drivingthemissionofmakinglifebetterforallpeopleaffectedbyTouretteandTicDisorders.

B: KEY ACCOMPLISHMENTS AND BREAKTHROUGHS

430 MEDICAL PROFESSIONALS representing 38 COUNTRIES convened at Tourette Association– led 1ST WORLD CONGRESS on Tourette Syndrome.

Since 2003, $1 of TAA

research grant funding has

helped investigators to obtain

approximately $10 in grant

funding for Tourette & related

conditions from the National

Institutes of Health (NIH)

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C: SCIENTIFIC DISCOVERIES

1. Insights Into the Causes of Tourette and Tic Disorders

TheTAAhasprovidedfunding,resourcesandexpertiseforresearch

worldwideaimedatdecipheringthecausesofTS.Theseeffortshaveled

tothefollowingadvances:

• ItisnowrecognizedthatTShasmultiplecauses.Currentconcepts

suggestacomplexinteractionbetweengeneticrisks,environmental

and/orotherfactors1-4.

• FamilyandtwinstudiesshowthatTSisahereditarydisorderand,if

aparenthasTS,his/herchildrenare10timesmorelikelytodevelop

thecondition.

• TSseemstosharesomegeneticbackgroundwithother

neurodevelopmentaldisorders,suchasOCD,ADHDandautism

spectrumdisorders.

• AlthoughresearchhasnotyetidentifiedgenesthatcauseorcontributetothemajorityofcasesofTic

Disorders,ourfinancialsupport,resourcesand/orexpertisehavehelpedtoidentifyraregeneticcauses

(SLITRK1 and HDC),chromosomalandvariationsofTS5-10:

• TheTouretteAssociationInternationalConsortiumforGenetics(TAAICG)anditscollaboratorshavestudied

geneticmaterialfromover2,400individualswithTSand4,100peoplewithoutTS.Itwasfoundthatindividuals

withTSwereupto20timesmorelikelytohaveabnormalities(eitherduplicatedordeletedgeneticmaterial)in

twogenes,NRXN1andCNTN6,thatareinvolvedinbraindevelopment.Together,abnormalitiesinthesegenes

accountforabout1%ofTScases.TheTAAICGalsofoundthatindividualduplicationsordeletionsinother

partsofthegenometogetheraccountforanother0.5%ofTScases.

• TAA-fundedresearchusingpatientregistriesinEuropeindicatethatpreand/orpostnatalfactors,suchas

parentalpsychologicalstate(i.e.mood,anxiety,depression),maybeimplicatedinthedevelopmentofTS.

Thus,TAAsupportforresearchhasprovidedabetterscientificunderstandingofthecausesofTSandrelated

disorders,andhasopenednewavenuesforexploration.Forexample,thediscoveryofHDCgenedefectsinTS

suggeststhatbrainhistaminesystemsareinvolvedinthedevelopmentofticsandthishaspromptedtheTAAto

fundtheclinicalevaluationofhistaminergicdrugsaspotentialtreatmentsfortics.

2. Brain Abnormalities Underlying TS

Brain abnormalities identified by neuroimaging studies

TheTAA,throughitsresearchgrantsprogramandNeuroimagingConsortium(TANIC),hasfundedMRIandother

imagingstudiestodeterminethebrainchangesassociatedwiththedevelopmentofTicDisorders11-13.Thesestudies

areimportantastheycanidentifybraintargetswhichmaybeexploitedfordevelopingtherapies,suchasDBSand

neuropharmacologicaldrugs.TheTAAhasfunded:

• Anatomicalstudieswhichdemonstrateadecreaseinthevolumeofacertainbrainarea(caudatenucleus),

thinningofthefrontalcortex,andalterationsinthecorpuscallosumofindividualswithTScomparedtothose

withoutthedisorder.

• Studiesthathavefoundalterationsintheactivitiesofcortico-striatal-thalamic-corticalnetworksinTS.

Tic DisordersHave Multiple Causes

GE

NET

ICS

ENVIRON

MEN

TAL

OTHER FACTORS

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TheseearlystudiespointtostructuralandfunctionalchangesintheTSbrain.TheTANICandotherTAA-funded

investigatorswillinfutureyearscontinuetoexplorepreviouslyexaminedandotherbrainareasforalterationsinTS

usinghigherresolutionequipment;greaterandbettercharacterizedsamples;andmorecomparableprotocolsacross

differentsites.Therealsoaremanyexcitingavenuesofstudyusingneuroimagingtechniques,whichinclude:

• ResearchexplaininghowthebraindiffersinindividualswithdifferentTicDisorders,andwhatbrainchangesare

associatedwiththealterationsinticexpressionovertime.Imagingstudiesalsomightleadtothedevelopmentof

teststopredicttheonsetandremissionoftics.

• Workdeterminingifdifferentgeneticsubgroupscorrelatewithdifferentbrainstructuresandfunctions.

• Studieselucidatingtheneuroimagingchangesassociatedwiththepremonitoryurgeasthissensationprecedesthe

developmentofticsinindividualswithTS.

• EffortstoidentifyhowbehavioraltherapieslikeCBIT,thatareeffectiveinreducingtics,alterbrainnetworks.

Postmortem studies discover lower neuronal numbers in the striatum

ResearchersatYaleUniversity(NewHaven,CT),fundedbytheTAA,studiedbrainsamplesfromtheTAABrainBank

andfoundthatthenumberofneuronsinaregionofthebrainknownasthestriatum(partofthebasalganglia)was

50%lowerinpeoplewithTScomparedtothosewithoutthedisorder14-16.Thisreductiononlyaffectedaspecificcell

type,parvalbumininhibitoryandcholinergicinterneurons,whichnormallyacttosuppressbrainexcitabilityandcontrol

movements.TherealsoislossofgeneexpressioninthestriatuminTS.Therefore,thelossofstriatalneuronsinTScould

contributetothegenerationoftics.

ResearchersarenowseekingtodeterminewhythereisareductionofneuronsinthestriatuminTS,i.e.dotheyfail

tobegeneratedduringbraindevelopmentordotheysubsequentlydegenerate?Itisalsoimportanttodetermineif

preventingthelossofneuronsinthestriatum,replacingthemwithstemcellsorenhancingtheirfunctionsusingdrugs

mightbeeffectivetreatmentstrategiesforTS.

Brain areas involved in vocal tic generation

TheTAAhasfundedneurophysiologicalstudiesto

determinethebrainnetworksthatareinvolvedin

ticgeneration.McCairnandcolleagues,whowere

fundedbytheTAA,showedthatmotorticsarea

consequenceoffocalabnormalitiesinthesenso-

rimotornetworksofthebrain,notablyinvolving

thebasalganglia17.Conversely,vocalticsandmany

ofthepsychologicalabnormalitiesassociatedwith

TSappeartoresultfromabnormalitiesinthelimbic/emotionalcircuits17.Theseresearchersalsohaverevealedan

imbalanceinamoleculecalledGABA,aneurotransmitterwhichinhibitsbrainactivity,suggestingthatdiscretebrain

circuitsmaybecometooexcitableandproducetheinvoluntarybehaviorsassociatedwithTS.

Why does tic expression fluctuate?

Itiswidelyknownthatticseverityandfrequencycanfluctuateoverbothshortandlongperiodsoftime.Thebiological

basisofthisisunknownandinsightscouldhelpinthemanagementoftics.Thus,theTAAisfundingstudiestodetermine

theroleofthecircadiansysteminTS.

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InvestigatorsattheUniversityofCalifornia-LosAngeles(LosAngeles,CA)arepresentlyexaminingcircadian

rhythmsinadultswithPersistentTicDisorders(PTDs)relativetohealthycontrolsthroughlab-basedmeasurement

ofeveningsalivarymelatoninriseduringdimlightconditions(i.e.dimlightmelatoninonset),circadianphase

preference(self-report),and24-hourrest/activityrhythms(establishedfrom10-dayactigraphyandsleepdiary

monitoring)18-19.Thisresearchissignificantascasestudieshaveshownthatmorningexposuretolighttherapy,

knowntoadvancecircadianphase,isassociatedwithmodesttolargeticreductions,potentiallysuggestingthe

presenceofcircadianabnormalities(i.e.,circadianphasedelay)inselectindividualswithPTDs.Thisphenomenon

maycontributetoticsymptomonset,course,andtreatmentresponse,andbelinkedtounderlyingPTDpatho-

physiology.FindingsmayenhanceourunderstandingoftheroleofcircadianrhythmsinTicDisordersandmay

providenewtargetsforfuturetreatmentdevelopment.

Brain excitability in TS and ADHD

ResearchersatCincinnatiChildren’sHospitalMedicalCenter(Cincinnati,OH),incollaborationwiththe

KennedyKriegerInstitute(Baltimore,MD),areusinganon-invasivetechniquecalledTranscranialMagnetic

Stimulation(TMS)toevaluatelevelsofinhibitorysignaling(whichhelpsourbrains“putonthebrakes”)and

neuroplasticity(abiologicalprocesswhichhelpsourbraincellsmakestrongerconnectionsforlearning)inchildren

withTSandADHD20-23.Thesebrain-basedmeasurementsprovideimportantinsightsaboutthedevelopingbrain

andhowitisaffectedbyTSaswellasbymedicationtreatment.Currently,researchersarecombiningthese

studieswithbrainimagingandwithtechniquestounderstandsensoryhypersensitivityproblemsinthese

children.Thegoalistocollectdatathat,inthefuture,couldinformdecisionsabouttreatmentandpossibly

providecompletelynewavenuesfortreatmentofseverecaseswithbrainstimulation.

3. Development of Animal Models of Tics

Animalmodelsofhumanconditionsarevaluableresearchtoolsastheyassisttheexplorationofcausesand

mechanismsofhumandiseases,aswellaspermitearlytestingofpotentialtreatmentsbeforetheyareexamined

inpeople.TheTAAhassupportedthedevelopmentofvariousanimalmodelsofTS,includingthe‘striatal

disinhibitionanimalmodel’,whichisgeneratedbyadministeringagentsintoasmallareaofthestriatum,abrain

areainvolvedinthecontrolofmotor,associativeandlimbicinformationflow24-25.Theneuronalchangesthat

stemfromthisfocallossofinhibitionleadtotheexpressionofmotorticsindifferentanimals,includingnon-human

primatesandrats,thusenablingthestudyofthemechanismunderlyingticexpression.

Recentstudiesusedthesemodelstoaddressthekeyquestionsof‘when’and‘where’ticsareexpressed.

Theresultsofthesestudiesrevealedthattheexactlocationofthedisinhibitionwithinthestriatumdetermines

thebodypartdisplayingthetics,whilesummationoftheinputfromthecortextothislocationdetermines

thetimingofindividualtics.Currently,scientistsareexpandingthismodeltoenablethestudyofcommon

comorbiditiesofTS,suchasADHD,andtoenablelongtermstudiesoftheinteractionbetweentheanimals’

behavior,stateandmedicationwiththerateandmagnitudeoftheirticexpression.

Thestriataldisinhibitionanimalmodelhelpedtounraveltheunderlyingneuralnetworksinvolvedintic

generation,thusenablingfuturetranslationalstudiesleadingtothedevelopmentofbehavioral,pharmacological

andmedical-devicebasedtreatmentsforticexpression.

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D: TREATMENT ADVANCES

TheTAAresearchgrantsandotherfundingmechanismshavesupportedstudiesexploringmedical,behavioral,

surgicalandnovelformsoftreatmentsforTSandrelatedconditions.Thesestudieshavenowincreasedtreatment

optionsforTSandhaveopenednewavenuesfortherapeuticexplorations.

1. Existing and Emerging Drug Therapies

TheTAAwasinstrumentalinfunding,recruitingsubjectsforand

otherwisecontributedtothedemonstrationofthebenefitsand

potentialsideeffectsofmanyoftheFDA-andnon-FDA-approved

drugscurrentlybeingusedtotreatTS(e.g.pimozide,haloperidol,

aripiprazole,risperidone)26,27.Indeed,clonidineandguanfacine,

whicharenowconsideredfirst-linepharmacologicaltreatments

forTS,wereshowninearlyTAA-supportedstudiestobeeffective

inreducingticseverity.

Abilify

Beginningin2004,TAA-fundedresearchersbegantoexamine

aripiprazole(Abilify),foreffectivenessandsafetyinindividuals

withTS.Thesestudiesfoundthataripiprazolewaseffective

inreducingticsinadultsandchildrenandwassafercompared

tootherdrugs.TheseearlyTAA-supportedinvestigations

promptedOtsukaPharmaceuticalstoconductalargescale

clinicaltrialofaripiprazoleforTS.TheTAAdroverecruitmentfor

theOtsukastudies,whichprovedhighlysuccessfulandledtotheFDAapprovalofthedrugforTSin2014.

Ecopipam

TheTAAhassupported($225,000)anddrivenpatientrecruitmentforaclinicaltrialofapromisingdrugcalled

ecopipam28.ThisdrugisthefirstinitsclasstointeractwithD1receptorsandblockdopaminewhichisthought

tobeoveractiveinTSandcontributetoticdevelopment.Inthefirstopen-labelstudy,andinasubsequentPhase

2bdouble-blind,placebo-controlled,randomizedtrial,ecopipamwasadministeredorallyforseveralweeksto

childrenoradultswithTS.PatientswereassessedusingtheYaleGlobalTicSeverityScoreTotalScale(YGTSS-TS),

whichisawell-validatedandstandardmeasureoftheclinicalefficacyofdrugstreatingTS.Researchersfoundthat

ecopipamcausedsignificantreductionsintheYGTSS-TSatbothtwoandfourweeksafterinitiatingtreatment.

Importantly,thedrugwaswelltoleratedwithnoclinicallysignificantchangesinstandardclinicallabtests,ECG’s,

heartproblems,sedationandnoincreasesinbodyweights,allofwhichoftenareseenwithmarketeddrugsforTS.

EcopipamwillnowundergoadditionalevaluationforTS.

2. Behavior Therapies

In2001,theTAAformedaBehavioralSciencesConsortium(BSC)comprisingseveralclinicians,scientistsandother

experts.ThegroupwasaskedtoworkcollaborativelytodevelopnonpharmacologicaltreatmentsforTS.TheTAA

investedapproximately$300,000tosupportseveralplanningmeetingsandsmallpilotstudies,whichresultedin

theconceptualizationofatherapycalledComprehensiveBehavioralInterventionforTics(CBIT)29,30.TheTAABSC

subsequentlyobtainedover$8millionfromNIMHtosupportfurtherresearchanddevelopmentofCBIT.

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Severalyearsago,theTAABSCconductedrandomized,controlled,clinicaltrialstoevaluatetheeffectiveness

ofseveralsessionsofCBITgivenover10weekscomparedtosupportivetherapy/educationin126children(ages

9-17)or122adults(ages16-69)withTicDisorders28,29.ItwasfoundthatCBITsignificantlyreducedticseverityand

therewerelittleornosignificantadverseeffects.Thesebenefitsweresimilartothoseseenwithmedicationsused

inthetreatmentofticsinTS.

CBIThasnowbecomeafirst-lineoftreatmentformanyindividualswithTicDisorders.TheTAA,throughits

BehaviorTherapyInstitute(BTI)andapartnershipwiththeCDC,hasbeenaggressivelyeducatingandtraining

thousandsofcareprovidersacrosstheUSonCBIT.Asaresult,theTAAhasagrowingreferraldatabaseofskilled

CBITpractitionerswhichisavailabletopatients.

TAA-fundedresearchandotherresearchersnowareworkingtooptimizetheCBITprotocoltoimprovepatient

complianceandadoptionbydiverseprofessionals(e.g.occupationaltherapists).Theyalsoareseekingto

developnovelmethodsofdeliveryofCBITusingtelemedicinestrategies(www.tichelper.com)andhome-based,

self-help,approachestoincreasepatientaccess,especiallyforunderservedregionsoftheUS.

3. Surgical Treatment – Deep Brain Stimulation

DeepBrainStimulation(DBS)isapromisingneurosurgicaltreatmentforTSthatmayimprovedisablingtics

insevere,therapyresistantformsofTS.TheTAAhasfundedresearchthroughourgrantsprogramandviathe

internationalDBSRegistrytodevelopandlaterseekFDA-approvalforthistreatmentstrategy31-33.Thisprojectso

farhasaccomplishedthefollowing:

• Researchhasdemonstratedthatdeepbrainstimulationofthethalamiccentromediannucleusiseffectivein

reducingticsinindividualswithsevereTS.

• NewguidelineshavebeenpublishedtoguidephysiciansandneurosurgeonsontheuseofDBSintreatingTS.

• Investigatorshavebeenanalyzingmedical,surgicalandadverseeventdataintheRegistrycollectedfrom163

TSDBSpatientsdrawnfrom31institutionsacross9countries.Theseanalyseshaveshownthat,ofthetotal

cohort,72%weremalewithanaverageageatsurgeryof29.5years,thoughtheyoungestpatientinthecohort

was13.OCDsymptomswerepresentin60%ofpatients,howeveronly20%hadself-injuriousbehavior.

• Thepooledone-yearoutcomesrevealedasignificantimprovementinticseverity.Theoneyearfollow-up

resultsfromthismulti-nationalDBSRegistryanddatabase

revealedclinicalbenefitsinmanypatients,however,therewere

moreside-effectsthanexpected.

TheRegistrydatawillaidpractitioners,educatepotentialTSDBS

candidatesandprovideusefulinformationtodriveimprovementofthe

procedure.

4. Novel Treatment Research

TheTAAhasahistoryoffundinginvestigationsintonoveltreatment

strategieswhichmaybecomeproventherapiesforticsandother

symptomsofTicDisorders.Thus,becauseofcredibleorpromising

preliminaryevidence,theTAAiscurrentlyfundingclinicalorscientific

studiesinseveralareas.Thesestudiesareongoingand,when

completed,findingswillbepublishedinpeer-reviewedjournalsand

12


madeavailabletothepublic.Importantly,someoftheseTAA-fundedstudieshavealreadyledtothefilingand

approvalofpatentsdescribingnoveltreatmentapproachesforTS.

Medical Cannabis

MedicalcannabishasbeenreportedtoreducesymptomsinTS

andotherneurologicalconditions.However,previousclinical

trialshavelackedsufficientsamplesizetoprovideconclusive

results.Thus,theTAAiscurrentlyfundingseveralgrantsto

evaluatevariousformulationsofmedicalcannabisunder

IRB-approved,regulatedprotocols34.

TheTAAisalsofundingresearchstudiestodevelopagents

thataresimilartotheactivecomponentsofmedicalcannabis

(i.e.cannabidiols,cannabinolsandtetrahydrocannabinols),to

determinehowtheyinteractwiththecannabinoidsystem/re-

ceptors,andevaluatetheirpotentialforreducingsymptomsof

TicDisorders.Indeed,TAA-fundedresearchexaminingthetherapeuticpotentialoftargetingthe

endocannabinoidsystemCB2receptors,usingligands,hasdemonstratedpositivelaboratoryresultsandUS

patentprotection(US9486419B2).

Thus,medicalcannabisanditsassociatedbrainsystemsrepresentpromisingtreatmentstrategiesforTS

andwillundergofurtherlaboratoryandclinicalexplorationinthefuture.

Dental orthotic devices

Therehavebeenreportsinthepublicdomainthatremovabledentalorthoticdevicescanreduceticsin

individualswithTS.Thus,in2011,theTAAbroughttogetherseveraldentistsandclinicalexpertsinTSto

collaborateontheevaluationofthispotentialtreatmentapproach.Thisledtothedevelopmentofaclinicaltrial

protocolwhichunderwentreviewandapprovalbytheTAA’sScientificAdvisoryBoard.Theprojectwasfunded

in2012bytheTAAwithagrantof$150K.

Thestudy,entitled“ProofofConceptStudyofanOralOrthotictoReduceTicSeverityinChronicTic

DisorderandTouretteSyndrome”,isbeingledbyDrs.JohnWalkupandShannonBennettattheWeillCornell

MedicalCollegeinNewYork34,35.Itisarandomized,controlled,feasibilitytrialofanactivevsshamoralorthoticto

reduceticseverityin24childrenandadolescentsages7-25yearswithTSorTicDisorders.Thestudyisunderway

andisexpectedtobecompletedDecember2017.

ThisisthefirstTAA-supportedclinicaltrialofadentalorthoticdevice.Ifthedatashowticreduction,thiswill

formthebasisofalarger,morecomprehensivetrialtoprovideabetterunderstandingoftheeffectivenessand

safetyofdentalorthoticdevicesasatreatmentforTicDisorders.

Other treatment approaches undergoing evaluation

• Biofeedbackusingimaginedfingermovementforticsuppression.

• Transdiagnostictreatmentaimedatspecificsymptomsratherthandiagnoses.

• TranscranialMagneticStimulation(TMS).

14

E. ESTABLISHING BEST CARE GUIDELINES AND PRACTICES: Centers of Excellence Program

TheTAACentersofExcellence(CofE)programaimstoimprovethequalityoflifeofpeoplewithTouretteSyndromeand

otherTicDisordersbypromotingthehighestlevelsofcare,research,education&training,andadvocacyandawareness

fortheseconditions36.

CofE Program Blueprint And Criteria

In2013,theTAAbroughttogetherleadingmedicalandscientificexpertsinTouretteandrelatedconditionstodevelop

aCofEblueprinttoreflectandguidetheneedsoftheTicDisorderscommunity.Immediatelythereafter,anopeninvita-

tionwasissuednationallytoreceiveapplicationsforthedesignationfromprospectivecenters.In2014,afteranextensive

assessmentprocessledbyanindependentAdvisoryandReviewCommittee(ARC),9centerscomprisingpremiermed-

icalandacademicinstitutionsacrosstheUSwerefoundtomeettheblueprintcriteriaandweredesignatedTAACofEs.

Asmandatedbytheblueprint,whichisavailableinfullonourwebsiteandsummarizedhere,allCentersarerequiredto

provide:

ExpertandCoordinatedCare:TAACofEsprovidetimelyandaccurateevaluationsofTSandrelatedconditions.

Thus,patientsmayreceivecoordinatedcareusingevidence-basedtreatmentandmanagementapproachesfrom

multidisciplinaryteamsofcareproviders.Clinicalservicesofferedinclude:

• ChildandAdultNeurologyandPsychiatrySpecialties

• AlliedHealthCareProviders

• Evaluations,DiagnosesandAdvice

• MedicalTreatments

• BehavioralTherapies(e.g.CBIT/CBT)

TAA Centers of Excellence for Tourette & Tic Disorders

WA

OR

ID

CA

PR

AKHI

Virgin Islands

NV

MT

WY

UT

AZNM

CO

NE

KS

ND

SD

TX

MN

IA

OK

MO

AR

LA

MS

WI

IL

TN

IN

MI

OH

KY

ALGA

FL

SC

NC

VAWV

PA

NY

MEVT

NH

MARI

CTNJ

DE

MD

DC

• CounselingandPsychologicalServices

• OccupationalTherapy

• DeepBrainStimulation(DBS)

• BotulinumToxinTherapy

15


Research:Centersconductorcollaborateonscientificandclinicalresearchstudieswithintheirowninstitutions

orelsewhere.TheseinvestigationsaimtoprovideabetterunderstandingofTS/TicDisorders,theirimpact,andto

advancethedevelopmentofmoreeffectiveandsafetreatments.

EducationandTraining:Centersprovidetrainingand

educationtohealthcareprofessionalsandresearcherson

TouretteSyndrome,Ticandrelateddisorders.Thesecenters

alsohelpeducatepatients,familiesandthegeneralpublicon

theseconditions.

AdvocacyandAwareness:TAACofEsworkwiththenational

Associationanditslocalchaptersandsupportgroupsto

improveawarenessandadvocateforTSintheirlocal

communitiesandnationally.

TAA CofE Work and Impact

TheTAACofEprogramisinitsinfancyandrequiresfurtherdevelopmentbeforeitsmissionisfullyattained.

Atpresentandannually,TAACofEs:

9 number of TAA Centers of Excellence, which are located in the nation’s most prestigious health care and university systems.

Each CofE cares for a total of

450 patients,

90 of which are newly

diagnosed cases, on average

per year. However, the number

and types of patients seen by

the various TAA CofEs vary

significantly due to geography.

Together train in the region of

210 residents & fellows

in Tic

Disorders and

other areas of neurology,

psychiatry, pediatrics, etc.

Host or participate in

approximately 150 events

(e.g. walks, support group

meetings, presentations, etc.)

annually within their

communities and nationally.

Collectively publish

approximately 80 paperson their research covering a

broad range of

clinical and

scientific studies

into Tic and

related disorders.

16


TAA CofE Locations

1. BAYLOR COLLEGE OF MEDICINE, HOUSTON, TX

Director:JosephJankovic,M.D.

Co-Director:SuzanneMouton-Odum,Ph.D.

Tel:(713)798-2273

2. CHILDREN’S MERCY HOSPITAL, KANSAS CITY, MO

Director:KeithCoffman,M.D.

Co-Director:JamesBatterson,M.D.

Tel:(816)346-1384

3. JOHNS HOPKINS HOSPITAL, BALTIMORE, MD

Director:HarveySinger,M.D.

Co-Director:MarcosGrados,M.D.

Tel:(410)955-4259

4. MASSACHUSETTS: GENERAL HOSPITAL, BOSTON, MA

Director:JeremiahScharf,M.D.,Ph.D.

Co-Director:SabineWilhelm,Ph.D.

Tel:(617)726-5532

5. NEW YORK STATE CONSORTIUM:

Weill Cornell Medical College, New York, NY

Director:JohnWalkup,M.D.

Co-Director:ShannonBennett,Ph.D.

Tel:(212)821-0789

Northwell Health, Manhasset, NY

Director:CathyBudman,M.D.

Co-Director:JaneZwilling,Psy.D.

Tel:(516)562-3051

University of Rochester Medical Center, Rochester, NY

Director:JonathanMink,M.D.,Ph.D.

Co-Director:HeatherAdams,Ph.D.

Tel:(585)275-2808

Icahn School of Medicine at Mount Sinai, New York, NY

Director:BarbaraCoffey,M.D.

Co-Director:WayneGoodman,M.D.

Tel:(212)659-1660

6. SOUTH EAST REGIONAL CONSORTIUM:

Emory University School of Medicine, Atlanta, GA

Director:JorgeL.Juncos,M.D.

Tel:(404)778-3444

University of Alabama at Birmingham, Birmingham, AL

Director:LeonDure,M.D.

Co-Director:JanRowe,OTR/L,FAOTA

Tel:(205)638-6820

University of Florida, Gainesville, FL

Director:MichaelOkun,M.D.

Co-Director:IreneMalaty,M.D.

Tel:(352)294-5400

Palmetto Health – USC Medical Group, Columbia, SC

Director:RebeccaLehman,M.D.

Tel:(803)434-7961

University of South Florida, St. Petersburg, FL

Director:TanyaMurphy,M.D.

Co-Director:AdamLewin,Ph.D.

(727)767-8230

SoutheastRegionalCofECoordinator

HeatherSimpson,MOT,OTR/L

Tel:(352)294-5385

7. UNIVERSITY OF CALIFORNIA, LOS ANGELES,

LOS ANGELES, CA

Director:JohnPiacentini,Ph.D.

Co-Director:JamesMcCracken,M.D.

Tel:(310)825-0122

8. UNIVERSITY OF UTAH, SALT LAKE CITY, UT

Director:MichaelHimle,Ph.D.

Co-Director:DavidShprecherD.O.

Tel:(801)585-7575

Website:www.TSUtah.info

9. YALE CHILD STUDY, NEW HAVEN, CT

Director:RobertKing,M.D.

Co-Director:MichaelBloch,M.D.

Tel:(203)785-5880

TAA Advisory and Review Committee

(SeesectionK)

18

F: ADVANCES AND CONSENSUS IN UNDERSTANDING THE NATURE AND OCCURRENCE OF TIC DISORDERS

TheTAAhasdrivenadvancesinunderstandingofTouretteandTicDisodersfordecades37.In2014,theTAA

broughttogetherover20thoughtleadersandexpertsinTStoreviewthestateofthefieldanddevelopaconsen-

sustoclarifyseveralmisunderstandingsontheoccurrenceofTSandrelateddisorders38.

Spectrum Disorders

TouretteSyndrome(TS)belongstoaspectrumofneurodevelopmentalconditionsreferredtoasTicDisorders.

ThisgroupalsoincludesChronicMotororVocalTicDisorders(CMVTD)andProvisionalTicDisorders(PTD).

Theseconditionssharemanysimilarities,butdifferonthebasisthatTSrequiresthepresenceofbothmotorand

vocalticsforatleast1year;whilethepresenceofeithermotororvocaltics(notboth)formorethan1yearis

requiredforadiagnosisofCMVTD.Individualswithticspresentforlessthan1yeararegivenadiagnosisofPTD.

Importantly,thespectrumofTicDisordersisnotlinearwithrespecttoseverity,aseachdisordercanbemoreor

lessseverethantheothersinthegroup.

19

F: ADVANCES AND CONSENSUS IN UNDERSTANDING THE NATURE AND OCCURRENCE OF TIC DISORDERS

Tic Disorders Are Not Rare

TSandotherTicDisordersarenotrare.Ticsoccurinasmanyas1in

5school-agedchildren39.Someoccurrencesmaybetransient,while

otherswillpersistintoadolescenceandadulthood.Thecombined

prevalenceofTSandotherTicDisordersisestimatedtobeover

10casesper1,000(1%,1:100),suggestingthatover1/2million

childrenhaveaTicDisorderintheUS40.Thebestestimateforthe

prevalenceofTSis6casesper1,000(0.6%,1:166)children,which

meansthatapproximately300,000childrenhavethecondition

intheUS(basedon2010Censusdata)40.Therearecurrentlyno

reliableprevalenceestimatesofTSandotherTicDisordersinadults,

buttheyareexpectedtobesubstantiallylessthaninchildrenastics

oftendeclinewithaging.

Comorbidities and Coprolalia

Manyassociatedconditions,themostcommonbeing

OCDandADHD,occurinupto80%ofindividuals

withTSandTicDisorders41.Coprolaliaisrelatively

rareinindividualswithTS(1in10),isnotrequiredfor

diagnosis,anddoesnotpersistinmanycases.

Impact

TicsandassociatedsymptomsinTicDisordersmay

rangefrommild/inconsequentialtomoderateto

severeand,insomecases,canbedebilitatingwitha

profoundlynegativeimpactonqualityoflife.Indeed,

manyindividualswithTicDisordersdonotneedor

seektreatment,whileothersrequiremultipleand

repeatedtherapeuticinterventionstomanagetics

andothersymptomsofco-occurringconditions.

Treatmentisgenerallyconsideredwhenticsarepainful,distressing,orinterferewithsocial,academicand

professionallife.Whenneeded,treatmentstrategiesforallTicDisordersarethesame,andmayincludemedication

and/orbehavioraltherapies(e.g.CBIT,CBT).Surgicaltreatments(e.g.DBS)continuetobedevelopedandshould

beconsideredonlyforthemostsevere,drug/behaviortherapy-refractorycasesofTicDisorders.

1 in 166CHILDREN

HAVE TOURETTE SYNDROME

1 in 100CHILDREN

HAVE TOURETTE SYNDROMEOR A TIC DISORDER

G: EDUCATION AND TRAINING

SinceTSwasdiscovered,therehasbeenalong

historyofmisconceptionsoftheconditionamong

thelaypublicandpoorunderstandingsofthedisorder

amonghealthcareproviders.Thishasledtostigma,

bullying,erroneousordelayeddiagnosis,andinade-

quatetreatmentoutcomes.Thus,theTAAresearchandmedicalprograms,incollaborationwithourexternalpartners,

haveledthewayineducatingandtrainingallsectorsoftheTScommunity.Theseeffortshaveachievedthefollowing:

1. Behavior Therapy Institute

ComprehensiveBehavioralInterventionforTics(CBIT),whichisacombinationofdifferentbehavioraltherapies,was

developedundertheTAA’sleadershipandhasproventobeaseffectiveasmedicationinreducingtics.Toassurethe

availabilityofhighlyskilledCBITproviders,theTAAlauncheditsTouretteSyndromeBehaviorTherapyInstitute(TS-BTI)

in2011toincreasethetrainingofhealthcareprofessionalsonCBIT,therebyacceleratingdisseminationofthistherapy.

TheTS-BTIisheldover2daysandfollowedbyapost-trainingconsultationphase.Atthistime,approximately362

professionalshavebeentrained,withnearlyhalf(175)whohavecompletedthecertificationprocess.

BTIshavebeenheldinseveralstates(Arizona,California,Florida,Illinois,Kentucky,Louisiana,Maryland,

Massachusetts,Missouri,NewYork,Utah,Virginia,andWashington,DC),andatseverallocationsinCanada

(Mississauga,NiagaraFallsandVancouver).Theseeventshavebeenattendedbycareprovidersfromallovertheworld

(Argentina,Australia,Canada,Germany,Taiwan,Spain,andPuertoRico).

TheTAAcontinuestodevelopabehaviortherapyreferrallistofqualifiedcareproviders,whichiscurrentlyavailable

toanyoneseekingtreatmentinformationforTS42.

252 number of medical professionals that the TAA has trained across 15 cities in the United States and Canada in CBIT

20

21


2. Tourette Health and Education Program (TAA-CDC Partnership)

Since2004,theTAAhasreceivedover$10millioningrantsfromtheUSCentersforDiseaseControlandPrevention

(CDC)supportingtheTouretteHealthandEducationProgram(THEP).ThisfundingwasmadepossiblebyTitle23

oftheChildren’sHealthAct,signedbyCongressinSeptemberof2000,andauthorizesaPublicHealth

EducationandResearchProgramonTouretteSyndrome.

TheTAA’spartnershipwiththeCDChasled

tothedevelopmentofauthoritativematerialsand

deliveryofover1,000freeeducationalopportuni-

ties(in-personandonline)tonearly350,000care

providers,schoolpersonnel,families,individuals,

andmembersofthegeneralpublic.Programtopic

areasincludediagnoses,management,impactof

co-occurringconditions,andlivingwithTS.Amongitsmanyaccomplishments,THEPhasplayedanimportantrole

ineffortstoincreaseinterestinandknowledgeofCBITasaneffectivetreatmentamongpractitioners.THEPalso

drivestheidentificationandadditionofcareproviderstotheTAAnationalreferralsdatabase42.

THEPcontinuestoexpanditsreachandimpactbystreamingprogramcontentonline,utilizingsocialmedia,

anddevelopingarobustseriesofresourcestobetterequipthecommunitywiththetoolsnecessarytonavigatethe

oftencomplexTSlandscape.

3. 1st World Congress on Tourette Syndrome & Tic Disorders

TheTAA,incollaborationwithitsinternationalpartners,TheEuropeanSocietyfortheStudyofTouretteSyndrome

(ESSTS)andTourettesActionUK,joinedforcestohostthe1stWorldCongressonTouretteSyndromeandTic

Disorders,heldinLondon,June24through26,201543.Thiswasthelargestgatheringofexpertsand

presentationoffindingsinthehistoryofthesedisorders.

Researchscientists,physicians,neurosurgeons,psychologists,socialworkers,residents,fellows,students

andothersfrom38countriesandsixcontinentsgatheredfortheinternationalmeeting.Presentationsand

discussiontookplaceinallareas,includingdrugdevelopment,genetics,comorbidconditions,surgicaltherapies

andbehavioraltreatmentsforchildrenandadultslivingwithTSandTicDisorders.Expertspresented185

scientificabstractsand161posterswithsignificantdiscoveriesanddevelopmentswhichhavethepotentialto

changeourunderstandingoftheseconditions.AcomprehensivelibraryofresearchabstractsfromtheCongress

isavailablefordownloadonline.Importantly,theCongressestablishedanewglobalworkforceandinternational

collaborationfocusedonTouretteandTicDisordersresearch.

The1stWorldCongressonTouretteandTicDisorderssettheprecedentforabroadexchangeofideas,

strategiesandpartnershipsforresearchanddiscoveryintoTouretteandTicDisorders.Theimpactofthe

CongresshasalreadyacceleratedprogressandwillcontinuetofacilitateadvancesinTSandTicDisorders

towardsthe2ndWorldCongressandbeyond.

The1stWorldCongresswassupportedbyagrant($10,000)fromNIH/NINDS,andbyvariousindustry

(NeurocrineBiosciencesandPsyadonPharmaceuticals)andindividualdonors.

To download abstracts from the World Congress, visit tourette.org/Abstracts

$10 Million Investment in the TAA by the CDC/federal government since 2005 to carry out public

health and education efforts

22


4. Authoritative Publications

TheTAAhassupportedthedevelopment,writingandpublicationofawiderangeofscientificandmedicalinformationon

TSandrelateddisorders.Thesehavebeendisseminatedwidelyandservetoinformandguideboththeprofessionaland

layindividualsinterestedinTourette.

TheTAAhassupportedresearchleadingtothepublicationofhundredsoforiginalscientificpapersandreviewsin

international,peer-reviewedjournals.

Theseincludesomeoftheworld’s

highestrankingjournals,suchas

JAMA,Neuron,Proceedingsofthe

NationalAcademyofSciences,

Nature,etc.

Ourorganizationhascommis-

sioned,writtenand/orfundedtheau-

thorshipofmanychaptersandbooks

onallaspectsofTourettewhichhave

andwillcontinuetoserveasessential

referencesonTourette.

TheTAAhasdevelopedawide

rangeofaudio-visualmaterialsthat

areusedregularlytotrainprofession-

alsonthediagnosisandmanage-

mentofTouretteSyndrome.These

publications,manyofwhicharesem-

inalandhighlycited,placestheTAA

asarguablythemostauthoritative

sourceofinformationonTourette

andTicDisordersintheworld.

Recent TAA-Supported Publications

a. AGuideToDiagnosisAndTreatmentofTouretteSyndrome.

b. AFamily’sGuideToTourette.EditedbyJohnT.Walkup,M.D.,JonathanW.Mink,M.D.,Ph.D.,KevinSt.P.McNaught,Ph.D.

c. TouretteSyndrome:10SecretsToAHappierLife.EditedbyMichaelS.Okun,M.D.

d. NavigatingTouretteSyndrome:ACareProvider’sGuideToDiagnosis,TreatmentAndSupport.

e. NavigatingTouretteSyndrome:APatient’sGuideToDiagnosis,TreatmentAndSupport.

f. 1stWorldCongressOnTourette&TicDisorders:FrontiersAbstractBook.EditedbyMarcScullin,MA

Tourette Publications By Year (1948 - 2016)

4,634 Total TourettePublications

250

200

150

50

0

Year of Publication TAA Founded

24

H: RESEARCH GRANTS & FELLOWSHIPS PROGRAM

TheTAAresearchgrantsand

fellowshipsprogramwasestablished

in1984withtheaimofproviding

fundingto34:(1)Explorenovel

conceptsinTicandrelated

disorders.(2)Generatepreliminary

datathatcanbeusedasthe

basisofgrantapplicationstoobtain

largerfundingresearchfromNIH

andotherfederalandnon-federal

entities.(3)Attractexperts

fromotherdisciplinesandretain

promisingmembersintheTSfield.

Thisprogramhasbeensuccessful

inall3aforementionedareas.

1. Overthepast30years,theTAA

investedover$21millionwhich

hasfunded442grantsand

fellowshipsto400Investigators

in13researchareas.Thepro-

gramhasalsoattainedglobal

reach,withawardsgoingto150prestigiousinstitutionsfrom16countrieson5differentcontinents.

2. Supportedthediscoveriesoutlinedelsewhereinthisdocument,includingthedevelopmentofCBIT,discovery

ofraregeneticcausesandriskgenesforTS,discoveryofalterationsinthebasalgangliainTS,thedevelopment

ofananimalmodeloftics,andtheexplorationofnoveltreatmentssuchasdentalorthoticdevicesandmedical

cannabis.

3. Between2003and2016,theTAAfunded134investigatorsforatotalofapproximately$15million.Fortynine

(approximately40%)ofthoseinvestigatorsfundedduringthisperiodhavegoneontoreceiveNIHfundingfor

127grants,worthapproximately$135million.Thus,every$1theTAAhasinvestedingrantshasresultedin

approximately$10offundingfromtheNIH.

4. HelpedSuzanneMouton-Odum,Ph.D.(PsycTech,LtD),DouglasWoods,Ph.D.(MarquetteUniversity,

Milwaukee,WI)andMikeHimle,Ph.D.(UniversityofUtah,Utah),toobtainaFederalsmallbusinessgrant

(5R44MH096344-03,$420,490)tocommercializebehaviortherapies(TicHelper.com).

5. Ledtodiscoveriesofnovelendocannibinoidsystem/CB2receptor-basedtreatmentstrategiesforTSwhich

successfullyobtainedUSpatentprotection(i.e.US9486419B2).

TAA Funded Grants & Fellowships Funding Per Year (1984 - 2016)

$21M Total Funding

Invested

$1,400,000

$1,050,000

$700,000

$350,000

$0

1984 1992 2000 2010 2016

Jeremiah Scharf M.D., Ph.D.

25

Jeremiah Scharf M.D., Ph.D. and Flora Vaccarino M.D.

6. Launchedthecareersofmanyprominentinvestigatorswhohave

becomeexpertsintheTSfield,includingJeremiahScharfM.D.,Ph.D.

(MassachusettsGeneralHospital,Boston,MA),co-chairoftheTAA

InternationalConsortiumforGenomics;andFloraVaccarinoM.D.

(YaleUniversitySchoolofMedicine,NewHaven,CT),amemberof

theTAACenterofExcellenceatYaleChildStudyCenter:

a. Dr.Scharfhasreceivedapproximately$200,000ingrantsfromthe

TAAoverthecourseofhiscareer.Moreimpressive,Dr.Scharfhas

receivedapproximately$4milliondollarsinfundingfromtheNIH

sincehisfirstawardfromtheTAAin2005.Every$1thattheTAA

hasinvestedinDr.JeremiahScharfsince2005hasresultedin$20of

fundingfromtheNIH.

b. Dr.Vaccarinohasreceivedapproximately$400,000ingrantsfrom

theTAAoverthecourseofhercareer.Inthetimesinceherfirst

TAAawardin2004,Dr.Vaccarinohasbeengrantedapproximately

$27milliondollarsinfundingfromtheNIH.Every$1thatthe

TAAhasinvestedinDr.FloraVaccarinosince2004hasresulted

inapproximately$75offundingfromtheNIH.

ThisastoundingreturnonTAAinvestmentforDrs.Scharf,Vaccarinoand

manyotherinvestigatorsdemonstratesnotonlythepowerofthegrants

andfellowshipsprogramtolaunchpromisingcareers,butitsoverallvalue

totheTourettecommunity.BothDrs.ScharfandVaccarinoareactive

membersoftheTAACentersofExcellenceteamattheirrespective

institutionsandDr.ScharfservesontheTAAScientificAdvisoryBoard.

Flora Vaccarino M.D.

TAA Funded Grants & Fellowships by Research Area (1984 - 2016)

442 Total Grants

Funded

Deep Brain Stimulation

Alternative Therapy

Clinical Phenotype & Behavior

Neuropathology

Epidemiology

Immunology

Behavior Therapy

Animal Model

Neuroimaging

Genetics

Drug Trial & Pharmacology

Neurophysiology &Neuroanatomy

Cell & MolecularBiology

4

13

13

17

19

21

28

43

44

53

57

75

56

26

I: DEVELOPMENT OF RESEARCH RESOURCES AND INFRASTRUCTURES

1. Research Grants and Projects Database

Since1984,theTAAhasawarded442researchgrantsandfellowshipstosupportscientific,clinicalandotherresearchinto

Ticandrelateddisorders34.Theseawardshavesupportedover400investigators,workingat150institutionsin16countries,

on5differentcontinents.Theprojectscover13areasofresearch:neurophysiologyandneuroanatomy,genetics,celland

molecularbiology,drugtrialandpharmacology,neuroimaging,animalmodel,behaviortherapy,immunology,epidemiology,

neuropathology,clinicalphenotypeandbehavior,alternativetherapy,anddeepbrainstimulation.

2. Brain Donor and Banking Program

TheTAAbraindonorandbankingprogramwasestablishedin1984andcontinuestoprovideresearcherswithsamplesneed-

edtodeterminethebrainchangesthatunderliethedevelopmentofTouretteandrelateddisorders44.Samplesarecollected,

maintainedanddistributedthroughpartnershipswithBrainBankDirector,Dr.RosalindaRoberts,attheUniversityofAla-

bamaandtheHarvardBrainTissueResourcesCenterattheMcLeanHospitalinBelmont,MA.Thesesampleshavebeenused

byresearcherstodiscoverneuronallossandgeneexpressionchangesinthestriatuminindividualswithTS.TheTAABrain

DonorandBankingProgramremainsavaluableresourceandisavailableforongoingandfuturestudiesinTicDisorders.

3. Patient Recruitment Program

Overtheyears,theTAA’spatientrecruitmentprogramhasbeenanimportantcomponentofseveralsuccessfulclinicaltrials45.

Throughourextensivechapternetworkandvastpartnershipswiththemostprestigiousacademicandmedicalinstitutions

aroundthecountry,theTAAhasbeenabletodriverecruitmentforseveralbreakthroughmedicationtrials.Mostnotably,the

TAApartneredwithOtsukaandwasanintegralpartinrecruitingparticipantsforstudiesthatledtothe2014FDAapprovalof

aripiprazole(Abilify)fortreatmentofTS,whichmarkedthefirstsignificantmedicationdevelopmentforTSindecades.

TheTAAisworkingwithothercompanies,includingPsyadonPharmaceuticals(ecopipam),NeurocrineBiosciences

(valbenazine)andAbideTherapeutics(ABX-1431),tobringnewmedicationsforTicDisorderstothemarket.Through

endeavorslikethePatientRecruitmentProgram,theTAAremainscommittedtoitsroleasanauthorityonevidence-based

treatmentsforTSandotherTicDisorders.

4. Referral Database and Public Inquiries

TheTAAhasbuiltareputationforprovidingthe

professionalandlaycommunitieswithauthoritative

informationonTSandTicDisorders,aswellasproviding

referralsforpeopleseekingtreatment.

• TheTAAhasdevelopedandmaintainsadatabase42

ofnearly1,500careproviders,includingMDs,PhDs,

OTs,RNs,physicians,surgeons,alliedprofessionals,

andothers.Thedatabaseiscontinuallyupdatedandis

availablethroughourwebsiteatalltimesforindividuals

searchingforTScareprovidersintheirgeographiclo-

cationsacrosstheUS.Tolocateaproviderinyourarea,

visitwww.tourette.org/find-a-doctor/.

• Annually,ofthenearly1000inquiriesthattheTAA

receivesbyphoneandelectroniccommunication,

60%relatetomedicalandscientificmatters.

TAA MAP Referral Database Provider Specialty Areas

Rehabilitation

Allergy & Immunology

Vocational Training

Psychopharmacology

Genetics

Special Education

Neurobehavioral Disorders

Depression & Anxiety

Cognitive Strategies

Psychotherapy

Movement Disorders

Nursing

Neurophysiology

General Medicine

Social Work

Behavioral Analysis

Counseling

Therapy

CBIT

Psychology

Psychiatry

Pediatrics

Neurology

Development & Behavior

NeurodevelopmentalDisabilities

405

329

259

245

191

101

62

56

56

45

37

17

16

15

13

13

11

8

8

3

2

2

2

1

1

1,899 Total

Providers

28

J: FOSTERING COLLABORATIONS BY BUILDING CONSORTIA

TheTAArecognizesthat,whilecompetitioninresearch

canbeadvantageous,itisequallyimportanttofacilitate

collaborationswheresharingexpertiseandresourcesare

requiredtodrivediscovery.Thus,wehaveestablishedand

manageseveralconsortiacomprisedofexpertsintheUS

andoverseas.

1. TAA International Consortium for Genomics

TheTAAICGwasfoundedin1986byTSgenetic

researchersintheUnitedStates,theNetherlands,

andCanada,andwasbroughttogetherbytheTAAto

exchangeideasandsharepreliminarydatawiththegoal

ofidentifyingTSsusceptibilitygenes47,48.Todate,the

TAAICGhasrecruitedandenrolled4,020independent

TScasesand3,500familymembersforgeneticstudies,

andhasestablishedcollaborationswithallothermajor

TouretteSyndromeconsortiaintheUSandEurope,

includingTICGenetics,TSGeneSEEandEMTICS.

Funding

TheTAAprovidedinitialseedfundingfortheTAAIGC

thatwasusedtoattracta$15millionUO1cooperative

grantandsubsequent$1.7millionARRAgrant,bothfrom

NINDS,fortheconsortium’swork.

Membership

TheTAAICGhas29membersintheUSandoverseas,

andiscurrentlyledbyCarolMathews,M.D.(Universityof

Florida,Gainesville,FL)andJeremiahScharf,M.D.,Ph.D.

(MassachusettsGeneralHospital,Boston,MA).

Goals

Theteamisworkingtounderstandtheunderlying

geneticcausesofTSthroughmultipleapproaches,

includinglinkage,genomewideassociationstudies

(GWAS),copynumbervariants(CNVs),exomesequenc-

ing,andendophenotypesstudies.Theyhavedeveloped

clinicalassessmenttoolsthatarenowthestandardfor

geneticstudiesinalloftheTSconsortia,aswellasweb-

basedassessmenttools.Consortiummembershaveinves-

tigatedthegeneticrelationshipsbetweenTS,OCD,ADHD

andmajorpsychiatricdisorders,andincollaborationwith

others,haveexaminedtherelationshipsbetweenTSand

othermajorneurologicaldisorders.

30


Research

Earlystudiesfocusedonparametriclinkageanalysesinlarge,multi-generationalTSfamiliesundertheassumptionthat

TSwasamonogenicdisorder.However,asevidencemountedtoindicatethepresenceofnon-Mendelianinheritance,

theTAAICGexpandedto11clinicalsitesintheUSA,Canada,Germany,theUK,andtheNetherlandstocollectTSaf-

fectedsiblingpairsfornon-parametricanalysesusingastandardizedphenotypicassessmentforTS,OCD,andADHD,

stillusedtodaybythethreeinternationalTSconsortia.

TheTAAICGwasawardedNIHfundingin2000tocollectadditionalsmallnuclearfamiliesandcompleteda

high-densitylinkagestudyofallexistingaffectedsibpairsandmulti-generationalfamilies(TAAICG,2007).These

analysesofover2,000individualsidentifiedagenome-widesignificantnon-parametriclinkagesignalonchromosome

2p,thoughsubsequentanalyseshavedemonstratedsignificantheterogeneityacrossthislocus,consistentwiththe

presenceofmultipledistinctsignalswithinthelinkageregion.WiththeadventoftheGWASera,theTAAICGchanged

itscollectiongoalstofocusonassociationstudiesusingbothparent-probandtriosandindividualTScases.These

collectionsservedasthebasisforthefirstTSGWASandparallelCNVanalysis.

Asitbecameclearthatsamplesizeisthemajorhindrancetogenediscoveryforcomplexneuropsychiatrictraits,

theTAAICGaddedadditionalrecruitmentsitesandnovelrecruitmentandassessmentmethods,suchasweb-based

assessmentsofpreviouslydiagnosedTScasesandremoteDNAcollectionusingcommerciallaboratoriesacrossthe

US.Theseonlineprotocolsfacilitatedthecollectionof1,600independentTScasesoverthecourseof2years,asam-

plethatservedasthebasisforthesecondTSGWAS,andCNVstudieswhosepreliminaryresultswerepresentedat

the1stWorldCongressonTouretteSyndromeandTicDisorders.

Eachoftheselarge-scaleTSgeneticstudieshasreliedheavilyonextendedcollaborationsanddatasharing,both

withintheTAAICGaswellasacrossadditionalUSandEuropeanresearchgroups.TheGillesdelaTouretteSyndrome

GWASReplicationInitiative(GGRI)consistsofmultipleTSresearchgroupsacrosstheUSA,Canada,France,Germany,

Austria,Hungary,Italy,GreeceandPoland,andformedoutofanNIHTSGeneticsWorkshopfollowingcompletionof

thefirstTSGWAS.TheGGRIcollaborativeresultedinboththetargetedreplicationstudydescribedaboveandacted

31


asanothermajorcontributingsourceforthesecondinternationalTSGWASandCNVstudies.Similarly,TIC

Geneticshascontributeddatafromover400TSparent-probandtriostothelatestTSGWAS.TAAICGandTIC

Geneticsalsoarecurrentlycollaboratinginajointanalysisofexomesequencingdataaimedatidentifying

recurrent,denovomutationsinTSparent-probandtriofamilies.

Mostrecently,alloftheabovecollaborativegroupsalsohavecontributedtheirGWASdatatothePsychiatric

GenomicsConsortium(PGC)andformedtheTScomponentoftheTSandOCDWorkingGroupofthePGC.

2. TAA Neuroimaging Consortium

TheTAANeuroimagingConsortium(TANIC)wasestablishedin2009witha

TAAgrantof$500,000,agiftfromtheAhmansonFoundation11,49.TheTANIC

isamulti-sitecollaborativeprojectledbyBradleySchlaggar,M.D.,Ph.D.and

KevinBlack,M.D.attheWashingtonUniversitySchoolofMedicine(St.Louis,

MO).The4otherparticipatingresearchsitesintheconsortiumare:

• NewYorkUniversity(NewYork,NY)underthedirectionofF.Xavier

Castellanos,M.D.,MichaelMilham,M.D.,Ph.D.,andAdrianaDiMartino,M.D.

• JohnsHopkinsUniversity/KennedyKriegerInstitute(Baltimore,MD)

underthedirectionofHarveySingerM.D.andStewartMostofsky,M.D.

• TheUniversityofCalifornia,LosAngeles(LA)underthedirectionofJohnC.Piacentini,Ph.D.and

JamesT.McCracken,M.D.

• MountSinaiSchoolofMedicine(NewYork,NY)underthedirectionofBarbaraCoffey,M.D.,M.S.

TheTANICaimstouseMRIandotherimagingtechniquestodeterminethebrainchangesunderlyingticsin

individualswithTSandotherTicDisorders.ResearchersfromtheaforementionedinstitutionssharedMRIscans

fromhundredsofchildrenwithorwithoutachronicTicDisorderandthefirstreportfromtheTANICexamined

brainstructureinover200children.WhitemattervolumewaslowerinTSintheorbitalandmedialprefrontal

cortex,whilegraymattervolumewasincreasedinTSinthehypothalamusandposteriorthalamus.Thesebrain

regionsareinvolvedinvariousprocesses,includingawarenessofinternalbodysensations,whichisimportant

giventheoccurrenceofpremonitorysensationsthatprecedeticsinmanypatients.FurtherresearchusingMRI

andothermethodswillclarifyexactlyhowandwhentheseabnormalitiesdevelopinTS.

Researchbytheneuroimagingconsortiumhasopenednewavenuesforcontinuedresearchtounderstand

thecausesoftics,andhasalsorevealednewbraintargetswhichwillbeexploitedinthefuturetodevelopnovel

treatmentsforTS.

3. TAA International DBS International Registry

TheTAAInternationalDeepBrainStimulation(DBS)Registrywasestablishedin2011withtheaimofadvancing

thedevelopmentandFDAapprovalofthispromisingsurgicaltreatmentforsevereformsofTS32,33,50.The

HIPAA-compliantdatabaseprojectisledbyMichaelOkun,M.D.attheUniversityofFlorida(Gainesville,FL)

underajointagreementwiththeTAA,andsupportedbygrantsfromtheTAAandMedtronic,Inc.($375,000).

Theprojecthasattractedover100physicians,neurosurgeons,scientistsandotherexpertsfrom31institutions

across9countries.Atpresent,thedatabasehascollectedmedical,surgical,andadverseeventdatafrom163

TSpatientswhohaveundergoneDBStreatmentsaroundtheworld.

33


DatafromtheDBSregistryarebeingutilizedtoanswerarangeofquestions,includingtheappropriateage

forsurgery,theoptimalbraintargetforanindividualpatient,andthebestpracticesforprogramming,medication

managementandthebestapproachtolimitadverseevents.Thusfar,analysesofcollecteddatahaveledtothe

publicationofimprovedguidelinesfortheuseofDBS,andapendingpublicationwillreportonsignificantclinical

benefitsandotheroutcomedataofthistreatmentapproach.

4. TAA Behavior Sciences Consortium

In2001,theTAAformedaBehavioralSciencesConsortiumcomprisingseveralcliniciansandscientists51.

ThegroupwasaskedtodevelopandtestanonpharmacologicaltreatmentforTS.TheTAAinvestedapproximately

$300,000tosupportseveralplanningmeetingsandsmallpilotstudies,whichresultedintheconceptualization

ofComprehensiveBehavioralInterventionforTics(CBIT).

TheTAABSCsubsequentlyobtainedover$8millionfromNIMHtosupportfurtherresearchanddevelopment

ofCBIT.ThegrouphassincepublishedseveralresearchpapersonCBIT,including2clinicaltrialsdemonstrating

theabilityofthistreatmentapproachtoreduceticsinchildrenandadultswithTS.

TheTAABSCiscontinuingitsworktofurtherdevelopCBIT,includingeffortstoimprovepatientcompliance

aswellastomodifyCBITsothatitcanbeadoptedbydiverseprofessionals(e.g.occupationaltherapists).Novel

methodsofdeliveryalsoarebeingexplored,notablytelemedicineandself-help/home-basedapproaches,to

increasepatientaccesstoCBIT,particularlyinunderservedregionsoftheUS.

5. TAA International Consortium for Medical Cannabis and Related Disorders in Tic Disorders

Thereisincreasinginterestinmedicalcannabis(marijuana)asapotentialtreatmentforticsandothersymptoms

inTS.ThisisbasedonreportsbybothTSpatientsandcareprovidersfollowingself-administrationbyindividuals

withthedisorder.Inaddition,researchhasshownthatvariousformulationsofmedicalcannabisorchemical

agentsactingontheendogenousbraincannabinoidsystemscanalterTS-relatedmotoractivityandbehaviorsin

experimentalanimals.Thus,theTAAiscontinuingtofundandotherwisesupportresearchinthisareaintheUS

andoverseas(seegrantsdatabase).Further,theTAAandothersareparticipatinginadvocacyeffortsintheUS

andabroadtoeaserestrictionsandregulationstofacilitateresearchintoandtheuseofmedicalcannabisasa

treatmentforTS.

GiventhediverseinterestsinexploringanddevelopingmedicalcannabisasatreatmentforTS,theTAAis

nowseekingtocoordinateandleadtheseeffortsthroughtheestablishmentofan“InternationalConsortium

forMedicalCannabisandRelatedDrugsinTicDisorders”(TAAICMCT).Thisconsortiumwillbecomprisedofre-

searchers,clinicians,advocates,anothersfromtheUS,Canada,Europeandothercountriesworkingcollaboratively

toadvanceresearchandpolicyinthisarea.Indeed,suchinternationalpartnershipisnecessarytodrivethisfield

consideringthewidevariabilityacrosscountriesintheeaseorpermissibilityofresearchstudies.

TheTAAICMCTisbeingmodeledfromothersuccessfulTAAconsortia,i.e.theInternationalDBSRegistry,

InternationalConsortiumonGenomics,BehavioralSciencesConsortiumandNeuroimagingConsortium,andis

expectedtodriveresearchinthispotentialtreatmentforTSintheyearsahead.

34

K: CREATING PARTNERSHIPS

Fromitsinception,theTAAhasrecognizedtheimportanceofcollaborationwithotherentitiestodriveitsmission

ofmakinglifebetterforallpeopleaffectedbyTouretteandTicDisorders.Thus,theorganizationhasdeveloped

manypartnershipswithfederalandnon-federalentities,pharmaceuticalandmedicaldevicecompanies,

academicinstitutions,medicalandhealthcarefacilitieswithintheUSandoverseas.Thesepartnershipshave

ledtomajorfundingforTSresearch,keyscientificadvances,disseminationofauthoritativeinformation,expert

educationandtrainings,andtheapprovalofnewtreatmentsfortheTS.SomeoftheTAA’skeypartnersinclude:

1. Federal Institutes

National Institutes of Neurological Disorders and Stroke

TheTAAandNINDSdevelopedacooperativefundingagreement,resultinginover$10millioninU01andARRA

researchgrantsfromNINDS,tosupporttheworkoftheTAAInternationalGenomicsConsortium.

National Institutes of Mental Health

TheTAABehavioralSciencesConsortiumwasawardedover$8millionfromNIMHtosupportthedevelopmentof

CBIT,anon-medicationtreatmentfortics.

Centers for Disease Control and Prevention

TheTAAandCDChaveanongoingpartnershipinwhichtheCDChasforthepast13yearsfunded(upto

$900,000annually,over$10milliontotal)aTAA-managededucationalprogram.Thisprogramdevelops

educationalmaterialsandimplementstrainingprogramsforbothlayandprofessionalsacrosstheUS.

2. Foundations and Institutions

American Brain Foundation/American Academy of Neurology

TheTAAandABF/AANhavedevelopedaco-fundingrelationshipinwhichbothorganizationscontributetofund

1or2fellowshipsannually,eachfor$150,000,tosupportthetrainingandworkofearlystageclinicianswhoare

interestedinTS.Thispartnershiphasthusfarfundedthefollowingprojects:

MatthewCapriotti,PhD/SanJoseStateUniversity

ProjectTitle:IncorporatingTeleCBITintoaHospital-basedTicClinic

JosephMcGuire,PhD/UniversityofCaliforniaLosAngeles

ProjectTitle:NeurocognitivePredictorsandNeuralCorrelatesofBehaviorTherapyforTouretteSyndrome

FlintEspil,PhD/StanfordUniversity

ProjectTitle:CorticalFunctioningandCorrelatesofBehaviorTherapyforYouthwithPersistentTicDisorders

Harvard Brain Tissue Resource Center

TheTAAhasalongstandingpartnershipwiththeHBTRCattheMcLeanHospital(Belmont,MA)whichhouses

andmanagesourorganization’scollectionofvaluablebraintissuesforresearch.Thiscollectionhasbeenusedto

discoverimportantbrainchangesinTS.

National Organization for Rare Disorders

TheTAAhashadalongandcollaborativehistoryworkingwiththeNORDtoadvancethecausesofdisordersthat

occurrelativelyinfrequently.

35

K: CREATING PARTNERSHIPS

Lupin Foundation

TheLupinFoundationhasprovidedfundingwhichhasbeenusedtosupporttheorganization’sresearchgrants

program.

Ahmanson Foundation

TheTAAisthankfultohavereceivedagiftof$500,000fromtheAhmansonFoundationtosupportthe

establishmentoftheTAANeuroimagingConsortium.TheprojectaimstouseMRIandotherimagingtechniques

todeterminethebrainchangesunderlyingticsinindividualswithTSandotherTicDisorders.TheTANIChas

alreadymadesignificantdiscoveriesofbrainabnormalitiesinTSandpointtonoveltargetsthatmightbeexplored

todevelopnewtreatmentsforthedisorder.

3. Pharmaceutical and Medical Devices Industry

Medtronic, Inc

Medtronichasprovideda$375,000,5-yeargranttosupportthedevelopmentoftheTAAInternationalDBS

RegistrywhichseekstoadvancethedevelopmentandFDA-approvalofthispromisingsurgicaltreatmentfor

severeformsofTS.

Otsuka Pharmaceutical, Inc.

TheTAAworkedextensivelywithOtsukaPharmaceuticaltodriverecruitmentofparticipantsforitsstudiesof

AbilifyasatreatmentforTourette.TheseclinicaltrialswerehighlysuccessfulandledtheFDAtoapproveAbilifyas

atreatmentforTicDisorders.

Psyadon Pharmaceuticals, Inc

In2011,theTAAestablishedapartnershipwithPsyadonPharmaceuticals,Inc.toadvancethedevelopmentof

ecopipam,anovelD1antagonist,asatreatmentforTS.TheTAAprovidedagrantof$225,000toPsyadonto

commenceanopen-labeltrialoftheecopipaminasmallgroupofpatientswithmoderate-severetics.Thetrial,

whichmightnothavestartedwithoutTAA-support,wassuccessfulandthedrugdemonstratedsignificantben-

efitswithfewmildadverseeffects.Basedontheseinitialpositiveresults,Psyadoninitiateda2nd,randomized,

placebo-controlled,clinicaltrialofecopipaminalargerpopulationofindividualswiththedisorder.Thedrugonce

againdemonstratedsignificantclinicalbenefitsandrelativelymildsideeffects.Psyadonisnowseekingtoconduct

furtherclinicaltrialsofecopipiamwhichhopefullywillleadtotheFDA-approvalofthedrugasatreatmentforTS.

Teva

TevahasprovidedtheTAAover$25,000tosupporttheorganization’sresearchgrantsprogram.

Abide Therapeutics

TheTAAsupportsAbideintheireffortstodevelopeffectivedrugsaspotentialtreatmentsforTS.Abide

generouslyprovidedtheTAAwitha$25,000sponsorship.

Neurocrine Bioscience and others

TheTAAiscurrentlyworkingwithotherpharmaceuticalcompaniestoassistwiththerecruitmentofsubjects

forclinicaltrialsofvariousdrugswhichhavethepotentialtobeeffectivetreatmentsforTS.TheTAAisalsothank-

fultohavereceivedvariouslevelsofsponsorshipsfromthesecompanieswhichhasbeenusedtosupport

theorganization’sresearchprograms.

36

L: GLOBAL NETWORK OF ADVISORS AND THOUGHT LEADERS

TheTAAhasestablishedaninternationalnetworkofexpertsand

thoughtleaderswhoadvisetheorganizationonallresearchrelat-

edmatters.Indeed,theTAA’sresearchandmedicalprogramshave

beendeveloped,implementedandassessedundertheguidanceof

hundredsofexpertsdrawnfromTouretteandotherfields.These

individualshavevoluntarilyprovidedexpertise,resourcesandtime

totheorganizationoverits45yearhistorytodriveresearchand

discoveryinTSandrelatedconditions.

Theprograms,advancesandimpactoutlinedinthisdocument

areattributedtotheselflesscontributionsoftheTAA’sadvisorsin

theUSandabroad.ThustheTAA,BODandthebroadercommuni-

tyofpeopleserved,arethankfultothefollowingandhundredsof

unlistedadvisorsfortheirselflessandcountlesscontributionstothe

missionofmakinglifebetterforallpeopleimpactedbyTSandTic

Disorders.

Scientific Advisory Board

TheSABcomprisesexpertsfromallareasofbiomedicalandclinical

research,andhasguidedtheTAAinreviewingandrecommending

researchgrantsandotherprojectsforfundingbyourorganization.

TheSABalsoworkswiththeTAAtosetfundingprioritiesand

advisestheTAAontheinterpretationofscientificdiscoveries.

TheSABhasbeenledbythefollowingindividuals:

1986–1987:ThomasN.Chase,M.D.

1992–1996:AnneB.Young,M.D.,Ph.D.

1997–2005:NealR.Swerdlow,M.D.,Ph.D.

2006–2010:PeterHollenbeck,Ph.D.andJonathanMink,M.D.,Ph.D.

2011–2016:TamaraHershey,Ph.D.andJonathanMink,M.D.,Ph.D.

2016–Present:CarolMathews,M.D.andPeggyNopoulos,Ph.D.

Medical Advisory Board

TheMABguidesthedevelopmentandmanagementoftheTAA’s

policiesandprogramsaimedatimprovingdiagnosis,careand

treatmentofpeoplewithTS.TheMABalsoassiststheTAAwith

providingauthoritativeanswerstoourmembership,media,public,

etc.,onawiderangeofmedicalandotherissuesrelatingtoTS.

TheMABhasbeenledbythefollowingindividuals:

2007–2012:JohnT.Walkup,M.D.

2012–2013:MichaelS.Okun,M.D.andJohnT.Walkup,M.D.

2013–2017:MichaelS.Okun,M.D.andDouglasW.Woods,Ph.D.

2017–Present:BarbaraCoffey,M.D.andKeithCoffman,M.D.

37

L: GLOBAL NETWORK OF ADVISORS AND THOUGHT LEADERS

Centers Of Excellence Advisory and Review Committee

TheCofEARCplaysacentralroleinadvisingtheTAAon

thedevelopment,implementationandoversightoftheCofE

program.Thisboardisdiverse,comprisingscientists,clinicians,

TAAchapter/supportgroupleadersandmembersoftheTAA

BoardofDirectors.

CarolA.Mathews,M.D.-UniversityofFlorida,Gainesville,FL

DouglasWoods,Ph.D.–MarquetteUniversity,Milwaukee,WI

PeterHollenbeck,Ph.D.-PurdueUniversity,WestLafayette,IN

EricBNestler,M.D.,Ph.D.-MountSinaiSchoolofMedicine,

NewYork,NY

KevinBlack,M.D.-WashingtonUniversityinSt.Louis,

St.Louis,MO

RuthBruun,M.D.-PrivatePracticePsychiatrist,NY

AndreaCavanna,M.D.,Ph.D.-UniversityofBirmingham,

Birmingham,UnitedKingdom

GeraldErenberg,M.D.-ClevelandClinic,Cleveland,OH

BradleySchlaggar,M.D.,Ph.D.-WashingtonUniversityin

St.Louis,St.Louis,MO

ReidAshinoff-TAABoardofDirectors

PaulDevore-TAABoardofDirectors

MonteRedman-TAABoardofDirectors

RandiZemsky-TAABoardofDirectors

ChuckBrackett-TAANorthernCaliforniaChapter

EllieJarvie,LCSW,CSAC-TAAWisconsinChapter

Epidemiology and Prevalence

TheTAAisexpertlyguidedonmattersrelatingtotheoccurrence

ofTSbyLawrenceScahill,MSN,Ph.D.(EmoryUniversity,

Atlanta,GA)

Other Contributors

TheTAAbenefitsfromtheadviceofmanyotheradvisors,

thoughtleadersandresearcherswhoworkwiththe

organizationonanasneededbasis.

38

TAAsupportforresearchhasledtokeyadvancesinmanyareasofinterestoverthepast45years.Theseincludea

betterscientificunderstandingofthecauses,brainchangesandoccurrencesofTicDisorders;increasededucation

andtrainingofcareproviderstoimprovediagnosesandmanagementoftheconditions;andthedevelopmentof

effectivetreatmentsforpatients.However,manyunmetneedsremain.Forexample:

• Weneedtoidentifyothergenesandenvironmental/lifestylefactorsthatcauseorincreasetheriskof

developingTicDisorders.

• ItisimportanttogarnerbetterestimatesoftheprevalenceandregionaldistributionofTicDisordersamong

childrenandadults.Thiswillhelptoidentifypotentialriskfactors,economicimpact,andtoattractsupportto

developprogramstomeettheneedsofallpeoplelivingwithTSandrelateddisorders.

• WemustacceleratetheeducationandtrainingprogramofprofessionsonTS,especiallyinunderservedareas,

tofurtherreducethedifficultiespeopleexperienceintryingtofindskilledcareproviders.

• Therecontinuestobeaneedformoreeffectiveandaccessibletreatmentchoiceswithfewersideeffects,

includingmedical,behavioral,surgicalandnoveltreatmentapproaches.

Intheyearsahead,theTAAwillfurtherdevelopitssuccesses,addressunmetneeds,exploreemerging

opportunitiesandopennewavenuesofresearchanddevelopment.Theseeffortswilldriveandfulfillthe

organization’smissiontomakelifebetterforallpeopleaffectedbyTSandTicDisorders.

M: THE FUTURE OF RESEARCH AND DEVELOPMENT IN TOURETTE AND TIC DISORDERS

40

Thefollowingkeypublicationsandotherreferencesrepresentvitaldevelopmentsandmilestonesinthe45-year

historyoftheTAA’sresearchandmedicalprograms.

Section C: Scientific Discoveries

1. GeorgitsiM,WillseyJ,MathewsC,StateM,ScharfJ,andPaschouP.(2016)TheGeneticEtiologyofTouretteSyndrome:

Large-ScaleCollaborativeEffortsonthePrecipiceofDiscovery.Front.Neurosci.10:351.

2. PaulsD.L.,FernandezT.V.,MathewsC.,StateM.W.,ScharfJ.M.(2014).TheinheritanceofTourettedisorder:areview.

J.ObsessiveCompuls.Relat.Disord.3:380–385.

3. HirschtrittME,LeePC,PaulsDL,DionY,GradosMA,IllmannC,KingRA,SandorP,McMahonWM,LyonGJ,CathDC,

KurlanR,RobertsonMM,OsieckiL,ScharfJM,MathewsCA;TouretteSyndromeAssociationInternationalConsortium

forGenetics.(2015)Lifetimeprevalence,ageofrisk,andgeneticrelationshipsofcomorbidpsychiatricdisordersin

Tourettesyndrome.JAMAPsychiatry.72:325-33.

4. MathewsCA,ScharfJM,MillerLL,Macdonald-WallisC,LawlorDA,Ben-ShlomoY.(2014)Associationbetweenpre-and

perinatalexposuresandTourettesyndromeorchronicticdisorderintheALSPACcohort.BrJPsychiatry.204:40-5.

5. WillseyJA,FernandezT,YuD,KingR,DietrichA,XingJ,SandersSJ,MandellJD,HuangAY,RicherPSmithL,

DongS,SamochaKE,TouretteInternationalCollaborativeGenetics(TICGenetics),TouretteSyndromeAssociation

InternationalConsortiumforGenetics(TSAICG),NealeBM,CoppolaG,MathewsCA,TischfieldJA,ScharfJM.(2017)

DeNovoCodingVariantsAreStronglyAssociatedwithTouretteDisorder.Neuron94:486-99.

6. AbelsonJF,KwanKY,O’RoakBJ,BaekDY,StillmanAA,MorganTM,MathewsCA,PaulsDL,RasinMR,GunelM,Davis

NR,Ercan-SencicekAG,GuezDH,SpertusJA,LeckmanJF,DureLS4th,KurlanR,SingerHS,GilbertDL,FarhiA,Louvi

A,LiftonRP,SestanN,StateMW.(2005)SequencevariantsinSLITRK1areassociatedwithTourette’ssyndrome.

Science.310:317-20.

7. Ercan-SencicekAG1,StillmanAA,GhoshAK,BilguvarK,O’RoakBJ,MasonCE,AbbottT,GuptaA,KingRA,PaulsDL,

TischfieldJA,HeimanGA,SingerHS,GilbertDL,HoekstraPJ,MorganTM,LoringE,YasunoK,FernandezT,SandersS,

LouviA,ChoJH,ManeS,ColangeloCM,BiedererT,LiftonRP,GunelM,StateMW.(2010)L-histidinedecarboxylaseand

Tourette’ssyndrome.NEnglJMed.362:1901-8.

8. HuangAY,YuD,DavisLK,SulJH,TsetsosF,RamenskyV,ZelayaI,RamosEM,OsieckiL,ChenJA,McGrathLM,

IllmannC,SandorP,BarrCL,GradosM,SingerHS,NothenMM,HebebrandJ,KingRA,DionY,RouleauG,BudmanCL,

DepienneC,WorbeY,HartmannA,Muller-VahlKR,StuhrmannM,AschauerH,StamenkovicM,SchloegelhoferM,

KonstantinidisA,LyonGJ,McMahonWM,BartaC,TarnokZ,NagyP,BattersonJR,RizzoR,CathDC,WolanczykT,

BerlinC,MalatyIA,OkunMS,WoodsDW,ReesE,PatoCN,PatoMT,KnowlesJA,PosthumaD,PaulsDL,CoxNJ,

NealeBM,FreimerNB,PaschouP*,MathewsCA*,ScharfJM*,CoppolaG*.RarecopynumbervariantsinNRXN1and

CNTN6increaseriskforTourettesyndrome,BiorXiv,2016;doi:https://doi.org/10.1101/062471

9. PaschouP,YuD,GerberG,EvansP,TsetsosF,DavisLK,KaragiannidisI,ChaponisJ,GamazonE,Mueller-VahlK,

StuhrmannM,SchloegelhoferM,StamenkovicM,HebebrandJ,NoethenM,NagyP,BartaC,TarnokZ,RizzoR,

DepienneC,WorbeY,HartmannA,CathDC,BudmanCL,SandorP,BarrC,WolanczykT,SingerH,ChouIC,GradosM,

PosthumaD,RouleauGA,AschauerH,FreimerNB,PaulsDL,CoxNJ,MathewsCA,ScharfJM.(2014)Genetic

associationsignalnearNTN4inTourettesyndrome.AnnNeurol.76:310-5.

N: KEY TAA-SUPPORTED PUBLICATIONS AND REFERENCES

41

10. YuD,MathewsCA,ScharfJM…PaulsDL.(2015)Cross-disordergenome-wideanalysessuggestacomplex

geneticrelationshipbetweenTourette’ssyndromeandOCD.AmJPsychiatry.172:82-93.

11. GreeneDJ,WilliamsIIIAC,KollerJM,SchlaggarBL,andBlackKJ.BrainstructureinpediatricTourettesyndrome.

(2016)MolPsychiatry.[Epubaheadofprint].

12. Bloch,M.H.,Leckman,J.F.,Zhu,H.,&Peterson,B.S.(2005).Caudatevolumesinchildhoodpredictsymptom

severityinadultswithTourettesyndrome.Neurology,65(8),1253-1258.

13. Church,J.A.,Fair,D.A.,Dosenbach.N.U.F.,Cohen,A.L.,Miezin,F.M.,Petersen,S.E.,Schlaggar,B.L.(2009)Control

networksinpediatricTourettesyndromeshowimmatureandanomalouspatternsoffunctionalconnectivity.

Brain,132:225-238.

14. KalanithiPS,ZhengW,KataokaY,DiFigliaM,GrantzH,SaperCB,SchwartzML,LeckmanJF,VaccarinoFM

(2005)Alteredparvalbumin-positiveneurondistributioninbasalgangliaofindividualswithTourettesyndrome.

ProcNatlAcadSciUSA102:13307-13312.

15. KataokaY,KalanithiPS,GrantzH,SchwartzML,SaperC,LeckmanJF,VaccarinoFM(2010)Decreasednumber

ofparvalbuminandcholinergicinterneuronsinthestriatumofindividualswithTourettesyndrome.JComp

Neurol518:277-291.

16. LenningtonJB,CoppolaG,Kataoka-SasakiY,FernandezTV,PalejevD,LiY,HuttnerA,PletikosM,SestanN,

LeckmanJF,VaccarinoFM(2016)TranscriptomeAnalysisoftheHumanStriatuminTouretteSyndrome.Biol

Psychiatry79:372-382.

17. McCairn,K.W.etal.(2016)APrimaryRoleforNucleusAccumbensandRelatedLimbicNetworkinVocalTics.

Neuron.89:300-307.

18. Coles,M.E.,&Strauss,G.P.(2015).Sheddinglightontics.PsychiatryResearch,225,743.

19. Niederhofer,H.(2009).BrightlighttherapymaybeatherapeuticoptionforTourette’sSyndrome.Acta

Neuropsychologica,7:283-285.

20. WuSW,MaloneyT,GilbertDL,etal.FunctionalMRI-navigatedRepetitiveTranscranialMagneticStimulationOver

SupplementaryMotorAreainChronicTicDisorders(2013).BrainStimul.

21. WuSW,GilbertDL.AlteredneurophysiologicresponsetointermittentthetaburststimulationinTourette

syndrome(2012).BrainStimul.5:315-319.

22. GilbertDL,ZhangJ,LippsTD,etal.AtomoxetinetreatmentofADHDinTouretteSyndrome:Reductioninmotor

cortexinhibitioncorrelateswithclinicalimprovement(2007).Clin.Neurophysiol.118:1835-1841.

23. GilbertDL,IsaacsKM,AugustaM,MacneilLK,MostofskySH.Motorcortexinhibition:amarkerofADHDbehavior

andmotordevelopmentinchildren(2011).Neurology.76:615-621.

24. IsraelashviliM.,Bar-GadI.,(2015)CorticostriatalDivergentFunctioninDeterminingtheTemporalandSpatial

PropertiesofMotorTics.JournalofNeuroscience,35:16340-51.

25. McCairnK.W.,BronfeldM.,BelelovskyK.andBar-GadI.(2009).Theneurophysiologicalcorrelatesofmotortics

followingfocalstriataldisinhibition,Brain,132:2102-13.


42

Section D: Treatment Advances

26. WaldonK,HillJ,TermineC,BalottinU,andCavannaAE.(2013)TrialsofpharmacologicalinterventionsforTourette

syndrome:asystematicreview.BehavNeurol.26:265-73.

27. LyonGJ,SamarS,JummaniR,HirschS,SpirgelA,GoldmanR,CoffeyBJ.(2009)Aripiprazoleinchildrenand

adolescentswithTourette’sdisorder:anopen-labelsafetyandtolerabilitystudy.JChildAdolescPsychopharmacol.

19:623-33.

28. GilbertDL,BudmanCL,SingerHS,KurlanR,ChipkinRE.(2014)AD1receptorantagonist,ecopipam,fortreatmentof

ticsinTourettesyndrome.ClinNeuropharmacol.37:26-30.

29. Piacentini,J.,Woods,D.W.,Scahill,L.,Wilhelm,S.,Peterson,A.L.,Chang,S.,...Walkup,J.T.(2010).Behavior

TherapyforChildrenWithTouretteDisorder.Jama303:1929.

30.Wilhelm,S.,Peterson,A.L.,Piacentini,J.,Woods,D.W.,Deckersbach,T.,Sukhodolsky,D.G.,...Scahill,L.(2012).

RandomizedTrialofBehaviorTherapyforAdultsWithTouretteSyndrome.ArchivesofGeneralPsychiatry,69,795.

31. RossiPJ,OpriE,ShuteJB,MolinaR,BowersD,WardH,FooteKD,GunduzA8,OkunMS.(2016)Scheduled,

intermittentstimulationofthethalamusreducesticsinTourettesyndrome.ParkinsonismRelatDisord.29:35-41.

32. DeebW,RossiPJ,PortaM,Visser-VandewalleV,ServelloD,SilburnP,CoyneT,LeckmanJF,FoltynieT,HarizM,Joyce

EM,ZrinzoL,KefalopoulouZ,WelterML,KarachiC,MalletL,HouetoJL,Shahed-JimenezJ,MengFG,KlassenBT,

MogilnerAY,PourfarMH,KuhnJ,AckermansL,KaidoT,TemelY,GrossRE,WalkerHC,LozanoAM,KhandharSM,

WalterBL,WalterE,MariZ,ChangiziBK,MoroE,BaldermannJC,HuysD,ZauberSE,SchrockLE,ZhangJG,HuW,

FooteKD,RizerK,MinkJW,WoodsDW,GunduzA,OkunMS(2016).TheInternationalDeepBrainStimulation

RegistryandDatabaseforGillesdelaTouretteSyndrome:HowDoesItWork?FrontNeurosci.25:170.

33. SchrockLE,MinkJW,WoodsDW,PortaM,ServelloD,Visser-VandewalleV,SilburnPA,FoltynieT,WalkerHC,

Shahed-JimenezJ,SavicaR,KlassenBT,MachadoAG,FooteKD,ZhangJG,HuW,AckermansL,TemelY,MariZ,

ChangiziBK,LozanoA,AuyeungM,KaidoT,AgidY,WelterML,KhandharSM,MogilnerAY,PourfarMH,WalterBL,

JuncosJL,GrossRE,KuhnJ,LeckmanJF,NeimatJA,OkunMS;TouretteSyndromeAssociationInternationalDeep

BrainStimulation(DBS)DatabaseandRegistryStudyGroup.(2015)Tourettesyndromedeepbrainstimulation:a

reviewandupdatedrecommendations.MovDisord.30:448-71.

34. TAAGrantsDatabasehttps://www.tourette.org/grant-database/

35. ClinicalTrials.govidentifier:NCT02067819

https://clinicaltrials.gov/ct2/show/record/NCT02067819?term=tourette+orthotic&rank=1

36. TAACentersofExcellenceProgramhttps://www.tourette.org/about-tourette/overview/centers-of-excellence/


43

Section F: Advances and Consensus In Understanding Of The Nature And Occurrence Of Tic Disorders

37. McNaughtKS,MinkJW.(2011)AdvancesinunderstandingandtreatmentofTourettesyndrome.NatRev

Neurol.7:667-76.

38. TheSpectrumofTouretteSyndromeandTicDisorders:AConsensusbyAdvisorsoftheTouretteAssociation

ofAmerica.(2014)AndreaE.Cavanna,M.D.,Ph.D.;KeithA.Coffman,M.D.;HeatherCowley,Ph.D.;StanleyFahn,

M.D.;MartinE.Franklin,Ph.D.,DonaldL.Gilbert,M.D.,M.S.;TamaraG.Hershey,Ph.D;JosephJankovic,M.D.;

MonicaM.P.Jones,M.D.;JamesF.Leckman,M.D.;RebeccaK.Lehman,M.D.;CarolA.Mathews,M.D.;IreneA.C.

Malaty,M.D.;KevinSt.P.McNaught,Ph.D.;JonathanW.Mink,M.D.,Ph.D.;MichaelS.Okun,M.D.;JanA.Rowe,

OT,OTR/L;LawrenceD.Scahill,MSN,Ph.D.;JeremiahM.Scharf,M.D.,Ph.D.;BradleyL.Schlaggar,M.D.,Ph.D.;

EvelynStewart,M.D.;JohnT.Walkup,M.D.;DouglasW.Woods,Ph.D.TAAPublication.

39. KurlanR,McDermottMP,DeeleyC,ComoPG,BrowerC,EapenS,AndresenEM,MillerB.(2001)Prevalenceof

ticsinschoolchildrenandassociationwithplacementinspecialeducation.Neurology.57:1383-8.

40.ScahillL,SpechtM,PageC.(2014)ThePrevalenceofTicDisordersandClinicalCharacteristicsinChildren.J

ObsessiveCompulsRelatDisord.3:394-400.

41. HirschtrittME,LeePC,PaulsDL,DionY,GradosMA,IllmannC,KingRA,SandorP,McMahonWM,LyonGJ,

CathDC,KurlanR,RobertsonMM,OsieckiL,ScharfJM,MathewsCA;TouretteSyndromeAssociation

InternationalConsortiumforGenetics.(2015)Lifetimeprevalence,ageofrisk,andgeneticrelationshipsof

comorbidpsychiatricdisordersinTourettesyndrome.JAMAPsychiatry.72:325-33.

Section G: Education And Training

42. TAAMedicalandAlliedProfessionalListinghttps://www.tourette.org/find-a-doctor/

43. 1STWorldCongressonTouretteandTicDisordershttp://touretteworldcongress.org/

Section I: Development of Research Resources and Infrastructures

44.BrainDonorAndBankingProgramhttps://www.tourette.org/about-tourette/overview/brain-bank-2/

45. PatientRecruitmentProgramhttps://www.tourette.org/research-medical/current-research-programs/

46.TAAGeneSampleCollectionhttps://www.findtsgene.org

Section J: Fostering Collaborations By Building Consortia

47. TAAInternationalConsortiumForGeneticshttps://www.findtsgene.org

48. MarianthiG,WillseyAJ,MathewsCA,StateM,ScharfJMandPaschouP(2015)TheGeneticEtiologyof

TouretteSyndrome:Large-ScaleCollaborativeEffortsonthePrecipiceofDiscovery.FrontNeurosci.10:351.

49. NeuroimagingConsortium(www.tourette.org/NIC)

50.TAAInternationalDBSRegistryhttps://www.tourette.org/research-medical/deep-brain-stimulation-overview/

51. BehaviorSciencesConsortium(www.tourette.org/BSC).


44

Theresearchprojects,advancesandaccomplishmentsdescribedinthisdocumentwereandareattributedtothe

thousandsofindividuals,families,volunteers,members,companies,organizations,federalinstitutes,researchers,

scientists,physiciansandotherswhohavedonatedmonies,time,expertiseandotherresourcestofacilitatethe

variousresearchprograms.TheseachievementsweredrivenandsupportedbytheTAABoardofDirectors,

Chapters,SupportGroups,StaffandAdvisoryBoards.TheTAAisthankfultoallthosewhohaveandcontinue

tocontributetothemissionofmakinglifebetterforallpeopleimpactedbyTourette,Ticandrelateddisorders.

O: ACKNOWLEDGEMENTS

There are many ways to support the Tourette community. Your involvement in our

events, contributions, and volunteerism helps ensure that the Tourette Association

of American can continue its work in making life better for all people affected by

Tourette and Tic Disorders. Visit Tourette.org to learn more today.

TAA SCIENTIFIC AND ADVISORY BOARDCarolA.Mathews,M.D.,Co-Chair–UniversityofFlorida,Gainesville,FL

PeggyC.Nopoulos,M.D.,Co-Chair–UniversityofIowaCarverCollegeofMedicine,IowaCity,IA

ErikaF.Augustine,M.D.-UniversityofRochesterMedicalCenter,Rochester,NY

ScottN.Compton,Ph.D.-DukeUniversityMedicalCenter,Durham,NC

DonaldL.Gilbert,M.D.,MS,FAAN,FAAP-CincinnatiChildren’sHospitalMedicalCenter,Cincinnati,OH

ArynGittis,Ph.D.-CarnegieMellonUniversity,Pittsburgh,PA

TamaraG.Hershey,Ph.D.-WashingtonUniversitySchoolofMedicine,St.Louis,MO

EllenJ.Hess,Ph.D.-EmoryUniversity,Atlanta,GA

JonathanW.Mink,M.D.,Ph.D.-UniversityofRochesterMedicalCenter,Rochester,NY

TanyaK.Murphy,M.D.,MS-UniversityofSouthFlorida,St.Petersburg,FL

LaurieOzelius,Ph.D.-MassachusettsGeneralHospital,Boston,MA

DavidA.Peterson,Ph.D.-TheSalkInstitute-LaJolla,CA

RosalindaRoberts,Ph.D.-UABSchoolofMedicine,Birmingham,AL

JeremiahM.Scharf,M.D.,Ph.D.-MassachusettsGeneralHospital,Boston,MA

TAA MEDICAL AND SCIENTIFIC ADVISORY BOARD

DouglasW.Woods,Ph.D.,Co-Chair-MarquetteUniversity,Milwaukee,WI

MichaelS.Okun,M.D.,Co-Chair-UniversityofFlorida,Gainesville,FL

BarbaraJ.Coffey,M.D.,M.S.,Co-ChairElect-IcahnSchoolofMedicineatMountSinai,NewYork,NY

KeithA.Coffman,M.D.,Co-ChairElect-Children’sMercyHospitals&Clinics-KansasCity,MO

ShannonBennett,Ph.D.-WeillCornellMedicalCollege,NewYork,NY

MartinE.Franklin,Ph.D.-UniversityofPennsylvaniaSchoolofMedicine,Philadelphia,PA

MichaelB.Himle,Ph.D.-TheUniversityofUtah,SaltLakeCity,UT

JoohiJimenez-Shahed,M.D.-BaylorCollegeofMedicine,Houston,TX

MonicaM.P.Jones,M.D.-SyracusePediatrics,Syracuse,NY

RebeccaK.Lehman,M.D.-PalmettoHealthUSCMedicalGroup,Columbia,SC

IreneMalaty,M.D.–UniversityofFlorida,Gainesville,FL

KirstenR.Müller-Vahl,M.D.–HannoverMedicalSchool,Hannover,Germany

ErikaNurmi,M.D.,Ph.D.-UniversityofCalifornia,LosAngeles,LosAngeles,CA

JanRowe,Dr.OT,OTR/L,FAOTA-Children’sofAlabama,Birmingham,AL

BradleyL.Schlaggar,M.D.,Ph.D.-WashingtonUniversityinSt.Louis,St.Louis,MO

SabineWilhelm,Ph.D.-MassachusettsGeneralHospital,Boston,MA

GENERAL COUNSELDentons

TheTAAAcknowledgesandthanksKevinMcNaught,Ph.D.(pastExecutiveVicePresident,

Research&MedicalPrograms),MarcScullin,MA(pastManager,ResearchandMedicalPrograms),

AlexandraGemma,MPH,CHES(pastCDCProgramDirector),JuditUngar(pastPresident),

andSueLevi-Pearl(pastVPofResearch&MedicalPrograms)fortheirincrediblerolesinthe

developmentoftheprogramsandaccomplishmentssetforthinthisprogressreport.

TAA NATIONAL BOARD OF DIRECTORS

RovenaSchirling,Chair

MonteRedman,FirstViceChair

MarcieKirkpatrick,SecondViceChair

AliceKane,ThirdViceChair

CindyKurtz,FourthViceChair

ReidAshinoff,Director

Dr.AzadAnand,Director

StephenBarron,Director

JosephCampolo,Director

SusanCourey,Ph.D.,Director

FredCook,FinanceCommitteeChair

PaulS.Devore,Director

JulieHaddon,Director

PeterHollenbeck,Ph.D.,Director

DavidKoch,Director

JeffreyKramer,Director

NancyKramer,Director

StephenMcCall,M.Ed.,Director

JulieMoelis,Director

BruceOchsman,Director

ChrisOvitz,Director

RobinSmall,Director

RandiZemsky,Director

42-40BellBlvd.,Suite205,Bayside,NY11361tourette.org 888-4TOURET

Facebook @TouretteAssociation Twitter @TouretteAssn

Instagram @TouretteAssociation YouTube @Tourette TV

TAA LEADERSHIPJohnMiller

President/CEO,TouretteAssociationofAmerica

DianaFelner

VicePresident,PublicPolicy

SonjaMason-Vidal,MBA

VicePresident,Finance&Administration

AmandaTalty

VicePresident,ResourceDevelopment&Marketing

DianaShineman,Ph.D.

VicePresidentofResearch&MedicalPrograms

ThispublicationwassupportedbytheGrantorCooperativeAgreementNumber,NU58DD005375-02,fundedbytheCentersforDiseaseControlandPrevention.ItscontentsaresolelytheresponsibilityoftheauthorsanddonotnecessarilyrepresenttheofficialviewsoftheCentersforDiseaseControlandPreventionortheDepartmentofHealthandHumanServices.

TAA CDC PROGRAM STAFFChelseaTollner,MPH

CDCProgramDirector

NatalieJoseph-Pauline,MPH

CDCProgramCoordinator

YaelGeller,MPH

CDCProgramAssociate

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