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ResearchfromUniversityofMiamiandTetraDiscoveryShowsPotentialofNovel DrugtoImproveMemoryafterTraumaticBrainInjury UniversityofMiamiMillerSchoolofMedicine/TheMiamiProjecttoCureParalysisandTetra DiscoveryPartnersStudyPublishedintheJournalofNeuroscience Miami,FL-July6,2016–Treatingratswithanexperimentaldrugatthreemonthsfollowingatraumatic braininjury(TBI)improvestheirlearningmemoryability,asreportedinanewstudypublishedonlinetodayin theJulyeditionofTheJournalofNeuroscience.Thedrug,aselectivephosphodiesterase4subtypeinhibitor (PDE4B),iscurrentlyunderdevelopmentbyTetraDiscoveryPartners,aprivatelyheldbiotechnologycompany andisbeingtestedasapotentialtherapyforTBIbyUniversityofMiami/MiamiProjectresearchers. Thepublication,entitledChronicCognitiveDysfunctionafterTraumaticBrainInjuryisImprovedwitha Phosphodiesterase4BInhibitor,wasauthoredbyColeenM.Atkins,Ph.D.,AssociateProfessor,Departmentof NeurologicalSurgery,UniversityofMiami,alongwithW.DaltonDietrich,Ph.D.,ScientificDirector,TheMiami ProjectandKineticConceptsDistinguishedChairinNeurosurgery,SeniorAssociateDeanforDiscoveryScience andProfessor,NeurologicalSurgery,NeurologyandCellBiologyandwithMarkE.Gurney,Ph.D.,CEOofTetra DiscoveryPartners.Inthisstudy,theresearchersreportedthattreatmentwiththePDE4Binhibitorreduced chroniccognitivedeficitsaftertraumaticbraininjuryandrescueddeficitsinhippocampallong-term potentiation.TheseresultssuggestthatPDE4Binhibitionhasthepotentialtoimprovelearningandmemory abilityandoverallfunctioningforpeoplelivingwithTBI. Traumaticbraininjury(TBI)iscausedbyanimpacttothehead.OneofthemostcommoncomplaintsafterTBI arelearningandmemorydifficulties.Nearly8outof10TBIsurvivorsfrombraininjurymustcopewithlearning problemsinthemonthstoyearsafterbraintrauma.However,therearepresentlynoeffectivetreatmentsto improveTBI-inducedlearningandmemoryimpairments.ThemostsuccessfultreatmentshavebeenRitalinand Aricept,butneitherarewellproventoimprovelearningafterbraintrauma. Inthereportedstudy,thescientistslookedatthebrainaftertraumatoidentifywhatchangesinthebrain occurredasaresult.Theyfoundthatbraintraumainhibitsaproteininneuronsthatiscriticalformemory formation,CREB. Duringnormallearningandmemory,thenumberofsynapticconnectionsbetweenneuronsincreasesand theseconnectionsalsobecomestronger.Theseincreasesinsynapticactivityduringlearningareduetoa moleculecalledcAMP.ElevatedcAMPthenleadstotheactivationofCREBandmemoryformation.Inthis study,researchersfoundthatTBIimpairsactivationofCREB.Theteamhypothesizedthatasubtype-selective PDE4BinhibitorthatraisescAMPlevelsandCREBactivationcouldreversethelearningdeficitsinducedbyTBI. Totestthishypothesis,theresearchersinducedTBIinratsandleftthemuntreatedforthreemonths.Atthree monthsaftertheirbraintrauma,theresearcherstreatedtheanimalswithaPDE4Binhibitorandthentested theirbehavioronlearningandmemorytasks.ThestudyrevealedthattreatmentwiththePDE4Binhibitor significantlyreversedtheTBI-induceddeficitsinthememory. “TreatingTBIsurvivorsduringthemonthstoyearsafterbraintraumaisaverypromisingareaofresearchand severalclinicaltrialsarealreadytacklingthisproblem,byusingdrugsrepurposedfromotherneurological disorderssuchasAlzheimer’sdisease,”saidDr.Dietrich.“ThisselectivePDE4BinhibitorfromTetraDiscovery Partnershasgreatpromise,restoringthelearningandmemoryperformanceofTBIanimalstonearlynoninjuredlevels.Thisprojectrepresentsanexcellentexampleofacollaborationbetweenacademicresearchers studyinganimalmodelsofbraininjuryandabiotechcompanywithexpertiseinhumanclinicaltrials.We expectthatthiscollaborationwithTetrawillyieldanewclinicaltrialusingthistherapeuticstrategyinhuman TBIsurvivors.” PreviouseffortstotargetPDE4asatherapeuticapproachtoTBIhavebeenhamperedbytheuseofnonselectivepan-PDE4inhibitors,whichhavebeenmarredbysignificantside-effects–notablynauseaandemesis. Inthesestudies,thePDE4B-selectiveinhibitorshowedpositiveeffectsoncognition,withoutemesis. “WeareveryencouragedbythesepreclinicalstudiesshowingthepotentialofselectiveinhibitionofPDE4Bas astrategyforrestoringcognitivefunctionduringrecoveryfromTBI,”saidMarkGurney,PresidentandChief ExecutiveOfficerofTetraDiscoveryPartners.“WelookforwardtocontinuingoureffortswiththeUniversityof MiamiMillerSchoolofMedicine’sMiamiProjecttoCureParalysistodevelopasuccessfultreatmentforthis importantmedicalneed.” ThestudywasfundedbytheNationalInstitutesofHealth,NIH/NINDS. Dr.AtkinsandDr.Dietrichareco-inventorsonUSPTO8,865,723patentwhichclaimstherapeuticuseofPDE4B inhibitorsfortreatingbraininjury.TetraDiscoveryPartnersistheownerofthispatentandDr.AtkinsandDr. Dietrichdonothaveequitystakesinthecompanyorthatpatent. TheMiamiProjecttoCureParalysis:In1985,BarthA.Green,M.D.andNFLHallofFamelinebacker NickBuonicontihelpedfoundTheMiamiProjecttoCureParalysisafterNick’sson,Marc,sustaineda spinalcordinjuryduringacollegefootballgame.Today,TheMiamiProjectistheworld’smost comprehensivespinalcordinjury(SCI)researchcenter,andadesignatedCenterofExcellenceatthe UniversityofMiamiMillerSchoolofMedicine.TheMiamiProject’sinternationalteamincludesmore than300scientists,researchers,cliniciansandsupportstaffwhotakeinnovativeapproachestothe challengesofspinalcordandbraininjuries. AboutTetraDiscoveryPartners TetraDiscoveryPartnersisaclinicalstagebiotechnologycompanydevelopingaportfoliooftherapeutic productsthatwillbringclarityofthoughttopeoplesufferingfromAlzheimer'sdiseaseandotherbrain disorders.Tetrausesstructure-guideddrugdesigntodiscovermechanisticallynovel,allostericinhibitorsof phosphodiesterase4(PDE4),whichplaysakeyroleinmemoryformationandlearning.Tetraisbotha recipientofaNIHBlueprintNeurotherapeuticsNetworkcooperativeresearchagreement,andalsoreceives majorfundingthroughtheNationalInstituteonAging,andtheNationalInstituteofMentalHealthSmall BusinessInnovationResearch(SBIR)program.TetraDiscoveryPartnersisheadquarteredinGrandRapids, MichiganandmaintainsabusinessofficeinCambridge,Massachusetts.Formoreinformation,pleasevisitthe company'swebsiteathttp://www.tetradiscovery.com. ### Contacts: ScottRoy TheMiamiProject (305)243-8939 [email protected] JoanKureczka Kureczka/MartinAssociatesforTetraDiscoveryPartners (415)821-2413 [email protected]
