早老性痴呆药物研究进展课件

HowtoaccelerateADresearch 2020 2 23 2 Contents CurrentsituationofAD 1 Whatarebigcompaniesdoing 2 Trends 3 Perspective 4 2020 2 23 3 1CurrentsituationofAD Population 37millionCauses toosophisticatedMarketdrugs Tarcrine Donepezil Rivastigmine Galanthamine Huperzine MemantineSomesocialactivitiesmaycorrelatewithAD butcannotdelaytheprogressofAD 2020 2 23 4 NatureReviews 2010 7 387 398 2020 2 23 5 2Whatarebigcompaniesdoing Abigcakeattractsalotofbigcompanies attention suchasPfizer Elan Merk Novartisandsoon 2020 2 23 6 BMCMedicine2009 7 7 2020 2 23 7 Tramiprosate ALZHEMED NeurochemInc ThePhaseIIItrialdidnotshowabeneficialeffectoncognitionorfunction sothedevelopmentprogramhasbeendiscontinued 2020 2 23 8 Vaccinesandantibodies AN 1792 Elan thefirst generationamyloidvaccine PhaseIItrialwasdiscontinuedowingtothedevelopmentofasepticmeningoencephalitisin6 ofthepatientsACC 001 Elan preventtheinductionofatoxiccellularimmuneresponse inaPhaseIIclinicaltrialBapineuzumab Elan Wyeth PhaseIII monoclonalantibodiesImmunoglobulinIgIV PhaseIII polyclonalantibodies 2020 2 23 9 2020 2 23 10 RAGEInhibitor Amyloidisknowntobindtoreceptorsforadvancedglycatedendproducts RAGE onthesurfaceofcellsandattheblood brainbarrier thisbindingmaycontributetoinflammationandneuronaldeath PF 04494700 anorallybioavailableantagonistofRAGE PhaseII 2020 2 23 11 secretaseinhibitors Tarenflurbil theenantiomerofthenon steroidalanti inflammatorydrugflurbiprofen modulatestheactivityof secretase failedinPhaseIIISemagacestat reductionofamyloidpeptidegenerationinbloodandcerebrospinalfluidofpatientswithADtreatedwithtolerabledoses inPhaseIII 2020 2 23 12 Tauaggregationinhibitor Rember Methyleneblue awidelyusedhistologydye hasbeenshowntointerferewithtauaggregation EnteringPhaseIII 2020 2 23 13 2020 2 23 14 Microtubulestabilizer NAP AL 108 derivedfromanaturalneurotrophicprotein canbedeliveredtothecentralnervoussystemviaintranasaladministration markedlyreducestauphosphorylation andpreliminaryhumanstudieshavebeenencouraging NowitisinPhaseIItrial 2020 2 23 15 Dimebon Pfizer PhaseIIItrial DimebonandDonepezil failed butPfizernowislaunchinganotherPhaseIIItrialaboutdimebonwithotherADdrugs 2020 2 23 16 PhaseIIItrialsofGinkgobiloba NSAIDs phenserine statins tarenflurbil tramiprosate andxaliprodenhavebeencompleted noneofthemdemonstratingadequateefficacy PhaseIItrialsofdimebon huperzineA intravenousimmunoglobulin andmethylthioniniumchloridewerereportedat2008 NineteencompoundsarecurrentlyinPhaseIItrials and3compounds AN1792 lecozotanSR andSGS742 failedatthisstageofdevelopment 2020 2 23 17 3Trends MultitargetAnti AlzheimerAgentsADmodelfurtherexplorethecausescoalitionandcooperation 2020 2 23 18 MultitargetAnti AlzheimerAgents NovelTacrine 8 HydroxyquinolineHybridsasMultifunctionalAgentsfortheTreatmentofAlzheimer sDisease withNeuroprotective Cholinergic Antioxidant andCopper ComplexingProperties 2020 2 23 19 2020 2 23 20 Bivalent CarbolinesasPotentialMultitargetAnti AlzheimerAgents 2020 2 23 21 ADmodel AplatformtoperformpharmacologicalevaluationofanimalmodelsofAlzheimer sdiseaseInthefuturedrugcandidatesmaybedirectlyusedtoanimalmodelsofAlzheimer sdisease 2020 2 23 22 Furtherexplorethecauses ThebrainofADpatientlikesalabyrinth 2020 2 23 23 Cooperation WhileeachofusisrunningintoastonewallwithAlzheimer s whatwillwedonext Allowresearcherstostudyalargerpoolofpatientswillhelpusseehowthediseaseprogresses identifysubgroups andhopefullydevelopmoresophisticatedcomputermodelsthatcouldsavetimeandmoneydevelopingdrugs 2020 2 23 24 4Perspective Whileitisnotpossibletopredictthesuccessofanyindividualprogram oneormorearelikelytoproveeffective DespitedisappointingresultsfromrecentlycompletedPhaseIIItrialsofseveralnovelcompounds theextentandbreadthofactivityatallphasesofclinicaldevelopmentsuggestthatnewpharmacotherapeuticoptionsforthetreatmentofADwillbecomeavailablewithinthenextdecade Itseemsreasonabletopredictthatinthenot too distantfuture asynergisticcombinationofagentswillhavethecapacitytoaltertheneurodegenerativecascadeandreducetheglobalimpactofthisdevastatingdisease ThankYou 2020 2 23 26 Reference 1MichaelSRafiiandPaulSAisen RecentdevelopmentsinAlzheimer sdiseasetherapeutics BMCMedicine2009 7 7 1741 7 15 2YvonneRook Bivalent CarbolinesasPotentialMultitargetAnti AlzheimerAgents J Med C XXXX Vol XXX NO XX3Mar aIsabelFern andez Bachiller NovelTacrine 8 HydroxyquinolineHybridsasMultifunctionalAgentsfortheTreatmentofAlzheimer sDisease withNeuroprotective Cholinergic Antioxidant andCopper ComplexingProperties J Med C XXXX XXX 000 000 4RaymondT Bartus ReginaldL DeanIII PharmaceuticaltreatmentforcognitivedeficitsinAlzheimer sdiseaseandotherneurodegenerativeconditions exploringnewterritoryusingtraditionaltoolsandestablishedmaps Psychopharmacology 2009 202