ParkinsonsDisease教學(xué)講解課件

Parkinson’sDiseaseAnOverviewofConventionalandExperimentalTreatmentsBackgroundParkinson’sdiseaseisadisorderthataffectsnervecellsinthepartofthebraincontrollingmusclemovementDiseaseisprogressive–signs/symptomsworsenovertimeEventuallyisdisabling,butprogressesgraduallyBelievedtobecausedbygenetics,environmentalfactorsoracombinationofthetwoParkinson’sDiseaseStatsFirstdesribedbyJamesParkinsonin1817Affects~1millionintheU.S.Onsettypicallybetween50-60yearsofage,andslowlyprogresseswithageAverageonsetis62.4yearsofageNeurologicalBasis“NeurodegenerativeDisease”:causedbydegeneration(dysfunctionanddeath)ofneuronswithinthebrain(nigrastriatalpathwayofthebasalganglia)NORMALBRAINFUNCTION–BasalGangliaCellsinsubstantianigraproduce/releasedopamineDopaminereleasedbySNneuronslandsonneuronsofotherbraincenters,controllingtheirfiringMaintargetsarecaudatenucleusandputamen(striatum)Thisbasalgangliapathwayisinvolvedinregulationofmovement NeurologicalBasisPARKINSON’SBRAINFUNCTION–BasalGangliaCellsofsubstantianigradegenerateThesecellscannolongerproduceadequateamountsofdopamineNeuronsofstriatum,etc.arenolongerwellregulated,thusdonotbehaveinnormalmannerResultsinlossofcontrolofmovements–leadstosymptomscharacteristicofParkinson’sdiseaseCharacteristicSymptomsMOTORtremorbradykinesiarigidity/freezinginplacelackoffacialexpressionposturalinstabilitystooped,shufflinggaitNONMOTORdiminishedsenseofsmelllowvoicevolumefootcrampssleepdisturbancedepressionconstipationdroolingConventionalTreatments:MedicationLEVODOPA(L-DOPA)precursortodopamine,convertedtodopaminebynervecellsinthebrainTreatmentwithdopaminenotpossible,becausedopaminecan’tcrossblood-brainbarrierGenerallycombinedwithcarbidopa(Sinemet)–helpslevodopagettothebrain+reducessomesideeffectsExtendeduseoftenproducesdyskinesias–uncontrolledmovements(writhing,twitching,shaking)amongotherminorsideeffectsConventionalTreatments:MedicationDOPAMINEAGONISTSnotchangedintodopamine,butratheractLIKEdopamineatbrainsynapseswheredopamineisusuallypresent(nigrostriatalpathwaysinParkinson’spatients)UsedbothasadjunctstoL-DopatherapyandinyoungerParkinson’sdiseasepatientsSideeffectssimilartolevodopa,butlesslikelytodevelopinvoluntarymovements,morelikelytocausehallucinationsConventionalTreatments:MedicationMAOInhibitors(Selegiline)COMTInhibitorsAnticholinergicsConventionalTreatments:SurgeryThalamotomyInvolvesdestructionofsmallamountsoftissueinthethalamus—majorcenterforrelayingmessages/transmittingsensationsCancauseslurredspeechandlackofcoordinationPallidotomyelectriccurrentusedtodestroysmallamountoftissueinthepallidum(globuspallidus)Mayimprovetremors,rigiditybyinterruptingpathwaybetweenglobuspallidusandthalamusConventionalTreatments:SurgeryDeepBrainStimulationimplantdevice,pacemaker-likeunittransmitsimpulsestoelectrodesplacedinsubthalamicnucleusProducessameeffectsoflesionsurgeries,butcanbeturnedonandoffExperimentalTreatment:SurgeryFetalCellTransplantTherapy

stemcellsobtainedviaabortedfetus,growninculture,transplantedintoParkinson’spatientatnigrostriatalpathwayNewcellsestablishconnectionsand“replace”cellsoriginallylost,thesecellsfunctionnormallyandevenproducedopamineAutologous“Self”Transplantanalagoustofetalcelltransplant,exceptthatprecursornervecellsaretakenfrompatientandcoaxedtoproducedopamine,thenimplantedbackintooriginalpatientReducesthreatofautoimmuneresponseandreduced“controversialbaggage”associatedwithFCTtherapyExperimentalTreatment:SurgeryRetinalPigmentedEpithelialCellTransplantDopamine-producingcellstakenfrompigmentedretinalepitheliumMechanismoftransplantanalagoustofetalcelltransplanttherapyIflossofcontactfromsubstrate,thesecellsdieConsequently,lowerriskofaberrantintegration—possiblecauseofdyskinesiasseeninsomeFCTpatientsSourcesAminoff,M.(2003).ParkinsonPrimer:OverviewofParkinson’sDisease.Retrieved November16,2005,from /site/pp.asp?c=9dJFJLPNB&b=71354.Thissourceprovidedmewiththemostofthebackgroundinformationnecessaryinexplainingthefoundationofthedisease.Thissourcewasespeciallyhelpfulindeterminingthecharacteristicsymptomsofthedisorderaswellasstatistics.Freed,C.R.,Green,P.E.,Breeze,R.E.,Tsai,W.,DuMouchel,W.,Kao,R.,Dillon,S.,et al. (1994).TransplantationofEmbryonicDopamineNeuronsforSevere Parkinson’s Disease.NewEnglandJournalofMedicine,344,(7),710-719.Thissourceplayedalargepartinwritingtheactualpaper.Inthisarticlewasinformationonthebackgroundofstemcells,implicationsinstemcellresearch,andmostbeneficial,theactualexperimentalprocedureitself.Lieberman,A.(2004).WhatisParkinson’sDisease?RetrievedNovember14,2005, from/WhatIsPa