Opportunities and Challenges of the Therapies Targeting CNS Regeneration PDF
Preview Opportunities and Challenges of the Therapies Targeting CNS Regeneration
Ernst Schering Research Foundation Workshop 53 Opportunities (cid:3)(cid:3) and Challenges of the Therapies Targeting CNS Regeneration D. Perez B. Mitrovic A. Baron Van Evercooren (Editors) (cid:3)(cid:3) (cid:4)(cid:5)(cid:4)(cid:5) (cid:1)(cid:1) Ernst Schering Research Foundation Workshop 53 Opportunities and Challenges of the Therapies Targeting CNS Regeneration Ernst Schering Research Foundation Workshop 53 Opportunities and Challenges of the Therapies Targeting CNS Regeneration H.D. Perez, B. Mitrovic, A. Baron Van Evercooren Editors With 19 Figures 123 SeriesEditors:G.StockandM.Lessl LibraryofCongressControlNumber:2004117277 ISSN0947-6075 ISBN-103-540-24082-9SpringerBerlinHeidelbergNewYork ISBN-13978-3-540-24082-2SpringerBerlinHeidelbergNewYork Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthe materialisconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherway,andstorageindata banks.Duplicationofthispublicationorpartsthereofispermittedonlyundertheprovisionsof theGermanCopyrightLawofSeptember9,1965,initscurrentversion,andpermissionforuse mustalwaysbeobtainedfromSpringer-Verlag.Violationsareliableforprosecutionunderthe GermanCopyrightLaw. SpringerisapartofSpringerScience+BusinessMedia springeronline.com (cid:1)c Springer-VerlagBerlinHeidelberg2005 PrintedinGermany Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoes notemply,evenintheabsenceofaspecificstatemant,thatsuchnamesareexemptfromthe relevantprotectivelawsandregulationsandthereforfreeforgeneraluse.Productliability:The publishercannotguaranteetheaccuracyanyinformationaboutdosageandapplicationcontained inthisbook.Ineveryinduvidualcasetheusermustchecksuchinformationbyconsultingthe relevantliterature. Editor:Dr.UteHeilmann,Heidelberg DeskEditor:WilmaMcHugh,Heidelberg ProductionEditor:MichaelHübert,Leipzig Coverdesign:design&production,Heidelberg Typesettingandproduction:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig 21/3150/YL–543210 Printedonacid-freepaper Preface The therapeutic options for the treatment of multiple sclerosis (MS) andotherneurodegenerativeandtraumaticdiseasessuchasspinalcord injury,Alzheimer’s,Parkinson’sdisease,etc.,haveundergoneenormous progress over recent years. Despite these encouraging developments, available therapies are only partially effective, and the ultimate goal is still farfrombeing attained. Improvedunderstanding ofthe cellular and molecular mechanisms of the pathogenesis of neurodegeneration and demyelination has led to a variety of new therapeutic targets and approaches. Inadditiontomodulationoftheinflammatoryprocess(MS)andclas- sicalneuroprotection(stroke,AD),therapeuticapproachesfocussingon activeremyelinizationandneuronalregenerationhavebecomeincreas- inglyimportant.Basedoncurrentconcepts,thisbooksummarizesnew therapeuticapproaches. Althoughitwasoncethoughtthatthecentralnervoussystem(CNS) of mammals was incapable of substantial recovery from injury, it is nowclearthattheadultCNSremainsresponsivetovarioussubstances that can promote cell survival and stimulate axonal growth. Among these substances are growth factors, including the neurotrophins and cytokines.Stemcelltherapiesfortheinductionofremyelinizationand neuroregeneration are reviewed. The potential role of a protective im- munityintheinductionofremyelinationandneuroregenerationisalso discussed. Different gene therapy approaches for the treatment of MS VI Preface and other neurodegenerative diseases such as Alzheimer’s disease and spinalcordinjury,etc.,arealsosummarized.Amajordrivingforceisthe understandingofthecommonregenerativeprocessesthatareimportant forthefunctionalrecoveryofCNS,regardlessoftheinitialcauseofthe damage. Therefore,themolecularandcellulareventsleadingtothedemyeli- nation, axonal loss, and neuronal death in different neurodegenerative diseasesarealsoreviewed. H.D.Perez, B.Mitrovic Contents 1 NewStrategiesforCNSRepair M.H.Tuszynski . . . . . . . . . . . . . . . . . . . . . . . . 1 2 HeterogeneityofMultipleSclerosis: ImplicationsforTherapyTargetingRegeneration H.Lassmann . . . . . . . . . . . . . . . . . . . . . . . . . 11 3 TheNeuroprotectiveEffectofInflammation: ImplicationsfortheTherapyofMultipleSclerosis R.Hohlfeld,M.Kerschensteiner,C.Stadelmann, H.Lassmann,H.Wekerle . . . . . . . . . . . . . . . . . . 23 4 FibroblastGrowthFactors inOligodendrocytePhysiologyandMyelinRepair L.Decker,F.Lachapelle,L.Magy,N.Picard-Riera, B.Nait-Oumesmar,A.Baron-VanEvercooren . . . . . . . . 39 5 WhiteMatterProgenitorCells ResideinanOligodendrogenicNiche F.J.Sim,S.A.Goldman. . . . . . . . . . . . . . . . . . . . 61 6 AttheInterfaceoftheImmuneSystem andtheNervousSystem:HowNeuroinflammation ModulatestheFateofNeuralProgenitorsInVivo F.-J.Mueller,S.R.McKercher,J.Imitola,J.F.Loring,S.Yip, S.J.Khoury,E.Y.Snyder . . . . . . . . . . . . . . . . . . . 83 VIII Contents 7 RemyelinationandRestorationofAxonalFunction byGlialCellTransplantation I.D.Duncan . . . . . . . . . . . . . . . . . . . . . . . . . 115 8 GeneandStemCellTherapy forAutoimmuneDemyelination S.Pluchino,M.Bacigaluppi,S.Bucello,E.Butti,M.Deleidi, L.Zanotti,G.Martino,R.Furlan . . . . . . . . . . . . . . 133 9 NovelGeneTherapeuticStrategies forNeurodegenerativeDiseases K.A.Maguire-Zeiss,H.J.Federoff . . . . . . . . . . . . . . 147 10 MeasuringInjuryandRepairofMyelinandNeurons inMultipleSclerosis D.L.Arnold,J.Chen . . . . . . . . . . . . . . . . . . . . . 173 PreviousVolumesPublishedinThisSeries . . . . . . . . . . . . 187 ListofEditorsandContributors Editors Perez,H.D. BerlexBiosciences,Richmond,CA94806,USA (e-mail:[email protected]) Mitrovic,B. BerlexBiosciences,Richmond,CA94806,USA (e-mail:[email protected]) BaronVanEvercooren,A. INSERM,Unit546,CHUPitié-Salpétrière,105Boulevarddel’Hôpital, 75634Paris,France (e-mail:[email protected]) Contributors Arnold,D.L. MontrealNeurologicalInstitute,McGillUniversity,3801UniversityStreet, Montreal,QuebecH3A2B4,Canada (e-mail:[email protected]) Bacigaluppi,M. NeuroimmunologyUnit,DepartmentofNeurology, SanRaffaeleScientificInstitute-DIBIT,ViaOlgettina,58,20132Milan,Italy Bucello,S. NeuroimmunologyUnit,DepartmentofNeurology, SanRaffaeleScientificInstitute-DIBIT,ViaOlgettina,58,20132Milan,Italy X ListofEditorsandContributors Butti,E. NeuroimmunologyUnit,DepartmentofNeurology, SanRaffaeleScientificInstitute-DIBIT,ViaOlgettina,58,20132Milan,Italy Chen,J. MontrealNeurologicalInstitute,McGillUniversity,3801UniversityStreet, Montreal,QuebecH3A2B4,Canada Decker,L. INSERMU368,EcoleNormaleSupe´rieure,46rued’Ulm, 75230Paris,Cedex05,France (e-mail:[email protected]) Deleidi,M. NeuroimmunologyUnit,DepartmentofNeurology, SanRaffaeleScientificInstitute-DIBIT,ViaOlgettina,58,20132Milan,Italy Duncan,I.D. DepartmentofMedicalSciences,UniversityofWisconsin-Madison, SchoolofVeterinaryMedicine,2015LindenDrive,Madison,WC53705-1102 Federoff,H.J. CenterforAgingandDevelopmentalBiology,UniversityofRochester, SchoolofMedicineandDentistry, 601ElmwoodAvenue,Box645,RoomI-9619,Rochester,NY14642,USA (e-mail:[email protected]) Furlan,R. NeuroimmunologyUnit,DepartmentofNeurology, SanRaffaeleScientificInstitute-DIBIT,ViaOlgettina,58,20132Milan,Italy Goldman,S.A. DivisionofCellandGeneTherapy,DepartmentofNeurology, UniversityofRochesterMedicalCenter, 601ElmwoodAvenue,MRBX,Box645,Rochester,NY14642,USA (e-mail:[email protected])
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