Opportunities and Challenges of the Therapies Targeting CNS Regeneration

200 Pages·2005·2.833 MB·English

by  M. H. Tuszynski (auth.), H. D. Perez, B. Mitrovic, A. Baron Van Evercooren (eds.)

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
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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])