Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.

Détails

ID Serval
serval:BIB_096EDA06E205
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.
Périodique
Science
Auteur(s)
Kordower J.H., Emborg M.E., Bloch J., Ma S.Y., Chu Y., Leventhal L., McBride J., Chen E.Y., Palfi S., Roitberg B.Z., Brown W.D., Holden J.E., Pyzalski R., Taylor M.D., Carvey P., Ling Z., Trono D., Hantraye P., Déglon N., Aebischer P.
ISSN
0036-8075 (Print)
ISSN-L
0036-8075
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
290
Numéro
5492
Pages
767-773
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.
Mots-clé
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Aging, Animals, Antigens, CD/analysis, Dihydroxyphenylalanine/analogs & derivatives, Dihydroxyphenylalanine/metabolism, Disease Models, Animal, Dopamine/metabolism, Female, Gene Expression, Genetic Therapy, Genetic Vectors, Glial Cell Line-Derived Neurotrophic Factor, Lentivirus/genetics, Macaca mulatta, Neostriatum/metabolism, Neostriatum/pathology, Nerve Degeneration/prevention & control, Nerve Growth Factors, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Neurons/enzymology, Parkinson Disease/metabolism, Parkinson Disease/pathology, Parkinsonian Disorders/metabolism, Parkinsonian Disorders/pathology, Psychomotor Performance, Substantia Nigra/metabolism, Substantia Nigra/pathology, Tyrosine 3-Monooxygenase/metabolism
Pubmed
Web of science
Création de la notice
06/02/2008 10:03
Dernière modification de la notice
20/08/2019 12:31
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