| Literature DB >> 11052933 |
J H Kordower1, M E Emborg, J Bloch, S Y Ma, Y Chu, L Leventhal, J McBride, E Y Chen, S Palfi, B Z Roitberg, W D Brown, J E Holden, R Pyzalski, M D Taylor, P Carvey, Z Ling, D Trono, P Hantraye, N Déglon, P Aebischer.
Abstract
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.Entities:
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Year: 2000 PMID： 11052933 DOI： 10.1126/science.290.5492.767
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728