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

J. H. Kordower, 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. Deglon, P. Aebischer

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    1081 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)767-773
    Number of pages7
    JournalScience
    Volume290
    Issue number5492
    DOIs
    StatePublished - Oct 27 2000

    ASJC Scopus subject areas

    • General

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    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., Deglon, N., & Aebischer, P. (2000). Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science, 290(5492), 767-773. https://doi.org/10.1126/science.290.5492.767