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, Jodi 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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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
Externally publishedYes

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Glial Cell Line-Derived Neurotrophic Factor
Primates
Parkinson Disease
Macaca mulatta
Haplorhini
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Substantia Nigra
Regeneration
Young Adult
Hand
Gene Expression
Neurons
Injections

ASJC Scopus subject areas

  • General

Cite this

Kordower, J. H., Emborg, M. E., Bloch, J., Ma, S. Y., Chu, Y., Leventhal, L., ... 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

Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. / Kordower, J. H.; Emborg, M. E.; Bloch, J.; Ma, S. Y.; Chu, Y.; Leventhal, L.; McBride, Jodi; 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.

In: Science, Vol. 290, No. 5492, 27.10.2000, p. 767-773.

Research output: Contribution to journalArticle

Kordower, JH, Emborg, ME, Bloch, J, Ma, SY, Chu, Y, Leventhal, L, McBride, J, Chen, EY, Palfi, S, Roitberg, BZ, Brown, WD, Holden, JE, Pyzalski, R, Taylor, MD, 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, vol. 290, no. 5492, pp. 767-773. https://doi.org/10.1126/science.290.5492.767
Kordower, J. H. ; Emborg, M. E. ; Bloch, J. ; Ma, S. Y. ; Chu, Y. ; Leventhal, L. ; McBride, Jodi ; 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. / Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. In: Science. 2000 ; Vol. 290, No. 5492. pp. 767-773.
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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.",
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AU - Ma, S. Y.

AU - Chu, Y.

AU - Leventhal, L.

AU - McBride, Jodi

AU - Chen, E. Y.

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AU - Ling, Z.

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AU - Deglon, N.

AU - Aebischer, P.

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N2 - 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.

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