Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF

M. E. Emborg, J. Moirano, J. Raschke, V. Bondarenko, R. Zufferey, S. Peng, A. D. Ebert, V. Joers, B. Roitberg, J. E. Holden, J. Koprich, J. Lipton, J. H. Kordower, P. Aebischer

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

This study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for glial derived neurotrophic factor (lenti-GDNF) or beta-galactosidase (lenti-LacZ). Functional analysis revealed that the lenti-GDNF, but not lenti-LacZ treated monkeys displayed behavioral improvements that were associated with increased fluorodopa uptake in the striatum ipsilateral to lenti-GDNF treatment. GDNF ELISA of striatal brain samples confirmed increased GDNF expression in lenti-GDNF treated aged animals that correlated with functional improvements and preserved nigrostriatal dopaminergic markers. Our results indicate that the aged primate brain challenged by MPTP administration has the potential to respond to trophic factor delivery and that the degree of neuroprotection depends on GDNF levels.

Original languageEnglish (US)
Pages (from-to)303-311
Number of pages9
JournalNeurobiology of Disease
Volume36
Issue number2
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Aging
  • GDNF
  • Gene transfer
  • Macaque
  • MPTP
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology

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