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

Neurobiology of Disease (Nov 2009)

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

Affiliations

M.E. Emborg: Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA; Corresponding author. Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA. Fax: +1 608 263 3524.
J. Moirano: Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA
J. Raschke: Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA
V. Bondarenko: Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA
R. Zufferey: Lausanne University, Switzerland
S. Peng: Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA
A.D. Ebert: Waisman Center, University of Wisconsin, Madison, WI, USA
V. Joers: Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA
B. Roitberg: Department Neurosurgery, University of Illinois, Chicago, IL, USA
J.E. Holden: Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA
J. Koprich: Toronto Western Hospital, Toronto, ON, Canada
J. Lipton: Department Psychiatry, University of Cincinnati, OH, USA
J.H. Kordower: Department Neurological Sciences, Rush University, Chicago, IL, USA
P. Aebischer: Waisman Center, University of Wisconsin, Madison, WI, USA

Journal volume & issue: Vol. 36, no. 2
pp. 303 – 311

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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