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

doi:10.1016/j.nbd.2009.07.022

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 journal › Article › peer-review

41 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 language	English (US)
Pages (from-to)	303-311
Number of pages	9
Journal	Neurobiology of Disease
Volume	36
Issue number	2
DOIs	https://doi.org/10.1016/j.nbd.2009.07.022
State	Published - Nov 2009
Externally published	Yes

Keywords

Aging
GDNF
Gene transfer
MPTP
Macaque
Parkinson's disease

ASJC Scopus subject areas

Neurology

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10.1016/j.nbd.2009.07.022

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@article{b3134bd078ef4e4898a6fb63cecc93a9,

title = "Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF",

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.",

keywords = "Aging, GDNF, Gene transfer, MPTP, Macaque, Parkinson's disease",

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

note = "Funding Information: This research was supported in part by NIH-NINDS grant NS40578 and WNPRC NIH-RARC base grant 5P51RR000167. ",

year = "2009",

month = nov,

doi = "10.1016/j.nbd.2009.07.022",

language = "English (US)",

volume = "36",

pages = "303--311",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Academic Press Inc.",

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T1 - Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF

AU - Emborg, M. E.

AU - Moirano, J.

AU - Raschke, J.

AU - Bondarenko, V.

AU - Zufferey, R.

AU - Peng, S.

AU - Ebert, A. D.

AU - Joers, V.

AU - Roitberg, B.

AU - Holden, J. E.

AU - Koprich, J.

AU - Lipton, J.

AU - Kordower, J. H.

AU - Aebischer, P.

N1 - Funding Information: This research was supported in part by NIH-NINDS grant NS40578 and WNPRC NIH-RARC base grant 5P51RR000167.

PY - 2009/11

Y1 - 2009/11

N2 - 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.

AB - 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.

KW - Aging

KW - GDNF

KW - Gene transfer

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KW - Macaque

KW - Parkinson's disease

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

Abstract

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