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Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus)

Eslamboli, A; Cummings, RM; Ridley, RM; Baker, HF; Muzyczka, N; Burger, C; Mandel, RJ; Kirik, Deniz LU and Annett, LE (2003) In Experimental Neurology 184(1). p.536-548
Abstract
Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a treatment for Parkinson's disease. Recombinant adeno-associated viral vectors expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of Parkinson's disease to promote functional regeneration after 6-OHDA lesions of the nigrostriatal system. The goal of the present study was to assess the anatomical and functional efficacy of rAAV-GDNF in the common marmoset monkey (Callithrix jacchus). rAAV-GDNF was injected into the striatum and substantia nigra 4 weeks prior to a unilateral 6-OHDA lesion of the nigrostriatal bundle. Forty percent of the dopamine cells in the lesioned substantia nigra of the rAAV-GDNF-treated monkeys survived, compared with 21% in... (More)
Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a treatment for Parkinson's disease. Recombinant adeno-associated viral vectors expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of Parkinson's disease to promote functional regeneration after 6-OHDA lesions of the nigrostriatal system. The goal of the present study was to assess the anatomical and functional efficacy of rAAV-GDNF in the common marmoset monkey (Callithrix jacchus). rAAV-GDNF was injected into the striatum and substantia nigra 4 weeks prior to a unilateral 6-OHDA lesion of the nigrostriatal bundle. Forty percent of the dopamine cells in the lesioned substantia nigra of the rAAV-GDNF-treated monkeys survived, compared with 21% in the untreated monkeys. Fine dopaminergic fibres were observed microscopically in the injected striatum of some rAAV-GDNF-treated monkeys, suggesting that rAAV-GDNF treatment may have prevented, at least in part, the loss of dopaminergic innervation of the striatum. Protection of dopamine cells and striatal fibre innervation was associated with amelioration of the lesion-induced behavioural deficits. rAAV-GDNF-treated monkeys showed partial or complete protection not only in the amphetamine and apomorphine rotation but also in head position and the parkinsonian disability rating scale. Therefore, our study provides evidence for the behavioural and anatomical efficacy of GDNF delivered via an rAAV vector as a possible treatment for Parkinson's disease. (C) 2003 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
behaviour, neuroprotection, marmoset monkey, glial cell line-derived neurotrophic factor, Parkinson's disease, gene therapy, adeno-associated viral vector
in
Experimental Neurology
volume
184
issue
1
pages
536 - 548
publisher
Academic Press
external identifiers
  • wos:000186804800055
  • pmid:14637123
  • scopus:0345257314
ISSN
0014-4886
DOI
10.1016/j.expneurol.2003.08.007
language
English
LU publication?
yes
id
c5042163-893c-49ac-ad16-5b9a595cc8c0 (old id 294585)
date added to LUP
2007-08-29 15:46:53
date last changed
2017-06-18 03:48:44
@article{c5042163-893c-49ac-ad16-5b9a595cc8c0,
  abstract     = {Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a treatment for Parkinson's disease. Recombinant adeno-associated viral vectors expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of Parkinson's disease to promote functional regeneration after 6-OHDA lesions of the nigrostriatal system. The goal of the present study was to assess the anatomical and functional efficacy of rAAV-GDNF in the common marmoset monkey (Callithrix jacchus). rAAV-GDNF was injected into the striatum and substantia nigra 4 weeks prior to a unilateral 6-OHDA lesion of the nigrostriatal bundle. Forty percent of the dopamine cells in the lesioned substantia nigra of the rAAV-GDNF-treated monkeys survived, compared with 21% in the untreated monkeys. Fine dopaminergic fibres were observed microscopically in the injected striatum of some rAAV-GDNF-treated monkeys, suggesting that rAAV-GDNF treatment may have prevented, at least in part, the loss of dopaminergic innervation of the striatum. Protection of dopamine cells and striatal fibre innervation was associated with amelioration of the lesion-induced behavioural deficits. rAAV-GDNF-treated monkeys showed partial or complete protection not only in the amphetamine and apomorphine rotation but also in head position and the parkinsonian disability rating scale. Therefore, our study provides evidence for the behavioural and anatomical efficacy of GDNF delivered via an rAAV vector as a possible treatment for Parkinson's disease. (C) 2003 Elsevier Inc. All rights reserved.},
  author       = {Eslamboli, A and Cummings, RM and Ridley, RM and Baker, HF and Muzyczka, N and Burger, C and Mandel, RJ and Kirik, Deniz and Annett, LE},
  issn         = {0014-4886},
  keyword      = {behaviour,neuroprotection,marmoset monkey,glial cell line-derived neurotrophic factor,Parkinson's disease,gene therapy,adeno-associated viral vector},
  language     = {eng},
  number       = {1},
  pages        = {536--548},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus)},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2003.08.007},
  volume       = {184},
  year         = {2003},
}