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Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model

Björklund, Anders LU ; Kirik, Deniz LU ; Rosenblad, C; Georgievska, B; Lundberg, Cecilia LU and Mandel, R J (2000) In Brain Research 886(1-2). p.82-98
Abstract
During the last few years, recombinant viral vectors derived from adenovirus (Ad), adeno-associated virus (AAV) or lentivirus (LV) have been developed into highly effective vehicles for gene transfer to the adult central nervous system. In recent experiments, in the rat model of Parkinson's disease, all three vector systems have been shown to be effective for long-term delivery of glial cell line-derived neurotrophic factor (GDNF) at biologically relevant levels in the nigrostriatal system. Injection of the GDNF encoding vectors into either striatum or substantia nigra thus makes it possible to obtain a regionally restricted over-expression of GDNF within the nigrostriatal system that is sufficient to block the toxin-induced degeneration... (More)
During the last few years, recombinant viral vectors derived from adenovirus (Ad), adeno-associated virus (AAV) or lentivirus (LV) have been developed into highly effective vehicles for gene transfer to the adult central nervous system. In recent experiments, in the rat model of Parkinson's disease, all three vector systems have been shown to be effective for long-term delivery of glial cell line-derived neurotrophic factor (GDNF) at biologically relevant levels in the nigrostriatal system. Injection of the GDNF encoding vectors into either striatum or substantia nigra thus makes it possible to obtain a regionally restricted over-expression of GDNF within the nigrostriatal system that is sufficient to block the toxin-induced degeneration of the nigral dopamine neurons. Injection of GDNF vectors in the striatum, in particular, is effective not only in rescuing the cell bodies in the substantia nigra, but also in preserving the nigrostriatal projection and a functional striatal dopamine innervation in the rat Parkinson model. Long-term experiments using AAV-GDNF and LV-GDNF vectors show, moreover, that sustained GDNF delivery over 3-6 months can promote regeneration and significant functional recovery in both 6-OHDA-lesioned rats and MPTP-lesioned monkeys. The impressive efficacy of the novel AAV and LV vectors in rodent and primate Parkinson models suggests that the time may now be ripe to explore these vector systems as tools for neuroprotective treatments in patients with Parkinson's disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glial cell line-derived neurotrophic factor, Neuroprotection, Parkinson’s disease, Gene-transfer, Adenovirus, Adeno-associated virus, Lentivirus
in
Brain Research
volume
886
issue
1-2
pages
82 - 98
publisher
Elsevier
external identifiers
  • pmid:11119690
  • scopus:0034672304
ISSN
1872-6240
DOI
10.1016/S0006-8993(00)02915-2
language
English
LU publication?
yes
id
519d6a78-f847-46e3-ac78-cb94011f2ce5 (old id 1117196)
date added to LUP
2008-07-03 09:21:59
date last changed
2017-11-19 03:36:56
@article{519d6a78-f847-46e3-ac78-cb94011f2ce5,
  abstract     = {During the last few years, recombinant viral vectors derived from adenovirus (Ad), adeno-associated virus (AAV) or lentivirus (LV) have been developed into highly effective vehicles for gene transfer to the adult central nervous system. In recent experiments, in the rat model of Parkinson's disease, all three vector systems have been shown to be effective for long-term delivery of glial cell line-derived neurotrophic factor (GDNF) at biologically relevant levels in the nigrostriatal system. Injection of the GDNF encoding vectors into either striatum or substantia nigra thus makes it possible to obtain a regionally restricted over-expression of GDNF within the nigrostriatal system that is sufficient to block the toxin-induced degeneration of the nigral dopamine neurons. Injection of GDNF vectors in the striatum, in particular, is effective not only in rescuing the cell bodies in the substantia nigra, but also in preserving the nigrostriatal projection and a functional striatal dopamine innervation in the rat Parkinson model. Long-term experiments using AAV-GDNF and LV-GDNF vectors show, moreover, that sustained GDNF delivery over 3-6 months can promote regeneration and significant functional recovery in both 6-OHDA-lesioned rats and MPTP-lesioned monkeys. The impressive efficacy of the novel AAV and LV vectors in rodent and primate Parkinson models suggests that the time may now be ripe to explore these vector systems as tools for neuroprotective treatments in patients with Parkinson's disease.},
  author       = {Björklund, Anders and Kirik, Deniz and Rosenblad, C and Georgievska, B and Lundberg, Cecilia and Mandel, R J},
  issn         = {1872-6240},
  keyword      = {Glial cell line-derived neurotrophic factor,Neuroprotection,Parkinson’s disease,Gene-transfer,Adenovirus,Adeno-associated virus,Lentivirus},
  language     = {eng},
  number       = {1-2},
  pages        = {82--98},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model},
  url          = {http://dx.doi.org/10.1016/S0006-8993(00)02915-2},
  volume       = {886},
  year         = {2000},
}