Sustained delivery of GDNF: towards a treatment for Parkinson's disease

Details

Serval ID
serval:BIB_B9B87CE64673
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Sustained delivery of GDNF: towards a treatment for Parkinson's disease
Journal
Brain Research. Brain Research Reviews
Author(s)
Zurn  A. D., Widmer  H. R., Aebischer  P.
ISSN
0165-0173 (Print)
Publication state
Published
Issued date
10/2001
Volume
36
Number
2-3
Pages
222-9
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Oct
Abstract
Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of nigral dopaminergic neurons. Although symptomatic therapies to substitute for the missing neurotransmitter dopamine are efficient at the early stages of the disease, the goal is to find alternative therapies which could protect dopaminergic neurons from the degenerative process. We have used two distinct gene therapy approaches to deliver the neuroprotective molecule glial cell line-derived neurotrophic factor (GDNF) in animal models of the disease: (i) an encapsulated genetically engineered cell line releasing GDNF (ex vivo gene therapy); and (ii) a lentiviral vector encoding the GDNF gene (in vivo gene therapy). Both approaches allowed protection of nigral dopaminergic neurons against lesion-induced cell death in rodent as well as monkey models of PD. Behavioral symptoms were also ameliorated in these animals. In addition, co-transplantation of embryonic dopaminergic neuronal grafts and a GDNF-releasing capsule allowed improvement of graft survival and differentiation, thereby accelerating behavioral recovery. These results should lead to clinical application in the near future.
Keywords
Animals Brain Tissue Transplantation/*methods Cells, Cultured Diffusion Chambers, Culture/methods Gene Therapy/instrumentation/*methods Genetic Vectors/*therapeutic use Glial Cell Line-Derived Neurotrophic Factor Humans *Nerve Growth Factors Nerve Tissue Proteins/genetics/secretion/*therapeutic use Parkinsonian Disorders/*genetics/physiopathology/*therapy Substantia Nigra/pathology/physiopathology/*surgery
Pubmed
Web of science
Create date
28/01/2008 8:44
Last modification date
20/08/2019 15:27
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