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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Snyder, R. O. Mandel, R. J. Spratt, S. K. Leff, S. E. |
| Description | Author Affiliation: Mandel RJ ( Department of Gene Therapy Applications, Cell Genesys Inc., 342 Lakeside Drive, Foster City, CA 94404, USA. rmandel@hisemail.com); |
| Abstract | A recombinant adeno-associated virus (rAAV) vector capable of infecting cells and expressing rat glial cell line-derived neurotrophic factor (rGDNF), a putative central nervous system dopaminergic survival factor, under the control of a potent cytomegalovirus (CMV) immediate/early promoter (AAV-MD-rGDNF) was constructed. Two experiments were performed to evaluate the time course of expression of rAAV-mediated GDNF protein expression and to test the vector in an animal model of Parkinson's disease. To evaluate the ability of rAAV-rGDNF to protect nigral dopaminergic neurons in the progressive Sauer and Oertel 6-hydroxydopamine (6-OHDA) lesion model, rats received perinigral injections of either rAAV-rGDNF virus or rAAV-lacZ control virus 3 weeks prior to a striatal 6-OHDA lesion and were sacrificed 4 weeks after 6-OHDA. Cell counts of back-labeled fluorogold-positive neurons in the substantia nigra revealed that rAAV-MD-rGDNF protected a significant number of cells when compared with cell counts of rAAV-CMV-lacZ-injected rats (94% vs. 51%, respectively). In close agreement, 85% of tyrosine hydroxylase-positive cells remained in the nigral rAAV-MD-rGDNF group vs. only 49% in the lacZ group. A separate group of rats were given identical perinigral virus injections and were sacrificed at 3 and 10 weeks after surgery. Nigral GDNF protein expression remained relatively stable over the 10 weeks investigated. These data indicate that the use of rAAV, a noncytopathic viral vector, can promote delivery of functional levels of GDNF in a degenerative model of Parkinson's disease. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 25 |
| Volume Number | 94 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1997-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Genetic Therapy Nerve Growth Factors Nerve Tissue Proteins Genetics Parkinson Disease, Secondary Therapy Animals Dependovirus Disease Models, Animal Gene Expression Genetic Vectors Glial Cell Line-Derived Neurotrophic Factor HeLa Cells Nerve Degeneration Metabolism Oxidopamine Toxicity Chemically Induced Pathology Rats, Inbred F344 Recombination, Genetic Substantia Nigra Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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