Journal article
Increased survival and function of SOD1 mice after glial cell-derived neurotrophic factor gene therapy
Human gene therapy, Vol.13(9), pp.1047-1059
2002
DOI: 10.1089/104303402753812458
PMID: 12067438
Abstract
Amyotrophic lateral sclerosis (ALS) is caused by a progressive degeneration of motor neurons. The cause of sporadic ALS is not known, but 1–2% of all cases are familial and caused by mutations in the copper–zinc superoxide dismutase (SOD1) gene. Transgenic SOD1 mice serve as a transgenic mouse model for these cases. Glial cell-derived neurotrophic factor (GDNF) has a potent trophic effect on motor neurons. Clinical trials in which growth factors have been systemically administered to ALS patients have not been effective, owing in part to the short half-life of these factors and their low concentrations at target sites. Gene transfer of therapeutic factors to motor neurons and/or their target cells, such as muscle, may overcome these problems. Previously, we and others have shown that intramuscularly administered adenovirus vector (AVR) results in foreign gene expression not only in muscle cells, but also in relevant motor neurons in the spinal cord, because of retrograde axonal transport. In this study we utilized an AVR to introduce GDNF into muscles of neonatal SOD1 mice. We showed that AVR-mediated GDNF expression delayed the onset of disease by 7 ± 8 days (mean ± SD), prolonged survival by 17 ± 10 days, and delayed the decline in motor functions (as determined on a rotating rod) by 7–14 days. These results demonstrate that gene delivery to muscle and motor neurons has the potential to treat devastating neurodegenerative diseases such as ALS.
Details
- Title: Subtitle
- Increased survival and function of SOD1 mice after glial cell-derived neurotrophic factor gene therapy
- Creators
- Gyula ACSADI - Department of Pediatrics, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesRoumen A ANGUELOV - Department of Pediatrics, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesMichael E SHY - Department of Neurology, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesHuibin Yang - Department of Pediatrics, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesGabor TOTH - Department of Pediatrics, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesRonald THOMAS - Department of Pediatrics, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesAgnes JANI - Department of Neurology, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesYuying Wang - Department of Pediatrics, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesEmilia IANAKOVA - Department of Neurology, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesSulaiman MOHAMMAD - Department of Neurology, Wayne State University, School of Medicine, Detroit, MI 48201, United StatesRichard A LEWIS - Department of Neurology, Wayne State University, School of Medicine, Detroit, MI 48201, United States
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.13(9), pp.1047-1059
- Publisher
- Liebert; Larchmont, NY
- DOI
- 10.1089/104303402753812458
- PMID
- 12067438
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Language
- English
- Date published
- 2002
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020621402771
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