Future Of Gene Therapy And Neurological Diseases

The ability to deliver genetic material to cells of a living organism has revolutionized the conduct of biological research and created new approaches in medicine. Although in its infancy, gene therapy offers has potential advantages over traditional pharmacological therapy: a permanent correction of genetic anomaly thereby precluding the need for repetitive dosing. Neurodegenerative disorders affect millions of people, account for billions of dollars in health care costs annually, and as a group of diseases are without available curative therapy. As technology improves, this will lead to a better understanding of the underlying molecular mechanisms that constitute the pathogenesis of neurodegenerative disease. With this, the full potential of gene therapy will be realized.

Figure 11 Delivery of AAV-GDNF exhibits neuroprotective effects on motoneurons in a mouse model of amyotrophic lateral sclerosis. Mice bearing the G93A human SOD1 mutation were injected intramuscularly at 9 weeks of age with 3 X 1010 particles of a GDNF-expressing AAV vector (AAV-GDNF) or a p-galactosidase control vector (AAV-LacZ). The illustrated photomicrographs depict the effect of GDNF on motoneurons that retained axonal projections. The neural tracer CTB was used to label motoneurons in the ventral horn at 110 days of age in wild-type (Panel A), AAV-LacZ-injected ALS mice (Panel B), and AAV-GDNF-injected ALS mice (Panel C) following intramuscular injection. AAV-GDNF vector-treated mice exhibited significantly more large CTB-labeled motoneurons than control treated ALS mice (Panel D). The value represents the CTP/Nissl ratio (average number of neurons per anterior horn). The shift in motoneuron size toward a smaller diameter was markedly retarded in AAV-GDNF vector-treated mice compared to AAV-LacZ treatment (Panel E). Scale bar, 50 ^m. (From Ref. 242, © 2002 Society for Neuroscience.)

Figure 11 Delivery of AAV-GDNF exhibits neuroprotective effects on motoneurons in a mouse model of amyotrophic lateral sclerosis. Mice bearing the G93A human SOD1 mutation were injected intramuscularly at 9 weeks of age with 3 X 1010 particles of a GDNF-expressing AAV vector (AAV-GDNF) or a p-galactosidase control vector (AAV-LacZ). The illustrated photomicrographs depict the effect of GDNF on motoneurons that retained axonal projections. The neural tracer CTB was used to label motoneurons in the ventral horn at 110 days of age in wild-type (Panel A), AAV-LacZ-injected ALS mice (Panel B), and AAV-GDNF-injected ALS mice (Panel C) following intramuscular injection. AAV-GDNF vector-treated mice exhibited significantly more large CTB-labeled motoneurons than control treated ALS mice (Panel D). The value represents the CTP/Nissl ratio (average number of neurons per anterior horn). The shift in motoneuron size toward a smaller diameter was markedly retarded in AAV-GDNF vector-treated mice compared to AAV-LacZ treatment (Panel E). Scale bar, 50 ^m. (From Ref. 242, © 2002 Society for Neuroscience.)

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