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Martha C. Bohn, PhDMedical Research Institute Council Professor
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Molecules and mechanisms that are involved in the development of the nervous system offer therapeutic strategies for the diseased and injured nervous system. For example, neurotrophic factors support the growth, survival and differentiation of specific types of neurons in the developing nervous system. Neurotrophic factors also influence survival and growth of neurons in the adult nervous system. Although these factors have therapeutic potential in the diseased and injured nervous system, the delivery of these labile proteins to specific neurons in the brain and spinal cord at effective levels is problematic. One approach is to use viral vectors to deliver neurotrophic factor genes to the central nervous system so that neurotrophic factors can be continuously synthesized in the desired location, or even in specific cell types.
The Bohn lab is making viral vectors of various classes incorporating neurotrophic factor genes and cellular marker genes using viral, cellular and regulatable promoters. In addition, vectors harboring genes that interfere with cell death or "anti-apoptotic" genes are also being made. These vectors are being compared and tested for specificity, levels of transgene expression and stability of expression in the nervous system. In vitro and in vivo experimental animal models of Parkinson’s disease and Lou Gehrig’s disease are being utilized to determine the efficacy of gene therapy with neurotrophic and/or anti-apoptotic factors on neurodegenerative processes. Studies are also in progress to determine how transgene expression in specific areas of the brain influences neurochemistry, gene expression and neuronal function in specific groups of neurons, as well as at the single neuronal level.
Connor, B., Kozlowski, D.A. , Schallert, T., Tillerson, J.L. , Davidson, B.L. and M.C. Bohn. The protective role of adenoviral vector mediated glial cell line-derived neurotrophic factor expression in the aged parkinsonian rat. Gene Therapy 6: 1936-1951 (1999).
Mohajeri, M.H., Figlewicz, D.A. and M.C. Bohn Intramuscular grafts of myoblasts genetically modified to secrete glial cell line-derived neurotrophic factor (GDNF) prevent motoneuron loss and disease progression in a mouse model of familial amyotrophic lateral sclerosis. Human Gene Therapy 10: 1853-1866 (1999).
Choi-Lundberg, D.L., Lin, Q. Chang, Y.-N., Chiang, Y. L., Hay, C. M., Mohajeri, H., Davidson,B.L. and M.C. Bohn, GDNF gene therapy protects dopaminergic neurons from degeneration in a rat model of Parkinson’s disease. Science 275, 838-841 (1997).
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View Publications by Martha Bohn listed in the National Library of Medicine (PubMed). |
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