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1615 Poydras Street - Suite 1000
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 Ronald Klein, PhD
Louisiana State University Health Sciences - Shreveport Areas of Research: Viral Vector Development for Neurological Diseases Our work involves gene transfer to the brain for the purposes of gene therapy and other types of functional studies, using the adeno-associated virus (AAV) vector system. Because the recombinant vectors are replication-incompetent and results to date in the rodent and non-human primate brain have not included any forms of pathology, this system appears to be safe, and the transgene expression is efficient and persistent. Neurotrophic factors are ideal therapeutic candidates to slow or reverse neurodegeneration, but the peptide factors are difficult to apply to the brain in a targeted and long-term manner. Studies are underway involving gene delivery of NGF, BDNF, and GDNF neurotrophic factors in animal lesioning models, monitoring therapeutic efficacy at the level of neuroprotection, neurochemistry, and behavior. Another aim is to develop novel transgenic models of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. While germ-line transgenic mice have provided a wealth of information about the genetic bases of these diseases, somatic cell gene transfer directly to brain sub-regions of adult animals offers unique advantages for modeling. We have established models of neurofibrillary tangles and Lewy pathology by expressing mutant forms of tau and alpha-synuclein, respectively. These models can further our understanding of the disease process as well be used to explore novel therapies. SELECTED PUBLICATIONS Gong, Y., Meyer, E.M., Meyer, C.A., Klein, R.L., King, M.A., and Hughes, J.A. Memory-related deficits following selective hippocampal expression of Swedish mutation amyloid precursor protein in the rat. Experimental Neurology, (2006) Klein, R.L., Dayton, R.D., Henderson, K.M., and Petrucelli, L. Parkin is protective for substantial nigra dopamine neurons in a tau gene transfer neurodegeneration model. Neuroscience Letters, (2006) 401(1-2): 130-135 Klein, R.L., Dayton, R.D., Leidenheimer, N.J., Jansen, K., Golde T.E., and Zweig, R.M. Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins. Molecular Therapy, (2006) March; 13(3): 517-527 Klein, R.L., Dayton, R.D., Lin, W.L., and Dickson, D.W. Tau gene transfer, but not alpha-synuclein, induces both progressive dopamine neuron regeneration and behavior in the rat. Neurobiology of Disease, (2005) October; 20(1): 63-73 Klein, R.L., Lin, W.L., Dickson, D.W., Lewis, J., Hutton, M., Duff, K., Meyer, E.M., and King, M.A. Rapid neurofibrillary tangle formation after localized gene transfer of mulanted tau. American Journal of Pathology, (2004) January; 164(1): 347-353 |
