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1 Acta Neurobiologiae Experimentalis

1 2009

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Growth factor gene delivery for Alzheimer's disease: from animal models to clinical trials

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Tuszynski M. , Nagahara A. , Schroeder B. , Coppola G. , Wang L. , Blesch A. , Rockenstein E. , Geschwind D. , Masliah E. , Koo E. , Chiba A.

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Nervous system growth factors have extensive effects on neuronal function and survival. Nerve growth factor (NGF) prevents the death and stimulates the function of basal forebrain cholinergic neurons in correlational models of Alzheimer’s disease (AD), leading to its translation to Phase 1 and 2 human clinical trials. Separately, Brain-Derived Neurotrophic Factor (BDNF) infl uences the survival and function of entorhinal cortical and hippocampal neurons in several animal models of AD, including transgenic mutant APP-expressing mice; aged rats and lesioned rats; and aged and lesioned primates. These benefi cial effects appear to occur independent of alteration in beta amyloid load. We are currently examining the extended safety and tolerability of BDNF gene delivery to the entorhinal cortex in additional animal studies, potentially leading to specifi c targeting of short term memory loss in future human AD trials. This talk will review the history and current status of growth factor gene delivery in AD and other neurodegenerative disorders.