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Nerve growth factor gene delivery: Animal models to clinical trials

Cell death is the final common pathway of cognitive decline in Alzheimer's disease (AD). Nervous system growth factors, or neurotrophic factors, are substances naturally produced in the nervous system that support neuronal survival during development and influence neuronal function throughout adulthood. Notably, in animal models, including primates, neurotrophic factors prevent neuronal death after injury and can reverse spontaneous neuronal atrophy in aging. Thus, neurotrophic factor therapy has the potential to prevent or reduce ongoing cell loss in disorders such as AD. The main challenge in clinical testing of neurotrophic factors has been their delivery to the brain in sufficient doses to impact cell function, while restricting their delivery to specific sites to prevent adverse effects from broad distribution. This article reviews progress in evaluating the therapeutic potential of growth factors, from early animal models to human clinical trials currently underway in AD. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007