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Viral vectors as tools to model and treat neurodegenerative disorders

The identification of disease‐causing genes in familial forms of neurodegenerative disorders and the development of genetic models closely replicating human central nervous system (CNS) pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions, including gene‐based therapies, the presence of the blood‐brain barrier and the post‐mitotic and poor regenerative nature of the target cells constitute important challenges. Efficient delivery systems taking into account the specificity of the CNS are required to administer potential therapeutic candidates. In addition, genetic models in large animals that replicate the late stages of the diseases are in most cases not available for pre‐clinical studies. The present review summarizes the potential of viral vectors as tools to create new genetic models of CNS disorders in various species including primates and the recent progress toward viral gene therapy clinical trials for the administration of therapeutic candidates into the brain. Copyright © 2005 John Wiley & Sons, Ltd.