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Prog Brain Res. 2004;146:441-9.

Nerve growth factor: from animal models of cholinergic neuronal degeneration to gene therapy in Alzheimer's disease.

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  • 1Department of Neurosciences-0626, University of California, San Diego, La Jolla, CA 92093, USA. mtuszynski@ucsd.edu

Abstract

Over the last 20 years it has been recognized that neurotrophic factors profoundly influence the development of the nervous system and have the potential to modify disease processes in the adult nervous system. The ability of nervous system growth factors to prevent or reduce neuronal degeneration in animal models of neurodegenerative diseases has led to several clinical trials. One of the main obstacles to the success of these trials has been the method of growth factor delivery: sufficiently high doses of neurotrophic factors must be achieved in the target region of the brain to efficiently modify disease processes, but delivery must be restricted to specific brain regions to prevent adverse effects. Recent advances in molecular medicine have made gene therapy in the nervous system a potentially realistic approach for the delivery of therapeutic molecules such as growth factors. As an alternative to conventional drug delivery, several gene therapy trials for the treatment of central nervous system diseases have started or will start in the near future. This chapter reviews the development of neurotrophic factor gene therapy for neurodegenerative diseases focusing on the therapeutic potential of nerve growth factor in Alzheimer's disease, currently the subject of a phase I clinical trial.

PMID:
14699979
[PubMed - indexed for MEDLINE]
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