Therapeutic strategies for Huntington's disease based on a molecular understanding of the disorder.

A mutation on chromosome 4p16.3 with an expanded polyglutamine tract has been identified as the cause of Huntington's disease (HD). The neuroscience and clinical community now faces the formidable challenge of using this information to develop a treatment against this fatal and currently untreatable disease. This article reviews the recent literature pertaining to HD and presents an overview of possible intervention strategies against the neurodegenerative process of HD. Because little is known about the physiological function of the HD gene, there are four biological levels at which therapies could be devised. Identification and cloning of the gene might direct novel therapies for HD using the following strategies: interference (1) at the DNA or (2) at the RNA level; (3) blocking the deleterious effect of the protein; and (4) physiological intervention using pharmacological agents or neural cell transplants.