1. ¹Department of Pharmacology, Dalhousie University Halifax, NS, Canada
2. ²Departments of Internal Medicine, Neurology, and Physiology & Biophysics, University of Iowa, Iowa City, IA, USA

Correspondence: Dr BL Davidson, Departments of Internal Medicine, Neurology, and Physiology & Biophysics, University of Iowa, Iowa City, IA 52242, USA. E-mail: beverly-davidson@uiowa.edu

Received 15 August 2005; Revised 5 September 2005; Accepted 12 September 2005; Published online 20 October 2005.

Abstract

Genetic diseases that are accompanied by central nervous system involvement are often fatal. Among these are the autosomal dominant neurogenetic diseases caused by nucleotide repeat expansion. For example, Huntington's disease (HD) and spinal cerebellar ataxia are caused by expansion of a tract of CAGs encoding glutamine. In HD and the other CAG-repeat expansion diseases, the expansion is in the coding region. Myotonic dystrophy is caused by repeat expansions of CUG or CCTG in noncoding regions, and the mutant RNA is disease causing. Treatments for these disorders are limited to symptomatic intervention. RNA interference (RNAi), which is a method for inhibiting target gene expression, provides a unique tool for therapy by attacking the fundamental problem directly. In this review, we describe briefly several representative disorders and their respective molecular targets, and methods to accomplish therapeutic RNAi. Finally, we summarize studies performed to date.