Huntington's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Huntington's Disease, including details on genetics, causes, symptoms, treatment.

Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model.

Nguyen T, Hamby A, Massa SM

Department of Neurology and Laboratory for Computational Neurochemistry and Drug Discovery, Veterans Administration Medical Center, University of California, San Francisco, CA 94121, USA.

In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expanded huntingtin exon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates. Clioquinol treatment of transgenic Huntington's mice (R6/2) improved behavioral and pathologic phenotypes, including decreased huntingtin aggregate accumulation, decreased striatal atrophy, improved rotarod performance, reduction of weight loss, normalization of blood glucose and insulin levels, and extension of lifespan. Our results suggest that clioquinol is a candidate therapy for Huntington's disease and other polyglutamine-expansion diseases.

Published 17 August 2005 in Proc Natl Acad Sci U S A, 102(33): 11840-5.
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