Researchers studying yeast cells have identified a metabolic enzyme as a potential therapeutic target for treating Huntington's disease, a fatal inherited neurodegenerative disorder for which there is currently no effective treatment. The group, whose results appear in the May issue of Nature Genetics, includes researchers from the University of Washington School of Medicine in Seattle and the University of Maryland School of Medicine in Baltimore. The paper was published online in advance at the journal's Web site, http://www.nature.com/ng/index.html.

The group performed a genetic experiment known as a loss-of-function suppressor screen, which searches for genes that, when switched off, reduce the toxic effects of the mutant protein associated with Huntington's. One of the genes they identified encodes an enzyme, called KMO, that has been previously implicated in the disease. The enzyme functions in a metabolic pathway that is activated at early stages of the disease in people with Huntington's, as well as in animal models of the disease.

"The nice thing about this finding is that there is a chemical compound available that inhibits KMO activity," said Dr. Paul Muchowski, assistant professor of pharmacology at the UW, who led the study. "We're in the midst of testing that compound in a mouse model of Huntington's disease."

Further support for KMO as a therapeutic target for Huntington's disease comes from a recent study led by Dr. Aleksey G. Kazantsev of Harvard Medical School. In this study, researchers used cell-based experiments to screen about 20,000 chemical compounds, and identified one that suppresses neurodegeneration in a fly model of the disease. That compound has a very similar chemical structure as the drug that inhibits the target identified by Muchowski's group. The results appeared in the Jan. 18, 2005, issue of the Proceedings of the National Academy of Sciences.

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Contact: Justin Reedy
jreedy@u.washington.edu
206-685-0382
University of Washington
6-Apr-2005

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