DIETARY SELENIUM SUPPLEMENTATION IN A MOUSE MODEL OF HUNTINGTON'S DISEASE

(WYO-438-09)

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive motor dysfunction, emotional disturbances, dementia, and weight loss. HD occurs worldwide, in all races and ethnic groups. Its prevalence is 5-10 cases per 100,000. There are about 30,000 affected individuals in the United States. The average age of onset is about 37 years; with a range from infancy to old age. Once symptomatic, affected individuals show early functional decline, and require increasing care and supervision for another 15-25 years before succumbing to the effects of the disease. Compared to other neurodegenerative diseases HD disproportionately consumes medical, social and family resources. Currently, there are no treatments that delay the onset or progression of human HD symptoms. The long-term goal of the proposed work is to address the hypothesis that dietary selenium supplementation delays the onset and / or progression of symptoms in HD mice. The hypothesis is based on our finding of low brain selenium in human HD brain. It is important to note that selenium deficiency is not the underlying cause for HD. We are proposing, however, that the HD mutation causes derangements of brain selenium metabolism, and that targeting this process by supplementation may be beneficial in HD. In the studies proposed, we will focus our efforts on the effects of dietary selenium modifications on biochemical measures of disease progression in Huntington's disease mouse brain. We will also undertake preliminary studies investigating the effect of supplementation on behavioral outcomes in these mice. If these studies show a protective effect of selenium in Huntington's disease mice then it suggests that a similar approach in human Huntington's disease may be worth investigating. The advantage of a dietary supplement as one part of the global management of Huntington's disease patients would be its low cost and availability.

USDA CRIS Project Information Link: 0217753