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U. Iowa researchers improve Huntington's disease symptoms in mice

Researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine have taken another step toward a potential treatment for Huntington's disease (HD). Using an approach called RNA interference (RNAi), the scientists reduced levels of the disease-causing HD protein in mice and significantly improved the movement and neurological abnormalities normally associated with the disease.HD is a devastating, inherited, neurodegenerative disease that is progressive and always fatal. The disease-causing gene produces a protein that is toxic to certain brain cells, and the subsequent neuronal damage leads to the movement disorders, psychiatric disturbances and cognitive decline that characterize this disease.

"Many of the current approaches aimed at treating HD are indirect and target the symptoms of the disease. RNA interference gives us the first opportunity to attack the fundamental problem and reduce protein expression from the disease gene," said Beverly L. Davidson, Ph.D., the Roy J. Carver Chair in Internal Medicine and UI professor of internal medicine, physiology and biophysics, and neurology. "Our study is the first demonstration that a therapy designed to inhibit protein production has a beneficial effect."

The study will appear this week in the Online Early Edition of the Proceedings of the National Academy of Sciences (www.pnas.org). Davidson is the senior author and Scott Harper, Ph.D., a postdoctoral researcher in Davidson's lab, is lead author.

Harper, Davidson and their colleagues used RNAi to treat a mouse model of HD. Viral vectors (stripped-down viruses) carrying the genetic instructions to make a RNA interference molecule were injected into the brains of genetically engineered mice before the disease symptoms appeared. The treated mice showed nearly normal movement, and the characteristic neurological damage also was significantly improved in comparison to untreated mice.

Detailed examination of the protein
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Source:University of Iowa


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