RNA interference reduces Huntington's symptoms in mice

In a mouse model of Huntington's disease, gene silencing with RNA interference (RNAi) markedly reduces expression of the disease-causing huntingtin protein, leading to a reduction in symptoms of Huntington's disease.

"Our findings that partial reduction of mutant huntingtin can have a profound impact on cellular and motor characteristics are very exciting," Dr. Beverly L. Davidson from the University of Iowa in Iowa City told Reuters Health."The data suggest that even slowing down, rather than stopping, the production of the mutant protein can give the cells a chance to catch up and clear up the problems caused by mutant huntingtin," she added.Huntington's disease, a fatal, dominant neurodegenerative disorder, is caused by polyglutamine expansion in the protein huntingtin. "This polyglutamine expansion causes the mutant huntingtin to take on a toxic property that we are continuing to better understand," Dr. Davidson explained.Therapies for Huntington's disease often attempt to reduce the toxic effects of the mutant huntingtin. In contrast, RNAi aims to treat the disease by getting rid of the mutant protein, thereby targeting the fundamental underlying pathological insult.Today, at the 8th annual meeting of the American Society of Gene Therapy in St. Louis, Dr. Davidson reported that an adeno-associated viral (AAV) vector containing small hairpin RNA directed against huntingtin injected into mice with Huntington's disease reduced mutant huntingtin protein levels by 40% compared with sham-treated control animals.This level of reduction in huntingtin protein levels led to statistically significant improvements in motor symptoms in treated animals, as determined by rotarod performance and gait analysis.The therapy also reduced striatal and cerebellar clumps of mutant huntingtin characteristic of Huntington's disease.This study provides support for further studies on RNAi as a potential treatment for Huntington's disease and related disorders, the authors conclude.(Source: Reuters Health: Megan Rauscher: Oncolink: June 2005.)