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Combination of gene therapy and gene silencing prevents neurodegenerative disease

University of Iowa researchers have shown for the first time that gene therapy delivered to the brains of living mice can prevent the physical symptoms and neurological damage caused by an inherited neurodegenerative disease that is similar to Huntington's disease (HD).

If the therapeutic approach can be extended to humans, it may provide a treatment for a group of incurable, progressive neurological diseases called polyglutamine-repeat diseases, which include HD and several spinocerebellar ataxias. The study, conducted by scientists at the UI Roy J. and Lucille A. Carver College of Medicine and colleagues at the University of Minnesota and the National Institutes of Health (NIH), appears in the August issue of Nature Medicine and in the journal's advanced online publication July 4.

"This is the first example of targeted gene silencing of a disease gene in the brains of live animals and it suggests that this approach may eventually be useful for human therapies," said senior study author Beverly Davidson, Ph.D., the Roy J. Carver Chair in Internal Medicine and UI professor of internal medicine, physiology and biophysics, and neurology. "We have had success in tissue culture, but translating those ideas to animal models of disease has been a barrier. We seem to have broken through that barrier."

Davidson and her colleagues used a viral vector (a stripped-down virus) to deliver small fragments of genetic material (RNA) to critical brain cells of mice with a disorder that mimics the human neurodegenerative disease spinocerebellar ataxia 1 (SCA1). The genetic material suppresses the disease-causing SCA1 gene in a process known as RNA interference.

Mice with the SCA1 gene that were treated with the gene therapy had normal movement and coordination. The gene therapy also protected brain cells from the destruction normally caused by the disease and prevented the build-up of protein clumps within the cells. In contrast, mice with the SCA1 di
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-335-9917
University of Iowa
4-Jul-2004


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