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ASO corrects striatal transcriptional abnormalities & protects function in HD mice
Date:8/26/2013

Amsterdam, NL, 26 August 2013 Findings from postmortem studies of the brains of Huntington's Disease (HD) patients suggest that transcriptional dysregulation may be an early step in the pathogenesis of HD before symptoms appear. Other studies report transcriptional alterations in the brains of some mouse models of HD. A new study has found transcriptional changes in mouse striatum which correlate with progressive motor and psychiatric deficits and, most importantly, reports for the first time, that an antisense oligonucleotide (ASO) may be used therapeutically to both correct striatal transcriptional abnormalities and improve motor and behavioral problems. The article is published in the latest issue of the Journal of Huntington's Disease.

"Down regulation of the expression of key molecules at the mRNA level could well be one of the underlying mechanisms leading to neuronal dysfunction in HD," says Lisa M. Stanek, PhD, of Genzyme Corporation's Rare Disease Unit, Framingham, MA. "The data presented here provide strong evidence that transcriptional correction has great potential as a novel therapeutic biomarker for HD."

Huntington's disease (HD) is an inherited progressive neurological disorder for which there is presently no cure. It is caused by a dominant mutation in the HD gene leading to expression of mutant huntingtin (HTT) protein. Expression of mutant HTT causes subtle changes in cellular functions, which ultimately results in jerking, uncontrollable movements, progressive psychiatric difficulties, and loss of mental abilities.

The current study focuses on what is happening early in the disease process before symptoms or even neuropathological changes are apparent. The authors believe that mutant HTT may be disrupting normal transcriptional processes in susceptible neurons. In genetics, transcription refers to the process by which genetic information is copied from DNA to RNA, resulting in formation of a specific prot
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Contact: Daphne Watrin
d.watrin@iospress.nl
31-206-883-355
IOS Press
Source:Eurekalert

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