RNA Interference Improves Motor and Neuropathological Abnormalities in a Huntington's Disease Mouse Model

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 16; pp. 5820 - 5825
• Main Authors: Harper, Scott Q., Staber, Patrick D., He, Xiaohua, Eliason, Steven L., Martins, Inês H., Mao, Qinwen, Yang, Linda, Kotin, Robert M., Paulson, Henry L., Davidson, Beverly L., Welsh, Michael J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 19.04.2005; National Acad Sciences
• Series: From the Cover
• Subjects: Alleles; Animal models; Animals; Antibodies; Biological Sciences; Cell Line; Disease Models, Animal; Gene Expression Regulation; Gene Silencing; Gene Transfer Techniques; Genetic Therapy; Humans; Huntingtin Protein; Huntington disease; Huntington Disease - genetics; Huntington Disease - pathology; Huntington Disease - therapy; Messenger RNA; Mice; Mice, Inbred Strains; Motor Activity - physiology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system diseases; Neurodegenerative diseases; Neurons; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Plasmids; RNA; RNA Interference
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0501507102

Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HD. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HD. Our data provide support for the further development of RNAi for HD therapy.