Suppression of Somatic Expansion Delays the Onset of Pathophysiology in a Mouse Model of Huntington’s Disease

• DOI: 10.1371/journal.pgen.1005267
• Publication Date: 2015-08-06T15:53:09Z
• Authors: Helen Budworth; Faye R. Harris; Paul Williams; Do Yup Lee; Amy Holt; Jens Pahnke; Bartosz Szczesny; Karina Acevedo-To...; Sylvette Ayala-Peña; Cynthia T. McMurray
• Keywords: Huntingtin Protein

Huntington's Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease expresses toxic protein, and whether further expansion adds toxicity unknown. We have created HD mouse model that resolves the effects expansions. show here suppressing substantially delays onset littermates inherit same allele. Furthermore, pharmacological inhibitor, XJB-5-131, inhibits lengthening repeat tracks, correlates rescue motor decline these animals. results provide evidence approaches offset progression are possible.