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

Helen Budworth, Faye R. Harris, Paul Williams, Do Yup Lee, Amy Holt, Jens Pahnke, Bartosz Szczesny, Karina Acevedo-Torres, Sylvette Ayala-Peña, Cynthia T. McMurray*

*Korrespondierende/r Autor/-in für diese Arbeit
45 Zitate (Scopus)

Abstract

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 allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.

OriginalspracheEnglisch
Aufsatznummere1005267
ZeitschriftPLoS Genetics
Jahrgang11
Ausgabenummer8
ISSN1553-7390
DOIs
PublikationsstatusVeröffentlicht - 01.08.2015

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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