National Academy of Sciences, Proceedings of the National Academy of Sciences, 37(115), 2018
Full text: Download
Significance In Huntington disease (HD) gene carriers the disease-causing mutant Huntingtin (m HTT ) is already present during early developmental stages, but, surprisingly, HD patients develop clinical symptoms only many years later. While a developmental role of Huntingtin has been described, so far new therapeutic approaches targeting those early neurodevelopmental processes are lacking. Here, we show that behavioral, cellular, and molecular changes associated with m HTT in the postnatal period of genetic animal models of HD can be reverted using low-dose treatment with a histone deacetylation inhibitor. Our findings support a neurodevelopmental basis for HD and provide proof of concept that pre-HD symptoms, including aberrant neuronal differentiation, are reversible by early therapeutic intervention in vivo.