Using PET to Map Epigenetic Changes in Huntington's Disease.

Massachusetts General Hospital, Boston MA

Investigators

Abstract

Early epigenetic changes and transcriptional dysregulation have emerged as a potentially early and significant pathophysiological mechanism in several neurodegenerative disorders. In HD, multiple studies have demonstrated differences in epigenetic marks and in the expression of genes in distinct regions of postmortem tissue and genetic mouse models and support an important role in the pathogenesis of HD. Other studies have also demonstrated the potential therapeutic benefit of several different HDAC inhibitors in HD transgenic mice. In this study, we will measure regional changes in HDAC expression in vivo, in both prodromal and early symptomatic HD, using a novel PET ligand. We will evalaute the distribution of HDACs in HD, determine how early these changes are present, and correlate regional changes with clinical measures. Given the continued development of novel HDAC inhibitors for HD and other neurodegenerative disorders, measuring HDAC expression in vivo by PET would provide a critically needed target engagement and pharmacodynamics marker. .