| Literature DB >> 21969577 |
Yi Hu1, Vanita Chopra, Raman Chopra, Joseph J Locascio, Zhixiang Liao, Hongliu Ding, Bin Zheng, Wayne R Matson, Robert J Ferrante, H Diana Rosas, Steven M Hersch, Clemens R Scherzer.
Abstract
Huntington disease (HD) is a progressive neurodegenerative disease that affects 30,000 individuals in North America. Treatments that slow its relentless course are not yet available, and biomarkers that can reliably measure disease activity and therapeutic response are urgently needed to facilitate their development. Here, we interrogated 119 human blood samples for transcripts associated with HD. We found that the dynamic regulator of chromatin plasticity H2A histone family, member Y (H2AFY) is specifically overexpressed in the blood and frontal cortex of patients with HD compared with controls. This association precedes the onset of clinical symptoms, was confirmed in two mouse models, and was independently replicated in cross-sectional and longitudinal clinical studies comprising 142 participants. A histone deacetylase inhibitor that suppresses neurodegeneration in animal models reduces H2AFY levels in a randomized phase II clinical trial. This study identifies the chromatin regulator H2AFY as a potential biomarker associated with disease activity and pharmacodynamic response that may become useful for enabling disease-modifying therapeutics for HD.Entities:
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Year: 2011 PMID： 21969577 PMCID： PMC3193232 DOI： 10.1073/pnas.1104409108
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205