Oral Presentation RACI Biomolecular Division Conference 2013

Targeting Chromatin Modulators as a Novel Treatment for Cognitive Impairment: Development of Isoform Selective Inhibitors of Histone Deacetylases (HDACs) (#14)

Edward Holson 1 , Florence Wagner 1 , Nadine Joseph 2 , Yan-Ling Zhang 1 , Dan Fass 3 , Stephen Haggarty 3 , Jacob Hooker 4 , Li-Huei Tasai 2 , Edward Scolnick 1
  1. Broad Institute of MIT and Harvard, Cambridge, MA, United States
  2. Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States
  3. Center for Human Genetic Research, Simches Research Center, Departments of Neurology & Psychiatry, Harvard Medical School, Boston, MA, United States
  4. Athinoula A. Martinos Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States

Deficits in cognition and memory are associated with many disease states including Alzheimer’s disease, Rubinstein Taybi Syndrome and Schizophrenia.  Altered acetylation states and the effects on specific gene expression and protein regulation underlie components of central nervous system (CNS) disorders.  Hypoacetylation states are found in neurological contexts and histone deacetylases (HDACs) offer an attractive target to remedy these altered acetylation states.  We describe our efforts to understand the biology of individual HDAC isoforms, optimize small molecule HDAC inhibitors with greater isoform selectivity, improve CNS drug properties and demonstrate efficacy in mouse models of learning and memory