2013 Grants - Haggarty

HDAC1 Activating Compounds as a Novel Therapeutic for Alzheimer's Disease

Stephen J. Haggarty, Ph.D.
Massachusetts General Hospital
Boston, Massachusetts

2013 New Investigator Research Grant

One characteristic of Alzheimer's disease is that nerve cells in the brain die, especially as the disease progresses beyond its early stages. One goal of research is to find ways to protect nerve cells, reducing their risk of dying. HDAC1 (histone deacetylase 1) is a protein found inside nerve cells that helps protect nerve cells from death; it does so by repairing damage to DNA (deoxyribonucleic acid).

Stephen J. Haggarty, Ph.D., and colleagues have developed a series of drug-like compounds that increase the activity of HDAC1; these compounds may protect nerve cells from some conditions that cause cell death. Dr. Haggarty and colleagues have proposed a series of experiments aimed at identifying the best drug-like compound for activating HDAC1. They will use chemical techniques to create different forms of their drug-like compounds and test them for their ability to protect nerve cells.

The researchers will use mice that have been genetically altered to experience nerve cell death similar to that found in people with advanced Alzheimer's disease. Dr. Haggarty and colleagues will then test the ability of their drug-like compounds to prevent nerve cell death. These studies may lead to the development of new drug candidates for testing in humans to prevent or slow the progression of Alzheimer's disease.