Steven Scott Schreiber, M.D.
University of California at Irvine
Irvine, California

2007 Investigator-Initiated Research Grant

During the earliest stages of Alzheimer’s disease, production of certain essential proteins in the brain declines. Such declines likely play a role in the disease’s development. In studies of related neurological disorders — Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS) — scientists have shown that enzymes called histone deacetylase (HDAC) inhibitors stimulate the production of essential proteins and may protect cells against pathological factors in these disorders.

Stephen Scott Schreiber, M.D., and colleagues have been studying the effects in Alzheimer’s disease of an HDAC inhibitor called nicotinamide. Preliminary research has found that nicotinamide treatment improves learning and memory skills in mice genetically engineered to develop Alzheimer-like disease. The treatment also reduces levels of a modified form of the protein tau. Abnormal tau accumulates into harmful tangles in Alzheimer’s.

For this proposed grant, Dr. Schreiber’s team will conduct a nicotinamide study with 50 people who have mild to moderate Alzheimer’s disease. Over a period of 24 weeks, some of the participants will receive the nicotinamide treatment, while the others will be given a placebo. Dr. Schreiber’s team will measure any differences in abnormal tau levels among the participants. Investigators will also test the participants’ learning and memory abilities, as well as their ability to carry out daily activities.

Results from this study may lead to novel HDAC-based treatments for mild to moderate Alzheimer’s disease. The results may also shed new light on the role of abnormal tau in Alzheimer’s.