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2007 Grant - Lindsley

Novel Approaches for the Treatment of Alzheimer's Disease

Craig Lindsley, Ph.D.
Vanderbilt University Medical Center
Nashville, Tennessee

2007 Investigator-Initiated Research Grant

Memory deficits and other dementia symptoms of Alzheimer's disease may be attributed to the dysfunction and death of brain cells in the cholinergic system, a complex network of cells that communicate through a messenger chemical called acetylcholine. Recent studies indicate that substances called muscarinic acetylcholine receptor (mAChR) agonists can improve the functioning of cholinergic cells. In addition, these substances have been shown to reduce levels of beta-amyloid in the brain. Beta-amyloid is a protein fragment that tends to accumulate into harmful clumps in Alzheimer's disease.

Despite their potential benefits, mAChR agonists have proven difficult to use in clinical trials because of harmful side effects. Craig Lindsley, Ph.D., and colleagues are working to develop safer and more clinically viable forms of these substances. All mAChR agonists function by binding to receptors, or "docking sites," on acetylcholine. Dr. Lindsley's team plans to engineer mAChR agonists that will bind only to specific acetylcholine receptors. The precise functioning of such agonists should make them more useful in future Alzheimer's research.

Results of this study could lead to novel drug therapies for Alzheimer's disease. The investigators hope to have such therapies ready for clinical trials within five to seven years.