Research Project: A novel modulator of membrane estrogen receptors for treating AD

Key Collaborator: Dr. Joseph Quinn, MD

The CART Fund will award Philip Copenhaver, Ph.D., Oregon Health & Science University, a 2017 Alzheimer’s research grant in the amount of $75,000. The grant will be awarded on May 16, 2017 at a meeting of The CART Fund in Orlando, Florida.

Alzheimer’s Disease (AD) involves the abnormal buildup of beta-amyloid and tau levels in the brain, but clinical trials designed to prevent their accumulation have been unsuccessful.   In contrast, a drug that could protect nerve cells against these toxic proteins might provide an alternative strategy for treating AD.  Intriguing studies on hormone replacement therapy revealed that giving estrogen to women reduced their risk of dementia, but long-term treatment with estrogen also increased the risk of stroke and could not be used to treat men at risk of AD.

Our collaborators have now identified a new compound (STX) that may provide the benefits of estrogen without its unwanted side effects.  In an animal model of stroke, STX protected nerve cells in the brain without causing the feminizing effects of estrogen, indicating that it can be safely given to both men and women.  Recently, we showed that STX also protects cultured nerve cells against amyloid toxicity, although its precise mechanism of action is still not clear.

Accordingly, this CART-funded project will investigate two key issues: (1) We will use mouse nerve cells grown in culture to identify which “cellular signals” are needed for STX to protect against amyloid toxicity.  (2) We will also use our mouse model of AD to test whether sustained STX treatment protects against the development of Alzheimer’s-related symptoms without causing unwanted side effects. These experiments will be crucial for developing STX into a drug for treating patients, with the ultimate goal of advancing STX into a clinical trial.

The Coins for Alzheimer’s Research Trust Fund (CART) is a project of the Rotary Clubs of North America. Founded in 1995 in Sumter SC, CART provides financial support for Alzheimer’s research projects that are yet to be supported by extensive preliminary data but have the potential to substantially advance biomedical research. Learn more at