‘Stripped down’ estrogen holds promise for treating dementia in women

MILWAUKEE _ Researchers from three Milwaukee-area universities have developed a “stripped-down” estrogen molecule that improves memory in an animal model of post-menopausal dementia, kickstarting new drug discovery for treating memory loss in women.

Memory loss and Alzheimer’s disease strike women three times more often than men as they age, a fact that is linked to a steep decline in the hormone estrogen during menopause. But estrogen replacement comes with harmful side effects, such as an increased risk of heart disease and breast cancer.

Karyn Frick of the University of Wisconsin-Milwaukee, Daniel Sem of Concordia University Wisconsin and William Donaldson of Marquette University created a compound that protects memory in a mouse model of menopause while minimizing the risks of traditional hormone replacement therapy. The research is funded by the National Institutes of Health.

Estrogens act throughout the body by binding to receptor proteins, the most prominent of which are estrogen receptors alpha and beta. Most of the detrimental side effects associated with hormone replacement therapy in menopausal women occur when estrogens bind to the alpha receptor. The new molecule, created in Donaldson’s lab, binds only to estrogen receptor beta.

“There are multiple forms of estrogen in hormone replacement,” said Frick, a UWM professor of psychology. “Some are beneficial for brain health and some aren’t. Our molecule is asmaller version of the most potent form of estrogen, called estradiol, which is particularly diminished in menopause.”

Frick’s research is among the first to link estrogen treatment to the specific chemical processes known to create memories, and she has shown that the molecular mechanisms underlying hormonal regulation of memory formation differ between males and females. Estrogens enhance male memory, too, and testosterone is converted to estrogens in their bodies for that purpose.

Frick aims to pin down how the new molecule acts in the brain to produce improved memory in both sexes.

The trio published the results of the testing in the Journal of Medical Chemistry this summer, and have also formed a startup company, Estrigenix Therapeutics Inc., which is devoted to developing drugs that affect estrogen biology. Their NIH grant was recently renewed for another three years to continue the translational work.

Although the research is promising, there is a long road ahead to develop a consumer-friendly version of the drug to market, said Sem, dean of Concordia’s Batterman School of Business. He estimates it will take another $2 million to get the compound into human clinical trials.

Estrigenix is one of 13 UW-Milwaukee faculty startups. The UWM Research Foundation has brokered 73 license or option agreements from a pool of 129 patents.

For more information, contact Karyn Frick, 414-229-6615, frickk@uwm.edu.

About UWM
Recognized as one of the nation’s 115 top research universities, UW-Milwaukee provides a world-class education to 27,500 students from 91 countries on a budget of $689 million. Its 15 schools and colleges include Wisconsin’s only schools of architecture, freshwater sciences and public health, and it is a leading educator of nurses and teachers. UW-Milwaukee partners with leading companies to conduct joint research, offer student internships and serve as an economic engine for southeastern Wisconsin. The Princeton Review named UW-Milwaukee a 2019 “Best Midwestern” university based on overall academic excellence and student reviews, and the Sierra Club has recognized it as Wisconsin’s leading sustainable university.