Stripped-down Estrogen Holds Promise for Treating Dementia in Women
Oct. 11, 2018 (UMW Report) Milwaukee — Researchers from three Milwaukee-area universities have developed a “stripped-down” estrogen molecule that improves memory in an animal model of postmenopausal 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 Institute of General Medical Sciences.
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 a smaller 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 2 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 start-ups. The UWM Research Foundation has brokered 73 license or option agreements from a pool of 129 patents.