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Concordia-led estrogen research effort holds promise for treating dementia in women

A “stripped-down” estrogen molecule developed by a trio of researchers from three Milwaukee-area universities has proven effective in improving memory in a model system for treating dementia in post-menopausal women.

Women are three times more likely than men to develop memory loss and Alzheimer’s disease as they age, and those memory deficits are linked to a decline in estrogens, hormones whose levels plunge during menopause. The advantage of the new estrogen molecule is it doesn’t carry the increased risk of breast and other cancers as traditional hormone replacement therapy does.

This academic year, the National Institutes of Health renewed a three-year grant awarded to the lead researcher of the project, Dr. Daniel Sem of Concordia University Wisconsin. Dr. Sem, along with Dr. Karyn Frick of the University of Wisconsin-Milwaukee and Dr. William Donaldson of Marquette University, co-authored two published articles that describe the new molecule, and over the summer, the team of researchers formed a startup company, Estrigenix Therapeutics, Inc., which will be devoted to developing drugs that affect estrogen biology.

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 are due to estrogens binding to estrogen receptor alpha. The new molecule is a smaller version of a particular type of estrogen called estradiol that selectively binds to estrogen receptor beta.

Although the trio’s research is promising, there is a long road ahead to developing a consumerfriendly version of the drug to market. Sem estimates it will take another $2 million to get the compound into human clinical trials. “Hormone replacement therapy is one of the more promising treatments for dementia for post-menopausal women at the moment, but because of interactions with estrogen receptor alpha, this therapy poses some risk to women,” says Dr. Sem, dean of Concordia’s Batterman School of Business and professor of business and pharmaceutical sciences. “Our compound, however, has shown statistically significant results in providing the memory enhancing effects of estrogens without the risk of cancer.”