Dan Sem

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.

Last week the National Institutes of Health announced the renewal of a three-year grant awarded to the lead researcher of the project, Daniel Sem of Concordia University Wisconsin. Sem, along with Karyn Frick of the University of Wisconsin-Milwaukee and William Donaldson of Marquette University, co-authored two articles published earlier this year 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.

“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 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.”

In a series of studies, Frick’s lab showed that administration of the new molecule, which was developed in Donaldson’s lab, enhances memory formation in a mouse model of menopause.

Although the trio’s research is promising, there is a long road ahead to developing a consumer-friendly version of the drug to market. Sem estimates it will take another $2 million to get the compound into human clinical trials.

In the meantime, over the summer the team of researchers obtained a patent for its drug lead molecule, and hopes to license it from their respective universities to Estrigenix. Estrigenix is Concordia’s second spin-out company, after Microlitics LLC, and the second patent the university has that is issued. This is Sem’s third NIH grant received as a principal investigator since joining Concordia from Marquette in 2010.

“Within the past eight years since forming our School of Pharmacy, Concordia has made significant strides to support research efforts,” Sem says. “It’s exciting to be among the first of no doubt many future efforts at research with human health implications.”       

Research reported in this publication is supported by the National Institute Of General Medical Sciences of the National Institutes of Health under award number R15 GM118304. The content is solely the responsibility of the universities involved and does not necessarily represent the official views of the National Institutes of Health.

— Kali Thiel is director of university communications for Concordia University Wisconsin and Ann Arbor. She may be reached at kali.thiel@cuw.edu or 262-243-2149.

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