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Shown from left, a healthy, estrogen-producing female mouse with ovaries and normal weight levels, an obese female mouse without ovaries, and a female mouse without ovaries after being treated with the GPER-activating compound G-1. (Images Courtesy of Eric Prossnitz, UNM)

A new University of New Mexico-developed drug to reduce obesity and treat diabetes could potentially hit the market in coming years.

The New Mexico Startup Factory, a local incubator of sorts created by the New Mexico Angels private investment group, launched a new company to take UNMs drug to market. And the National Institutes of Health just approved a $300,000 grant to conduct animal studies on the efficacy and safety of the compound, developed by a team of UNM scientists with additional assistance from New Mexico State University.

DEXA scans high-precision X-rays that measure bone density, fat content and body mass show the effects of G-1 on the previously-obese female mouse on the right, compared with the non-treated obese female mouse on the left.

If the NIH-backed animal testing goes well, it could lead to another grant of up to $2 million, potentially paving the way for human clinical trials in a few years, said lead research scientist Eric Prossnitz, a cell biologist and physiologist who heads the Division of Molecular Medicine in the UNM Health Sciences Center Department of Internal Medicine.

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This initial grant will help finance the first phase of pre-clinical animal trials over the next year, Prossnitz said. After that, well seek NIH approval for a two-year grant of up to $1 million per year to do much more detailed studies in animals. If the stars line up and we have enough money, we could then approach the U.S. Food and Drug Administration to proceed with clinical human trials.

The forthcoming studies must first prove the efficacy, and above all, the safety of using the drug in animals before the FDA would consider human trials.

Eric Prossnitz

We need to first make sure of any and all side effects or potential toxicity, Prossnitz said.

The drug has already produced promising results in previous studies with obese mice of both genders, resulting in significantly reduced body weight, decreased circulating cholesterol, increased energy expenditure, improved glucose tolerance and restored insulin sensitivity, Prossnitz said.

The drug, called Tespria, is based on a compound called G-1, which Prossnitz and his team discovered nearly 15 years ago. G-1 acts as an agonist, or activator, for the G-Protein Coupled Estrogen Receptor (GPER), which interacts with the female reproduction hormone estrogen. G-1 mimics the effects of estrogen, which naturally docks with GPER molecules, causing reactions in the GPER that can impact a variety of bodily functions, such as reducing pressure in blood vessels or generating anti-inflammatory effects on cells.

GPER, when activated by estrogen, basically turns things on and off in the body. Prossnitzs team discovered that the G-1 compound causes the same reactions without actually involving estrogen.

John Elling

That generated a lot more research over the years to discover the myriad of things that GPER, when activated, actually does in the body, and to look at potential use of G-1 to activate GPER to fight disease, such as cancer, which is often connected with estrogen.

Those studies led a Pennsylvania company, Linnaeus Therapeutics Inc., to license the use of G-1 from UNM to develop drugs to help fight things like breast cancer and melanoma. Linnaeus is now conducting FDA-sanctioned human trials on people with advanced cases of melanoma, said Lisa Kuuttila, CEO of UNM Rainforest Innovations, UNMs technology transfer office.

G-1 seems to have pretty widespread applications for cancer, Kuuttila said. Linnaeus has made a lot of progress with promising results in clinical trials.

Given G-1s anti-cancer potential, Prossnitz team began looking at its ability to also activate GPER against metabolic diseases associated with estrogen. Lack of estrogen in menopausal women, for example, can cause loss of bone density and obesity.

Our studies showed that G-1 reverses the effects of a lack of estrogen, effectively treating both obesity and diabetes in female and male mice, Prossnitz said. In female mice, we found G-1 mimics the effects of estrogen by activating GPER without actually increasing or changing estrogen levels.

In males, estrogen can produce undesirable side effects. But since G-1 only mimics the impact of estrogen without actually involving that hormone, UNM scientists were able to treat male mice as well, Prossnitz said.

That encouraged the New Mexico Angels to form a new company, GPER G-1 Development Group, providing seed funding to move forward, said company CEO John Elling.

We licensed the use of G-1 from UNM to treat obesity and diabetes, because there are good indications that it works, Elling said.

Its still not exactly clear what GPER activation through G-1 actually does in the body. One possibility is that it activates brown fat, which burns energy rather than storing it like other fats, thereby burning up excess calories, Prossnitz said.

It increased the energy levels in mice, he said. Thats the Holy Grail to expend more energy and burn more fat without decreasing food intake or increasing activity levels.

NMSU regents professor Jeffrey Arterburn is assisting in research, and NMSUs Arrowhead Innovation Fund provided additional seed money for GPER G-1, said Arrowhead Center Director Kathryn Hansen.

Its exciting to have jointly owned technology with UNM and a high-quality research team doing basic lab work together, Hansen said. Theres potential here for real impact on obesity and diabetes.

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Federal funding will advance animal studies of obesity, diabetes using UNM-developed drug - Albuquerque Journal