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Assistant professor of physiology and neurobiology Jianjun Sun will test existing drugs for contraceptive properties that could eliminate mental health side effects. (Bri Diaz/UConn Photo)

Contraceptives for women involve alterations of systemic hormones in the woman’s body. But these approaches often have undesirable side effects, and can increase risk factors for other diseases.

Now, UConn researcher Jianjun Sun has received a Grand Challenge Explorations Phase I award from the Bill & Melinda Gates Foundation to pursue a different approach to contraceptives.

The Grand Challenges Explorations initiative supports innovative thinkers worldwide to explore ideas that can break the mold in how we solve persistent global health and development challenges. The grant, titled “Develop Novel Platforms to Accelerate Contraceptive Drug Discovery,” is one of more than 55 awarded worldwide in this round.

The work will examine existing drugs for properties that block ovulation without interfering with a woman’s hormone cycle. It has the potential to provide effective contraception while eliminating associated mental health side effects, like depression.

“We have so many contraceptive medicines, but all of them are steroid-based, and can cause mental health problems,” says Sun, an assistant professor of physiology and neurobiology in the College of Liberal Arts and Sciences. “We need to work to find alternative methods.”

During normal ovulation, an egg contained in a follicle bursts out of the wall of a woman’s ovary and travels to the oviduct, where it can be fertilized. Sun’s research seeks to disrupt this process, preventing entirely the rupture of the follicle itself, and causing the egg to disintegrate.

Sun and his lab studied this ovulatory process in detail in fruit flies and determined for the first time that the genetic factors and compounds involved in egg release are similar between flies and humans.

“We’ve already proved that many components of the rupture processes are actually conserved between flies and mammals,” says Sun. “Now what we’re trying to do is to find drugs that can inhibit the rupture.”

By combining information on the factors contributing to egg release with studies on rare conditions that can disrupt follicle rupture, like luteinized unruptured follicle syndrome, Sun’s group aims to identify specific compounds that can disrupt follicle rupture and could be candidates for non-steroidal contraceptive development.

With the Gates Foundation grant, Sun and his colleagues plan to scan roughly 1,000 drugs that are already approved by the FDA for the presence of these disrupting compounds. Because some of these drugs have fertility defects as a side effect, Sun’s group can quickly pinpoint those that may interfere with the ovulation process.

“The idea is that many of these drugs already show some side effects that cause an ovulation problem,” he says. “We want to see if the problem is caused by issues with follicle ruptures.”

Using a library of approved drugs will help speed the drug discovery process, a major priority in the Gates Foundation charge. Sun’s group has already screened about 100 of these drugs, and has thus far found two promising drugs containing molecular targets for follicle rupture.

More than just the advantage of decreasing mental health side effects, like depression, Sun also says that a drug that inhibits ovulation could be simpler.

“If you can directly disrupt this rupture, maybe women would only need to take one pill a month,” he notes.

The 18-month, $100,000 award is meant to support a pilot study, which for Sun will include a research technician and laboratory supplies. Sun will apply for Phase II funding at the$1 million level. Funding at this level would allow Sun’s group to test candidate drugs in mice and expand their drug screen to include more drug libraries that are not yet approved, but can be modified for contraceptive purposes.

“This is not just the development of one drug, but the development of a platform to screen for many possible new drugs,” Sun says. “I’m quite excited.”

Grand Challenges Explorations is a \$100 million initiative funded by the Bill & Melinda Gates Foundation. Launched in 2008, over 1,220 projects in more than 65 countries have received Grand Challenges Explorations grants.

By: Christine Buckley, College of Liberal Arts and Sciences

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