The GLP-1 peptide craze that has transformed weight-loss treatment could soon expand to the bedroom and under the sheets.
Washington State University Regents Professor Jon Oatley has received a $274,849 grant from the Washington Research Foundation to help prepare Alphatide – a promising peptide-based male contraceptive he developed that works by targeting and inhibiting proteins essential for sperm development – for human clinical trials. Like GLP-1 medications, Alphatide is based on a peptide, a short chain of amino acids, but it targets an entirely different biological process.
“The World Health Organization estimates roughly 50% of pregnancies are unintended globally, and a majority of those unintended pregnancies end in abortion, and in low-income countries, those are not always medically approved abortions,” said Oatley, who is based in the WSU College of Veterinary Medicine’s School of Molecular Biosciences. “Right now, men have few options for contraception beyond condoms and vasectomy. Advancing this technology toward clinical trials brings us a step closer to providing a safe, effective, and reversible option that could have a far-reaching impact.”
The two-year grant will support the final preclinical studies needed before regulatory approval can be given to begin testing Alphatide in people. The work will generate data on how the peptide behaves in the body, including where it distributes, how long it remains active, and how quickly it clears the system.
The peptide-based approach may offer advantages over other experimental contraceptives. Peptides can provide greater target specificity and are broken down naturally by the body into amino acids after use, potentially reducing the risk of unintended side effects, Oatley said.
“To my knowledge, nobody else is working on peptides for male contraception, even though they’re kind of a rage right now with GLP-1 inhibitors,” he said. “This grant will allow us to generate the data that we will need for us to apply to the U.S. Food and Drug Administration for human clinical trials. I think we can get there within three years.”
The project builds on years of research by Oatley and his team into the biological mechanisms that control sperm production. Their work identified a critical interaction between two proteins, ARRDC5 and TEX38, found only in male reproductive tissue and essential for fertility.
Using computational modeling, Oatley screened FDA-approved compounds for those most likely to disrupt the interaction between the two proteins. One peptide emerged as a promising candidate, prompting Oatley’s team to model and evaluate more than 2,000 variations designed to improve stability, solubility, and effectiveness. That effort ultimately produced Alphatide.
Oatley’s studies in mice have shown the contraceptive effect is reversible and does not appear to cause adverse health effects.
Because Alphatide targets proteins specific to sperm development, Oatley said the approach may offer advantages over other male contraceptives currently under development.
“Some of the other strategies are not specific to the sperm production process,” Oatley said. “What we’re targeting is really specific to sperm development.”
Oatley and the WSU Office of Research have filed a provisional patent and are working with a start-up to explore the commercial potential of the work in humans.
While the research is aimed at developing a contraceptive for men, Oatley said the proteins targeted by Alphatide appear in the testicular tissue of virtually every male species, raising the possibility the drug could provide alternatives to surgical castration in livestock and companion animals.
The Washington Research Foundation is a Seattle-based nonprofit that supports life science and enabling technology innovation across Washington state. Through its technology commercialization program, the foundation provides funding to help researchers advance promising discoveries from the laboratory toward commercial development, licensing opportunities, and public use. Since 1981, WRF has awarded more than $190 million in grants to support research and innovation.
