A promising approach to developing male contraceptive pills

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Baylor College of Medicine researchers have unveiled a new non-hormonal, “sperm-specific” approach that provides a promising option for male contraception.

“We focused on a novel approach that involved identifying a small molecule that would inhibit serine/threonine kinase 33 (STK33), a protein specifically required for fertility in both men and mice,” said Dr. Martin Matsuk, director of the Center for Drug Discovery and chief of the Department of Pathology and Immunology at Baylor. .

Previous research has shown that STK33 is essential for functional spermatogenesis. Disabling the Stk33 gene in mice makes them infertile due to abnormal sperm and poor sperm motility. In men, a mutation in the STK33 gene leads to infertility caused by defects in the sperm themselves without damage to the testicle.

“STK33 is therefore a viable target with minimal safety concerns for male contraception,” Matsuk said.

Researchers discovered powerful STK33 inhibitors, and succeeded in producing modified versions of them to make them more stable, effective, and selective.

The first author of the study, Dr. Angela Kuo, said: “Among these modified versions, CDD-2807 was found to be the most effective.”

“Next, we tested the efficacy of CDD-2807 in our mouse model,” explained co-author Courtney M. Sutton. “We evaluated several doses and treatment schedules and then determined sperm motility and count in the mice, as well as their ability to fertilize females.”

It was shown that the compound CDD-2807 crossed the blood-testicular barrier, and reduced sperm motility, numbers, and fertility in mice at low doses, without signs of toxicity from treatment or accumulation of the compound in the brain.

"Importantly, the contraceptive effect was reversible. After a period of not using CDD-2807, the mice regained sperm motility and numbers and became fertile again," Sutton added.

“In the next few years, our goal is to further evaluate the STK33 inhibitor and compounds similar to CDD-2807, to determine their effectiveness as a reversible male contraceptive,” Matsuk said.

The study was published in the journal Science .