New Male Birth Control Temporarily Disables Sperm

Researchers are advancing toward a non-hormonal, reversible, and safe male contraceptive by effectively targeting a key protein involved in sperm fertility. Temporarily inhibiting this protein would allow men to control their contraceptive window, similar to oral contraceptives for women, but without additional side effects or lasting impacts on fertility.

Prior knowledge indicated that a mutation in the serine/threonine kinase 33 (STK33) gene leads to male sterility. Baylor College of Medicine researchers discovered a small-molecule compound capable of temporarily inhibiting STK33, resulting in the same outcome.

Although not the initial non-hormonal sperm-targeted therapy, this study identifies a novel target as the scientific community persists in its ongoing pursuit of a male contraceptive pill.

The Ongoing Quest for a Male Birth Control Pill

“Despite ongoing research into various strategies for male contraceptives, a birth control pill for men remains elusive,” stated Dr. Martin Matzuk, director of the Center for Drug Discovery at Baylor and corresponding author of the study. “Our focus in this study was on a novel approach—identifying a small molecule capable of inhibiting serine/threonine kinase 33 (STK33), a protein essential for fertility in both men and mice.”

“STK33 presents a promising target with minimal safety concerns for male contraception,” he emphasized.

The team screened their extensive “multi-billion compound collection” to identify potential STK33 inhibitors, which they then optimized for stability, specificity, and potency in trials involving mice.

“Among these optimized compounds, CDD-2807 demonstrated the highest effectiveness,” reported Dr. Angela Ku, the first author from the Matzuk lab at Baylor.

“We subsequently assessed the efficacy of CDD-2807 in our mouse model,” explained co-author Courtney M. Sutton, also from the Matzuk lab. “We evaluated various doses and treatment regimens, examining sperm motility and quantity in the mice, as well as their ability to fertilize females.”

CDD-2807 successfully penetrated the blood-testis barrier, directly targeting STK33 and impacting sperm count and mobility, effectively inhibiting fertility even at a low dosage.

Reassuring Results from Animal Studies

“We were encouraged to observe that the mice exhibited no signs of toxicity from the treatment with CDD-2807, and that the compound did not accumulate in the brain, nor did the treatment affect testis size,” stated Sutton. “Crucially, the contraceptive effect was reversible. Following a period without CDD-2807, the mice regained sperm mobility and count, and regained fertility.”

While the availability of this contraceptive at pharmacies is unlikely in the near future, the team plans to conduct further assessments of CDD-2807 and other potential compounds.

“Our objective is to conduct additional evaluations of this STK33 inhibitor and similar compounds to CDD-2807 in primates, to assess their efficacy as reversible male contraceptives,” remarked Matzuk.

Nevertheless, whether this target molecule would yield similar effects on human sperm remains to be determined.

However, the quest for the inaugural temporary contraceptive for men remains ongoing. Other research avenues have explored methods such as gel injections to obstruct sperm release, ultrasound pulses to eliminate sperm, and the development of binders and inhibitors with similar aims of producing non-hormonal, non-viable sperm.

Read the original article on: New Atlas

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