Promising new male contraceptive drug shows efficacy in mouse study sponsored by Promega

A recent study has shown promising results for a novel, non-hormonal reversible contraceptive for men, tested effectively in mice. The research, sponsored by Promega, was published on May 23rd in the journal Science by a collaborative team from Baylor College of Medicine and Lawrence Berkeley National Laboratory.

The team developed a small molecule inhibitor named CDD-2807, which significantly reduced fertility in male mice without any evident toxicity. Importantly, the fertility of the mice returned once the drug was discontinued. This approach offers a fresh alternative to current male contraceptive methods, which predominantly involve synthetic testosterone derivatives like dimethandrolone undecanoate (DMAU) and 11b-MNTDC. These hormonal methods are in clinical trials but have potential side effects similar to those associated with female birth control.

Unlike hormone-based methods, the new strategy focuses on inhibiting the enzyme serine/threonine kinase 33 (STK33), linked to male sterility when mutated in both humans and mice. A comprehensive screening of a DNA-encoded drug library led the researchers to identify promising compounds, culminating in the design of CDD-2807.

The efficacy of CDD-2807 was evaluated through two different experimental protocols on male mice. In the first protocol, mice were injected with either a control solution or CDD-2807 at 15 mg/kg twice daily for 21 days and then paired with fertile female mice. A month later, the control group sired an average of seven offspring per female, while the treated group produced significantly fewer, with some producing almost no offspring. By the second month, none of the treated mice had any offspring, while control mice continued to sire large litters.

In the second protocol, mice received a higher dose of CDD-2807 (50 mg/kg) once daily. The control group again produced an average of seven pups per female, whereas the treated group had substantially reduced fertility, with only one treated mouse producing a single pup in the first month and none in the second month.

To test the reversibility of the contraceptive effect, the drug was discontinued, and the mice were paired with new female mates. In the lower dose protocol, the treated mice resumed normal fertility within a month, matching the litter sizes of the control group. In the higher dose protocol, fertility was restored within two months.

Throughout the study, none of the treated mice exhibited weight loss or fatalities, indicating the treatment's safety. Additionally, there was no change in the size of their testes, a side effect observed with other male contraceptive drugs in similar studies. The researchers concluded that their findings support the potential of non-hormonal approaches in developing a male contraceptive pill.

Despite these promising results, researchers emphasize that human studies are necessary to confirm the drug's viability as a male contraceptive. Jarrett Holdaway and Gunda Georg from the University of Minneapolis College of Pharmacy, in an accompanying commentary, noted that for commercial success, the drug must be orally bioavailable, which remains a significant hurdle. They also highlighted the need to address long-term safety concerns before any potential approval.

The research team plans to continue developing CDD-2807, exploring its application as a therapeutic target and testing new versions of the drug in primate studies.