The possible non-hormonal male contraceptive immobilizes sperm for about three hours so that fertility is reduced without altering sexual function.
The moment a man walks into a pharmacy and asks for the ‘male pill‘ is closer. At least so believes Lonny Levin, professor of Pharmacology at Weill Cornell Medical Center in New York. Levin is, along with Jochen Buck, also a pharmacologist at this university, the main author of the research known today where the efficacy of a contraceptive molecule has been shown in male mice.
But for that moment to come true, the results of the study in an experimental model have to be replicated in other experiments with animals and, if all goes well, in clinical trials. However, the truth is that the development of possible drug He has started his journey on the right foot. This is reflected in the results of the experiment published in this week’s issue of Nature Communications. Research, supported by the US National Institutes of Health (NIH), identifies a potential non-hormonal contraceptive that could be taken shortly before sexual activity to inhibit fertility for a time, capacity that would be recovered the next day.
The candidate amale pill it works blocking an essential enzyme in sperm function, soluble adenyl cyclase. This protein is necessary to activate the sperm’s ability to swim and mature, so that it can travel through the female reproductive tract and fertilize the egg.
Luz Candenas de Lujn, senior scientist at the CSIC and researcher in Reproduction Biology at the Chemical Research Institute, who has not participated in the work, states in statements collected by SMC Spain that “What is interesting about this study is that the drug targets a very specific enzyme in sperm (one of the isoforms, ADCY10, is expressed almost exclusively in these cells) and although there are other, more widely distributed isoforms, I think they’ve hit the nail on the head.”
A key that has been touched almost by chance, as sometimes happens in science. Levin’s and Buck’s groups were not initially seeking a male contraceptiveInstead, they joined forces to isolate the soluble cellular signaling protein adenylyl cyclase (sAC), which had resisted biochemicals for years. Finally, after two years of effort, they succeeded, and thus they merged their teams into a laboratory where they focused their research on sAC.
In 2018, one of the lab’s postdoctoral scientists, Melanie Balbach, discovered while working on sAC inhibitors as a possible treatment for an ocular condition that mice given were given a sAC blocking drug produced sperm that could not propel forward. Looking at that effect in more detail, they found that another team found that men who lacked the gene that codes for sAC were infertile but were otherwise healthy, leading them to consider sAC inhibition as a safe contraceptive option.
The compound, baptized TDI-11861, has shown in several tests that a single dose administered orally immobilizes mouse sperm. and their maturation is prevented, without interfering in the sexual functioning of the animals.
In the experiments, the male mouse showed normal mating behavior with the females, but without fertilizing them, despite 52 different attempts. Contraceptive efficacy was maintained at 100% during the first two hours, and at 91% after a third hour was added.. In contrast, male mice treated with an inactive control substance fertilized nearly a third of their partners.
The effect of the compound wears off three hours after, when the spermatozoa begin to recover their motility. Within 24 hours, almost all function normally again, and the males regain their fertility. No side effects were recorded by the compound that was administered continuously for six weeks in males or females.
“Our inhibitor works within 30 minutes to an hour,” Balbach says in a Cornell University statement. “All other experimental hormonal or non-hormonal male contraceptives take weeks to reduce sperm count or in incapacitating them to fertilize eggs”, he adds, alluding to other forms of male contraception under investigation, a field that, for the moment, has only garnered frustrated attempts.
“It takes weeks to reverse the effects of other hormonal and non-hormonal male contraceptives in development,” he continues. “Since sAC inhibitors wear off in a matter of hours and men would only take them as often as necessary, they could allow them to make day-to-day decisions about their fertility.”
Key to the work has been the collaboration of the Tri-Institutional Therapeutic Discovery Institute (TDI), an organization that works with Cornell University, Memorial Sloan Kettering Cancer Center, and Rockefeller University to accelerate early-stage drug discovery.
For the scientist Luz Candenas de Lujn, “Other attempts have been made to develop male contraceptives, but so far none of these drugs have made it into the clinic.. Although this research has been carried out in mice and clinical trials are necessary to corroborate the efficacy of the drug in humans, this study opens the door to the development of the first single-use male contraceptive pill, offering an interesting alternative to exclusive use of oral contraceptives in women”.
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