A daily pill drastically reduced sperm counts in mice with no side effects, but many male contraceptives have previously failed in human trials
23 March 2022
A non-hormonal male contraceptive pill is 99 per cent effective at preventing pregnancy in mice with no observed side effects. Human trials are being planned, but some researchers warn that safety concerns could yet prevent the drug from reaching the market.
Despite many attempts at making an effective and safe male contraceptive, no treatment has passed human clinical trials. Most have been based on hormones, but non-hormonal contraceptives tend to have fewer side effects, says Md Abdullah al Noman at the University of Minnesota in Minneapolis.
“Safety is very important for birth control pills because people are not taking it for a disease, so they are less tolerant of side effects,” says Noman.
He and his colleagues gave male mice a daily dose of a molecule called YCT529 over a four-week period, and found that their sperm count plummeted. Between four and six weeks after the mice stopped receiving the treatment, they could reproduce normally again with no observable side effects.
“When we went to even 100 times higher dose than the effective dose, the compound didn’t show any toxicity,” says Noman, who presented the results today at the American Chemical Society Spring 2022 conference in San Diego, California.
The team tested more than 100 molecules to identify a drug candidate that targets a protein called retinoic acid receptor alpha (RAR-α). Inhibiting this protein blocks the effects of retinoic acid, a derivative of vitamin A that plays an important role in cell development and sperm formation.
Previous research has shown that mice that were genetically edited so they lacked the RAR-α gene experienced no side effects apart from the inability to produce sperm.
Noman and his colleagues have now licensed their drug to a private company, YourChoice Therapeutics, which is aiming to carry out human trials in the US later this year.
While Noman and his team didn’t observe any side effects in mice, this doesn’t guarantee that the drug will be safe in humans, says Richard Anderson at the University of Edinburgh, UK. “If you were developing a drug that’s targeting a completely novel pathway, I think it would be appropriate to be cautious about safety when there isn’t a track record in that field.”
The vitamin A signalling system plays a number of important roles in bodily systems. “It seems to me inherently unlikely that a compound with such activity would be free of side effects,” says Richard Sharpe, also at the University of Edinburgh.
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