Over time, the TDI-11861 was finalized. In mice, the drug did not affect sexual function and did not cause any side effects. And most importantly, a day later the sperm was back to normal.
Of course, there is a big caveat: mice are not people. But humans also have the sAC enzyme, and in men it is also involved in sperm movement. Buck and Levin are confident that this strategy can be safe for humans. another team’s report for 2019, which describes two infertile men with mutations in the gene responsible for the development of sAC. The men were otherwise healthy, except that they had a higher risk of kidney stones. (Mice bred without this gene have increased eye pressure, which men without this gene did not.)
To test the safety of their compound, the Cornell team pumped it continuously into male and female mice for six weeks. They noted no side effects, including kidney problems. They are now testing the compound in rabbits, which have more human-like reproductive organs.
Many male contraceptive efforts have used hormones, most notably testosterone, to suppress sperm production. But like hormonal birth control for women, these drugs can have many negative side effects, including mood swings, weight gain, and decreased libido. Both female and male hormonal birth control also take weeks to become fully effective in preventing pregnancy. A trial of hormone gel for men sponsored by the National Institutes of Health shows promising results, but the gel must be applied daily to the upper arms to keep sperm levels low enough for effective contraception.
Some men may prefer a non-hormonal temporary option. “I think this is a really great idea and it will be greatly appreciated by many people who might not want to take a pill every day,” says Gunda Georg, a professor of medicinal chemistry at the University of Minnesota who does male research. and female contraceptives and did not participate in the new work. “I think we need to have many different contraceptive options for men as well as for women.”
George’s laboratory developed a non-hormonal pill, dubbed YCT529, which targets a protein called retinoic acid receptor alpha and is involved in sperm formation. In mice, it significantly reduced sperm count and was 99 percent effective in preventing pregnancy after taking it daily for four weeks.
Although Buck and Levin are also working on pills, they are less effective than injections for drug delivery. The stomach tends to break them down, and Levine says the current version of their mix should be a fairly large pill. The researchers created Sacyl Pharmaceuticals to further refine their sAC inhibitors and bring them to human clinical trials. “We’re trying to get a formulation that’s a nice little pill,” says Levine.
They also recognize that the active compound wears off too quickly, which can lead to unwanted pregnancies if not taken at exactly the right time, so they hope to increase the window of effectiveness to 18 hours or so. Although there are still many trials ahead, if all goes well, perhaps this will play a role in future Valentine’s Days. “Presumably you could take it at dinner and then within an hour, like Viagra, you would be ready for sexual activity,” says Lindsey.