Imagine if men could take their own version of the birth control pill? This day may be closer than we realise, considering the headway that has been made in the development of the first ever drug to offer non-hormonal and reversible male birth control.
“Non-hormonal targets are urgently needed,” says James Bradner, a physician at the Dana-Farber Cancer Institute in Boston, Massachusetts. Bradner and his colleagues have developed a drug they’ve called JQ1, which inhibits a testes-specific protein called BRDT that is vital for fertility.
The added bonus is that it doesn’t seem to affect sex drive either—at least not in mice.
The types of hormones that make men infertile have more severe side effects than those used in the female pill. That is why a non-hormonal option for male contraception is preferable to hormonal treatments.
JQ1 is an effective contraceptive with mice
All sperm cells develop from germ cells. At an early stage of this process, BRDT enters the nucleus and switches on relevant parts of the genome that instruct the cell to mature into a sperm cell. JQ1 binds to BRDT at exactly the same part of the protein that sticks to the genome, preventing it from giving instructions to the cell. “It’s like removing the Post-it note that reminds the cell to turn into a sperm cell,” says Bradner.
When mice were given daily injections of two different doses of JQ1 over a three- or six-week period, they saw at least a 90 per cent decrease in sperm count and at least a 75 per cent decrease in sperm cell motility. The decrease in the sperm count was so considerable at the higher dose that all of the mice eventually became infertile. Importantly, though, within two months of stopping the drug treatment, mouse fertility was completely restored.
“There was no obvious effect on the mojo of the animals,” says Bradner. There were no significant side effects that occurred, testosterone levels appeared normal and mating behavious were also unaffected.
Drug derivatives of JQ1 are currently being tested in clinical trials for people with cancer. “This is a refreshingly novel approach, and the studies are of top quality and are highly convincing,” says Richard Sharpe, specialist in male reproductive health at the University of Edinburgh, UK. “The approach used appears highly effective and fully reversible, at least in the relative short-term. And there are no obvious adverse effects in offspring sired by treated males after they had been taken off the treatment.”
Improvements that need to be made
Sharpe points out that there are still several challenges to overcome on the route to the human equivalent of the drug –such as creating an oral version rather than the injectable form used in the rodents trials. He says it is very important that they can ensure that the drug is reversible in the long run – and that there are no adverse subsequent results on offspring conceived at a later stage.
But even amidst all these challenges. This is still the most promising new approach in controlling male fertility that he has seen to-date.
“Developing a small molecule as a contraceptive is highly challenging considering that the users will accept only very minor side effects, considering that they are not sick,” says Aarnoud C. van der Spoel at Dalhouse University in Halifaz, Canada. He says more investigations into the long term effects and side effects of the drug are critical.
“The work is impressive, with highly promising results,” says van der Spoel. “There is a world-wide unmet need for alternative approaches for family planning, and additional methods to achieve this goal are to be applauded.”