New cancer drug affects sperm, study shows. Finally, a male birth control pill?

Researchers tinkering around with a cancer drug said Thursday it might also work as a male birth control pill.

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Tests in mice show it can make testicles "forget" how to make sperm — yet the mice became completely fertile again and fathered normal babies after they stopped getting the drug. The drug isn't ready to test in people yet, but if it worked, would provide a hormone-free way to help men control when they have families.

“These findings suggest that a reversible, oral male contraceptive may be possible,” said Dr. James Bradner, of Dana-Farber Cancer Institute and Harvard Medical School, who helped lead the study published in the journal Cell.

Many teams have tried, and failed, to make a male birth control pill. Recently, Scottish researchers discovered a gene necessary for sperm production, opening hopes for a hormone-free male contraceptive. Bradner and colleagues believe this one might work if it turns out it really does just temporarily stop men from making sperm, with no other side-effects.

Female contraceptives interfere with hormones such as estrogen, but it turns out that messing with the “male hormone” testosterone doesn’t necessary affect fertility and has a range of unwanted side-effects, including breast enlargement. Drug companies have steered clear.

Bradner’s team was working to develop a new cancer drug. They developed a molecule called JQ1, named after a chemist in the lab, Jun Qi, Ph.D.

This molecule affects a structure on tumor cells called BRD4, which seems to make cells “remember” they are cancer cells. Just like a key fits into a lock, JQ1 can slide up against BRD4 and inactivate it, making the cells “forget” to be tumors. Bradner’s lab is getting ready to test it against lung cancer, some blood cancers and other tumors.

When making a new cancer drug it's important to be sure it won’t have side-effects on healthy cells, so Bradner started looking around for structures similar to BRD4 that might play an important role in human health. He found BRDT. The "T" in the molecule "stands for testicles,” Bradner said.

“We started to wonder whether BRDT might be involved in the memory of how to make sperm,” Bradner said. “We wondered whether JQ1 would enter the testicle, inhibit BRDT and cause the testicles to forget how to make sperm.”

But Bradner’s lab is a cancer lab, not a fertility lab. He contacted fertility specialist Dr. Martin Matzuk of Baylor College of Medicinein Houston.

The two academic labs collaborated via Skype and Internet file-sharing programs, something that never would have happened between competing private drug companies.

Matzuk's lab had already tested mice that completely lacked BRDT in their cells and knew they were infertile. “If a mouse without the gene would be infertile, of course if you had a drug that blocked that gene expression, the mouse would also be infertile,” Matzuk said.

Tests showed they were. Even better, when they stopped giving mice the drug, they became fertile again and fathered healthy mouse pups.

Matzuk’s team looked at human versions of the BRDT protein, and found JQ1 inactivated it, too.

While they injected the mice, Matzuk says there’s no reason the drug couldn’t be given as a pill. But he said most people might want some kind of longer-term delivery system, like an injectable or an implant. But even if the pill is an effective contraceptive, it's unclear whether women would trust men to take a daily pill, Matzuk points out.

While it doesn’t look like JQ1 affects anything else in the body, the teams plan further cancer trials of the drug. Meanwhile, they are tracking male cancer patients to see if they also become infertile while taking it.

Dr. William Bremner, an expert in fertility at the University of Washington in Seattle, called the work exciting and says the need for more safe contraceptives is dire. The World Health Organization says half a million women die every year globally from complications due to pregnancy and childbirth. The U.S. Centers for Disease Control and Prevention says more than 360,000 American teenagers give birth every year, and tens of thousands more have abortions.

“Men should be given additional opportunities to participate in safe contraception, both to allow them more control over their own fertility and to ease the health burden of unwanted pregnancies and contraception incurred by women,” Bremner wrote in a commentary in Cell.

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