A Boston laboratory working to develop anti-cancer drugs has accidently discovered a hormone-free application of one of their drugs that could be used as a male birth control drug, according to a report in the Boston Globe.
The drug’s effects are reversible, answering the question about whether the infertility is permanent, and it does not reduce the male sex drive.
The drug was being originally tested as part of a broader cancer research effort at the Boston laboratory. This is not the first time a drug was discovered accidently in the laboratory. The first naturally occurring antibiotic drug penicillin was discovered in 1928 when a mold developed on a staphylococcus culture plate. The discovery of penicillin changed the course of medicine and has enabled physicians to treat formerly severe and life-threatening illnesses such as bacterial endocarditis, meningitis, pneumococcal pneumonia, gonorrhea and syphilis.
"There is no effect on the mouse's mojo. The animals exhibit the normal sexual behaviors and frequency of copulation," said Dr. James Bradner of the Dana-Farber Cancer Institute in Boston, whose study appears in the journal Cell.
What's more, the effect is completely reversible. Once doctors stopped giving the drug to mice, they were able to sire healthy litters, with no apparent side effects, Bradner said in a Reuters report.
Scientists have been searching for a male birth control drug for 50 years, and this discovery could change the dynamic of birth control between men and women. Men for the first time could be in control of their fertility, much the same women have since taking birth control pills.
The most significant discovery was the fact that the drug could interfere with normal sperm development, rendering male mice infertile. But, importantly, when the mice were taken off the regimen, they could sire normal offspring.
Researchers are working to refine the substance so that it will target only a protein found in the testicles, in hope the work could lead to an experimental drug and, in turn, a new form of birth control.
Actual approval by the Food and Drug Administration and use of the drug is a few years in the future; still, it proves to be a historical discovery in medicine.
Shrinking cancer tumors appears to have little in common with interfering with sperm’s ability to move and increase in number. But according to Dr. James Bradner’s mind when the Dana-Farber Cancer Institute oncologist led an effort two years ago to craft a molecule researchers hoped would help spawn cancer-fighting drugs, they had no idea they would discover a male birth control drug.
Their serendipitous discovery is not unusual in science, which is also exemplified by the discovery of penicillin.
But the hurdles to male contraceptive development remain high.
“Everybody would like a better solution than condoms and birth control pills,” said Dr. David Clapham, a professor of pediatric cardiology at Children’s Hospital Boston.
Because the drugs would be given to healthy men, researchers have to focus on safety and ensure that any eventual birth control medication does not have side effects. That will be especially important, Clapham said, considering that the molecule they are starting with was initially of interest for use in chemotherapy, according to WebMD.
Similarly, female birth control pills, which transformed women’s control over their reproductive abilities, were in some ways tackling a simpler problem.
Dr. John Amory, a professor at the University of Washington School of Medicine who has worked on hormonal treatments for men and a drug that interferes with the maturation of sperm, said that in some ways it is a numbers game.
A birth control method for women must prevent just one egg a month from being fertilized. Men, though, with every heartbeat generate roughly 1,000 sperm, whose numbers would have to be reduced by 99 percent for a contraceptive to be effective.
“I was thrilled to see this work,” Amory said of the new study. “It’s a really good lead in terms of the nonhormonal approach to male contraception.”
Bradner normally sees patients with blood cancers and runs a laboratory aimed at cancer drug discovery. Two years ago, his laboratory created a molecule that targeted a particular gene that appeared to help cancer cells “remember” their identity. They called the compound JQ1, named after the scientist, Jun Qi, who developed the compound.
Birth Control Options for Men Limited
It has been 50 years since the birth control pill for women was introduced, forever changing contraception for women. Men, however, have only had two options for decades, a vasectomy and condoms.
Research to develop a birth control pill for men has largely focused on manipulating male sex hormones, but this approach has proven challenging, says William J. Bremner, MD, PhD, of the University of Washington School of Medicine.
One major challenge has been the presence of a sperm-testis barrier, which prevents larger molecules from reaching the site where sperm production occurs.
The small molecule compound developed in the Dana-Farber lab, known as JQ1, easily crosses this barrier.
JQ1 targets a testes-specific protein called BRDT that is critical for sperm production.
Along with colleague Martin Matzuk, MD, of Baylor College of Medicine, where the studies in mice were conducted, the Dana-Farber team is also working to develop a drug that specifically targets BRDT.
That is important because the more specific a drug is, the safer it is likely to be.
Bremner tells WebMD that earlier attempts to develop a non-hormonal male pill have failed because the drugs were not specific enough to turn off sperm production without causing unintended harm.
Though Bremner says he is optimistic that new birth control options for men are on the horizon, he says a non-hormonal male pill is, at best, several years away.
“We are probably not talking about something that is going to be available in the next two years or even five,” he says. “But this research represents a new biologic approach and it is certainly promising.”