Published August 16, 2012
Researchers have developed a prototype for an oral male contraceptive, raising expectations that a birth control pill for men may enter clinical trial testing within a year, according to a new study.
Scientists tested a compound, called JQ1, in mice and found it was able to penetrate the blood-testis barrier and disrupt spermatogenesis – the process in which sperm develop and become mature. As a result, the mice showed a reduction in the number and quality of sperm produced and were rendered infertile.
More importantly, after discontinuing use of the compound, normal sperm production resumed – showing that the compound’s effects are reversible. JQ1 did not appear to have an impact on testosterone production, mating behavior or health of offspring conceived after use.
“An ideal contraceptive has 100 percent efficacy, complete reversibility and a lack of on or off-target side effects, meaning its extremely well-tolerated,” senior study author Dr. James Bradner, from the Dana-Farber Cancer Institute, told FoxNews.com.
He added that while it appears that JQ1 meets much of these criteria in mice, testing must be done in humans to confirm its efficacy.
The compound works by binding to male germ cells (which almost exclusively make sperm) to block the function of a protein called BRDT. Essentially, the compound causes BRDT to forget what it is supposed to be doing.
“[The protein] develops amnesia – it forgets how to make sperm as long as the mice are administered the drug,” Bradner explained.
Scientists originally discovered JQ1 in cancer studies as a therapeutic agent. As with male germ cells, the compound causes tumor cells – BRD4 cells, specifically – in lung and blood cancers to forget their function and stop them from dividing and causing harm in the body.
“It can trick cancer cells into believing they’re not cancer,” Bradner said. “Under a microscope, you can literally watch them become non-cancerous.”
Taking into account that BRD4 and BRDT cells are largely the same in terms of structure and function, Bradner realized the compound may also have potential as a male contraceptive and reached out to reproductive expert Dr. Martin Matzuk at Baylor College of Medicine.
“[Matzuk] was really excited about it, which was what got us really excited about it,” Bradner said.
The compound is a departure from previous studies which looked at a chemical called ENU. ENU targets a gene called Katnal1 and disrupts sperm’s ability to move through the testes.
According to Matzuk and Bradner, while the finding is an important advancement in fertility studies, the problem with ENU is that it is a potential mutagen that can damage the DNA.
“For healthy men, you do not want to give a drug that could cause mutations in the germline or have the possibility of causing cancer in the future,” Matzuk told FoxNews.com.
While JQ1 is much more targeted and thus avoids those adverse effects, Bradner emphasized it is merely a prototype of an ‘ideal’ contraceptive.
“As a molecular locksmith, it’s like having an illustration of the key fitting in the keyhole,” Bradner said. “Using this information, we have been developing next generation molecules to prompt human clinical trials.”
The study was published in the journal Cell.