“This project for us started very much as a side project,” says Bradner. “We planned together to do a critical first experiment to explore the effects of JQ1 on sperm count and motility. We went right in vivo. And we were shocked at how well the drug worked.”
In one experiment involving about a dozen male mice, the half that had received BRDT daily for three weeks had a sperm count of just over 1 million stored in a part of their epididymis, an order of magnitude lower than their control counterparts, which had 10 million sperm in that same section. The drug also hampered sperm motility and shrank the animals’ testes—a sign, says Bradner, that it was working (though it is not a desirable side effect in humans).
Further tests demonstrated that a high-dose regimen of the drug for several months prevented the male mice from siring pups, though the fertility of the mice rebounded after the drug was removed. “The pups are totally normal,” Bradner says, noting that they performed well on behavioral tests and had normal fertility.
Birth defects remain a “key concern” should the drug move forward toward human trials one day, according to William Bremner, an endocrinologist at the University of Washington in Seattle who was not involved in the current study. But he says that there is good reason to continue studying JQ1 as a potential male contraceptive. “There is reasonable similarity of mice and humans [regarding] spermatogenesis and the blood-testes barrier. Not complete, but close, so mice are reasonable predictors of a human effect.”
But given that people typically use contraceptives for years on end, Mruk would like to see longer studies of the drug to really assess its safety profile. “Short-term side effects can be identified rather quickly,” she says, “but long term side-effects can take decades to fish out.”
Bradner agrees that many follow-up experiments remain to be done. For one, he notes, “it’s unanswered what the role of BRDT is in spermatogenesis”, although it appears to have a key role in the transcription of genes. Bradner has reached out two drug companies, Britain’s GlaxoSmithKline and Tensha Therapeutics of Cambridge, Massachusetts, both of which have worked on inhibitors for the class of proteins to which BRDT belongs. “Both companies expressed some interest,” he says.
The story does not end there for JQ1—just last week researchers from the Boston University School of Medicine found evidence suggesting that it might activate latent HIV in immune cells, and could therefore potentially be useful in eradicating the virus from the body.
This article is reproduced with permission from Nature Medicine. The article was first published on August 16, 2012.
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Add CommentCancer is a major problem in the United States. But its incidence in the United States is so much higher than it is in most other countries, and so low in east Asia, that one must conclude that lifestyle choices, particularly those of diet, of the United States must play a role. Assuming that 0.02% of the population has a genetic determinacy for cancer, the higher rate probably reflects physiological degeneration. There are about 50 things a human must take in or be exposed to for that human to function normally. These include the two essential oils, or fatty acids, Omega 3 and Omega 6. The deprivation of either of these, as well as the possible inclusion of other required things, over time, will lead to the degeneration of the human body. Cancer is one symptom of this degeneration. It takes a while to develop; that is why cancer victims tend to be older people, aside from the 0.02% who have the genetic determinacy for cancer.
Reply | Report Abuse | Link to thisSo, agaist cancer there is at least a question whether drugs are required. But if these drugs can help fight HIV, and can safely serve as a male contraceptive, those are the positive side of drug development.