(Dr. Wolgemuth is professor of genetics and development and of obstetrics and gynecology; and Dr. Chung is an associate research scientist, both at Columbia University Medical Center).
Bristol-Myers dropped its interest when it found that the compound also was in the company's words "a testicular toxin." The paper did not elaborate on how the drug caused infertility, so Dr. Wolgemuth and her team tested the drug in mice to find out; they noted that the changes it caused were similar to what one sees with vitamin A-deficiency and loss of function of RARalpha.
"We were intrigued," said Dr. Wolgemuth. "One company's toxin may be another person's contraceptive."
To investigate whether the compound prevented conception at even lower levels than those cited in the company's study, Dr. Wolgemuth and her team placed the treated male mice with females and found that reversible male sterility occurred with doses as low as 1.0mg/kg of body weight for a 4-week dosing period.
One advantage of using a non-steroidal approach, the researchers say, is avoiding the side effects commonly associated with steroidal hormone-based methods.
Male steroid-based options have been plagued with adverse effects, including ethnic variability in efficacy, as well as an increased risk of cardiovascular disease and benign prostatic hyperplasia.
Another side effect of hormonal options for men has been diminished libido. That drawback will also likely be avoided if a method involving manipulation of the retinoid receptor pathway proves successful.
"We have seen no side effects, so far, and our mice have been mating quite happily," said Dr. Wolgemuth.
The researchers say the drug will not affect vision. Although dietary vitamin A is responsible for the production of light-sensitive receptors in the eye, it does not use the RARs in this process.
|Contact: Karin Eskenazi|
Columbia University Medical Center