Male Pill on the Horizon: Drug disables mouse sperm but wears off quickly

A practical birth control pill for men has long been on medicine’s wish list. Now, researchers have discovered that a new oral drug created to ease a genetic disorder could have contraceptive benefits.

ALTERED STATES. Compared with a normal mouse sperm (left), a sperm exposed to NB-DNJ is deformed (right). After the drug treatment stops, sperm cells become normal again (inset). van der Spoel et al./PNAS

To date, the only government-approved male birth control methods are condom use and vasectomy (SN: 9/30/00, p. 222: Experimental hormone-based contraceptives, such as testosterone-progestin injections, block men’s sperm production. But these can take up to 10 weeks to become effective and don’t wear off for months after they’re discontinued.

The promising drug, known as N-butyldeoxynojirimycin or NB-DNJ, might offer another choice, say researchers at the University of Oxford in England. They report that in low doses, the drug prevents sperm cells from developing normally in mice.

Moreover, NB-DNJ has relatively few other side effects, and its contraceptive action is readily reversed.

The Oxford researchers stumbled upon NB-DNJ’s potential birth control effects while exploring its potential use in treating diseases of the nervous system. During that research, male mice exposed to the drug became temporarily infertile. “So, we started a study to look at what this drug was doing to male-mouse fertility,” says Frances M. Platt.

She and her colleagues spiked mouse feed with varying doses of NB-DNJ and gave it to male mice for 5 weeks. A control group received unspiked nourishment. In mating tests that followed, those females coupling with the control males produced normal litters. Treated males–even those administered low doses of the drug–didn’t impregnate females.

The researchers found that NB-DNJ damages sperm nuclei and mitochondria, impairing the cells’ swimming. The drug also thwarts the formation of the acrosome–a cap on the sperm’s head that normally enables the gamete to penetrate an egg.

These effects are reversible. Sperm of the mice treated with any dose of NB-DNJ returned to normal by 3 weeks after the researchers stopped administering the drug. “The males have to go through one round of making new sperm cells, and then they acquire fertility again,” says Platt. The pups sired by these mice grew to adulthood with no obvious abnormalities, report Platt and her colleagues in an upcoming Proceedings of the National Academy of Sciences.

In another test, male mice regained fertility even after taking NB-DNJ for

6 months. “For a laboratory mouse, that is a substantial portion of its lifetime,” which normally lasts 2 years, says research-team leader Aarnoud C. van der Spoel.

Last month, the European Union approved a version of NB-DNJ called miglustat for Gaucher’s disease, a debilitating genetic disorder. But any researchers who aspire to turn NB-DNJ into a contraceptive will have to jump other hurdles, says Diana Blithe of the National Institute of Child Health and Human Development in Bethesda, Md. For example, use of NB-DNJ by healthy men for birth control will require further scrutiny of the known toxic effects, such as damage to sperm internal parts.

“Whether or not this compound will lead to contraception depends on its safety profile,” says Blithe.

NB-DNJ appears less risky than some other promising drugs that lack its good features, says Ronald Swerdloff of the Harbor-UCLA Research and Education Institute in Torrance, Calif. He adds, NB-DNJ “is a long way from a final, tested product, but it seems to be an exciting lead.”


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