Promising discovery targets sperm to create temporary sterility, with no other side effects. Depositphotos –
Scientists already knew that a serine/threonine kinase 33 (STK33) gene mutation results in the male being sterile. When Baylor College of Medicine researchers found a small-molecule compound that could knock out STK33 temporarily, it produced the same result. While not the first non-hormonal sperm-targeted therapy, this research finds a new target as the science world continues its long quest to find ‘the pill’ for men.
“Although researchers have been investigating several strategies to develop male contraceptives, we still do not have a birth control pill for men,” said corresponding author Dr Martin Matzuk, director of the Center for Drug Discovery at Baylor. “In this study we focused on a novel approach – identifying a small molecule that would inhibit serine/threonine kinase 33 (STK33), a protein that is specifically required for fertility in both men and mice.
“STK33 is therefore considered a viable target with minimal safety concerns for contraception in men,” he added.
The team screened its “multi-billion compound collection” to locate potential STK33 inhibitors, which they then modified to make more stable, targeted and powerful for trials on mice.
“Among these modified versions, compound CDD-2807 turned out to be the most effective,” said first author Dr Angela Ku, from the Matzuk lab at Baylor.
“Next, we tested the efficacy of CDD-2807 in our mouse model,” said co-author Courtney M. Sutton, also of the Matzuk lab. “We evaluated several doses and treatment schedules and then determined sperm motility and number in the mice as well as their ability to fertilize females.”
CDD-2807 was able to cross the blood-testis barrier, heading straight for STK33 and affecting sperm numbers and motility, effectively thwarting fertility even at a low drug dose.
“We were pleased to see that the mice did not show signs of toxicity from CDD-2807 treatment, that the compound did not accumulate in the brain, and that the treatment did not alter testis size,” said Sutton. “Importantly, the contraceptive effect was reversible. After a period without compound CDD-2807, the mice recovered sperm motility and numbers and were fertile again.”
While we’re still not likely to be able to grab a packet of these at the drugstore anytime soon, the team will move onto further testing of CDD-2807 and other potential candidate compounds.
“Our goal is to further evaluate this STK33 inhibitor and compounds similar to CDD-2807 in primates to determine their effectiveness as reversible male contraceptives,” Matzuk said.
Of course, it remains to be seen if this target molecule could have the same impact on human sperm.
Still, we’re yet to crack this elusive code that would produce the very first temporary contraceptive product for men. Other research has included gel injections that block the release of sperm, ultrasound pulses that kill them and even similar binders and inhibitors to offer a non-hormonal to produce unviable sperm.
This latest study was published in the journal Science.
Source: Baylor College of Medicine
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