A gene therapy shot might keep cats from getting pregnant without being spayed

Invasive surgeries to spay cats could one day be a thing of the past, replaced instead with a single shot.  

An injected gene therapy given to female cats prevented them from getting pregnant, researchers report June 6 in Nature Communications. None gave birth to a litter of kittens even after mating with a fertile male. The tactic, if it holds up in further testing, could offer a more efficient way to control a global population of feral cats that numbers in the hundreds of millions.

“We love domestic cats, but they are killers out in the environment,” says Bill Swanson, a conservation biologist at the Cincinnati Zoo & Botanical Garden. Every year, free-roaming cats around the world probably kill billions of birds and small mammals (SN: 1/29/13). Spaying both feral and pet cats can help to keep feline populations, and their casualties, under control.  

The experimental gene therapy targets anti-Müellerian hormone, also known as Müllerian inhibiting substance, a protein that helps fetal sex organs develop. After injection, a modified virus introduces the gene that makes the hormone into the cats’ cells. The cells then make more anti-Müellerian hormone than normal. High levels of the protein may prevent a cat’s ovaries from releasing eggs by keeping follicles — the structures that house and release eggs — in a dormant state.

In the new study, Swanson and colleagues treated six female cats with the gene therapy. Three received a high dose and another three received a lower dose. An additional three control cats got a placebo. None had any severe side effects.

The team housed all nine cats together with a fertile male in two, four-month-long trials. One trial took place eight months after treatment; the second, with a different male, happened nearly two years after the injection. In both trials, the control cats gave birth to litters after mating with males only once. But none of the six treated cats became pregnant, despite two of them mating with the males.

The proof-of-concept study is “the first real sign of hope that we could do something besides spaying cats,” says Julie Levy, a veterinarian at the University of Florida in Gainesville who was not involved in the study. The single-dose injection is especially promising to control feral populations, eliminating the need to bring wild-living cats into a clinic for surgery or trap animals more than once to administer multiple doses.

Past alternatives to surgery, such as vaccines, proved ineffective over the long term. Vaccines teach the body to attack foreign invaders. Crafting a contraceptive vaccine targeted at the pituitary, which releases the hormones that spark ovulation, was difficult. “Your whole immune system is tuned to know what’s you, and it should not attack, and what is foreign, and it should attack,” Levy says. Diseases can develop when immune responses learn to attack the body itself. 

Many researchers tried to develop various vaccines as a cat contraceptive, but “we gave up,” Levy says.  

The experimental gene therapy could be a better approach because it doesn’t rely on the immune system and instead makes more of something that the body already has, so the immune system ideally won’t get involved at all.

What’s more, the gene is delivered to muscle cells, says David Pépin, a reproductive biologist at Massachusetts General Hospital and Harvard Medical School. There, the cell makes the hormone using small, circular strings of DNA. These strings float around the cell and aren’t inserted into the cell’s instruction manual, the DNA housed inside the nucleus. Because muscle cells generally don’t die, the DNA can stick around for a lifetime.

The study reports results after two years, Pépin says, but to date the team has followed the cats for more than four. Because gene therapy can last for a lifetime in other animals, including people, it’s likely that, with proper dosing, the same would be true for cats.

In the study, two of the treated cats mated with males. One mated a total of nine times yet still never got pregnant. Zooming in on all the cats’ hormones revealed that the treated females didn’t ovulate, but other hormones involved in reproduction and estrus — also known as heat, a time when female cats are ready to mate — remained intact.

The four treated cats that never bred with the males had spikes in estrogen levels, one sign of estrus. But you’d never have guessed that based on the cats’ behavior, Swanson notes. The females didn’t allow the males to breed, a sign those females weren’t in heat.

Males pursuing a ready-to-breed female are incredibly persistent if she’s in estrus, he says. A male will become restless, endlessly following a female and attempting to mount her if he thinks it’s possible to breed. “It’s like velociraptors in Jurassic Park testing the fence. All the time they’re testing these cats if they’re in estrus.”  

That’s the kind of annoying behavior that makes people not want cats in their neighborhoods, Levy says. For her, the ideal cat contraception would keep females from allowing any males to breed with them. Hopefully that would stop fertile, disruptive males from yowling, spraying urine to mark territory and fighting other males when chasing a female rendered infertile by gene therapy. 

It will still be years before the treatment makes it to vet offices, if approved by the U.S. Food and Drug Administration and similar agencies around the world. Swanson, Pépin and colleagues are still tweaking the gene and method of delivery, exploring how to make it as effective as possible as well as cost-effective to make. Clinical studies with more cats are also required to verify the injection’s safety and efficacy.

Still, “it’s a really different way to do contraception,” Pépin says. And anti-Müellerian hormone is common among animals, so it may be possible to expand to other invasive species. Pépin and others are even exploring ways to leverage the hormone in humans as a nonpermanent form of contraception (SN: 8/22/17). There’s still a lot to learn, “but I think there’s a great opportunity here.”