Of the approximately 600 million house cats in the world, around 80 percent live as strays. In order to reduce animal suffering, animal protection organizations try to sterilize as many street cats as possible, but the surgical procedure is complex and expensive. In a feasibility study, researchers have now tested a possible alternative. With a gene therapy injection, they increased the level of the anti-Müllerian hormone in the cats and thus prevented them from becoming pregnant. A single injection worked for several years and had a good safety profile. Larger studies are to follow.
The anti-Müllerian hormone (AMH) plays an important role in the differentiation of the sexual organs during embryonic development. In male embryos, the testicles produce the hormone and ensure that the precursors of the uterus and fallopian tubes regress and male sexual characteristics develop. In sexually mature women, AMH is also produced in the ovaries. A high AMH level indicates that many follicles capable of maturing are available and a woman has a good chance of conceiving. However, studies in mice have shown that excessively high levels of AMH inhibit follicle maturation and thus prevent ovulation.
Gene therapy instead of surgical sterilization
A team led by Lindsey Vansandt from the Cincinnati Zoo and Botanical Garden in Ohio used this observation to develop a new approach to birth control in cats: To do this, the team created a slightly modified version of the cat’s AMH gene. This causes AMH production even in normally non-hormonally active cells. To introduce the modified gene into the cat’s cells, the researchers used a viral vector that is already being used successfully for gene therapies in humans. For the feasibility study, they injected the gene therapy vector with the altered AMH gene into the thigh muscle of six adult cats. Half of the animals received a high dose and the other half a low dose. Three other cats served as a control group.
After the injection, the team observed and examined the cats regularly. “We did not find any significant side effects,” the team said. Blood tests showed that the gene therapy was indeed having the desired effect: “A single injection of the gene therapy vector triggers the cat’s muscles to produce AMH, which is normally only produced in the ovaries, and increases the total AMH level by a factor of 100,” reports Co -Author David Pépin of Harvard Medical School in Boston. Other blood values, including the level of other sex hormones, remained largely unaffected.
Successful contraception
To find out whether the high AMH level actually prevents the cats from becoming pregnant, the researchers allowed a male tomcat with the nine cats twice for four months each. They recorded on video how often the individuals mated. In addition, they examined weekly by ultrasound whether a cat had become pregnant. “After both mating phases, all cats from the control group each gave birth to two to four healthy kittens,” report Vansandt and her team.
Of the six cats treated with gene therapy, four showed no interest in mating. But the two treated cats, which mated with the tomcat several times during the experiments, did not become pregnant either. “These results strongly suggest that elevated AMH above normal levels inhibits ovulation and leads to contraception in the cat,” the researchers said. The increased AMH level was maintained over the entire observation period of two years without the cats showing any side effects. “We are confident that these contraceptive values will be maintained in the animals for much longer,” says Pépin’s colleague Philippe Godin.
A long way into practice
However, before the procedure can be used in practice, larger studies must first confirm that it is in fact as safe and effective as the proof of concept suggests. In addition, the infrastructure to produce enough active substance for millions of stray cats and to make it available at a reasonable price is still lacking.
“This technology may be a little ahead of its time,” says Pépin. “Our goal is to show that safe and effective permanent contraception in pets is possible through gene therapy. It is our hope that as human gene therapy increases, so will the manufacturing capabilities of viral vectors, making it feasible to administer this contraceptive to control cat populations in the wild.” offer a new way of sparing your own cat a surgical procedure and still effectively preventing it from becoming pregnant.
Source: Lindsey Vansandt (Cincinnati Zoo and Botanical Garden, Ohio) et al., Nature Communications, doi: 10.1038/s41467-023-38721-0