Revolution in Pet Sterilization: Gene Therapy Offers Long-Term Contraception for Cats

Scientists at Massachusetts General Hospital have achieved a groundbreaking milestone by successfully testing a single dose of gene therapy as a long-term contraception method for cats, presenting a viable alternative to surgical spaying. The research study demonstrated the safety and tolerance of the gene therapy over a two-year period. While further studies are necessary to confirm and address scalability, these findings offer a promising alternative to the current practice of surgical spaying.

The current lack of contraceptives capable of providing permanent sterilization in companion animals has made surgical spaying, involving the removal of the ovaries and uterus, the most widely employed method for controlling unwanted reproduction in female cats.

For the first time, researchers at Massachusetts General Hospital (MGH), in collaboration with Mass General Brigham (MGB), have shown that a single dose of anti-Müllerian hormone (AMH) gene therapy can induce long-term contraception in domestic cats, potentially serving as a safe and effective substitute for surgical spaying. The study, published in Nature Communications, marks a significant advancement in the field.

During previous research focused on evaluating AMH (also known as Müllerian inhibiting substance or MIS) as a means of preserving ovarian reserve in women undergoing chemotherapy, senior author David Pépin, PhD, Associate Director of the Pediatric Surgical Research Laboratories at Massachusetts General Hospital and an Associate Professor at Harvard Medical School, discovered that raising the level of AMH beyond a certain threshold suppressed the growth of ovarian follicles, effectively preventing ovulation and conception.

“AMH is a naturally occurring non-steroidal hormone produced by the ovaries in human females and other mammals, and in the testes in males,” explained Patricia K. Donahoe, MD, a co-author of the study and the Director of Pediatric Surgical Research Laboratories and Chief Emerita of Pediatric Surgical Services at Massachusetts General Hospital.

Pépin and his collaborators were the first to publish the contraceptive potential of AMH in rodents back in 2017. Subsequently, they directed their focus towards felines. To elevate AMH levels in female domestic cats, the researchers developed an adeno-associated viral (AAV) gene therapy vector containing a slightly modified version of the feline AMH gene. Human therapies utilizing similar AAV vectors to deliver various therapeutic genes have proven to be both safe and effective, receiving approval from the FDA.

“With a single injection of the gene therapy vector, the cat’s muscles begin producing AMH, which is typically only generated in the ovaries, thereby raising the overall AMH level to about 100 times higher than normal,” Pépin explained.

Six female cats were subjected to the gene therapy at two different doses, while three cats served as control subjects. A male cat was introduced into the female colony for two four-month-long mating trials. The researchers closely monitored the female cats for over two years, assessing the treatment’s impact on reproductive hormones, ovarian cycles, and fertility.

While all the control cats produced kittens, none of the cats treated with the gene therapy became pregnant. Suppressing ovarian follicle development and ovulation did not affect crucial hormones such as estrogen. No adverse effects were observed in any of the treated female cats, indicating that, at the tested doses, the gene therapy proved safe and well tolerated.

“The treatment maintained high AMH levels for over two years, and we are confident that these contraceptive levels will persist in the animals for an extended period,” said veterinarian Philippe Godin, DVM, PhD, co-author and research fellow at MGH. However, he emphasized the need for additional studies involving a larger number of cats to confirm these promising findings.

The collaborative research team consists of investigators from MGH, the Center for Conservation and Research of Endangered Wildlife at the Cincinnati Zoo and Botanical Garden, and the Horae Gene Therapy Center at the University of Massachusetts Medical School. Their work received substantial funding from The Michelson Found Animals Foundation, which is offering a $25-million prize to scientists working on developing a single-treatment nonsurgical sterilization method for cats and dogs. The foundation also provides grant funding to support research aimed at finding a practical solution meeting all the prize criteria.

“A non-surgical sterilant for community and companion animals is long overdue and will transform animal welfare,” commented Gary K. Michelson, MD, founder and co-chair of Michelson Philanthropies and the Michelson Found Animals Foundation. “This breakthrough discovery is a major milestone in our quest to provide pet owners with an alternative to surgical spay and neuter.”

Acknowledging that the infrastructure required to produce enough doses for sterilizing millions of cats through gene therapy is not yet in place, Pépin remarked, “This technology may be a little ahead of its time.” Nevertheless, he expressed hope that as the manufacturing capability for producing viral vectors increases with the growing prevalence of gene therapy in humans, delivering this contraceptive solution in the field to control unowned outdoor cat populations will become feasible.

Reference: “Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene” published on June 6, 2023, in Nature Communications. DOI: 10.1038/s41467-023-38721-0

The Michelson Prize & Grants, a program of The Michelson Found Animals Foundation co-chaired by Dr. Gary K. Michelson and Alya Michelson, the Joanie Bernard Foundation, and the department of Surgery of the Massachusetts General Hospital provided significant funding for this research. Co-authors of the study include Lindsey M. Vansandt, Marie-Charlotte Meinsohn, Guangping Gao, Dan Wang, and William F. Swanson.

Frequently Asked Questions (FAQs) about Gene Therapy for Cats

More about Gene Therapy for Cats

• Nature Communications: “Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene” (DOI: 10.1038/s41467-023-38721-0) – Link to article
• The Michelson Found Animals Foundation – Website
• Massachusetts General Hospital – Website
• Mass General Brigham – Website
• Cincinnati Zoo and Botanical Garden, Center for Conservation and Research of Endangered Wildlife – Website
• Horae Gene Therapy Center, University of Massachusetts Medical School – Website