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Last month, an article was published in Nature Communications by a team of scientists from the Cincinnati Zoo and Botanical Garden, the Horae Gene Therapy Center, and Massachusetts General Hospital [7-9]. They tested a gene therapy injection as an alternative to spaying and neutering for cat birth control, and the results are exciting.
Why do we need cat birth control?
80% of the estimated 600 million domestic cats in the world are strays or feral [4, 9]. Cat overpopulation leads to more disease and greater loss of birds and other small animals from predation [2-6]. Animal shelters become overrun with homeless kittens and cats, and many are ultimately killed. Cats reproduce very quickly, so it doesn’t take long for a few to become a serious overpopulation issue. The only method of sterilization currently available is spay/neuter surgery. It is effective and permanent, but there are drawbacks.
Surgical sterilization has to be performed by a veterinarian at a surgical clinic [2]. It’s an invasive procedure for females, and both sexes are supposed to have a recovery period, including medication [2]. It’s also expensive [2, 6]. Those resources are in short supply, even more so in developing countries [1, 2, 6]. Thus, there has been interest in non-surgical cat contraception for years. Previous attempts have included vaccines targeting the pituitary gland, toxins targeting reproductive cells, and RNA-silencing drugs to shut down the genetic mechanism of conception [1, 3, 5]. All were either ineffective or unsafe [3, 5].
The Alliance for Contraception in Cats and Dogs (ACC&D) was founded in 2000 with the goal of finding a one-time, permanent, non-surgical contraceptive that would help to curb the overpopulation of homeless cats and dogs [1, 5]. ACC&D wasn’t involved in this study, but ACC&D President Joyce Briggs said, “This research is a huge leap—we’re really excited about it” [1, 5]. She also noted that the lead author, Dr. Lindsey Vansandt, is someone they have worked with before on a contraceptive vaccine called GonaCon [1].
The organization that provided the primary funding for the Vansandt research team has a similar goal. The Michelson Found Animals Foundation was founded in 2009 by inventor Gary Michelson [1, 2, 5]. Its goal is also a single-use, permanent, non-surgical dog and cat birth control, although specifically as a marketable product [1, 2]. Toward this end, the Michelson Found Animals Foundation created the Michelson Prize, $50 million (USD) in research funding plus $25 million if successful [1, 2, 5, 7]. So far, they have given out 41 grants [1, 5].
David Grimm, a journalist for Science, explained that it can be very difficult to get funding for this kind of research; most of the money goes toward studying the human body. So the Michelson Prize grants have been a huge boost to searching for a better companion animal contraceptive. [2]
The Experiment
Dr. David Pepin didn’t have his eyes on the Michelson Prize at first, however. Pepin was looking for ways to help women with ovarian cancer preserve their fertility [6-8]. He was studying anti-Müllerian hormone (AMH), sometimes called Müllerian inhibiting hormone (MIS), which made by the ovarian follicles of female mammals [1, 2, 4-8]. An ovarian follicle is a layer of cells around an egg that nourish the egg as it grows and matures.
Pepin was trying to learn more about what AMH does, so he injected an extra copy of the AMH gene into female mice [2, 4, 5]. This technique, sometimes called gene therapy, does not change the native DNA. It adds new, free-floating pieces of DNA into the cells, complete with all the information the cells need to read the “instructions” on the new piece of DNA. Gene therapy has been used to treat genetic diseases in humans, hence the name, but in this case Pepin was using the same procedure for research purposes to see how the mice would respond to high levels of AMH. He was surprised when the mice’s ovaries shrank, stopped producing eggs, and became infertile [1, 2, 4-6].
“We thought, well, this is a very interesting tool, but what can we use it for?” Pepin said [4]. He decided to submit an application for a Michelson Prize grant, and Bill Swanson, Director of Animal Research at the Cincinnati Zoo, happened to review it [1, 2, 4, 5]. Swanson had actually been working on an opposite project, trying to increase breeding in captive big cats [2, 5]. However, the Cincinnati Zoo maintains a research colony of domestic cats, and Swanson thought Pepin’s proposal was a great idea, so a partnership was struck [2, 4, 5].
The study was small, with three groups of only three she-cats each [3-5, 7, 9]. The nine cats were all named after former first ladies: Michelle, Betty, Abigail, Nancy, Dolly, Barbara, Rosalyn, Jacque and Mary [4]. The domestic cat gene for AMH was constructed into a piece of DNA that the cats’ cells could read, and then that piece of DNA, named fcMISv2, was taken up by the harmless AAV9 virus [9]. Viruses are used in gene therapy because they naturally have the ability to insert genetic material into cells. Three cats served as a control group and were injected in the thigh muscle with AAV9 viruses that were empty, no DNA to inject [3, 7, 9]. Three cats were injected with a lower dose of viruses carrying the gene, and the other three received a higher dose [3, 7-9].
The experimental cats’ muscle cells successfully incorporated the fcMISv2 DNA and began to make AMH [9]. According to Pepin, “A single injection of the gene therapy vector causes the cat’s muscles to produce AMH, which is normally only produced in the ovaries, and raises the overall level of AMH about 100 times higher than normal” [7, 8]. Although their AMH levels increased, only progesterone decreased in response [5, 9]. Their other hormone levels remained the same, their hormone cycles were unaffected, and they showed no signs of adverse side effects [2, 3, 5, 7-9].
During two mating trials, two different toms were each introduced to the nine she-cats for four months at a time [3, 5, 7, 9]. All of the cats in the control group mated, became pregnant, and gave birth to kittens [3, 5, 7-9]. Only two of the cats who received gene therapy even allowed the toms to mate, and none of them ever became pregnant or had kittens [3, 5-9]. At the end of the two-year study, they were maintaining steady, elevated AMH levels, and the scientists are cautiously optimistic that this method may be a permanent contraceptive [5, 7-9].
What happens next?
It remains unclear exactly how AMH functions as kitty birth control [1, 2, 5, 9]. The researchers believe that the elevated levels of AMH prevent she-cats’ follicles from developing and thereby prevent ovulation [2-5, 9]. However, more research is needed to understand exactly how AMH works, and to answer lingering questions.
For instance, is this sterilization truly permanent [1, 2, 6]? The scientists who authored the study believe it is, but they only tested those cats for two years, so no one can say for sure yet that it doesn’t eventually wear off. Are there any negative side effects that they didn’t catch in such a small study [6]? Could AMH work for dogs, too [1, 2, 5, 6]? That is an important goal of this kind of research, not to mention a requirement to win the Michelson Prize [1, 5]. There are also concerns about cost, as that is often what prevents people from spaying and neutering cats now [1, 2]. If a new AMH shot will cost as much or more than surgically sterilizing cats, the convenience of the one-dose injection won’t really matter [1, 2].
Pepin, Swanson, and the Michelson Foundation are already in talks with the Food and Drug Administration about a larger trial and the possibility of bringing an AMH drug to market [2, 5, 6], so keep your ear to the ground. In the meantime, GonaCon, the cat birth control vaccine that study author Lindsey Vansandt worked on with ACC&D, has shown promise as well and may actually be closer to becoming available [1]. Either way, this area of study appears to be accelerating, and there may be more exciting news to come in the next few years.
As for the cats from the study, they were all put up for adoption after the research concluded [4]. This is something the Cincinnati Zoo does with their research participants–Bill Swanson already has three cats he adopted from previous studies [4]. I couldn’t find out if all nine have been adopted yet, so if you live in the Cincinnati area and are looking for a new feline friend, email [email protected]. The cats’ new owners are asked to bring them back to the zoo for a yearly check-up to monitor their hormone levels and make sure there haven’t been any side effects [4].
References
- Clifton, Merritt. (2023, June 8). No, the wait for a single-shot chemosterilant for cats has not ended. Animals 24-7. https://www.animals24-7.org/2023/06/08/no-the-wait-for-a-single-shot-chemosterilant-for-cats-has-not-ended/
- Crespi, S. (Producer). (2023, June 8). Contraception for cats, and taking solvents out of chemistry [Audio podcast episode]. In Science Podcast. American Association for the Advancement of Science. https://www.science.org/content/podcast/contraception-cats-and-taking-solvents-out-chemistry
- de Jesús, E. G. (2023, June 6). A gene therapy shot might keep cats from getting pregnant without being spayed. ScienceNews. https://www.sciencenews.org/article/gene-therapy-shot-cats-spay-pregnant
- Golembiewski, K. (2023, June 6). Nonsurgical cat contraception could help curb overpopulation, study says. CNN. https://www.cnn.com/2023/06/06/world/cat-contraceptives-scn/index.html
- Grimm, D. (2023, June 6). Hello kitty, goodbye kittens? Gene therapy spays cats without surgery. Science. doi: 10.1126/science.adj0979
- Katsnelson, A. (2023, June 6). Gene therapy may offer birth control for cats. The New York Times. https://www.nytimes.com/2023/06/06/science/cats-birth-control.html
- Ridings, M. (2023, June 6). Birth control for cats? Harvard Gazette. https://news.harvard.edu/gazette/story/2023/06/birth-control-for-cats-is-effective-but-ahead-of-its-time/
- Today’s Veterinary Business. (2023, June 19). Gene therapy shows promise in feline contraception. https://todaysveterinarybusiness.com/gene-therapy-0623/
- Vansandt, L. M., Meinsohn, M., Godin, P., Nagykery, N., et al. (2023). Durable contraception in the female domestic cat using viral-vectored delivery of a feline anti-Müllerian hormone transgene. Nature Communications, 14, 3140. https://doi.org/10.1038/s41467-023-38721-0
Published July 9th, 2023
