Cat sterilization using gene therapy could revolutionize animal welfare 

An innovative study has revealed the potential of a non-surgical cat sterilization technique for domestic cats. For the first time, a team of researchers at Massachusetts General Hospital (MGH), part of the Mass General Brigham (MGB) system, have showcased the ability of a single dose of gene therapy to induce long-lasting contraception in cats. 

The findings, published in the journal Nature Communications, could revolutionize animal welfare and provide a viable alternative to surgical spaying.

Until now, controlling unwanted reproduction in female cats was chiefly carried out by spaying, which involves the surgical removal of the ovaries and uterus. Presently, no contraceptives exist that can offer permanent sterilization in pets.

Game-changing discovery for cat population control

The discovery of the contraceptive potential of the anti-Müllerian hormone (AMH) – a hormone naturally produced by ovaries in females and testes in males – paved the way for this breakthrough. Dr. Patricia K. Donahoe, co-author of the study and the director of Pediatric Surgical Research Laboratories at MGH, noted that AMH is a non-steroidal hormone that occurs naturally.

Dr. David Pépin, a senior researcher at MGH and Harvard Medical School, was the first to realize that a surge in AMH could impede the growth of ovarian follicles, thus preventing ovulation and conception. The realization came about while he was researching the use of AMH to protect ovarian reserve in women undergoing chemotherapy.

Following the initial findings, published in 2017, Dr. Pépin and his team applied the AMH research to cats. By creating an adeno-associated viral (AAV) gene therapy vector, they were able to significantly increase AMH levels in domestic cats. This vector carried a modified version of the feline AMH gene. Notably, similar AAV vectors have been approved by the FDA and successfully used in human therapies to deliver therapeutic genes.

How gene therapy works for cat sterilization

“The cat’s muscles start producing AMH following a single injection of the gene therapy vector. This raises the overall AMH level about 100 times higher than usual,” said Dr. Pépin.

The research team put the theory to the test, treating six female cats with two different doses of the gene therapy. They kept three cats as controls and observed them all for over two years. 

During this time, they exposed the female cats to a male for two mating trials, each lasting four months. Throughout the trial period, the researchers closely monitored the cats’ reproductive hormones, ovarian cycles, and fertility.

Research team thrilled with the results

In contrast to the control cats, all of whom produced kittens, none of the cats receiving the gene therapy became pregnant. Remarkably, despite suppressing ovarian follicle development and ovulation, the treatment had no negative impact on essential hormones like estrogen and caused no adverse effects, highlighting its safety and tolerability.

“The treatment maintained high AMH levels for over two years, and we’re confident that those contraceptive levels will be sustained in the animals for much longer,” said study co-author Dr. Philippe Godin. He stressed, however, that further research involving a larger number of cats was necessary to confirm these promising results.

The groundbreaking cat sterilization study was made possible by funding from The Michelson Found Animals Foundation. This foundation is offering a $25-million prize to scientists who develop a non-surgical sterilization method for cats and dogs. 

Dr. Gary K. Michelson, founder of Michelson Philanthropies and the Michelson Found Animals Foundation, commended the team’s breakthrough discovery: “This is a major milestone in our quest to provide pet owners with an alternative to surgical spay and neuter. A non-surgical sterilant for community and companion animals will transform animal welfare.”

The future is now for gene therapy cat sterilization

Dr. Pépin acknowledged that the technology might seem ahead of its time. The infrastructure needed to manufacture enough doses of cat sterilization procedures using gene therapy isn’t yet in place. 

However, the researcher remains optimistic about the possibilities: “Our goal is to show that safe and effective permanent contraception in companion animals can be achieved using gene therapy. And we hope that as the manufacturing capability of producing viral vectors increases with the rise of gene therapy in humans, delivering this contraceptive in the field to control unowned outdoor cat populations will become feasible.”

The innovative research involved a collaborative team 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.

The study marks a monumental leap in the field of animal welfare, offering a potentially transformative alternative to current cat sterilization practices. However, the findings need further research and the development of adequate manufacturing infrastructure for widespread implementation. Regardless, the research indicates a bright and hopeful future for non-surgical contraceptive methods in animal populations.

More about surgical spaying

Spaying is a common veterinary procedure performed for cat sterilization and to sterilize other female pets to prevent them from reproducing. The technical term for this procedure is an ovariohysterectomy. This surgical operation involves the removal of the uterus and ovaries in female animals.

Simplified overview of the process:

Preparation

The pet is typically put under general anesthesia to ensure it doesn’t feel any pain during the surgery. The veterinarian may also conduct a pre-operative examination to check the animal’s overall health and readiness for the procedure.

The operation

The veterinarian makes a small incision, usually on the animal’s abdomen. Through this incision, both ovaries and the uterus are removed.

Recovery

After the operation, the incision is sutured closed. Post-operative care involves keeping the animal comfortable while the surgical wound heals and watching for any signs of complications. The animal may be prescribed pain medication and/or antibiotics, and it may be necessary to limit its physical activity for a while.

Spaying has several benefits beyond preventing unwanted litters of pets. It eliminates the risk of ovarian and uterine diseases, such as pyometra (a potentially life-threatening uterine infection) and ovarian and uterine cancers. Spaying can also reduce the risk of mammary cancer, especially if performed before the pet’s first heat cycle.

Moreover, spaying eliminates the heat cycle, which in some animals can cause behaviors that might be problematic for pet owners, like yowling or trying to escape to find a mate.

Risks

However, as with any surgical procedure, spaying does come with risks, such as complications from anesthesia or the possibility of post-operative infection. Veterinarians usually take precautions to minimize these risks, and for most pets, the benefits of being spayed far outweigh the potential downsides.

The timing of the procedure can vary but is often performed when the pet is several months old. It’s a topic you should discuss with your vet, as the optimal timing can depend on the specific animal and its overall health.

More about gene therapy

Gene therapy is a revolutionary medical approach that uses genes to prevent or treat disease. The concept is based on introducing, removing, or changing genetic material within a person’s cells. As of my knowledge cutoff in September 2021, there are mainly four types of gene therapy:

Replacing a mutated gene 

This approach involves replacing a mutated or defective gene with a healthy copy.

Inactivating or knocking out a mutated gene

If a gene mutation causes a problematic protein to be made, the mutated gene can be turned off so it no longer produces the harmful protein.

Introducing a new gene

A new gene could be introduced into the body to help it fight a particular disease. This strategy is often used for diseases that are not caused by gene mutations, such as certain types of cancer.

Editing genes 

By using tools like CRISPR/Cas9, scientists can edit the genome in a more precise manner, altering the sequence of a specific gene.

Gene therapy is administered through a carrier, or “vector”, often a virus that has been genetically altered to carry human DNA. The most common type of vector used in gene therapy is a virus, because viruses are naturally good at infiltrating cells. 

These vectors are usually viruses that have been genetically altered to carry human DNA. Adeno-associated viruses (AAV) are often used because they do not cause disease.

Gene therapies can be conducted ex vivo (outside the body) where cells are taken from the patient, modified in the lab, and then returned to the patient, or in vivo (inside the body) where the genes are delivered directly into the patient’s cells.

The promising future of gene therapy

Gene therapy holds great promise and has potential to treat a number of diseases such as inherited disorders, some types of cancer, and certain viral infections. Several gene therapies have been approved by regulatory authorities like the US FDA for conditions including certain types of leukemia (Kymriah, Yescarta), spinal muscular atrophy (Zolgensma), and a specific type of inherited blindness (Luxturna).

While gene therapy has immense potential, it also comes with challenges and risks. These include immune reactions, issues with the delivery of the genetic material to the right cells, the possibility of causing a harmful mutation, and issues related to the production and regulatory approval of such treatments. Furthermore, gene therapies are often extremely expensive.

Research in the field of gene therapy is ongoing and could expand the treatment options for many conditions in the future. However, a lot of work still needs to be done to ensure that these therapies are safe, effective, and accessible.

Noteworthy financial backing came from 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. Co-authors of the study include Lindsey M. Vansandt, Marie-Charlotte Meinsohn, Guangping Gao, Dan Wang, and William F. Swanson.

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