Gene therapy produces long-term contraception in female domestic cats
The study's findings offer a potential alternative to surgical spaying


Date:
June 6, 2023
Source:
Massachusetts General Hospital
Summary:
Researchers have demonstrated that a single dose of anti-Mu"llerian
hormone (AMH) gene therapy can induce long-term contraception
in the domestic cat, potentially providing a safe and effective
alternative to surgical spaying.


Facebook Twitter Pinterest LinkedIN Email

==========================================================================
FULL STORY ========================================================================== Currently there are no contraceptives capable of producing permanent sterilization in companion animals. Spaying, the surgical removal of the ovaries and uterus, is the most widely used strategy to control unwanted reproduction in female cats.

For the first time, researchers at Massachusetts General Hospital (MGH),
a founding member of Mass General Brigham (MGB), and their collaborators
have demonstrated that a single dose of anti-Mu"llerian hormone (AMH)
gene therapy can induce long-term contraception in the domestic cat, potentially providing a safe and effective alternative to surgical
spaying. The research is published in the latest issue of Nature Communications.

During previous research to evaluate AMH (also known as Mu"llerian
inhibiting substance, or MIS) as a method to protect ovarian reserve in
women undergoing chemotherapy, senior author David Pe'pin, 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." says Patricia K.

Donahoe, MD, a co-author of this study and the Director of Pediatric
Surgical Research Laboratories and Chief Emerita of Pediatric Surgical
Services at Massachusetts General Hospital.

In 2017, Pe'pin and his collaborators were the first to publish the contraceptive potential of AMH in rodents.

The team then turned their attention to felines. To raise AMH levels in
female domestic cats, the researchers created an adeno-associated viral
(AAV) gene therapy vector with a slightly altered version of the feline
AMH gene. Human therapies using similar AAV vectors to deliver various therapeutic genes have proven to be safe and effective and have been
approved by the FDA.

"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," says Pe'pin.

The researchers treated six female cats with the gene therapy at two
different doses, and three cats served as controls. A male cat was
brought into the female colony for two four-month-long mating trials. The researchers followed the female cats for more than two years, assessing
the effect of the treatment on reproductive hormones, ovarian cycles,
and fertility.

All the control cats produced kittens, but none of the cats treated with
the gene therapy got pregnant. Suppressing ovarian follicle development
and ovulation did not affect important hormones such as estrogen. There
were no adverse effects observed in any of the treated female cats, demonstrating that at the doses tested, the gene therapy was safe and
well tolerated.

"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," says veterinarian Philippe Godin, DVM, PhD,
co-author and research fellow at MGH. Additional studies in a larger
number of cats are needed to confirm these promising findings, he adds.

The collaborative research team, which includes investigators from MGH,
the Center for Conservation and Research of Endangered Wildlife at the Cincinnati Zoo and Botanical Garden, and at the Horae Gene Therapy
Center at the University of Massachusetts Medical School, received
funding from The Michelson Found Animals Foundation, which is offering a $25-million prize to scientists to develop a single-treatment nonsurgical sterilization method for cats and dogs. The foundation also provides grant funding to support research that could lead to a practical solution that
meets all the prize criteria.

"A non-surgical sterilant for community and companion animals is long
overdue and will transform animal welfare," said 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."
"This technology may be a little ahead of its time," acknowledges Pe'pin, noting that the infrastructure needed to produce enough doses to sterilize millions of cats via gene therapy does not yet exist. "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." Major funding
for this research was provided by theMichelson Prize & Grants, a program
ofThe Michelson Found Animals Foundation, co-chaired by Dr. Gary K.

Michelson and Alya Michelson, theJoanie Bernard Foundation, and
thedepartment of Surgery of the Massachusetts General Hospital.

Co-authors include Lindsey M. Vansandt, Marie-Charlotte Meinsohn,
Guangping Gao, Dan Wang, and William F. Swanson.

* RELATED_TOPICS
o Plants_&_Animals
# Cats # Life_Sciences # Animals # Mating_and_Breeding #
Dogs # Endangered_Animals # CRISPR_Gene_Editing # Cloning
* RELATED_TERMS
o Cat o Cat_flea o Spaying_and_neutering o Gene o Gene_therapy
o Cat_intelligence o Allele o DNA_repair

========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Vansandt, L.M., Meinsohn, MC., Godin, P. et al. Durable
contraception in
the female domestic cat using viral-vectored delivery of a
feline anti- Mu"llerian hormone transgene. Nat Commun, 2023 DOI:
10.1038/s41467-023- 38721-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/06/230606111636.htm

--- up 1 year, 14 weeks, 1 day, 10 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)