MSGID: 1:317/3 648007fd   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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.   
      
      
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   FULL STORY   
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   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   
      
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   Story Source: Materials provided by Massachusetts_General_Hospital. Note:   
   Content may be edited for style and length.   
      
      
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   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   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230606111636.htm   
      
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