Dr. John V. Ioia, MD, PhD

Mitral Valve Disease or more appropriately Myxomatous Mitral Valve disease is the most common acquired heart disease in small dog breeds, can also affect larger dogs and is the primary cause of a new murmur in an older pet.  When speaking with Cavalier owners, breeders and veterinarians, one would think it is endemic to the breed and the product of the history of the Cavalier’s heritage.  Fortunately, careful breeding programs have improved longevity in the breed and have lessened or prolonged the presentation of the disease.  Still, MVD represents a major health concern for the Cavalier, and a burden to the Cavalier owner in terms of veterinary expense and early demise of many cherished pets.

You can imagine the excitement when several years ago the Board and Officers of the ACKCSC and its Charitable Health Trust met with Cell-Biology and Genetics researchers from Harvard and Tufts University and were informed of a project called Rejuvenate Bio, which might arrest or possibly reverse the process of myxomatous change in the valve leaflets.

The team had identified genes that had the potential to treat heart failure.  The team had also found a way to encapsulate the DNA for delivery to involved animals.  The idea was to administer one injection of the therapy to dogs diagnosed with heart failure.  This is adeno-associated virus (AAV) gene therapy.  The therapy changes protein levels, stopping remodeling in the heart. The dog becomes healthier and happier and requires only one treatment and not daily medication.

The Board and Officers were overjoyed at the presentation and the early results shown in mice and then supported the experimental venture.  This occurred at an ACKCSC Annual meeting and its National Specialty, and the Board elected to open this presentation to its membership.  The acceptance and support by members and regional clubs was simply amazing in terms of emotion and financial committment.

So, let’s review the concepts:

  • The treatment is a gene therapy similar to others that have been approved for use in humans. It introduces an Adeno-viral-like particle.
  • It does not edit or change any genetic material in the animal.
  • It introduces a new piece of DNA into the dog’s cells, which then produces a beneficial protein with the potential to treat this age-related disease.
  • This newly introduced piece of DNA is not passed on to the next generation and is not transmissible between dogs.
  • The use of AAV has been well established in dogs and humans, initially as pre-clinical models and through other work at their labs
  • Dogs have been shown to handle AAV with minimal immune responses in outside experiments which have been confirmed
  • If successful, a dog will require just one treatment, which is meant to last greater than10 years.

Thus far the experiment has been very successful, moving from mice and beagles to the first 12 Cavalier volunteers.  The chosen volunteers were all senior dogs with MVD with murmurs and in a pre-cardiac failure (CHF) condition.  Dogs were followed over a year by auscultation and doppler exams and there have been no adverse events. We were allowed to see one of the Cavaliers, a senior girl who was in Stage 2B as were all the other subjects.  Stage 2B is a precursor to CHF[1].  The change was amazing. Whether Rejuvenate Bio can reverse MVD remains to be seen but it does appear to arrest the process and by so doing seems to improve the cardiac function and the quality of canine life.

The Pilot Program is expanding and is setting up a manufacturing and safety run trial, as well as securing approval to allow marketing through Veterinarians for dogs with MVD to validate their experimental results.  The future is very exciting.

https://www.veterinary-practice.com/article/staging-and-management-of-canine-mitral-valve-disease