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Gene Therapy for Canine Heart Failure

Researchers at the Wyss Institute and Harvard Medical School are developing a novel cardio-protective gene therapy to stop the progression of heart failure in dogs. As part of the technical development, the Wyss Institute is planning to launch a study in dogs with Mitral Valve Disease (MVD).

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Gene Therapy for Canine Heart Failure
Photo of a Cavalier King Charles Spaniel. Credit: Morrison Media/Shutterstock

Frequently Asked Questions:

What is MVD?

The Mitral Valve is a one-way valve that separates two chambers in the heart and prevents retrograde flow into the upstream chamber. Over time the Mitral Valve may degenerate, prolapse, and allow backflow of blood in the left atrium, a condition called Mitral Valve Disease, which leads to increased left atrial volume and congestive heart failure.

How would the therapy under development work?

The new therapy currently under development is a gene therapy similar to others being developed and nearing approval in humans. It does not edit or change any genetic material in animals but rather introduces a new piece of DNA into the dog’s cells that leads to the production of a beneficial protein with the potential to stop the progression of MVD. This is done by halting the build-up of scar tissue in the heart, which is correlated with the progression of heart failure. This newly introduced piece of DNA is not passed on to the next generation, and is not transmissible between dogs.

What have we shown so far?

We have demonstrated the ability of this new approach to stop the progression of heart failure in mice. After receiving our treatment, mice with heart failure had cardiac measurements that are similar to those of normal mice and exhibited 85% less scar tissue in their hearts compared with mice that received a mock therapy (unpublished data). We have also recently launched a safety study in lab dogs and have seen that the therapy by itself produces no adverse side effects thus far.

Are you editing the genome or using CRISPR?

No, we are not editing the genome nor using CRISPR. We are using an older and more proven technology that leaves the animals’ genetic material untouched and intact. The therapeutic effects of our approach are achieved by supplying extra pieces of DNA that remain separate from the animals’ original genome and produce a potentially beneficial protein for combatting heart failure.

What dog breeds and diseases could this treatment be relevant for?

We are planning to test our new therapy in dogs with MVD across all breeds. Since the treatment works to suppress fibrotic processes, we believe it could be applied to other heart diseases such as Dilated Cardiomyopathy (DCM) in the future. DCM is a condition characterized by a primary thinning of chamber walls and subsequent weakness of the cardiac muscle that eventually leads to congestive heart failure, and/or sudden death in affected dogs.

How does this affect breeding programs? Will this mask dogs that have heart failure and allow them to continue to breed? Shouldn’t we just try to breed MVD out of the dog population?

While breeding MVD out of the dog population may be worthwhile, efforts to date have been unsuccessful for a number of reasons. For example, MVD symptoms often do not present until later in life after the start of breeding, and genetic tests have yet to identify a single gene or specific combination of genes that can accurately predict MVD or identify a predisposition for MVD. In the meantime, we are doing our best to create a treatment that may extend and improve the quality of life for the dogs we love.

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