We are developing a novel cardio-protective gene therapy to stop the progression of heart failure in dogs. As a part of the technical development, we will launch a study in dogs with Mitral Valve Disease (MVD) in the fall of 2019. This study will provide valuable information that will aid our effort to address MVD.
We are excited to be working with the American Cavalier King Charles Spaniel Club (ACKCSC) and proud to be sponsored by the ACKCSC Charitable trust.
What is MVD?
Mitral Valve Disease (MVD) is caused by a malfunction of the Mitral Valve. 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 or prolapse, allowing a back-flow of blood into the left atrium. The consequences are an increase in left atrial volume, congestive heart failure and eventually death.
How would our therapy work?
Our therapy is a gene therapy similar to others that have been approved for use in humans. It does not edit or change any genetic material in animals. Instead, it introduces a new piece of DNA into the dog’s cells, which then produces 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 connected 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 you seen so far?
Our approach has demonstrated the ability 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normal mice and exhibited up to 85% less scar tissue in their hearts, compared with mice that received a mock therapy (unpublished data). We launched a safety study in dogs and have seen that the therapy produces no adverse side effects.
Are you editing the genome or using CRISPR?
No, we are not editing the genome, nor are we 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 produces a beneficial protein for combating heart failure.
For which dog breeds and diseases could this treatment be relevant?
We will test our new therapy in dogs with MVD across all breeds, but are starting with a trial in Cavalier King Charles Spaniels. 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. DCM 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 is 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. Genetic tests have yet to identify a single gene (or specific combination of genes) that can accurately predict, 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 that we love.