03101-A: Enhancing Autophagy to Control Canine Myxomatous Mitral Valve Disease

Grant Status: Open

Grant Amount: $16,200
Brendan M. Corcoran, MVB, PhD; The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh
January 1, 2023 - June 30, 2024

Sponsor(s):

Breed(s): Cavalier King Charles Spaniel
Research Program Area: Cardiology
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Abstract

Development of novel treatments to control degenerative diseases requires understanding of their molecular biology. Myxomatous mitral valve disease (MMVD) is one such disease, is the most important chronic degenerative cardiovascular disease of the dog, with no treatments to prevent, control or reverse valve pathology. In our laboratory we have shown important changes in the mechanisms controlling cell persistence in diseased valves likely contributes to valve degeneration over many years. We have confirmed that the diseased valve interstitial cells (VICs) enter what known as a senescent staff and the mechanism that  normally prevent this from happening are blunted or not functioning. We have also fond that by enhancing  a mechanism called autophagy we can overcome senescence and transition diseased VICs back to a normal healthy state. These data suggest suggest that autophagy is a key regulator of MMVD and a is a promising potential therapeutic target to treat MMVD in dogs. Interestingly there are a variety of readily available flavonoid products (found in foodstuffs) that can enhance autophagy. In this project we plan to examine the efficacy of these products and other pharmacological agents using our well established cell culture system, validated measures and complex molecular analysis techniques. This study aims to clarify the contribution of the autophagy pathway to development of MMVD and contribute data to inform potential future clinical trials or development of future treatments, that may even be in the form of dietary supplements.

Publication(s)

None at this time.

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