908: Serotonin Type 2A Receptor Antagonist Therapy for Preventing the Progression of Myxomatous Mitral Valve Disease

Grant Status: Closed

Grant Amount: $62,424.27
Dr. Mark A. Oyama, DVM, University of Pennsylvania
January 1, 2008 - January 31, 2012
Sponsor(s): Chinook Health Fund
Breed(s): -All Dogs
Research Program Area: Treatment

Abstract

Background: Canine myoxmatous mitral valve disease is very common in older dogs and is similar to the human disorder. Serotonin (5HT) related mechanisms has been found in the certain forms of human heart valve disease, and a beginning study by the investigators has shown heightened 5HT signaling in diseased canine mitral valve interstitial cells (MVIC). Objective: The researchers are investigating the hypothesis that 5HT signaling contributes to the progression of canine myxomatous mitral valve disease. The reseachers seek to 1) further characterize the 5HT signaling pathway in normal and diseased human and canine mitral valve specimens, 2) determine the effects of 5HT-2A receptor antagonism in diseased canine MVIC, 3) perform a dose escalation (Phase I) study of a candidate 5HTR-2A receptor antagonist, ketanserin, in client-owned dogs with myxomatous mitral valve disease, and 4) perform a controlled comparison (Phase II) study in dogs using ketanserin. Ultrasound studies and measurement of neurohormonal markers will assess effects of therapy on progression of mitral valve disease. This study represents a novel translational study that targets a potential underlying pathogenesis of canine mitral valve disease.

Publication(s)

- Oyama, Ma and Levy, Rj (2010) Insights into Serotonin Signaling Mechanisms Associated with Canine Degenerative Mitral Valve Disease. Journal of Veterinary Internal Medicine. 24, 27-36. http://dx.doi.org/10.1111/j.1939-1676.2009.0411.x

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