01982: Personalized Medicine: The Intersection of Genotype and Drug Responsiveness in the Treatment of Canine Pulmonary Hypertension

Grant Status: Closed

Grant Amount: $27,971
Joshua A Stern, DVM; University of California, Davis
January 1, 2014 - December 31, 2016

Sponsor(s): American Bullmastiff Association

Breed(s): -All Dogs
Research Program Area: Cardiology
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Abstract

Genetic background is thought to alter the way animals and humans respond to disease and drug therapy. The unique DNA signature of an individual is now recognized as a pivotal influence on disease outcome during treatment and has become the central concept propelling the study of pharmacogenomics and individualized medicine. Dr. Stern will apply this cutting-edge knowledge to pulmonary hypertension in dogs, a common disease with serious consequences including exercise intolerance, respiratory distress, and sudden death. Dr. Stern has identified a mutation in the gene phosphodiesterase 5A (PDE5A), the target of a drug called sildenafil, and believes this mutation may influence responsiveness of dogs to the drug. Dr. Stern will evaluate the responsiveness of dogs to sildenafil through pre- and post- echocardiogram, identification of biological markers of disease, and quality of life questionnaires. Differences between treatment responses will be compared to genotype. He aims to establish a diagnostic test that allows clinicians to make treatment recommendations on a personalized basis and tailor the therapeutic approach to treatment of pulmonary hypertension.

Publication(s)

Visser, L. C., Wood, J. E., & Johnson, L. R. (2020). Survival characteristics and prognostic importance of echocardiographic measurements of right heart size and function in dogs with pulmonary hypertension. Journal of Veterinary Internal Medicine. https://doi.org/10.1111/jvim.15826

Visser, L. C., Im, M. K., Johnson, L. R., & Stern, J. A. (2016). Diagnostic Value of Right Pulmonary Artery Distensibility Index in Dogs with Pulmonary Hypertension: Comparison with Doppler Echocardiographic Estimates of Pulmonary Arterial Pressure. Journal of Veterinary Internal Medicine, 30(2), 543–552. https://doi.org/10.1111/jvim.13911

Ueda, Y., Johnson, L. R., Ontiveros, E. S., Visser, L. C., Gunther-Harrington, C. T., & Stern, J. A. (2019). Effect of a phosphodiesterase-5A ( PDE5A ) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension. Scientific Reports, 9(1), 6899. https://doi.org/10.1038/s41598-019-43318-z

Johnson, L. R., & Stern, J. A. (2019). Clinical features and outcome in 25 dogs with respiratory-associated pulmonary hypertension treated with sildenafil. Journal of Veterinary Internal Medicine. https://doi.org/10.1111/jvim.15679

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