A review of the underlying genetics and emerging therapies for canine cardiomyopathies |
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| Institution: | 1. Program for Applied Research and Development in Genomic Medicine, College of Pharmacy, University of Florida, 1225 Center Drive, Gainesville, FL, 32610, USA;2. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, PO Box 100136, Gainesville, FL, 32610, USA;3. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA;4. Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, 1333 Center Dr, Gainesville, FL, 32603, USA;5. Department of Neurology, College of Medicine, University of Minnesota, 516 Delaware Street SE, Minneapolis, MN, 55455, USA;1. Department of Veterinary Medical Sciences, Alma Mater Studiorum – University of Bologna, via Tolara di Sopra 50, 40064, Ozzano dell''Emilia, Italy;2. Freelance Veterinary Cardiologist, Bologna, Italy;3. Clinica Veterinaria Sasso Marconi, viale Verde 7, 40037, Sasso Marconi, Italy;4. Clinica Veterinaria San Sebastiano, via Boari 22, 04026, Minturno, Italy;5. Department of Veterinary Sciences, University of Parma, Strada del Taglio 10, 43126 Parma, Italy;1. Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 204 Duck Pond Drive, Blacksburg, VA 24061-0442, USA;2. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA;3. Department of Veterinary Sciences, University of Parma, Strada del Taglio 10, 43126 PR, Italy;4. Department of Clinical Science, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Science, Box 7054, Uppsala, Sweden;5. CVCA Cardiac Care for Pets, 1209 Cromwell Bridge Road, Towson, MD 21286, USA;6. CVCA Cardiac Care for Pets, 165 Fort Evans Road NE, Leesburg, VA 20176, USA;2. Department of Veterinary Sciences, University of Parma, Strada del Taglio, 10, 43126, Parma, Italy;1. Anicura Albano Animal Hospital, Rinkebyvägen 21, Danderyd, Sweden;2. Department of Clinical Sciences Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden |
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| Abstract: | Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications. |
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| Keywords: | Dilated cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy Gene therapy Gene editing Clustered regularly interspaced short palindromic repeats |
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