TY - JOUR
T1 - A review of the underlying genetics and emerging therapies for canine cardiomyopathies
AU - Shen, L.
AU - Estrada, A. H.
AU - Meurs, K. M.
AU - Sleeper, M.
AU - Vulpe, C.
AU - Martyniuk, C. J.
AU - Pacak, C. A.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Arrhythmogenic right ventricular cardiomyopathy
KW - Clustered regularly interspaced short palindromic repeats
KW - Dilated cardiomyopathy
KW - Gene editing
KW - Gene therapy
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U2 - 10.1016/j.jvc.2021.05.003
DO - 10.1016/j.jvc.2021.05.003
M3 - Review article
C2 - 34147413
AN - SCOPUS:85110055766
SN - 1760-2734
VL - 40
SP - 2
EP - 14
JO - Journal of Veterinary Cardiology
JF - Journal of Veterinary Cardiology
ER -