A review of the underlying genetics and emerging therapies for canine cardiomyopathies

L. Shen, A. H. Estrada, K. M. Meurs, M. Sleeper, C. Vulpe, C. J. Martyniuk, C. A. Pacak

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
JournalJournal of Veterinary Cardiology
Early online dateMay 21 2021
DOIs
StateE-pub ahead of print - May 21 2021

Bibliographical note

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes of Health (grant number T32 HG008958 ).

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • Arrhythmogenic right ventricular cardiomyopathy
  • Clustered regularly interspaced short palindromic repeats
  • Dilated cardiomyopathy
  • Gene editing
  • Gene therapy

PubMed: MeSH publication types

  • Journal Article
  • Review

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