PDF(Pubmed)
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.
摘要：
心肌病如扩张型心肌病和致心律失常性右心室心肌病在大型犬中很常见，并且预后总体较差。研究表明，这些疾病具有强烈的品种偏好，和选择性育种历来被建议降低受影响品种的疾病患病率。这些疾病的治疗通常是姑息性的，旨在减缓疾病进展并在心力衰竭发展时控制心力衰竭的临床症状。发现心肌病的特定基因突变，如Boxer致心律失常性右心室心肌病中的纹状体蛋白突变和DobermanPinschers中的丙酮酸脱氢酶激酶4和肌动蛋白突变，加强了我们筛选和选择性繁殖个体的能力，试图生产不受影响的后代。这些疾病相关突变的发现也为基因治疗的发展开辟了道路,包括基因转移和基因组编辑方法。这篇综述文章讨论了狗心肌病的已知遗传学，回顾了现有的基因治疗策略及其在犬中的发展状况，并讨论了这些技术在治疗心脏病的临床转化中的持续挑战。虽然使用这些新兴技术仍然存在挑战，基因治疗领域的指数增长为未来的临床应用带来了巨大的希望。
