PDF(Pubmed)
Abstract：
The myosin inhibitor mavacamten has transformed the management of obstructive hypertrophic cardiomyopathy (HCM) by targeting myosin ATPase activity to mitigate cardiac hypercontractility. This therapeutic mechanism has proven effective for patients with HCM independent of having a primary gene mutation in myosin. In this issue of the JCI, Buvoli et al. report that muscle hypercontractility is a mechanism of pathogenesis underlying muscle dysfunction in Laing distal myopathy, a disorder characterized by mutations altering the rod domain of β myosin heavy chain. The authors performed detailed physiological, molecular, and biomechanical analyses and demonstrated that myosin ATPase inhibition can correct a large extent of muscle abnormalities. The findings offer a therapeutic avenue for Laing distal myopathy and potentially other myopathies. This Commentary underscores the importance of reevaluating myosin activity\'s role across myopathies in general for the potential development of targeted myosin inhibitors to treat skeletal muscle disorders.
摘要：
肌球蛋白抑制剂mavacamten通过靶向肌球蛋白ATPase活性来减轻心脏收缩过度，从而改变了阻塞性肥厚型心肌病（HCM）的治疗。这种治疗机制已被证明对患有HCM的患者有效，而与肌球蛋白中的原发性基因突变无关。在本期JCI中，Buvoli等人。报告说，肌肉过度收缩是Laing远端肌病的潜在肌肉功能障碍的发病机制，一种以改变β肌球蛋白重链杆区的突变为特征的疾病。作者进行了详细的生理，分子，和生物力学分析，并证明肌球蛋白ATPase抑制可以在很大程度上纠正肌肉异常。这些发现为Laing远端肌病和其他潜在的肌病提供了治疗途径。该评论强调了重新评估肌球蛋白活性在整个肌病中的作用对于靶向肌球蛋白抑制剂治疗骨骼肌疾病的潜在发展的重要性。
