Aficamten治疗梗阻性肥厚型心肌病的研究进展

    Aficamten in the treatment of obstructive hypertrophic cardiomyopathy

    • 摘要: 梗阻性肥厚型心肌病(obstructive hypertrophic cardiomyopathy,oHCM)是临床较为多见的遗传性心肌病,现代医学研究认为其主要病因是心肌肌小节蛋白的编码基因发生变异,目前的常规药物治疗只能缓解患者症状,无法从分子层面解决疾病问题。心肌肌球蛋白抑制剂的出现为oHCM患者治疗带来了新的选择。与第一代肌球蛋白抑制剂Mavacamten相比,第二代药物Aficamten通过与心肌肌球蛋白的特异性变构位点结合,从而抑制心肌的过度收缩,改善患者左心室流出道梗阻,减轻临床症状。本文就oHCM的发生机制、Aficamten的作用机制及临床研究进展进行综述。

       

      Abstract: Obstructive hypertrophic cardiomyopathy (oHCM) is an inherited heart disease primarily caused by mutations in the gene that encodes myosin. Conventional pharmacological interventions focus on symptom relief rather than addressing the underlying pathophysiological mechanisms. In recent years, the development of cardiac myosin inhibitors has introduced a new therapeutic approach for managing oHCM. In comparison to Mavacamten, Aficamten, a second-generation myosin inhibitor, specifically binds to a distinct site on cardiac myosin, thereby inhibiting excessive myocardial contraction. This in turn alleviates left ventricular outflow tract obstruction and reduces clinical symptoms. This article reviews the mechanism of oHCM, the action mechanism of Aficamten, and the progress in clinical research on Aficamten.

       

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