Mavacamten:从机制到临床

Mavacamten:From Mechanism to Clinical Studies

肥厚型心肌病是一种以左心室心肌肥厚为特征的心肌疾病,目前其治疗仍存在巨大未被满足的临床需求。Mavacamten是一种口服的选择性心肌肌球蛋白三磷酸腺苷酶变构抑制剂,是全球首个直接靶向肥厚型心肌病病理生理机制的创新型治疗药物。早期动物实验发现应用Mavacamten可使小鼠心肌收缩力恢复正常,抑制心室壁肥厚进展。临床研究证实Mavacamten能改善运动能力,减轻左心室流出道梗阻,改善心功能和健康状况。美国食品和药物管理局已批准其用于治疗症状性纽约心脏病协会心功能Ⅱ~Ⅲ级的梗阻性肥厚型心肌病成人患者,以改善功能能力和症状。本文对肥厚型心肌病治疗现状、Mavacamten的作用机制和最新临床研究进展进行综述。

Hypertrophic cardiomyopathy(HCM)is a primary myocardial disorder characterized by left ventricular hypertrophy.The current limited treatment leaves a significant unmet need for HCM.Mavacamten is a first-in-class,oral,selective,allosteric inhibitor of cardiac myosin ATPase,which targeted the pathophysiological mechanism of HCM.Early-stage animal studies found that administration of Mavacamten normalized myocardial contractility and suppressed the development of ventricular hypertrophy in mice.Clinical studies demonstrated that treatment of Mavacamten improved exercise capacity,left ventricular outflow tract obstruction,New York Heart Association(NYHA)functional class and health status in patients.U.S.Food and Drug Administration recently approved Mavacamten for the treatment of adults with symptomatic NYHA classⅡ~Ⅲobstructive HCM to improve functional capacity and symptoms.This review aims to summarize the current management of HCM,mechanism and latest clinical studies of Mavacamten.