Hypertrophic cardiomyopathy (HCM) is a complicated, heterogeneous genetic condition that causes left ventricular hypertrophy, fibrosis, hypercontractility, and decreased compliance. Despite the advances made over the past 3 decades in understanding the molecular and cellular mechanisms aggravating HCM, the relationship between pathophysiological stress stimuli and distinctive myocyte growth profiles is still imprecise. Currently, mavacamten, a selective and reversible inhibitor of cardiac myosin ATPase, is the only drug approved by the US FDA for the treatment of HCM. Thus, there is an unmet need for developing novel disease-specific therapeutic approaches. This article provides an overview of emerging therapeutic targets for the treatment of HCM based on various molecular pathways and novel developments that are hopefully soon to enter the clinical study. These newly discovered targets include the dual specificity tyrosine-phosphorylation-regulated kinase 1B, the absence of the melanoma 1 inflammasome, the leucine-rich repeat kinase 2 enzyme, and the cluster of differentiation 147.

Graphical Abstract

中文翻译：

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肥厚型心肌病的新治疗途径

肥厚型心肌病 (HCM) 是一种复杂的异质遗传性疾病，可导致左心室肥厚、纤维化、收缩过度和顺应性降低。尽管过去 30 年在理解 HCM 加重的分子和细胞机制方面取得了进展，但病理生理应激刺激与独特的心肌细胞生长特征之间的关系仍然不精确。目前，mavacamten是一种选择性、可逆的心肌肌球蛋白ATP酶抑制剂，是美国FDA唯一批准用于治疗HCM的药物。因此，开发新的疾病特异性治疗方法的需求尚未得到满足。本文概述了基于各种分子途径和新进展的 HCM 治疗新兴治疗靶点，这些靶点有望很快进入临床研究。这些新发现的靶标包括双重特异性酪氨酸磷酸化调节激酶 1B、黑色素瘤 1 炎性体的缺失、富含亮氨酸的重复激酶 2 酶和分化簇 147。

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