针对肥厚表型心肌病发病机制治疗新药研发进展

刘彦博; 田庄; 张抒扬

doi:10.12376/j.issn.2097-0501.2023.01.005

针对肥厚表型心肌病发病机制治疗新药研发进展

doi: 10.12376/j.issn.2097-0501.2023.01.005

刘彦博^{1, 2},
田庄^{1, 2, ,},
张抒扬¹

1.
中国医学科学院北京协和医院心内科，北京 100730
2.
中国医学科学院北京协和医院国际医疗部，北京 100730

基金项目:

中国医学科学院医学与健康科技创新阶段工程 2021-I2M-1-003

详细信息

通信作者:
田庄，E-mail：tianzhuangcn@sina.com

中图分类号: R542.2
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- 被引次数: 0
出版历程
- 收稿日期: 2021-12-28
- 修回日期: 2022-01-05
- 网络出版日期: 2023-03-07

Progress in New Therapies Targeting the Pathogenesis of Cardiomyopathywith Hypertrophic Phenotype

LIU Yanbo^{1, 2},
TIAN Zhuang^{1, 2
, ,},
ZHANG Shuyang¹

1.
Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
2.
Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

Funding:

Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences 2021-I2M-1-003

More Information

Corresponding author: TIAN Zhuang, E-mail: tianzhuangcn@sina.com

摘要

摘要: 肥厚型心肌病(HCM)是一种以心肌肥厚为临床表型特征的心肌病。其病因主要为编码肌小节蛋白基因突变，此外, 其他系统性疾病也会导致心肌病变，主要表现为心肌肥厚，如先天性代谢性疾病(溶酶体贮积病)、系统性淀粉样变[转甲状腺素蛋白淀粉样变(ATTR)]和法布雷病等。既往缺乏针对HCM病因和发病机制的治疗药物。近年来，这些治疗药物问世并取得了良好效果。Mavacamten通过抑制肌球蛋白重链的ATP活性来降低心肌收缩力以改善心肌肥厚，可显著降低患者的左心室流出道(LVOT)压差、心室壁张力和心肌损伤。氯苯唑酸通过抑制转甲状腺素蛋白(TTR)的解离及后续淀粉样物质的生成与沉积，可降低转甲状腺素蛋白心脏淀粉样变(ATTR-CA)患者的死亡率，改善心功能。基因沉默药物、基因编辑技术有效减少异常TTR水平。利用基因重组技术体外合成α半乳糖苷酶A的替代治疗，可有效降低法布雷病心脏受累患者的左心室质量指数(LVMi)、改善心功能、降低心绞痛发作次数及患者死亡率。
- 肥厚型心肌病 /
- 肌球蛋白抑制剂 /
- 氯苯唑酸 /
- 酶替代疗法 /
- 转甲状腺素蛋白心脏淀粉样变
Abstract: Hypertrophic cardiomyopathy (HCM) is cardiomyopathy with a clinical phenotype of cardiac hypertrophy. The etiology includes genetically defective encoding sarcomeres, congenital metabolic diseases such as lysosomal storage diseases, systemic amyloidosis such as transthyretin amyloidosis(ATTR), and Fabry disease. Previous therapies did not target the etiology and pathogenesis and therefore were less effective. In recent years, treatments targeting different mechanisms of myocardial hypertrophy have achieved good results. Mavacamten can reduce myocardial contractility by inhibiting ATP activity, thereby significantly improving left ventricular outflow tract(LVOT) obstruction, cardiac contractility, ventricular tension, and limitting myocardial damage. By inhibiting the dissociation of transthyretin(TTR) and subsequent formation and deposition of the amyloid fibril, tafamidis can reduce the mortality and morbidity of patients with transthyretin cardiac amyloidosis(ATTR-CA). Gene silencing and gene editing technology can reduce abnormal TTR levels. Synthesis of α-galactosidase A by gene recombination technology in vitro can effectively reduce left ventricular mass index(LVMi), improve cardiac function, reduce angina attacks and decrease mortality of Fabry disease.
- hypertrophic cardiomyopathy /
- myosin inhibitor /
- tafamidis /
- enzyme replacement therapy /
- transthyretin cardiac amyloidosis
注释:

作者贡献：刘彦博、田庄负责相关研究资料的收集，以及本文的起草工作; 田庄、张抒扬参与修改文章的关键内容。

利益冲突：所有作者均声明不存在利益冲突。

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参考文献(26)

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