Mavacamten特异性治疗肥厚型心肌病的研究进展

杨昭, 杨旭明, 杜来景. Mavacamten特异性治疗肥厚型心肌病的研究进展[J]. 临床心血管病杂志, 2022, 38(4): 267-271. doi: 10.13201/j.issn.1001-1439.2022.04.003
引用本文: 杨昭, 杨旭明, 杜来景. Mavacamten特异性治疗肥厚型心肌病的研究进展[J]. 临床心血管病杂志, 2022, 38(4): 267-271. doi: 10.13201/j.issn.1001-1439.2022.04.003
YANG Zhao, YANG Xuming, DU Laijing. Research progress of Mavacamten in the treatment of hypertrophic cardiomyopathy[J]. J Clin Cardiol, 2022, 38(4): 267-271. doi: 10.13201/j.issn.1001-1439.2022.04.003
Citation: YANG Zhao, YANG Xuming, DU Laijing. Research progress of Mavacamten in the treatment of hypertrophic cardiomyopathy[J]. J Clin Cardiol, 2022, 38(4): 267-271. doi: 10.13201/j.issn.1001-1439.2022.04.003

Mavacamten特异性治疗肥厚型心肌病的研究进展

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Research progress of Mavacamten in the treatment of hypertrophic cardiomyopathy

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  • Mavacamten是一种小分子肌球蛋白抑制剂,在治疗人类肥厚型心肌病(HCM)的潜在药物的筛选中被发现。Mavacamten可逆地抑制肌球蛋白与肌动蛋白的结合,抑制肌节力的产生,降低心肌高收缩性。临床试验也进一步证明其可以降低左心室流出道压力,减轻临床症状。现就Mavacamten的作用机制、临床价值及最新发现作一综述。
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  • [1]

    Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in(Young)Adults[J]. Circulation, 1995, 92(4): 785-789. doi: 10.1161/01.CIR.92.4.785

    [2]

    Semsarian C, Ingles J, Maron MS, et al. New perspectives on the prevalence of hypertrophic cardiomyopathy[J]. J Am Coll Cardiol, 2015, 65(12): 1249-1254. doi: 10.1016/j.jacc.2015.01.019

    [3]

    Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines[J]. Circulation, 2020, 142(25): e558-e631.

    [4]

    Spudich JA. Three perspectives on the molecular basis of hypercontractility caused by hypertrophic cardiomyopathy mutations[J]. Pflugers Arch, 2019, 471(5): 701-717. doi: 10.1007/s00424-019-02259-2

    [5]

    Alsulami K, Marston S. Small Molecules acting on Myofilaments as Treatments for Heart and Skeletal Muscle Diseases[J]. Int J Mol Sci, 2020, 21(24).

    [6]

    Green EM, Wakimoto H, Anderson RL, et al. A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice[J]. Science, 2016, 351(6273): 617-621. doi: 10.1126/science.aad3456

    [7]

    Maron BJ, Maron MS. Hypertrophic cardiomyopathy[J]. Lancet, 2013, 381(9862): 242-255. doi: 10.1016/S0140-6736(12)60397-3

    [8]

    Force T, Bonow RO, Houser SR, et al. Research priorities in hypertrophic cardiomyopathy: report of a Working Group of the National Heart, Lung, and Blood Institute[J]. Circulation, 2010, 122(11): 1130-1133. doi: 10.1161/CIRCULATIONAHA.110.950089

    [9]

    Landstrom AP, Weisleder N, Batalden KB, et al. Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans[J]. J Mol Cell Cardiol, 2007, 42(6): 1026-1035. doi: 10.1016/j.yjmcc.2007.04.006

    [10]

    Ingles J, Doolan A, Chiu C, et al. Compound and double mutations in patients with hypertrophic cardiomyopathy: implications for genetic testing and counselling[J]. J Med Genet, 2005, 42(10): e59. doi: 10.1136/jmg.2005.033886

    [11]

    Girolami F, Ho CY, Semsarian C, et al. Clinical features and outcome of hypertrophic cardiomyopathy associated with triple sarcomere protein gene mutations[J]. J Am Coll Cardiol, 2010, 55(14): 1444-1453. doi: 10.1016/j.jacc.2009.11.062

    [12]

    林丽容, 卢荔红, 胡雪群, 等. 家族性肥厚型心肌病MYBPC3基因变异及其临床表型分析[J]. 临床心血管病杂志, 2021, 37(6): 557-560. https://www.cnki.com.cn/Article/CJFDTOTAL-LCXB202106013.htm

    [13]

    Anderson RL, Trivedi DV, Sarkar SS, et al. Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers[J]. Proc Natl Acad Sci U S A, 2018, 115(35): E8143-E8152.

    [14]

    Spudich JA. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases[J]. Biophys J, 2014, 106(6): 1236-1249. doi: 10.1016/j.bpj.2014.02.011

    [15]

    Lionne C, Brune M, Webb MR, et al. Time resolved measurements show that phosphate release is the rate limiting step on myofibrillar ATPases[J]. FEBS Lett, 1995, 364(1): 59-62. doi: 10.1016/0014-5793(95)00356-E

    [16]

    Toyoshima YY, Kron SJ, McNally EM, et al. Myosin subfragment-1 is sufficient to move actin filaments in vitro[J]. Nature, 1987, 328(6130): 536-539. doi: 10.1038/328536a0

    [17]

    Scellini B, Piroddi N, Dente M, et al. Mavacamten has a differential impact on force generation in myofibrils from rabbit psoas and human cardiac muscle[J]. J Gen Physiol, 2021, 153(7).

    [18]

    Nag S, Trivedi DV. To lie or not to lie: Super-relaxing with myosins[J]. Elife, 2021, 10: e63703. doi: 10.7554/eLife.63703

    [19]

    Nelson SR, Li A, Beck-Previs S, et al. Imaging ATP Consumption in Resting Skeletal Muscle: One Molecule at a Time[J]. Biophys J, 2020, 119(6): 1050-1055. doi: 10.1016/j.bpj.2020.07.036

    [20]

    Mamidi R, Li J, Doh CY, et al. Impact of the Myosin Modulator Mavacamten on Force Generation and Cross-Bridge Behavior in a Murine Model of Hypercontractility[J]. J Am Heart Assoc, 2018, 7(17): e009627. doi: 10.1161/JAHA.118.009627

    [21]

    Awinda PO, Bishaw Y, Watanabe M, et al. Effects of mavacamten on Ca2+ sensitivity of contraction as sarcomere length varied in human myocardium[J]. Br J Pharmacol, 2020, 177(24): 5609-5621. doi: 10.1111/bph.15271

    [22]

    Awinda PO, Watanabe M, Bishaw Y, et al. Mavacamten decreases maximal force and Ca2+ sensitivity in the N47K-myosin regulatory light chain mouse model of hypertrophic cardiomyopathy[J]. Am J Physiol Heart Circ Physiol, 2021, 320(2): H881-H890. doi: 10.1152/ajpheart.00345.2020

    [23]

    Sparrow AJ, Sievert K, Patel S, et al. Measurement of Myofilament-Localized Calcium Dynamics in Adult Cardiomyocytes and the Effect of Hypertrophic Cardiomyopathy Mutations[J]. Circ Res, 2019, 124(8): 1228-1239. doi: 10.1161/CIRCRESAHA.118.314600

    [24]

    Grillo MP, Erve J, Dick R, et al. In vitro and in vivo pharmacokinetic characterization of mavacamten, a first-in-class small molecule allosteric modulator of beta cardiac myosin[J]. Xenobiotica, 2019, 49(6): 718-733. doi: 10.1080/00498254.2018.1495856

    [25]

    Stern JA, Markova S, Ueda Y, et al. A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy[J]. PLoS One, 2016, 11(12): e0168407. doi: 10.1371/journal.pone.0168407

    [26]

    Heitner SB, Jacoby D, Lester SJ, et al. Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial[J]. Ann Intern Med, 2019, 170(11): 741-748. doi: 10.7326/M18-3016

    [27]

    Ho CY, Mealiffe ME, Bach RG, et al. Evaluation of mavacamten in symptomatic patients with nonobstructive hypertrophic cardiomyopathy[J]. J Am Coll Cardiol, 2020, 75(21): 2649-2660. doi: 10.1016/j.jacc.2020.03.064

    [28]

    Heitner SB, Jacoby D, Lester SJ, et al. Mavacamten treatment for obstructive hypertrophic cardiomyopathy: A clinical trial[J]. Ann Intern Med, 2019, 170(11): 741-748. doi: 10.7326/M18-3016

    [29]

    Geske JB, McKie PM, Ommen SR, et al. B-type natriuretic peptide and survival in hypertrophic cardiomyopathy[J]. J Am Coll Cardiol, 2013, 61(24): 2456-2460. doi: 10.1016/j.jacc.2013.04.004

    [30]

    Seydelmann N, Liu D, Krämer J, et al. High-sensitivity troponin: A clinical blood biomarker for staging cardiomyopathy in Fabry disease[J]. J Am Heart Assoc, 2016, 5(6).

    [31]

    Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy(EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2020, 396(10253): 759-769. doi: 10.1016/S0140-6736(20)31792-X

    [32]

    Saberi S, Cardim N, Yamani M, et al. Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM Cardiac Magnetic Resonance Substudy Analysis[J]. Circulation, 2021, 143(6): 606-608. doi: 10.1161/CIRCULATIONAHA.120.052359

    [33]

    Desai MY, Wolski K, Owens A, et al. Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy[J]. Am Heart J, 2021, 239: 80-89. doi: 10.1016/j.ahj.2021.05.007

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出版历程
收稿日期:  2021-07-08
刊出日期:  2022-04-13

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