Mavacamten: A Novel Disease-Specific Treatment for Hypertrophic Cardiomyopathy

被引：2

作者：

Capilupi, Michael J. ^{[1
]}

Frishman, William H. ^{[2
,3
,4
]}

机构：

[1] Brown Univ, Dept Med, Providence, RI USA

[2] New York Med Coll, Westchester Med Ctr, Dept Med, Valhalla, NY USA

[3] New York Med Coll, Westchester Med Ctr, Dept Cardiol, Valhalla, NY USA

[4] New York Med Coll, Dept Med, 40 Sunshine Cottage Rd, Valhalla, NY 10595 USA

来源：

CARDIOLOGY IN REVIEW | 2023年 / 31卷 / 01期

关键词：

mavacamten; Myk461; hypertrophic cardiomyopathy; obstructive hypertrophic cardiomyopathy; HCM; HCM; SENSITIVITY;

D O I：

10.1097/CRD.0000000000000433

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal thickening of the myocardium, leading to left ventricular outflow tract obstruction. Current treatments for HCM include non-disease-specific medications such as beta blockers or invasive interventions. Mavacamten has been studied for its effects on adenosine triphosphatase, myocardial-specific sarcomeric proteins, and myocardial tissue calcium sensitivity. Given these properties, mavacamten could be used as a disease-specific treatment for HCM. Clinical trials of mavacamten have shown improvements in left ventricular outflow tract obstruction among other favorable improvements in biochemical markers and the clinical symptoms of the disease. While trials to date have been relatively small, mavacamten shows promise as a future disease-specific treatment for HCM.

引用

页码：45 / 51

页数：7

共 18 条

[1] Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers [J].

Anderson, Robert L. ;

Trivedi, Darshan V. ;

Sarkar, Saswata S. ;

Henze, Marcus ;

Ma, Weikang ;

Gong, Henry ;

Rogers, Christopher S. ;

Gorham, Joshua M. ;

Wong, Fiona L. ;

Morck, Makenna M. ;

Seidman, Jonathan G. ;

Ruppel, Kathleen M. ;

Irving, Thomas C. ;

Cooke, Roger ;

Green, Eric M. ;

Spudich, James A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (35) :EB143-EB152

[2] Mavacamten decreases maximal force and Ca2+ sensitivity in the N47K-myosin regulatory light chain mouse model of hypertrophic cardiomyopathy [J].

Awinda, Peter O. ;

Watanabe, Marissa ;

Bishaw, Yemeserach ;

Huckabee, Anna M. ;

Agonias, Keinan B. ;

Kazmierczak, Katarzyna ;

Szczesna-Cordary, Danuta ;

Tanner, Bertrand C. W. .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2021, 320 (02) :H881-H890

[3] Effects of mavacamten on Ca2+sensitivity of contraction as sarcomere length varied in human myocardium [J].

Awinda, Peter O. ;

Bishaw, Yemeserach ;

Watanabe, Marissa ;

Guglin, Maya A. ;

Campbell, Kenneth S. ;

Tanner, Bertrand C. W. .

BRITISH JOURNAL OF PHARMACOLOGY, 2020, 177 (24) :5609-5621

[4] 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].

Desai, Milind Y. ;

Wolski, Kathy ;

Owens, Anjali ;

Naidu, Srihari S. ;

Geske, Jeffrey B. ;

Smedira, Nicholas G. ;

Schaff, Hartzell ;

Lampl, Kathy ;

McErlean, Ellen ;

Sewell, Christina ;

Zhang, David ;

Edelberg, Jay M. ;

Sehnert, Amy J. ;

Nissen, Steven E. .

AMERICAN HEART JOURNAL, 2021, 239 :80-89

[5] Targeted Medical Therapies for Hypertrophic Cardiomyopathy [J].

Fumagalli, Carlo ;

De Gregorio, Maria Grazia ;

Zampieri, Mattia ;

Fedele, Elisa ;

Tomberli, Alessia ;

Chiriatti, Chiara ;

Marchi, Alberto ;

Olivotto, Iacopo .

CURRENT CARDIOLOGY REPORTS, 2020, 22 (02)

[6] A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice [J].

Green, Eric M. ;

Wakimoto, Hiroko ;

Anderson, Robert L. ;

Evanchik, Marc J. ;

Gorham, Joshua M. ;

Harrison, Brooke C. ;

Henze, Marcus ;

Kawas, Raja ;

Oslob, Johan D. ;

Rodriguez, Hector M. ;

Song, Yonghong ;

Wan, William ;

Leinwand, Leslie A. ;

Spudich, James A. ;

McDowell, Robert S. ;

Seidman, J. G. ;

Seidman, Christine E. .

SCIENCE, 2016, 351 (6273) :617-621

[7] In vitro and in vivo pharmacokinetic characterization of mavacamten, a first-in-class small molecule allosteric modulator of beta cardiac myosin [J].

Grillo, Mark P. ;

Erve, John C. L. ;

Dick, Ryan ;

Driscoll, James P. ;

Haste, Nicole ;

Markova, Svetlana ;

Brun, Priscilla ;

Carlson, Timothy J. ;

Evanchik, Marc .

XENOBIOTICA, 2019, 49 (06) :718-733

[8] Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy A Clinical Trial [J].

Heitner, Stephen B. ;

Jacoby, Daniel ;

Lester, Steven J. ;

Owens, Anjali ;

Wang, Andrew ;

Zhang, David ;

Lambing, Joseph ;

Lee, June ;

Semigran, Marc ;

Sehnert, Amy J. .

ANNALS OF INTERNAL MEDICINE, 2019, 170 (11) :741-+

[9] Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy [J].

Ho, Carolyn Y. ;

Mealiffe, Matthew E. ;

Bach, Richard G. ;

Bhattacharya, Mondira ;

Choudhury, Lubna ;

Edelberg, Jay M. ;

Hegde, Sheila M. ;

Jacoby, Daniel ;

Lakdawala, Neal K. ;

Lester, Steven J. ;

Ma, Yanfei ;

Marian, Ali J. ;

Nagueh, Sherif F. ;

Owens, Anjali ;

Rader, Florian ;

Saberi, Sara ;

Sehnert, Amy J. ;

Sherrid, Mark, V ;

Solomon, Scott D. ;

Wang, Andrew ;

Wever-Pinzon, Omar ;

Wong, Timothy C. ;

Heitner, Stephen B. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2020, 75 (21) :2649-2660

[10] A small-molecule modulator of cardiac myosin acts on multiple stages of the myosin chemomechanical cycle [J].

Kawas, Raja F. ;

Anderson, Robert L. ;

Ingle, Sadie R. Bartholomew ;

Song, Yonghong ;

Sran, Arvinder S. ;

Rodriguez, Hector M. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (40) :16571-16577

← 1 2 →