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Cardiac myosin binding protein-C: a novel sarcomeric target for gene therapy

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Abstract

Through its ability to interact with both the thick and thin filament proteins within the sarcomere, cardiac myosin binding protein-C (cMyBP-C) regulates the contractile properties of the myocardium. The central regulatory role of cMyBP-C in heart function is emphasized by the fact that a large proportion of inherited hypertrophic cardiomyopathy cases in humans are caused by mutations in cMyBP-C. The primary dysfunction in cMyBP-C-related cardiomyopathies is likely to be abnormal myofilament contractile function; however, currently, there are no effective therapies for ameliorating these contractile defects. Thus, there is a compelling need to design novel therapies to restore normal contractile function in cMyBP-C-related cardiomyopathies. To this end, concepts gleaned from various structural, functional, and biochemical studies can now be utilized to engineer cMyBP-C proteins that, when incorporated into the sarcomere, can significantly improve contractile function. In this review, we discuss the rationale for cMyBP-C-based gene therapies that can be utilized to treat contractile dysfunction in inherited and acquired cardiomyopathies.

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Acknowledgments

This work was supported by a grant (RO1HL114770) from the National Heart, Lung and Blood Institute.

Conflict of interest

Dr. Stelzer holds a provisional patent for cMyBP-C gene delivery for correction of contractile dysfunction in hypertrophic cardiomyopathy. The other authors have no conflicts to disclose.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 2109 Adelbert Rd, Robbins E522, Cleveland, OH, 44106, USA

    Ranganath Mamidi, Jiayang Li, Kenneth S. Gresham & Julian E. Stelzer

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  1. Ranganath Mamidi
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  2. Jiayang Li
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  3. Kenneth S. Gresham
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  4. Julian E. Stelzer
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Correspondence to Julian E. Stelzer.

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Mamidi, R., Li, J., Gresham, K.S. et al. Cardiac myosin binding protein-C: a novel sarcomeric target for gene therapy. Pflugers Arch - Eur J Physiol 466, 225–230 (2014). https://doi.org/10.1007/s00424-013-1412-z

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  • DOI: https://doi.org/10.1007/s00424-013-1412-z

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