title: Cardiac myosin binding protein-C: a novel sarcomeric target for gene therapy.
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.
authors: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 2109 Adelbert Rd, Robbins E522, Cleveland, OH, 44106, USA.
authors: Ranganath
authors: R
authors: Mamidi
authors: Jiayang
authors: J
authors: Li
authors: Kenneth S
authors: KS
authors: Gresham
authors: Julian E
authors: JE
authors: Stelzer
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000628:therapy; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C