Therapeutic Strategies Targeting Inherited Cardiomyopathies

Abstract

Purpose of review Cardiomyopathies due to genetic mutations are a heterogeneous group of disorders that comprise diseases of contractility, myocardial relaxation, and arrhythmias. Our goal here is to discuss a limited list of genetically inherited cardiomyopathies and the specific therapeutic strategies used to treat them. Recent findings Research into the molecular pathophysiology of the development of these cardiomyopathies is leading to the development of novel treatment approaches. Therapies targeting these specific mutations with gene therapy vectors are on the horizon, while other therapies which indirectly affect the physiologic derangements of the mutations are currently being studied and used clinically. Many of these therapies are older medications being given new roles such as mexiletine for Brugada syndrome and diflunisal for transthyretin amyloid cardiomyopathy. Newer targeted therapies such as the inhibitor of myosin ATPase MYK-461 has been shown to suppress the development of ventricular hypertrophy, fibrosis, and myocyte disarray and is being studied as a potential therapy in patients with hypertrophic cardiomyopathy. Summary While this field is too large to be completely contained in a single review, we present a large cross section of recent developments in the field of therapeutics for inherited cardiomyopathies. New therapies are on the horizon and their development will likely result in improved outcomes for patients inflicted by these conditions.

Pigs with δ-sarcoglycan deficiency exhibit traits of genetic cardiomyopathy

“…The involvement of heterogeneous genetic contribution [4] has hindered the development of pharmaceutical agents and therapies specific to genetic cardiomyopathy [5]. Although next-generation therapies, including gene therapy and cell-based therapy, hold promise for curing this intractable disease [6][7][8][9][10][11], availability of animal models for genetic cardiomyopathy is vital for developing these novel therapies [12][13][14].…”

Update on heart failure management and future directions

“…New drugs that act on cardiac myosin have been developed and tested for efficacy in specific diseases. Mavacamten, which acts as an inhibitor of cardiac myosin ATPase and reduces cardiac contractility, is under investigation in patients with obstructive HCM [109]. PIONEER-HCM (NCT02842242) is a phase 2 trial of mavacamten.…”

Miocardiopatía no compactada y restrictiva en pediatría: dos tipos de enfermedades del miocardio que son importantes saber reconocer

“…Existen actualmente avances prometedores en terapia génica con la creación de nuevas moléculas capaces de aumentar el transporte de calcio a nivel sarcoplásmico y actuar como inhibidores o desensibilizadores de este a nivel intracelular. Estudios en animales con el uso de Parvalbumina, proteína de unión al calcio que permite su secuestro en el citosol de las células musculares, han sido exitosos en mejorar la relajación miocárdica, pero aún no hay experiencia en humanos 47,48 .…”