Inherited cardiomyopathies--Novel therapies

• Published in: Pharmacology & therapeutics (Oxford) Vol. 155; pp. 36 - 48
• Main Authors: Leviner, Dror B, Hochhauser, Edith, Arad, Michael
• Format: Journal Article
• Language: English
• Published: England 01-11-2015
• Subjects: Animals; Cardiomyopathies - drug therapy; Genetic Diseases, Inborn - drug therapy; Humans; Rare Diseases - drug therapy; Hypertrophic cardiomyopathy; Amyloidosis; Arrhythmogenic cardiomyopathy; Dilated cardiomyopathy; Gene therapy; Duchenne muscular dystrophy
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2015.08.003

Cardiomyopathies arising due to a single gene defect represent various pathways that evoke adverse remodeling and cardiac dysfunction. While the gene therapy approach is slowly evolving and has not yet reached clinical "prime time" and gene correction approaches are applicable at the bench but not at the bedside, major advances are being made with molecular and drug therapies. This review summarizes the contemporary drugs introduced or being tested to help manage these unique disorders bearing a major impact on the quality of life and survival of the affected individuals. The restoration of the RNA reading frame facilitates the expression of partly functional protein to salvage or alleviate the disease phenotype. Chaperones are used to prevent the degradation of abnormal but still functional proteins, while other molecules are given for pathogen silencing, to prevent aggregation or to enhance clearance of protein deposits. The absence of protein may be managed by viral gene delivery or protein therapy. Enzyme replacement therapy is already a clinical reality for a series of metabolic diseases. The progress in molecular biology, based on the knowledge of the gene defect, helps generate small molecules and pharmaceuticals targeting the key events occurring in the malfunctioning element of the sick organ. Cumulatively, these tools augment the existing armamentarium of phenotype oriented symptomatic and evidence-based therapies for patients with inherited cardiomyopathies.