Conventional Approaches to the Therapy of Hereditary Myopathies

Abstract

The aim of the work was to analyze the available therapeutic options for the conventional therapy of hereditary myopathies.Materials and methods. When searching for the material for writing a review article, such abstract databases as PubMed and Google Scholar were used. The search was carried out on the publications during the period from 1980 to September 2022. The following words and their combinations were selected as parameters for the literature selection: “myopathy”, “Duchenne”, “myodystrophy”, “metabolic”, “mitochondrial”, “congenital”, “symptoms”, “replacement”, “recombinant”, “corticosteroids”, “vitamins”, “tirasemtiv”, “therapy”, “treatment”, “evidence”, “clinical trials”, “patients”, “dichloracetate”.Results. Congenital myopathies are a heterogeneous group of pathologies that are caused by atrophy and degeneration of muscle fibers due to mutations in genes. Based on a number of clinical and pathogenetic features, hereditary myopathies are divided into: 1) congenital myopathies; 2) muscular dystrophy; 3) mitochondrial and 4) metabolic myopathies. At the same time, treatment approaches vary significantly depending on the type of myopathy and can be based on 1) substitution of the mutant protein; 2) an increase in its expression; 3) stimulation of the internal compensatory pathways expression; 4) restoration of the compounds balance associated with the mutant protein function (for enzymes); 5) impact on the mitochondrial function (with metabolic and mitochondrial myopathies); 6) reduction of inflammation and fibrosis (with muscular dystrophies); as well as 7) an increase in muscle mass and strength. The current review presents current data on each of the listed approaches, as well as specific pharmacological agents with a description of their action mechanisms.Conclusion. Currently, the following pharmacological groups are used or undergoing clinical trials for the treatment of various myopathies types: inotropic, anti-inflammatory and antifibrotic drugs, antimyostatin therapy and the drugs that promote translation through stop codons (applicable for nonsense mutations). In addition, metabolic drugs, metabolic enzyme cofactors, mitochondrial biogenesis stimulators, and antioxidants can be used to treat myopathies. Finally, the recombinant drugs alglucosidase and avalglucosidase have been clinically approved for the replacement therapy of metabolic myopathies (Pompe’s disease).