Possibility of exon skipping therapy for Duchenne muscular dystrophy in Russian patients: present and future

Abstract

Background. Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in children, that occurs between one and three years of age. DMD is caused by pathogenic and likely pathogenic variants in the DMD gene, which lead to a deficit of various isoforms of the dystrophin protein, the main protein of the muscle cytoskeleton. Drugs aimed at slowing the progression of the disease are being actively developed around the world. One of the perspective approaches to pathogenetic therapy is therapy using exon skipping. As a result of this treatment, the reading frame is restored due to the exon skipping enabling the production of truncated dystrophin.Aim. To evaluate the applicability of exon skipping therapy in Russian patients with DMD.Materials and methods. The applicability of therapy aimed at exon skipping was analyzed for a sample of 1519 patients admitted to the laboratory of DNA diagnostics of the Research Centre for Medical Genetics with a referral diagnosis of Duchenne/Becker muscular dystrophy from October 1, 2018 to September 1, 2023.Results. As a result of the study and analysis of the spectrum of mutations in the DMD gene among patients with DMD in the Russian Federation, the theoretical applicability of exon skipping therapy was assessed: for 29.3 % of patients this approach to treatment is applicable. The proportions of patients for whom existing exon skipping therapies are available were also estimated. In total, skipping of frequent exons 51, 53, 45 is applicable for 14.6 % of patients. Conclusion. One of the effective and accessible types of therapy for DMD is exon skipping. This type of therapy is mutation-specific. In this regard, the assessment of applicability will allow us to estimate the proportion of patients for whom a particular exon skipping will be available.

Keywords

• duchenne/becker muscular dystrophy
• gene dmd
• pathogenetic therapy
• exon skipping