Vol 16, No 1 (2026)

Background. The authors present the Russian experience of clinical use of a gene therapy drug in the treatment of progressive Duchenne muscular dystrophy through exon 53 skipping, using the only drug of this class registered in Russia, viltolarsen (Viltepso^®), as an example. It is approved for the treatment of patients with amenable DMD gene deletions, however, real-world clinical efficacy across different age groups requires further clarification.

Aim. To evaluate the efficacy of viltolarsen in real world clinical practice in the Russian Federation, depending on age at treatment initiation and functional status.

Materials and methods. The study included 48 patients aged 1.83 to 17.58 years with deletion mutations correctable by exon 53 skipping (del 43–52, 45–52, 48–52, 49–52, 50–52, 52) treated with viltolarsen. Patients were stratified into 4 cohorts: 1) ambulatory patients who initiated therapy under 4 years of age (n = 4); 2) ambulatory patients who initiated therapy at 4–7 years of age (n = 20); 3) ambulatory patients who initiated therapy at ≥8 years of age (n = 19); 4) non-ambulatory patients at therapy initiation (n = 5). Standard functional tests, pulmonary function and cardiac function were assessed. Mean treatment duration was 2.1 ± 1.1 years.

Results. Viltolarsen, depending on the age of therapy initiation, improves and/or stabilizes functional parameters in ambulatory children with Duchenne muscular dystrophy, and significantly prolongs the age of ability to walk independently: 18 out of 19 patients in cohort 3 at high risk of loss of ambulation (mean age 11.6 ± 1.6 years old) maintained the ability to walk, whereas control group patients lost this function at 8.9 ± 0.9 years old (p < 0.01). Loss of ambulation in the studied cohort was associated with sharp deviations from typical child development: extreme obesity, growth spurts, cardiorespiratory problems. In patients who started therapy after loss of independent ambulation, no marked deterioration in mean cardiac function and respiratory function was observed during the follow-up period. No signs of clinically significant renal function deterioration during the follow-up period, as determined by cystatin C levels, were observed (0.896 ± 0.027 (n = 26) versus 0.941 ± 0.021 (n = 47), p >0.05).

Conclusion. Preliminary study results have shown that viltolarsen improves and/or stabilizes functional outcomes in ambulatory children with DMD, significantly prolongs the age of independent ambulation, and stabilizes cardiorespiratory parameters in non-ambulatory patients. Early initiation of comprehensive multidisciplinary management of patients with Duchenne muscular dystrophy is required as a mandatory basis for pathogenetic therapy.

The relevance of this work is determined by the fact that comorbid disorders in children with cerebral palsy – such as pain, cognitive impairment, epilepsy, dysphagia, sensory deficits and other associated conditions – shape a complex clinical profile already in early childhood. These conditions, rather than motor impairment alone, become key barriers to effective rehabilitation, social participation and maintenance of an acceptable quality of life. Despite advances in rehabilitation medicine, delayed recognition and management of comorbidities remain a major cause of persistent disability, underscoring the need to systematically summarize current evidence. The present analysis not only describes the characteristics of the most frequent comorbid conditions, but also identifies several key patterns. Pain in children with cerebral palsy is shown to be polymorphic and frequently chronic, and its assessment in early childhood requires the use of specialized scales. A clear relationship is demonstrated between the severity of motor impairment and the risk of cognitive decline, along with a high prevalence of speech disorders, among which dysarthria predominates. Particular attention is given to epilepsy and dysphagia, which directly threaten survival through malnutrition and respiratory complications. The main value of this review lies in the critical synthesis of data on diagnostic approaches adapted for infants, nonverbal children and those with severe motor limitations, as well as in the discussion of how comorbidity shapes the clinical course of cerebral palsy and why the focus must shift towards the earliest possible multidisciplinary management, starting from the time of diagnosis, in order to preserve rehabilitation potential and improve quality of life in this vulnerable population.

Nemaline myopathies are a heterogeneous group of congenital structural myopathies characterized by rod-shaped inclusions in the sarcoplasm and/or nuclei of muscle fibers. Pathogenic variants in the ACTA1 gene represent the second most frequent cause of nemaline myopathies, with 90 % exhibiting autosomal dominant inheritance. Homozygous pathogenic variants typically are manifested by severe infantile phenotype 2B, whereas the phenotypic spectrum of mild and moderate forms has yet to be systematically categorized.

This article presents an 8-year-old patient with homozygous actinopathy (NM_001100.4(ACTA1):c.661G>C (p.Val221Leu)) corresponding to the typical phenotype of congenital myopathy-2A. Distinctive features of this case were the presence of distal hand joint hypermobility, rimmed vacuolar changes on histological analysis, and abnormal white matter signal intensity on neuroimaging. Magnetic resonance pattern of fatty infiltration and edematous changes in the pelvic girdle and lower extremity muscles were also presented. Combined inheritance of pathogenic homozygous variants in the COQ8A gene (formerly ADCK3) (NM_020247.5(COQ8A):c.1189G>A (p.Val397Met)) required differential diagnosis with primary coenzyme Q₁₀ deficiency, which may involve skeletal muscle pathology.