Svetlana B. Artemyeva

Background. Long-term clinical efficacy data are typically limited when medicines are added to the procurement lists of the Krug Dobra Foundation. Moreover, the absence of standardized criteria for evaluating treatment effectiveness complicates longitudinal assessment of patients in real-world clinical practice. This issue is particularly important in spinal muscular atrophy (SMA) and progressive Duchenne muscular dystrophy (DMD), two severe disabling diseases for which the Foundation provides several disease-modifying therapies. Objective: To develop a set of criteria for monitoring the effectiveness of pharmacotherapy in patients with SMA and DMD receiving treatment through the Krug Dobra Foundation. Materials and methods. The study was conducted in two stages. The first stage comprised a systematic review of comparative studies of medicines provided through the Krug Dobra Foundation for the treatment of SMA and DMD to identify a comprehensive set of potential criteria. This was followed by a series of expert meetings involving physicians responsible for prescribing and monitoring disease-modifying therapy for these conditions. Results. The study produced sets of criteria for monitoring treatment effectiveness in patients with SMA and DMD, covering motor, respiratory, and cardiovascular function. For patients with SMA, the criteria included various motor function scales selected according to the patient's age and motor abilities, as well as parameters related to noninvasive ventilation and swallowing function. For patients with DMD, criteria were developed to assess motor abilities according to ambulatory status, together with respiratory and cardiovascular parameters. Conclusion. The proposed sets of criteria are intended to standardize the evaluation of treatment effectiveness in patients with SMA and DMD across healthcare institutions in the Russian Federation and provide a basis for informed decisions regarding the continued provision of treatment through the Krug Dobra Foundation.

Background. Duchenne muscular dystrophy (DMD) is an irreversible, progressive fatal genetic disorder caused by the absence of functional dystrophin protein in muscle due to mutations in the DMD gene. Exon-skipping therapy for DMD aims to increase the amount of functionally active protein dystrophin. Casimersen, a drug for skipping exon 45, is indicated for patients with certain deletions. Clinical studies have confirmed an increase in dystrophin levels and improved motor activity in patients with DMD treated with casimersen. Aim. To present the experience of treating patients with DMD who were eligible for exon 45 skipping therapy. Materials and methods. Twenty-eight patients with DMD who received exon 45 skipping therapy were observed. Patients were assessed for functional status, motor tests (Six-Minute Walk Test, North Star Ambulatory Assessment) dynamics, and respiratory function with dynamic assessment of functional vital capacity. Results. Most outpatients showed stabilization of their condition with preservation of the ability to move independently, improvement or stability in functional (Six-Minute Walk Test, North Star Ambulatory Assessment) and timed test indicators, as well as stabilization of upper limb function and absence of progression of respiratory function decline in non-ambulatory patients. Conclusion. The safety and tolerability of casimersen therapy were generally good in all patients with DMD in our sample. All patients who initiated casimersen therapy in the early outpatient stage remained in this stage at the analysis date.

Spinal muscular atrophy 5q (5q SMA) is one of the most prevalent autosomal recessive disorders globally. The underlying cause of 5q SMA is attributed to variants in SMN1. To date, there are no reported cases of gene-based therapy in rare patients with 5q SMA caused by subtle SMN1 variants of unknown clinical significance. We included 10 patients with the clinical manifestations of 5q SMA associated with intragenic variants in combination with a heterozygous SMN1 deletion in this retrospective study. Previously reported pathogenic or likely pathogenic variants were identified (e.g., c.*3+1del, c.815A>G (p.Tyr272Cys), and c.821C>T (p.Thr274Ile)). Variants of unknown clinical significance were also found, including a recurrent, previously unreported variant c.80A>C (p.Gln27Pro). We also report detailed molecular genetic and clinical data on 9 patients with 5q SMA. In addition, we provide results from the cohort of patients with gene-based therapy, consistent with data from patients with a homozygous SMN1 deletion.

Introduction. Spinal muscular atrophy (SMA) 5q is a progressive neuromuscular disorder caused by a mutation in the SMN1 gene. Pathogenetic therapy has significantly altered the natural course of the disease but has not ensured complete restoration of previously lost motor functions. Given the persistence of muscle weakness, rehabilitation remains a crucial component of comprehensive patient management. Objective of the study. To assess the volume and structure of rehabilitation in patients with SMA types 1–3 receiving pathogenetic therapy and determine its association with the trend in motor development based on the number of motor skills.Materials and methods. The study included one hundred forty three patients with SMA types 1–3 (59 — SMA 1; 52 — SMA 2; 32 — SMA 3) aged of 0–18 years. The median time from the disease onset to the initiation of pathogenetic therapy was 6.0 [3.0; 13.0] months in SMA type 1, 45.0 [14.0; 90.0] months in SMA type 2, and 100.0 [67.0; 147.5] months in SMA type 3. The observation period was 3 years from the initiation of pathogenetic therapy. Functional status was assessed using eight motor skills according to WHO criteria. The volume of rehabilitation was determined through interviews and medical documentation. Statistical analysis was performed using SPSS Statistics, version 26.0 (IBM, USA).Results. During pathogenetic therapy, patients with SMA type 1 demonstrated positive developmental course by the end of the follow-up period: head control increased from 35.6% to 82.5%, rolling from 1.7% to 67.5%, independent sitting was achieved in 75% of children, and 15% developed the ability to bear weight on their legs. In patients with SMA type 2, pathogenetic therapy resulted in stabilization of basic functions and a moderate increase in more complex motor skills (crawling improved from 12.5% to 17.4%; supported standing from 8.3% to 21.7%; assisted walking from 2.1% to 13%; independent walking — 7.9%). In the SMA type 3 group, motor progress on therapy was characterized mainly by preservation of existing skills with some improvements (e.g., an increase in the frequency of crawling to 42.9% and a single case of new-onset independent walking in a baseline “sitter”). In baseline “walkers” with SMA type 3, stabilization was observed. A significant association was identified between the number of acquired motor skills and the volume of rehabilitation in patients with SMA type 1, as well as in baseline “sitters” with SMA types 2 and 3 (p ≤ 0.014). In SMA type 1, regular comprehensive rehabilitation resulted in significantly higher motor skill scores compared with all other approaches (ppadj < 0.001). In SMA type 2, regular forms of rehabilitation (comprehensive or home-based) demonstrated advantages over course-based rehabilitation (ppadj ≤ 0.024). In the SMA type 3 group, among “sitters,” course-based rehabilitation during the year led to a better motor response to therapy compared with children receiving no rehabilitation (ppadj = 0.028).Conclusions. Regular rehabilitation interventions, especially when combined with center-based rehabilitation courses, were associated with better motor responses to pathogenetic therapy in both SMA type 1 patients and baseline “sitters” with SMA types 2 and 3. These findings confirm the important role of continuous rehabilitation as part of the standard of care for SMA, serving as a necessary condition for achieving optimal motor progress under modern pathogenetic therapeutic approaches.Compliance with ethical standards. The study was approved by the local ethics committee of the Pirogov Russian National Research Medical University (protocol No. 226 dated February 20, 2023).Contributions:Papina Yu.O — literature review, data collection and analysis, manuscript preparation, formulation of conclusions;Stevanovich A.R. — literature review, manuscript preparation;Melnik E.A. — manuscript editing, formulation of conclusions;Artemyeva S.B. — study coordination;Vlodavets D.V. — study coordination, manuscript editing.All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.Funding. The study had no sponsorship.Conflict of interest. The authors declare no conflict of interest.Received: November 3, 2025Accepted: December 1, 2025Published: January 31, 2026

Introduction. Spinal muscular atrophy (SMA) 5q is a progressive neuromuscular disorder caused by a mutation in the SMN1 gene. Pathogenetic therapy has significantly altered the natural course of the disease but has not ensured complete restoration of previously lost motor functions. Given the persistence of muscle weakness, rehabilitation remains a crucial component of comprehensive patient management. Objective of the study. To assess the volume and structure of rehabilitation in patients with SMA types 1–3 receiving pathogenetic therapy and determine its association with the trend in motor development based on the number of motor skills.Materials and methods. The study included one hundred forty three patients with SMA types 1–3 (59 — SMA 1; 52 — SMA 2; 32 — SMA 3) aged of 0–18 years. The median time from the disease onset to the initiation of pathogenetic therapy was 6.0 [3.0; 13.0] months in SMA type 1, 45.0 [14.0; 90.0] months in SMA type 2, and 100.0 [67.0; 147.5] months in SMA type 3. The observation period was 3 years from the initiation of pathogenetic therapy. Functional status was assessed using eight motor skills according to WHO criteria. The volume of rehabilitation was determined through interviews and medical documentation. Statistical analysis was performed using SPSS Statistics, version 26.0 (IBM, USA).Results. During pathogenetic therapy, patients with SMA type 1 demonstrated positive developmental course by the end of the follow-up period: head control increased from 35.6% to 82.5%, rolling from 1.7% to 67.5%, independent sitting was achieved in 75% of children, and 15% developed the ability to bear weight on their legs. In patients with SMA type 2, pathogenetic therapy resulted in stabilization of basic functions and a moderate increase in more complex motor skills (crawling improved from 12.5% to 17.4%; supported standing from 8.3% to 21.7%; assisted walking from 2.1% to 13%; independent walking — 7.9%). In the SMA type 3 group, motor progress on therapy was characterized mainly by preservation of existing skills with some improvements (e.g., an increase in the frequency of crawling to 42.9% and a single case of new-onset independent walking in a baseline “sitter”). In baseline “walkers” with SMA type 3, stabilization was observed. A significant association was identified between the number of acquired motor skills and the volume of rehabilitation in patients with SMA type 1, as well as in baseline “sitters” with SMA types 2 and 3 (p ≤ 0.014). In SMA type 1, regular comprehensive rehabilitation resulted in significantly higher motor skill scores compared with all other approaches (ppadj < 0.001). In SMA type 2, regular forms of rehabilitation (comprehensive or home-based) demonstrated advantages over course-based rehabilitation (ppadj ≤ 0.024). In the SMA type 3 group, among “sitters,” course-based rehabilitation during the year led to a better motor response to therapy compared with children receiving no rehabilitation (ppadj = 0.028).Conclusions. Regular rehabilitation interventions, especially when combined with center-based rehabilitation courses, were associated with better motor responses to pathogenetic therapy in both SMA type 1 patients and baseline “sitters” with SMA types 2 and 3. These findings confirm the important role of continuous rehabilitation as part of the standard of care for SMA, serving as a necessary condition for achieving optimal motor progress under modern pathogenetic therapeutic approaches.Compliance with ethical standards. The study was approved by the local ethics committee of the Pirogov Russian National Research Medical University (protocol No. 226 dated February 20, 2023).Contributions:Papina Yu.O — literature review, data collection and analysis, manuscript preparation, formulation of conclusions;Stevanovich A.R. — literature review, manuscript preparation;Melnik E.A. — manuscript editing, formulation of conclusions;Artemyeva S.B. — study coordination;Vlodavets D.V. — study coordination, manuscript editing.All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.Funding. The study had no sponsorship.Conflict of interest. The authors declare no conflict of interest.Received: November 3, 2025Accepted: December 1, 2025Published: January 31, 2026

Duchenne muscular dystrophy is the most severe form of hereditary myopathies in boys, caused by mutations in the DMD gene, located on the X chromosome at the Xp21.2–p21.1 locus and encoding the dystrophin protein. The most common mutations are deletions of one or more exons (about 70 % of cases), which disrupt the reading frame and lead to the synthesis of a shortened and non-functional dystrophin protein, which causes the breakdown of skeletal muscle fibers (rhabdomyolysis) and progressive muscle weakness. The disease clinically manifests at the age of 2–5 years and rapidly progresses to the loss of the ability to walk independently by 8–12 years and death in the second or third decade of life due to respiratory and cardiac failure. The authors present Russian experience in the use of a gene therapy drug for the treatment of Duchenne muscular dystrophy using the exon skipping method, exemplified by the only registered drug of this class in Russia for Duchenne muscular dystrophy therapy – viltolarsen (Viltepso®).

Duchenne muscular dystrophy (DMD) is an X-linked hereditary disease that manifests in early childhood and progresses with age, leading to loss of mobility and respiratory and cardiac failure. The globally recognized gold standard for DMD treatment is corticosteroids. However, until recently, only deflazacort (Emflaza) had received approval from the U.S. Food and Drug Administration (FDA) for the indication of DMD. All other drugs in this group were used off-label. At the end of 2023, the FDA, followed by the European Medicines Agency (EMA), registered another drug from the corticosteroid group – vamorolone (Agamree). In 2024, vamorolone received approval in the United Kingdom and China. Thus, all leading global regulators currently recognize vamorolone as a corticosteroids for the treatment of DMD.

Background. Spinal muscular atrophy 5q (SMA) is a severe genetic neuromuscular disorder, which is primarily manifested through musclar weakness. Previously, cognitive development in the natural course of SMA was considered normal. The introduction of etiopathogenetic therapy has altered the disease trajectory, led to new phenotypes, improved survival rates, and outlined the importance of studying the development of emotional, cognitive, and communicative domains, and adaptive behavior in SMA patients.Aim. To conduct a comprehensive assessment of emotional, cognitive, and adaptive domains, as well as speech development, in patients with genetically confirmed SMA, including cases, which were identified through newborn screening programs and were asymptomatic at the initiation of etiopathogenetic therapy, and to identify factors influencing neuropsychic development in SMA patients.Materials and methods. The study included 87 SMA patients receiving etiopathogenetic therapy, aged 0–12 years (median age at testing – 57.0 [37.0; 103.0] months). The Developmental Profile-3 (DP-3) instrument was used to assess neuropsychic development. Statistical analysis was performed using SPSS Statistics v.26.0 (IBM, USA).Results. Children who received therapy at the presymptomatic stage (6.9 % of the cohort) showed no deficits in any assessed developmental domains. These results significantly differed from those of SMA types 1, 2, and 3 in motor skills (padj 0.001) and adaptive behavior (padj ≤0.026). Patients with SMA types 1, 2, and 3 exhibited severe motor impairments (reduced motor skills in 93.0 %, 89.7 %, and 88.9 % of children, respectively) and adaptive deficits (impairments in ≥55 % of each group). SMA type 1 patients additionally demonstrated delays in social emotional (39.5 %), cognitive (30.2 %), and communicative (39.5 %) domains. Children with lower functional status (“lying”) had more pronounced delays in adaptive, social emotional, and cognitive domains (p ≤0.048). In SMA type 1, fewer SMN2 gene copies and earlier disease onset correlated with more severe deficits in emotional, cognitive, and adaptive domains, as well as in speech development (SMN2 copies: p ≤0.034; age of onset: p ≤0.012). SMA type 1 patients with dysphagia showed lower scores across all subscales except motor skills (p ≤0.015). Chronic respiratory insufficiency was associated with reduced scores in all five subscales: in SMA type 1, motor skills, adaptive, social emotional, and cognitive domains were affected (p ≤0.045); in SMA type 2, adaptive, social emotional, and cognitive domains were affected (p ≤0.018). Delayed therapy initiation correlated with lower motor and adaptive scores in SMA types 1 (p ≤0.012), 2 (p ≤0.002), and 3 (p ≤0.048), and with worse social emotional and cognitive outcomes in SMA type 2 (p = 0.001).Conclusion. SMA patients exhibit not only motor impairments but also adaptive and socialization deficits, as well as delays in communicative and cognitive development. A standardized approach to identifying these impairments should be developed, and developing tailored rehabilitation methods is important as well. Initiating etiopathogenetic therapy at the presymptomatic stage may prevent neuropsychiatric manifestations of SMA.

Spinal muscular atrophy 5q (SMA) is one of the most common inherited neuromuscular diseases in children with an autosomal recessive type of inheritance. Homozygous deletion of exons 7 or 7–8 of the SMN1 gene encoding the motor neuron survival protein is responsible for 95 % of cases. SMA is characterized by a steadily progressive course with the development of paresis, muscle atrophy, loss of previously acquired motor skills, respiratory failure and skeletal deformities. The introduction of pathogenetic therapy in recent years has significantly changed the trajectory of SMA – patients survive, restore previously lost motor skills and acquire new ones. The clinical classification, which includes 5 types of SMA, is currently not a reliable reflection of the functional state of the child in dynamics. In 2005, a functional classification was recommended based on the patient’s current status: non-sitters (lying), sitters, and walkers. The article provides a summary of historical concepts regarding functional classification in SMA patients, as well as the criteria used in clinical trials and observations. We proposed criteria for categorizing SMA patients into a specific functional class by analyzing the available literature and making recommendations on using the classification in real clinical practice.

Introduction. Spinal muscular atrophy 5q is a common childhood disease in the practice of a pediatrician and pediatric neurologist. Despite the introduction of neonatal screening in the Russian Federation since 2023, there is a cohort of patients who were not included in neonatal screening and the relevance of knowledge of the clinical symptoms of SMA remains.Aim. To study the reasons for delayed diagnosis of spinal muscular atrophy in the Russian Federation.Materials and methods. We analyzed the data of the registry of 1452 patients with SMA: the time of delay in diagnosis from the onset of the first clinical symptoms, identified the first clinical symptoms and analyzed erroneous primary diagnoses that increased the time of correct diagnosis. Patients were divided into two groups: group 1 of patients (1170) born before 2019, the second group of patients (274) born from 2019 to 2023. An analysis of the medical records of 330 patients with SMA observed at the Veltischev Scientific Research Institute was conducted in order to analyze the clinical symptoms of SMA that were underestimated by primary care physicians and led to a delay in correct diagnosis.Results. In the 1st group of patients, 146 patients with SMA type 1, 531 SMA type 2, 493 – SMA type 3, 8 – SMA type 4 were registered. The delay in diagnosis was 4 months, 2 years 4 months, 5 years 2 months, 11 years, respectively. In the 2nd group of patients, 176 patients with SMA type 1, 81 – SMA type 2, 17 – SMA type 3 were registered. The delay in diagnosis was SMA1 – 2 months, SMA2 – 6 months, SMA3 – 6 months. Since 2019, there has been a significant decrease in the delay in diagnosis, especially for SMA types 2 and 3 up to 6 months. The primary and most significant clinical symptoms for patients with different types of SMA are determined.Conclusions. Underestimating of clinical symptoms of spinal muscular atrophy leads to late molecular genetic diagnosis of the disease. The identified initial clinical signs of spinal muscular atrophy of different types will allow primary care physicians to suspect the disease in time and refer patients for confirmatory molecular genetic diagnostics.