Background: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by the absence of functional dystrophin, leading to progressive muscle degeneration, inflammation, and alterations in the central nervous system. The sustained inflammatory response in DMD increases glial activation and the release of tumor necrosis factor alpha (TNF-α), which contributes to muscle fiber damage. Here, we investigated the anti-inflammatory and neuroprotective effects of Etanercept, a TNF-α receptor-blocking therapeutic, on the spinal cord of MDX mice, a widely used model of DMD. Methods: Adult male MDX and control C57BL/10 mice received vehicle or Etanercept (3, 6, or 12 mg/Kg, intraperitoneally (i.p.)) every 72 h for two weeks, along with daily gait assessment. At the end of treatment, flow cytometry and immunolabeling analyses were performed in the lumbar spinal cord. Results: Etanercept at 12 mg/Kg reduced astrogliosis and microglial activation; restored synaptic markers, including synaptophysin, glutamic acid decarboxylase 65 (GAD-65), and vesicular glutamate transporter 1 (VGLUT-1); and decreased pro-inflammatory cytokines. The treatment reduced GFAP+/TNF-α+ astrocytes and significantly downregulated Th1 lymphocyte polarization in treated MDX mice. These cellular effects were accompanied by improvements in locomotor function. Conclusions: Together, our findings indicate that TNF-α blockade by Etanercept exerts neuroprotective and anti-inflammatory actions in the spinal cord of dystrophic mice, providing new insights into the impact of TNF-α signaling on neuroinflammatory processes in DMD.

Animal models and human 2D culture models have been instrumental for investigating skeletal muscle diseases and the development of therapeutics. However in vivo models and 2D cultures are limited in their translation to clinical application. These limitations are most evident through the success of myostatin inhibitors for improving mass and function in mice studies followed by unsuccessful clinical trials in patients with sarcopenia and Duchenne Muscular Dystrophy (DMD) (3-4). Although clinical trials of myostatin inhibitors have often reported increases in lean muscle mass, efficacy endpoints of improved muscle function are typically not achieved (3-4). Additionally, studies of age-related muscle atrophy, sarcopenia, have unique barriers to translation such as age-related gene expression changes and sex related muscle aging that is not conserved between species (1-2). Due to these challenges, our team developed a donor-derived 3D skeletal muscle platform housed in standard 24-well imaging plates. This platform was then utilized to investigate retention of sex- specific characteristics in 3D muscle cultures and the effectiveness of astaxanthin (ASTX) to improve contractile signaling and function in healthy and clinically sarcopenic 3D cultures. Initial characterization and validation were carried out in samples from healthy male and female donors. Contractile function recorded through digital image correlation (DIC) analysis during electrical stimulation was similar between male and female 3D muscles, but females displayed elevated type 1 fiber proportions compared to males. Female muscle also displayed elevated levels of OPA1 and TFAM protein levels along with decreased Akt signaling. Overall, female muscle exhibited a greater reliance on mitochondrial energy utilization and reduced protein synthesis indicating retention of sex-specific characteristics in 3D culture. Samples from young female and clinically sarcopenic female donors were studied in this platform for functional differences in force production, fatigue susceptibility, and contractile protein signaling following fatigue with or without astaxanthin antioxidant therapy. Astaxanthin was assessed at 1μM, 10μM, and 25μM in young cultures and only 10μM in sarcopenic cultures due to limitations in cell quantity for 7 days. Although there were no significant effects on force outputs or fatiguability for either group, 10μM rescued P38 and Akt signaling in the sarcopenic samples restoring levels to those exhibited by young DMSO- treated controls. Additionally, 10μM and 25μM in the young cohort suppressed Akt signaling indicating astaxanthin may negatively impact this critical pathway for exercise adaptation in healthy muscle. Although astaxanthin did not improve functional performance in the clinically sarcopenic or young female 3D muscle samples, clenbuterol was evaluated as a positive control for improving performance in young muscle and showed a nearly two-fold increase in both twitch and tetanic force response in 1μM treated samples compared to DMSO controls. These findings support the utilization of this muscle platform for assessing functional differences among drug treatments and untreated donor groups.

Safety and efficacy of fordadistrogene movaparvovec in ambulatory participants with Duchenne muscular dystrophy (CIFFREO): a phase 3, double-blind, randomised, placebo-controlled study.

Lumbopelvic stabilization-based physiotherapy and rehabilitation and urotherapy for lower urinary tract dysfunction in Duchenne Muscular Dystrophy: a randomized controlled trial.

With implementation of newborn screening (NBS) for Duchenne muscular dystrophy (DMD), creatine kinase-muscle (CK) values will be reported on newborns. Maternal, labor, delivery, and newborn factors may elevate CK levels, raising concern for DMD. Predictive modeling could aid hyperCKemia interpretation while awaiting diagnostic confirmation. In this single-center, prospective cohort study, parents of 8365 newborns were offered DMD-NBS. Electronic health records provided data on candidate predictors of hyperCKemia defined by values > 97th or 99th percentiles, or 2000 ng/mL in babies with normal DMD sequences. Exposures included maternal, newborn and perinatal factors. Associations between predictors and hyperCKemia were evaluated using univariate logistic regression. A multivariable prediction model for the 97th percentile was derived using backward stepwise logistic regression and externally validated in a cohort of 2672 newborns. HyperCKemia > 97th percentile was the main outcome. Univariate analyses revealed associations between hyperCKemia and maternal ethnicity, primiparity, labor and delivery complications, oxytocin induction or augmentation, duration of ruptured membranes, forceps or vacuum-assisted delivery, neonatal resuscitation, sex, gestational age, birth weight, and Apgar scores. Lower odds of hyperCKemia were associated with later hour-of-life at sample collection and birth by cesarean section. The final model included parity, shoulder dystocia, forceps or vacuum-assisted delivery, gestational age, neonatal resuscitation, Apgar score (1 min), and time of sample collection. Elevated CK levels may be used for DMD-NBS. Multiple perinatal factors are associated with transient non-DMD hyperCKemia. Our model considers the potential combined impact of such factors and generates a non-disease likelihood for preliminary hyperCKemia interpretation.

Noninvasive longitudinal assessment of early-stage Duchenne muscular dystrophy: In vivo diaphragm imaging in mdx mice.

Corticosteroid therapy in Duchenne muscular dystrophy: Management and new insights.

Protocol for in vivo analysis of muscle function in porcine models for muscular dystrophies.

The social profile and quality of life of families with children with Duchenne muscular dystrophy are important factors for improving the organization of medical and social care for rare disabling diseases. The relevance of the study is determined by the high medical and social significance of Duchenne muscular dystrophy, which is accompanied by severe progressive motor impairment in children and a pronounced impact on all aspects of family life, amid limited domestic data on this issue. Objective: to investigate the social profile of families raising children with Duchenne muscular dystrophy and to assess the quality of life of parents. Materials and methods. A survey of families with children with Duchenne muscular dystrophy was conducted from June to December 2024. Two instruments were used: a self-developed questionnaire to assess the social profile of the family and the validated 36-item Short Form Health Survey to evaluate quality of life. Data were statistically processed using Microsoft Excel and IBM SPSS Statistics version 23. Results. Seventy families participated in the study. Quality of life data were analyzed for 68 respondents. Parents reported moderately reduced scores in emotional well-being, social interaction, cognitive functioning, communication, anxiety, and daily activities. Physical health and family relationships were rated at a satisfactory level. The findings indicate a pronounced psychoemotional and social burden on parents of children with Duchenne muscular dystrophy, independent of the child’s clinical characteristics. Conclusions. The results demonstrate the systemic impact of Duchenne muscular dystrophy on family quality of life, with chronic psycho-emotional stress and social vulnerability among parents. Identified features of the social profile and quality of life should be considered when developing comprehensive medical and social support programs for families. Application of results. The findings can be used in planning specialized medical care, organizing psychological support, developing regional medical and social programs, and improving the care system for children with rare inherited diseases.

Background/Objectives: Recombinant adeno-associated virus (AAV) vectors have revolutionized gene therapy for monogenic diseases such as Duchenne muscular dystrophy (DMD). However, high systemic doses required for muscle transduction cause a spectrum of toxicities ranging from transient hepatic inflammation to fatal multi-organ failure leading to death. These adverse events have reshaped the risk–benefit considerations for gene therapy in DMD. Methods: We conducted a narrative review describing complications associated with AAV-mediated gene therapies in the DMD field. PubMed and Clinicaltrials databases were used to search for peer-reviewed manuscripts published between 1987 and 2025. Publicly available abstracts and press releases were also used to describe AAV-mediated adverse events that have been discovered. Priority was given to large prospective cohorts, meta-analyses, and high-impact publications. Results: We outlined the mechanistic basis of AAV toxicity—spanning innate and adaptive immune activation, vector–host interactions, transgene overexpression, and host vulnerability—and discussed their therapeutic implications for DMD. We also highlighted ongoing strategies for vector re-design, immune modulation, patient selection, and regulatory adaptation, aiming to improve efficacy with safety in the next generation of muscular dystrophy gene therapies. Conclusions: Patient safety remains the number one priority in the AAV-mediated gene therapies field. Achieving long-term benefits requires continued optimization of existing vectors, implementation of strict criteria for patient selection, and regulation of immune responses, with close collaboration and transparent dialog among scientists, clinicians, and regulatory agencies, informed by both successful cases as well as tragic deaths reported in the fields of neuromuscular diseases.

Duchenne muscular dystrophy (DMD) management is guided by established clinical standards, yet real-world implementation data in Spain remain limited. The DMD-NEEDS study aimed to characterize the pediatric management landscape as reported by a select cohort of specialists within the national pediatric neurology community. This non-interventional, cross-sectional, web-based survey involved 41 pediatric neurologists from the Spanish Society of Pediatric Neurology (SENEP) who actively manage patients with DMD. The study focuses specifically on the pediatric stage and the transition to adult care. Clinicians reported that a slight majority of patients (53.7%) were diagnosed between 2 and 3years of age, frequently within 6 months of symptom onset. Multiplex ligation-dependent probe amplification (MLPA) was the primary diagnostic tool for 92.7% of participating clinicians, frequently supplemented by gene sequencing (80.5%) or genetic panels (75.6%) to confirm single point mutations and duplications. Estimated loss of ambulation typically occurred between ages 11 and 13 years, with major clinical complications emerging between ages 12 and 17 years. Adherence to pharmacological standards was high: 95.1% of respondents prescribed corticosteroids as first-line therapy, and 89.7% specifically utilized a high-dose deflazacort regimen (0.9mg/kg/day). Despite these trends, 31.7% of respondents lacked access to multidisciplinary care teams, and 58.5% reported that health-related quality-of-life questionnaires are not utilized in routine practice. These findings reveal a proactive clinical landscape characterized by early diagnosis and high adherence to international pharmacological standards. However, persistent gaps in multidisciplinary access and patient-centered monitoring highlight critical unmet needs. The implementation of a dedicated multidisciplinary framework and standardized management protocols is essential for optimizing the care of patients with DMD.

Pan-immune-inflammation value as a predictor of loss of ambulation in duchenne muscular dystrophy: a retrospective cohort study.

An Assessment of Paediatricians' Knowledge and Perspectives of Duchenne Muscular Dystrophy in Oman

Duchenne muscular dystrophy (DMD) is a lethal pediatric degenerative muscle disease for which there is no cure. Robust preclinical models that recapitulate major clinical features of DMD are required to investigate efficacy of potential DMD therapeutics. Rat models of DMD have emerged as promising small animal models to accomplish this; however, there have been no comprehensive studies investigating the functional skeletal muscle decrements associated with the modeling of DMD in rats. CRISPR/Cas9 gene editing was used to generate a dystrophin-deficient Sprague-Dawley muscular dystrophy rat (MDR). Biochemical and immunofluorescent analyses were performed to confirm loss of dystrophin in striated muscles of this rat model. In situ and ex vivo muscle function was assessed in wild-type (WT) and MDR muscles at 3, 6, and 12 months of age, followed by histopathological analyses. MDR muscle tissues exhibited loss of full-length dystrophin and reduced content of other dystrophin glycoprotein complex members. MDR extensor digitorum longus (EDL) muscles and diaphragms displayed pronounced and progressive muscle weakness beginning at 3 months of age, compared to WT littermates. EDLs also exhibit susceptibility to eccentric contraction-induced damage. Functional deficits in soleus muscles were less severe and were associated with a right shift in force-frequency relationship. MDR muscles display progressive histopathology including degenerative lesions, fibrosis, regenerative foci, and modest adipose deposition. MDR is a preclinical model of DMD that exhibits many translational features of the human disease, including a large dynamic range of muscle decrements, that has high utility for the evaluation of potential therapeutics for DMD.

Duchenne muscular dystrophy is the hereditary progressive neuromuscular disease associated with mutations in the DMD gene encoding dystrophin protein and is characterized by striated muscles and cardiomyocytes impairment. It is X-linked recessive disorder and more prevalent in males. Females are carriers of the pathological mutation. It leads to impediment to diagnosis of this disease in women. Mild and severe clinical manifestations can also appear in women and they are attributable to chromosomal aberrations on the short arm of X-chromosome (Xp21.2) and skewed X-chromosome inactivation. The article presents a case of Duchenne muscular dystrophy in a girl with a nonsense mutation in the DMD gene. Primary diagnosis was suspected by gastroenterologist due to elevated levels of creatine phosphokinase and transaminase. The importance of diagnosis in preclinical stage of the disease is highlighted, moreover it became significantly relevant with appeared therapeutic options for patients with this mutation.

To test sensitivity of the Segmental Assessment of Trunk Control (SATCo) to changes in neutral vertical (NV) head and trunk control in children with neuromuscular disorders (NMD) and compared with typically developing (TD) children. In this observational cross-sectional study, SATCo was applied in 19 children with NMD (10y6 m(3y7 m), 2 female) and 19 TD children (7y10 m(4y12 m), 6 female). Statistical differences between condition (NMD and TD), segment (seven trunk segments), and control type (static, active, and reactive control), and relationship between age and SATCo outcomes were analysed with linear mixed-effects models (LME). SATCo scores were measurably different between conditions (F(1, 39.6) = 151.0, p < .001), segments (F(6, 138.3) = 23.3, p < .001), control type (F(2, 33.0) = 6.3, p = .005), and interactions condition segment (F(6, 138.3) = 23.3, p < .001) and condition control type (F(2, 33.0) = 6.3, p = .005). A significant relationship between decreasing active control and increasing age in 10 children with Duchenne muscular dystrophy confirmed measurable decline in trunk control following diagnosis. The results showed that SATCo is sensitive to differences in trunk control status in NMD. While still ambulatory, children with NMD presented already a measurable trunk control deficit at varying segments. SATCo has potential as an outcome measure for therapeutic interventions or effectiveness of treatments promoting NV trunk control in children with NMD and needs further study.What this paper addsNeutral vertical head/trunk control was different between NMD and TD childrenSATCo is sensitive to head/trunk control differences between NMD and TD childrenAmbulant children with NMD showed measurable head/trunk control deficit at various segmentsSATCo detected subtle head/trunk control changes in early disease stages of NMDActive segmental trunk control declines with increasing age in Duchenne muscular dystrophy.

Background: Traditional quality-adjusted life-year (QALY)–based cost-effectiveness analyses (CEAs) may inadvertently penalize treatments extending survival in populations with disabilities. Duchenne muscular dystrophy (DMD) is a rare, progressive disease diagnosed during childhood with significant morbidity, premature mortality, and considerable healthcare costs. The impact of delaying mortality on CEAs for DMD is unclear. Objective: To evaluate the impact of delaying nonfatal progression and/or mortality using a QALY-based CEA for three hypothetical DMD treatments, assessing if treatment value increases by delaying morbidity and/or mortality. Methods: A previously published, five-state QALY-based cost-effectiveness model for analyzing treatments in an early ambulatory DMD population was replicated, validated, and adapted to include an early nonambulatory (ENA) population. Maximum annual treatment price was determined for three hypothetical treatments individually compared for each population with standard of care (SoC): (A) delays nonfatal progression and mortality; (B) delays nonfatal progression; or (C) delays mortality. A 10-year delay was assessed for all three. Willingness-to-pay (WTP) thresholds ranged from $50 000 to $200 000/QALY. Results: In both populations, QALYs gained vs SoC were highest for the hypothetical treatment delaying both nonfatal progression and mortality. Maximum annual treatment price was highest for the hypothetical treatment delaying nonfatal progression only (both populations and all WTP thresholds). Delaying mortality alone consistently had a negative annual valuation (not cost-effective even at $0 price), ranging from $−8685 to $−2148 (EA population) and $−13 253 to $−3278 (ENA population). For all treatments, valuation for the ENA population was consistently lower. Discussion: These model results illustrate that delaying both nonfatal progression and mortality is less valuable in a traditional CEA than delaying nonfatal progression alone, even when the additional survival is at the patient’s best possible health and lowest costs. These results emphasize the significant shortcomings of QALY-based CEAs for assessing the value of potential life-extending treatments for progressive, disabling diseases, like DMD. Conclusions: These results suggest that within a traditional CEA, delaying mortality decreases a DMD treatment’s value estimate, countering society’s values and norms for desired life extension in vulnerable populations. These limitations must be carefully considered when interpreting model results and highlight the need for applying other value assessment methodologies.

Children with Duchenne Muscular Dystrophy (DMD) often experience impairments in trunk control and balance, which may negatively impact their functional abilities. This study aimed to investigate the relationships between trunk control, balance and functional skills in ambulatory children with DMD. Thirty-two ambulatory boys with DMD aged 5-12 years (mean age: 8.59 ± 2.14 years) participated in the study. Assessments included the Trunk Control Measurement Scale (TCMS), Paediatric Functional Reach Test (PFRT), Timed-Up-and-Go Test (TUG) and Paediatric Evaluation of Disability Inventory (PEDI). Self-care scores on the PEDI were significantly correlated with TCMS-selective movement control (r = 0.424, p = 0.016) and PFRT (r = 0.566, p = 0.001). Mobility scores were correlated with TCMS-static sitting balance (r = 0.512, p = 0.003), selective movement control (r = 0.518, p = 0.002), dynamic reaching (r = 0.664, p < 0.001), PFRT (r = 0.350, p = 0.049) and TUG (r = -0.600, p < 0.001). No significant correlations were found between PEDI-social function scores and trunk control or balance measures (p > 0.05). The findings suggest that trunk control and balance are important contributors to functional performance, particularly in self-care and mobility domains, in ambulatory children with DMD. ClinicalTrials.gov identifier: NCT06379906.

The DMD gene, the largest gene in the human genome, is particularly prone to exonic deletions or duplications due to recombination events during gametogenesis, with frameshift deletions typically seen in Duchenne muscular dystrophy (DMD) and in-frame deletions with Becker muscular dystrophy or X-linked dilated cardiomyopathy. Dystrophic changes in the muscles result in elevated creatine kinase levels. DMD deletions are also associated with cognitive challenges. In this case series, we present three unrelated families with the incidental finding of in-frame DMD deletions on chromosome microarray, two involving exons 49-51 and one involving exons 45-60. All of the children are asymptomatic or minimally symptomatic with normal echocardiograms and inherited the deletion from their maternal grandfathers who are asymptomatic into their 60s.The identification of incidental DMD deletions on chromosome microarray can have important implications in terms of diagnosis, screening and follow-up, prognostication and family planning. The finding of a familial in-frame DMD deletion in an asymptomatic maternal grandfather is reassuring with regard to prognosis and disease course. When a maternally inherited in-frame DMD deletion is identified in an asymptomatic young male, or unexpectedly at the time of invasive prenatal testing, it is crucial to test both maternal grandparents.

Muscle degeneration is the hallmark of muscular dystrophies-genetically heterogeneous disorders traditionally approached through the lens of molecular pathogenesis or symptomatic management in isolation. Here, we present a deliberately interdisciplinary synthesis that bridges molecular genetics, clinical phenotyping, and evidence-based orthopedic decision-making to address a significant critical gap: the lack of genotype-informed, function-oriented frameworks for musculoskeletal complications. We re-evaluate disease entities-not only by their molecular etiology (e.g., DMD, LMNA, DUX4 dysregulation), but through the prism of orthopedic manifestations as diagnostic gateways and therapeutic milestones. For instance, early rigid spine in LMNA-related dystrophy is not merely a sign of contracture, but a red flag demanding cardiac risk stratification before surgical planning, in alignment with current consensus. Similarly, scoliosis management in Duchenne muscular dystrophy is discussed through quantitative decision thresholds (Cobb angle ≥ 20-30°, FVC ≥ 30-35%) derived from long-term outcome studies, rather than general clinical recommendations. Critically, we confront challenges posed by disease-modifying therapies: patients now survive into their 30s and 40s, yet develop novel, therapy-exacerbated orthopedic phenotypes (e.g., steroid-induced osteoporosis, atypical spinal rigidity). Therefore, we argue that precision orthopedics-tailored surveillance, genotype-stratified intervention timing (e.g., D4Z4 repeat-guided monitoring in FSHD, and realistic functional goal-setting (e.g., scapular arthrodesis for overhead function)-should become the gold standard of care. For example, desminopathies may show marked phenotypic variability even within the same mutation. Our review thus serves not only as a molecular overview, but as a practical roadmap for neurologists, geneticists, orthopedic surgeons, and rehabilitation specialists seeking to translate genomic insights into durable functional outcomes.