Neuromuscular Disorders最新文献

{"title":"38PClinical course and treatment of anti-mitochondrial M2 antibody-positive myositis: a single-center retrospective case series","authors":"Y. Nishimori,&nbsp;N. Eura,&nbsp;K. Sugie","doi":"10.1016/j.nmd.2025.105501","DOIUrl":"10.1016/j.nmd.2025.105501","url":null,"abstract":"<div><div>We reported that anti-mitochondrial M2 antibody (AM2A)-positive myositis may be an independent subtype of autoimmune myositis based on clinicopathological and statistical analysis. It is still unknown how effective conventional immunotherapy is among patients with AM2A-positive myositis. We chose 13 AM2A-positive patients who underwent muscle biopsy from January 2017 to March 2025. We retrospectively examined their clinical history including reactivity to immunotherapy. There were 6 men and 7 women. The mean age at muscle biopsy was 58 ± 4.1 years. The average of pre-biopsy disease duration was 27.5 ± 24.3 months. Twelve patients showed high creatine kinase (CK), and 3 had severe muscle weakness with an MMT score lower than 4 in the extremities and/or the neck muscles. Although all patients are ambulatory, 4 patients had respiratory failure and 2 of them needed mechanical ventilation support. All patients showed arrhythmia and/or cardiac dysfunction on echocardiogram. Except for 2 patients who have not been treated, 11 patients had prednisolone as the first line. Six had additional medication, including immunosuppressants and/or intravenous immunoglobulin. Five patients exhibited a favorable clinical course, whereas symptoms relapsed as the medication dosage was reduced in 4 patients. In addition, the arrhythmia persisted in 2 of them despite improvement of muscle strength. Immunotherapy including prednisolone and intravenous immunoglobulin was ineffective in one patient with ventilation support and he died with comorbidity. Another patient was weaned from the ventilator and walked by himself. However, he suddenly died of unknown causes after discharge from hospital. Although most of the patients showed good response to immunotherapy in the early state, some experienced difficulties with treatment. Cardiac problems could remain in the long term. We need to carefully follow up on the condition including cardiac function with AM2A-positive myositis.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105501"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"52PClinical and radiological profile of a cohort of anti-HMGCR myopathy","authors":"S. Vengalil,&nbsp;S. Ahmed,&nbsp;S. Nashi,&nbsp;D. Menon,&nbsp;A. Mahadevan,&nbsp;A. Nalini","doi":"10.1016/j.nmd.2025.105515","DOIUrl":"10.1016/j.nmd.2025.105515","url":null,"abstract":"<div><div>Anti-HMGCR myopathy is an immune-mediated necrotizing myopathy. We undertook this study to know the clinical and radiological features of a cohort of anti-HMGCR myopathy. Retrospective study of 10 patients of anti-HMGCR myopathy, seen in NIMHANS, India, from March 2023-March 2025. Details of clinical features and lab investigations were collected. MRI muscle was done using 3T Aera MRI (axial T1, T2, and T2-weighted fat-saturated images). Edema was scored in STIR using Modified Stramare scoring and fatty infiltration in T1 using Mercuri scoring. 10 patients. Mean age at evaluation-34.8+20.7 years. Male:female 8:2. Mean duration of illness was 20.8+36.2 months. (8 patients onset within a year). Initial clinical feature was proximal lower limb (LL) weakness in 9, upper limb in 1. History of statin exposure noted in one. Neck flexor weakness (7), facial weakness (5), exertional myalgia (3), bulbar involvement (3), distal LL weakness (3) and respiratory muscle weakness (1) were the other features. One patient was wheelchair bound. None had cardiac involvement. Mean Creatine Kinase (CK) was 10499+3787 IU/L. Biopsy (n=6) showed necrosis in 5, myophagocytosis in 2, perifascicular atrophy 2, sparse endomysial inflammatory infiltrate in 1. CT chest (n=8) - no Interstitial lung disease. MRI muscle showed that Hip/Gluteus region had highest fatty infiltration (mean score 0.85), followed by Thigh Posterior (0.73) and Obturator (0.73). The Leg region had the lowest level (0.41). 60% of all muscles had normal muscle tissue (Score 0), while 30% had mild fatty infiltration (Score 1). Severe (score 3) and complete fatty replacement (Score 4) were less common. Posterior leg muscles had mean edema score of 2.33 while the obturator group had the least score of 1.25. 70% of muscles in each group had scores of 2 and 3. Anti-HMGCR Myopathy may have subacute onset, high CK. Cardiac and respiratory involvement are rare. MRI muscle showed distinct patterns.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105515"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"166PEarly functional trajectories in young boys with Duchenne muscular dystrophy: a 24-month international study using the NSAA","authors":"G. Coratti ,&nbsp;S. Paolucci ,&nbsp;G. Baranello ,&nbsp;J. Expósito-Escudero ,&nbsp;A. Wolfe ,&nbsp;M. Brooke ,&nbsp;M. Pane ,&nbsp;A. Nascimento ,&nbsp;S. Messina ,&nbsp;F. Ricci ,&nbsp;A. D'Amico ,&nbsp;L. Bello ,&nbsp;C. Bruno ,&nbsp;V. Sansone ,&nbsp;R. Masson ,&nbsp;V. Nigro ,&nbsp;F. Muntoni ,&nbsp;E. Mercuri ,&nbsp;International DMD network","doi":"10.1016/j.nmd.2025.105519","DOIUrl":"10.1016/j.nmd.2025.105519","url":null,"abstract":"<div><div>This study investigated 24-month trajectories of the North Star Ambulatory Assessment (NSAA) total score and its timed items—the 10-meter walk/run (10MWR) and time to rise from floor (TRF)—in 315 ambulant boys with genetically confirmed Duchenne muscular dystrophy (DMD), aged 4 to 7 years, across Italian (n=113), UK (n=196), and Spanish (n=6) national networks. Assessments were performed at baseline, 12, 18, and 24 months. The 315 boys had a total of 523 24-month paired assessments. The NSAA score improved at 24 months in the group with an age at baseline of 4 years (n=102): +5.06 and 5 years(n=133): +2.16, while declined in the group aged at baseline of 6 years (n=138): -2.95 and 7 years (n=141): -5.51. 10MWR improved at 24 months in the group with an age at baseline of 4 years (n=102): –1.11s and 5 years(n=133): -0.74s, while it declined in the group aged at baseline of 6 years (n=138): +1.47s and 7 years (n=141): +2.14s. TRF improved at 24 months in the group with an age at baseline of 4 years (n=102): –1.14s, while it declined in the group aged at baseline of 5 years (n=132): +1.28s, of 6 years (n=135): +5.00 s and 7 years (n=138): +6.59s. We used a linear mixed model to identify factors influencing NSAA score over time, with time, TRF at baseline, 10MWR at baseline, age at baseline, and NSAA at baseline as predictors. Random effects were included to account for repeated measures within patients. The analysis found a significant decline in NSAA scores over time. Poorer baseline TRF, 10MWR performance, and older age at baseline were all associated with lower NSAA scores over time. These findings highlight the variability in early disease progression across the different measures in young boys with DMD and underscore how baseline values can help to identify distinct trajectories. Stratification by baseline values may support more individualized monitoring and inform clinical trial design in this age group.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105519"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"178PTwo-year stride-level evaluation of ambulatory function in ambulant DMD patients above 4 years old","authors":"M. Poleur ,&nbsp;G. Parinello ,&nbsp;E. Vrščaj ,&nbsp;A. Dolanska ,&nbsp;P. Nowakowski ,&nbsp;C. Anghelescu ,&nbsp;L. Szabo ,&nbsp;M. Leanca ,&nbsp;A. Mirea ,&nbsp;S. Kodsy ,&nbsp;A. Saleh ,&nbsp;D. Osredkar ,&nbsp;J. Haberlova ,&nbsp;A. Potulska-Chromik ,&nbsp;N. Butoianu ,&nbsp;P. Delmar ,&nbsp;P. Strijbos ,&nbsp;D. Eggenspieler ,&nbsp;L. Servais ,&nbsp;the ActiLiège-Next study group","doi":"10.1016/j.nmd.2025.105531","DOIUrl":"10.1016/j.nmd.2025.105531","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is characterized by severe and progressive muscle weakness. Assessing investigational drug efficacy in a reasonable timeframe is challenging due to a lack of objective, reliable, and sensitive outcome measures. The wearable sensor ActiMyo/Syde was developed to assess motor function accurately and precisely at the stride level during daily life. One variable derived from these sensor data, SV95C (measuring the 5% most rapid strides), was recently qualified as primary endpoint for ambulant DMD by the European Medicines Agency. To gather 3-year longitudinal functional data using this sensor, ambulant DMD patients and controls were enrolled in the ActiLiège-Next study. Patients were asked to wear sensors at both ankles daily during the first 3-12 months and for 1 month every 3 months afterwards, and controls were asked to wear them for 1 month every 12 months. Eighty-seven ambulant DMD patients aged 4 to 14 years (median: 8.0y) and 37 controls (9.8y) were enrolled. As of Jan 2025, &gt;95% of patients showed good adherence with sensor wear at baseline. SV95C reliability was excellent, with an intraclass correlation coefficient of 0.96 for patients and 0.87 for controls. The Spearman correlation with North Star ambulatory assessment, 6-minute walk test, 4-stair climbing test and time to rise from floor was 0.65, 0.54, -0.71 and -0.66, respectively (n=76-81; p&lt;0.001). For patients between 4 and 8 years old, mean SV95C improved from baseline at 6 months (0.08m/s, SRM [standardized response mean]=0.55, n=37), and then declined at 12 and 18 months (-0.06m/s, SRM=ns, n=27; and -0.13m/s, SRM=-0.52, n=18, respectively). Patients ≥8 years old experienced a marked decline at 6, 12 and 18 months: -0.09m/s (SRM=-0.51, n=30), -0.15m/s (SRM=-0.99, n=24) and -0.24m/s (SRM=-2.10, n=16), respectively. These data confirm the excellent reliability, external validity and responsiveness of SV95C in ambulant DMD above 4 years old. All available 18- and 24-month data will be shared at the congress.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105531"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"41PTreatment outcomes in idiopathic inflammatory myopathies based on pathology and autoantibody profiles: a single-center study of 127 cases","authors":"N. Eura,&nbsp;Y. Nishimori,&nbsp;A. Yamanaka,&nbsp;T. Shiota,&nbsp;H. Tanaka,&nbsp;T. Ohashi,&nbsp;H. Shimizu,&nbsp;M. Yamaoka,&nbsp;N. Yamada,&nbsp;N. Iguchi,&nbsp;A. Tanaka,&nbsp;M. Sugata,&nbsp;H. Nanaura,&nbsp;T. Kiriyama,&nbsp;K. Sugie","doi":"10.1016/j.nmd.2025.105504","DOIUrl":"10.1016/j.nmd.2025.105504","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders affecting skeletal muscle and various organs. Although myositis-specific autoantibodies (MSAs) aid in diagnosis, treatment strategies remain suboptimal. Large-scale, subtype-specific outcome studies are limited. We retrospectively analyzed 127 IIM patients who underwent muscle biopsy at our institution between 2009 and 2023. Inclusion required pathological confirmation, excluding inclusion body myositis and secondary myositis related to collagen diseases or immune checkpoint inhibitors. MSAs were detected in 97 patients (76%). Among MSA-positive cases, dermatomyositis (DM: 27.1%) and immune-mediated necrotizing myopathy (IMNM: 27.1%) were most common, followed by antisynthetase syndrome (ASS: 14.4%) and polymyositis (PM: 2.7%). DM was linked to anti-TIF1-γ, MDA5, Mi-2, and NXP-2 antibodies (in that order); IMNM to SRP, HMGCR, and AMA-M2. HMGCR-positive patients had the highest CK levels. Interstitial lung disease (ILD) was seen in 90% of MDA5, 67% of Mi-2, and 50% of SRP cases. Malignancies occurred in all antibody subtypes except MDA5, NXP-2, and HMGCR, and originated from diverse organ systems. Seven of 13 traceable malignancy cases died within 3 years of IIM diagnosis. Notably, AMA-M2-positive patients showed a high frequency of respiratory failure unrelated to ILD (40%) and cardiac events such as arrhythmias or heart failure (89%). All patients received glucocorticoids. Immunosuppressants were used in 80% of MDA5, 60% of HMGCR, and 47% of ASS cases. The most frequently used immunosuppressant was tacrolimus, followed by methotrexate and azathioprine. IVIg was limited to four severe cases. At 3 years, the mean prednisolone dose was 8.4 ± 5.5 mg; only SRP-positive patients reached &lt;5 mg/day. Orthopedic complications such as fractures occurred in 9.2%. This study highlights clinical diversity and treatment challenges in IIM. Despite improved diagnostics, more effective, tailored therapies are urgently needed.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105504"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"175PA prognostic score for time to loss of ability to rise from supine in Duchenne muscular dystrophy (DMD)","authors":"F. Muntoni ,&nbsp;J. Signorovitch ,&nbsp;J. Marden ,&nbsp;N. Done ,&nbsp;S. Wang ,&nbsp;H. Akbarnejad ,&nbsp;H. Kang ,&nbsp;T. Li ,&nbsp;S. Ward ,&nbsp;A. Manzur ,&nbsp;N. Goemans ,&nbsp;V. Straub ,&nbsp;E. Mercuri ,&nbsp;L. Servais","doi":"10.1016/j.nmd.2025.105528","DOIUrl":"10.1016/j.nmd.2025.105528","url":null,"abstract":"<div><div>Loss of ability to rise from supine (LoR) is an early milestone in DMD that reduces independence in daily living and marks the progression towards loss of ambulation. Previous research has identified single thresholds of rise from supine (RFS) time as prognostic for LoR (e.g., &gt;5s). We used machine learning to develop a prognostic score for time to LoR based on multiple data-driven thresholds and patient characteristics that are easily assessed in clinical practice and routinely included in clinical trials. Longitudinal data from 595 boys with DMD were drawn from UZ Leuven, PRO-DMD-01, North Star UK, iMDEX, and placebo arms from trials of tadalafil, ataluren, and drisapersen. LoR was defined as the first assessment with timed RFS ≥30s, graded RFS of 1, or NSAA rise score of 0. A Weibull survival classification and regression tree model was used to identify risk groups. Candidate predictors included age, height, weight, BMI, steroid regimen, type, and duration, RFS, 10-meter walk/run (10MWR), and NSAA items. Patients had a mean ±standard deviation baseline age of 8.3±2.1 years, with RFS time of 6.1±4.2s, and NSAA total score of 24.9±5.8. The fitted model identified 5 risk groups showing excellent risk stratification, with median times to LoR of 0.3, 0.7, 1.5, 2.7, and 4.5 years (log-rank p&lt;0.001). Risk groups differed by baseline RFS with thresholds at &lt;5s, &lt;10s, and &lt;21s, with further stratification by NSAA sit-to-stand score (0/1 vs 2). The model explained 42.2% of variation in time to LoR, comparable to more complex survival models with both continuous measures and age and 10MWR included as additional predictors (pseudo-R² 44.8%). This prognostic score, based on readily assessable functional measures, provides clinically meaningful differentiation of times to LoR. Upon validation in independent data, this model could inform the design of clinical trials seeking to enrich for levels of LoR risk and benchmark LoR outcomes for patients receiving novel therapies.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105528"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"04ODenervated human muscle fibers promote reinnervation via neurotrophic factor release in SMA and ALS","authors":"R. Gokul-Nath ,&nbsp;C. Collins ,&nbsp;L. Valverde ,&nbsp;C. Lleixa ,&nbsp;J. Verdú-Díaz ,&nbsp;A. Di Lorenzo ,&nbsp;P. Llarch ,&nbsp;L. Querol ,&nbsp;C. Marini-Bettolo ,&nbsp;R. Rojas-García ,&nbsp;J. Diaz-Manera","doi":"10.1016/j.nmd.2025.105462","DOIUrl":"10.1016/j.nmd.2025.105462","url":null,"abstract":"<div><div>Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neuromuscular disorders characterized by the progressive degeneration of motor neurons, leading to skeletal muscle denervation, weakness, and atrophy. However, the molecular pathways underlying the muscle response to denervation in human tissue remain poorly defined. We performed single-nucleus RNA sequencing (snRNA-seq) and ATAC-seq on muscle biopsies from patients with SMA type 3 (n = 7), ALS (n = 4), and age- and sex-matched healthy controls (n = 5). Data were analyzed using a custom bioinformatics pipeline based on Seurat and Harmony. Key findings were validated by immunofluorescence (IF) on additional muscle samples. To assess functional implications, rat spinal cord neurons were cultured in vitro with factors identified from muscle transcriptomic analyses. Fibro-adipogenic progenitor (FAP) cells were isolated from patient and control samples and subjected to single-cell RNA sequencing to identify transcriptionally distinct subpopulations. snRNA-seq revealed a significant increase in satellite and inflammatory cell populations, along with a reduction in myofiber and smooth muscle cell numbers in SMA and ALS muscle. Pseudobulk analysis showed that genes upregulated in SMA and ALS were enriched for pathways related to vascular development, cell projection organization, cell adhesion, synaptic remodelling, and neuronal development. A subpopulation of muscle fibers was identified in both SMA and ALS, characterized by elevated expression of genes involved in synaptic maintenance and axonal guidance, including MUSK, LRP4, COL19A1, EFNA5, and NTN1. ATAC-seq confirmed accessible chromatin regions at loci related to neuromuscular junction maintenance and neuronal growth, suggesting transcriptional readiness for protein expression. Immunofluorescence confirmed increased expression of these proteins in patient biopsies. Furthermore, rat spinal cord neurons cultured with muscle-derived neurotrophic factors such as EFNA, NTN1, and BDNF exhibited enhanced dendrite outgrowth. FAPs from patient muscle displayed upregulation of extracellular matrix components and neurotrophic factors implicated in neuronal support and synaptic repair. Our study reveals that denervated muscle fibers actively engage in a compensatory, pro-regenerative response by releasing neurotrophic factors aimed at restoring neuromuscular connectivity. These factors may serve as valuable biomarkers for disease progression and represent promising therapeutic targets for enhancing reinnervation in SMA and ALS. Future work should explore their potential in combination therapies aimed at modulating the muscle microenvironment to support motor neuron recovery.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105462"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"169PComparison of western-blot, mass spectrometry and simple-western methods shows that simple-western is the most sensitive method to detect µ-dystrophin","authors":"L. Buscara ,&nbsp;S. Genries-Ferrand ,&nbsp;C. Varela Moreira ,&nbsp;N. Stiet ,&nbsp;G. Cedrone ,&nbsp;C. Sagrere ,&nbsp;F. Salsac ,&nbsp;R. El-Khoury ,&nbsp;E. Bertil-Froidevaux ,&nbsp;C. Georger ,&nbsp;S. Blaie ,&nbsp;L. Thibaut ,&nbsp;F. Cao ,&nbsp;S. Braun ,&nbsp;G. Perret ,&nbsp;M. Blatzer ,&nbsp;N. Daniele","doi":"10.1016/j.nmd.2025.105522","DOIUrl":"10.1016/j.nmd.2025.105522","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD), a rare X-linked genetic disorder affecting male children, leads to progressively severe muscle dysfunction often associated with respiratory and/or cardiac insufficiencies and premature death. The pathology is caused by out-of-frame mutations in the DMD gene, leading to absence of dystrophin, a large muscle protein. As the large size of dystrophin cDNA impedes its packaging in AAV vectors, various shorter micro-dystrophin (µDys) transgenes are used for clinical development. Different analytical methods may be used to measure the µDys levels from muscle biopsies. GNT-016, a clinical trial investigating an AAV-based µDYS, uses the simple-western (SW) method for quantifying the therapeutic product. In an effort to document the differences in methodologies, we performed a side-by-side comparison of 3 methods used in DMD clinical trials. Total proteins extracted from DMDmdx rats’ muscles sampled after intravenous treatment with an AAV8-spC5-12-µDYS were used for the quantification of µDYS in dose-response experiments performed by nano LC/MS mass spectrometry, western-blot and SW methodologies. SW is a capillary-based electrophoretic method allowing separation and detection of proteins in a single device. Both mass spectrometry and SW prove advantageous compared to western-blot in terms of reproducibility and repeatability (CV&lt;25% for SW and CV&lt;8% for mass spectrometry). However, SW is over 4,000 times more sensitive than the 2 other methods. Considering the limited amounts of patient’s tissue available to measure dystrophin quantities, sensitivity appears to be a key factor. SW variability is lower than the recommended guidelines and easier to set-up than mass spectrometry, which requires very specific equipment and technical expertise. This method, used for the quantification of µDYS expression in our clinical trial, was globally consistent with the immunohistological results performed on the same samples.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105522"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Welcome to the 30th World Muscle Society Congress","authors":"","doi":"10.1016/j.nmd.2025.106211","DOIUrl":"10.1016/j.nmd.2025.106211","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 106211"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"54VPDistinct histopathological features of juvenile idiopathic inflammatory myopathies: a quantitative comparative study","authors":"F. Hakim ,&nbsp;S. Sakka ,&nbsp;M. Snoussi ,&nbsp;O. Boudawara ,&nbsp;K. Moalla ,&nbsp;N. Bouattour ,&nbsp;S. Daoud ,&nbsp;N. Charfi ,&nbsp;L. Sellami ,&nbsp;S. Marzouk ,&nbsp;T. Boudawara ,&nbsp;M. Damak","doi":"10.1016/j.nmd.2025.105517","DOIUrl":"10.1016/j.nmd.2025.105517","url":null,"abstract":"<div><div>Juvenile idiopathic inflammatory myopathies (JIIM), defined by onset before 18 years of age, are rare autoimmune disorders that can present with distinct clinical and serological profiles. However, specific histopathological features in JIIM remain underexplored. This study aims to identify histological characteristics distinct to JIIM through a quantitative comparative analysis. We conducted a retrospective study on patients diagnosed with IIM at a Tunisian neurology center, following the 2017 ACR-EULAR criteria. Histopathological features were analysed through a review of available slides, including fiber atrophy, necrosis, ischemia, regeneration, fibrosis, and inflammatory infiltrates, graded with a predefined scoring system. Available muscle samples were collected and examined for immunohistochemical markers (CD4, CD8, CD20, CD31, CD68, anti-MxA). Histological findings in juvenile patients were collected compared to those in adults. We included 13 juvenile cases from 100 IIM patients (13%). The mean age of JIIM was 12± 5,2 years (range: 3–17). Sex ratio: 0.18. JIIM included 10 dermatomyositis patients (2 anti-Mi2, 1 anti-NXP-2, 1 seronegative) and 3 overlap myositis (1 scleromyositis, 1 lupus-associated myositis, 1 anti-Jo-1 anti-synthetase syndrome). Juvenile onset was correlated with severe fiber atrophy (38.4%, p=0.024) with a perifascicular atrophy extended into the endomysium (53.8%, p=0.01). It was also associated with severe inflammatory infiltrates (46%, p=0.02), primarily in the perivascular region (84.6%, p=0.23). However, inflammatory cell types, vascular injury, and MXA staining did not show a specific pattern related to juvenile onset. JIIM is characterized by distinct histopathological features, including pronounced inflammatory infiltrates and perifascicular atrophy. These findings highlight the age-specific mechanisms in JMII, which may be associated with more severe outcomes.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105517"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}