Neuromuscular Disorders最新文献

{"title":"26PTherapeutic outcomes and prognostic determinants in juvenile myasthenia gravis","authors":"S. Puppala,&nbsp;V. Tandon,&nbsp;S. Sundaram,&nbsp;S. Nair","doi":"10.1016/j.nmd.2025.105489","DOIUrl":"10.1016/j.nmd.2025.105489","url":null,"abstract":"<div><div>Juvenile myasthenia gravis (JMG) is a rare autoimmune neuromuscular disorder characterized by onset before 18 years of age. Although it shares clinical similarities with adult myasthenia gravis (MG), differences exist in disease severity, antibody profiles, and thymic pathology. This study aimed to evaluate therapeutic outcomes and identify predictors of clinical response in JMG patients treated at a single tertiary care center. A retrospective observational analysis was conducted on inpatient records of JMG patients with symptom onset at ≤18 years, admitted between 1999 and 2020. Prepubertal onset was defined as ≤12 years. Clinical and demographic data were analyzed, with treatment outcomes assessed according to the Myasthenia Gravis Foundation of America (MGFA) guidelines. A good outcome was defined as achieving complete stable remission, minimal manifestations, or clinical improvement. Sixty JMG patients (63.3% female) with a mean age of onset of 11.4 years were followed for an average of 7 years (range 1–22). At initial presentation, 56.6% exhibited generalized symptoms. Anti-acetylcholine receptor and muscle-specific kinase antibodies were positive in 68.5% and 5% of cases, respectively. Prepubertal onset was observed in 33 patients, with ocular symptoms being significantly more prevalent in this group compared to post-pubertal group (66.7% vs. 14.8%, p&lt;0.001). Three patients with ocular onset progressed to generalized myasthenia when assessed at follow up. Immunotherapy was administered to 71.6% of patients, with all receiving glucocorticoids and 38.3% receiving steroid-sparing agents. Thymectomy was performed in 47.5% of cases, with no thymomas identified. A good outcome was achieved in 83.3% of patients, while 15% had suboptimal outcomes, including one fatality due to immunosuppressant-related toxicity. Crisis at presentation was noted in three post-pubertal patients, and relapse rates (16 patients) were similar across prepubertal and post-pubertal groups. Ocular MG (OMG) patients responded significantly better to acetylcholinesterase inhibitors alone (p=0.036), though overall treatment responses did not differ between ocular and generalized groups or between prepubertal (78.8%) and post-pubertal (88.8%) patients. More than three-quarters of patients with JMG achieved good outcomes. OMG was associated with earlier age of presentation and good response to acetylcholinesterase inhibitors alone, with outcomes comparable to generalized myasthenia.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105489"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204348","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":"180PExploring motor function decline in lower and upper extremity function across different genotypes in Duchenne muscular dystrophy","authors":"E. Fleerakkers ,&nbsp;J. Broos ,&nbsp;R. Hoek ,&nbsp;Y. Krom ,&nbsp;M. Michaels ,&nbsp;H. Kan ,&nbsp;H. van Duyvenvoorde ,&nbsp;M. van der Holst ,&nbsp;E. Niks","doi":"10.1016/j.nmd.2025.105533","DOIUrl":"10.1016/j.nmd.2025.105533","url":null,"abstract":"<div><div>In patients with Duchenne muscular dystrophy (DMD) loss of lower limb function precedes prior to arm function. Additionally, the risk of losing ambulation (LoA) as a clinical milestone is associated with specific genotypes. However, it is less clear if the timing of losing lower and upper limb milestones is related and if the same genotypes are related to loss of hand-to-mouth movement (LoHM) as major upper limb milestone. Outpatient clinical data from DMD patients at Leiden Univ Med Center was obtained from the Dutch Dystrophinopathy Database. Patients were categorized by location of the pathogenic variant (proximal ≤exon 44 vs. distal ≥exon 45) and by exon skipping eligibility (amenable to skipping of exon 44, 45, 51, or 53). The association between age at LoA and LoHM (defined as PUL 2.0 entry score &lt;3) was tested using Spearman correlation. Kaplan-Meier curves were used to visualize the time to LoA and LoHM. Timing of LoA and LoHM were compared across different subgroups using log-rank tests. A total of 120 patients were included (mean baseline age: 9.9 y, SD 7.35; mean follow-up: 6.64 y, SD 4.37; average 7.4 visits/patient). Eighty patients reached LoA (mean age at LoA 10.7 y (SD 2.05)) and 41 LoHM (mean age at LoHM 18.1 y (SD 5.88)). LoA and LoHM were moderately correlated (r=0.421, p=0.003). The mean time to LoA was 2.9 years earlier in exon 51 skippable patients than in exon 44, without reaching statistical significance (p=0.186). However, a significant difference was observed in time to LoHM, the mean time to LoHM was 6.6 years earlier in exon 51 skippable patients than in exon 44 (p=0.017). In the other subgroups no significant differences were observed. Our data show that earlier LoA is associated with earlier LoHM and that the group amenable to exon 51 skipping experiences earlier LoHM than those eligible for exon 44 skipping. These results may serve as a predictive marker for upper limb function and support clinical monitoring and decision-making.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105533"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204351","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":"181PAAV gene therapy with delandistrogene moxeparvovec in two-year old patients with Duchenne muscular dystrophy: clinical efficacy measured by digital endpoints","authors":"C. Grotski ,&nbsp;L. Servais ,&nbsp;D. Eggenspieler ,&nbsp;E. Henricson ,&nbsp;P. Strijbos ,&nbsp;P. Sidiropoulos ,&nbsp;R. Finkel ,&nbsp;C. McDonald","doi":"10.1016/j.nmd.2025.105534","DOIUrl":"10.1016/j.nmd.2025.105534","url":null,"abstract":"<div><div>Clinical assessment of the efficacy of AAV microdystrophin gene therapy in very young Duchenne muscular dystrophy patients below the age of 4 years is a challenge. We utilized the EMA qualified digital endpoint Stride velocity 95th centile (SV95c) measured by the Syde wearable device (SYSNAV) to assess the clinical efficacy over 12 months following administration of AAV microdystrophin gene therapy with delandistrogene moxeparvovec in very young ambulatory patients with DMD. Two patients with Duchenne muscular dystrophy (2 years and 2 years 3 months at baseline/pre-infusion) were treated with delandistrogene moxeparvovec as part of the Sarepta Therapeutics Study SRP-9001-103 (ENDEAVOR). Under a separate protocol, patients wore the Syde device for two to 4 weeks consecutively prior to treatment and at 3-, 6-, 9- and 12-months post-treatment. External comparator data were obtained from the ActiLiège-Next study (NCT05982119), a multicenter natural history study of ankle wearable technology in DMD patients &lt;4 years. Adherence to bilateral ankle monitoring was excellent with &gt; 50 hours of data collected at all time points. Baseline values of SV95c were 1.27 m/s and 1.13 m/s in the treated patients in comparison to a mean +SD of 1.31 (+0.25) m/s in n=13 external comparators. The 9-month change in SV95c was +0.36 m/s and +0.35 m/s in the two treated patients versus mean 9-month changes of +0.08 m/s (+ 0.14) in 3 steroid-treated and +0.23 m/s (+ 0.10) in 8 steroid naïve comparators of up to four years of age. Continued improvements in treated patients beyond that observed in natural history comparators have been seen at 12 months. Improvements were documented using SV95c in two of the youngest delandistrogene moxeparvovec treated patients with DMD to date and the improvements in mobility in the community over 9 to 12 months appear to be greater than that seen with or without steroids in very young external comparators. Use of ankle wearable technology providing the SV95c digital endpoint appears promising as an approach to assessing clinical efficacy of gene therapy in very young patients with DMD ages two years and above.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105534"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204352","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":"183PThe impact of genotype on north star ambulatory assessment in individuals with Duchenne muscular dystrophy treated with corticosteroids: a single-center study of 416 patients","authors":"K. Bonarrigo ,&nbsp;C. Goldsbury ,&nbsp;P. Horn ,&nbsp;P. Vilaisaktipakorn ,&nbsp;L. Reebals ,&nbsp;A. Zygmunt ,&nbsp;C. Tian","doi":"10.1016/j.nmd.2025.105536","DOIUrl":"10.1016/j.nmd.2025.105536","url":null,"abstract":"<div><div>Previous studies have shown that certain genotypes in Duchenne muscular dystrophy (DMD) result in variable disease severity. Some of these studies included individuals treated and not treated with corticosteroids while others included multiple sites with varying care standards. This study aims to assess motor function in ambulatory DMD, as measured by the North Star Ambulatory Assessment (NSAA), and its correlation to genotypes in a large cohort of individuals with DMD treated with corticosteroids at a single center. This retrospective review included medical records of individuals with DMD who were treated with corticosteroids for at least 12 consecutive months. Encounters were excluded if individuals were receiving disease-modifying therapy or in clinical trials. Data were analyzed using a linear model with repeated measures. 2098 encounters from 416 individuals were included. NSAA scores for the entire cohort improved in early childhood until plateauing around age 6 to 8.5 years, followed by a progressive decline at age 9 years. Four exon-skippable groups were compared at ages 7, 10, and 14 years to the rest of the cohort. For exon 51 skip-amenable group, NSAA scores at age 7 years were 2.46 points lower (p=.009) but declined less rapidly than the rest of the cohort. For exon 53 skip-amenable group, NSAA scores at age 7 years were 2.54 points lower (p=.029) and declined at a similar rate compared to the rest of the cohort. For exon 44 and 45 skip-amenable groups, there was no significant difference in NSAA scores at these ages compared to the rest of the cohort. These findings are in line with previous observations of genotype-phenotype correlations in DMD and provide enhanced information for trial design and clinical management.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105536"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204355","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":"36PUnderstanding muscle biopsy pain: what to expect during and after","authors":"B. Labella ,&nbsp;G. Brochier ,&nbsp;M. Beuvin ,&nbsp;A. Chanut ,&nbsp;E. Lacene ,&nbsp;C. Labasse ,&nbsp;A. Madelaine ,&nbsp;F. Levy-Borsato ,&nbsp;S. Leonard-Louis ,&nbsp;G. Bassez ,&nbsp;D. Seilhean ,&nbsp;T. Evangelista","doi":"10.1016/j.nmd.2025.105499","DOIUrl":"10.1016/j.nmd.2025.105499","url":null,"abstract":"<div><div>Open muscle biopsy (OBM) is a valuable diagnostic tool, but patients frequently express concerns about the surgical risks and potential discomfort. The aim of this observational study is to describe the characteristics of pain encountered during and after OBM and to assess the prognostic factors that may influence patient’s pain perception. Patients aged &gt; 18 years who underwent OBM at the Pitié-Salpêtrière Hospital in Paris and provided informed consent were enrolled in the study. Clinical data and frailty assessment were collected prior to the intervention. Following OBM, patients completed a detailed questionnaire, including the numerical rating scale (NRS) for pain assessment, and the PHQ-9 questionnaire. Follow-up phone calls were performed at 15 and 30 days. Eighty-four patients (25 males) were enrolled, with a mean pain score of 2.5 on the NRS. The most painful phase of the OBM was the sampling collection phase (52/84, 61.9%), followed by the local anesthesia phase (17/84, 20.2%). Overall global satisfaction, including medical communication, service comfort and biopsy procedure, was rated as 9/10. No major complications were observed in the follow-up period, available for 63 patients. Twenty-one patients (38.8%) reported mild pain (NRS 1-3), usually lasting up to 48 hours, while eight patients (12.7%) experienced moderate pain (NRS 4-6). Overall, only twenty-four patients (38.1%) took an antalgic treatment after OBM, with paracetamol being the first line analgesic (22/24, 91.4%), yielding a good therapeutic response. Pre-interventional anxiety wasn’t associated with higher pain perception during OBM. Pain experienced during OBM is usually mild. After OBM, patients generally report little to no discomfort. Therefore, OBM is a safe and well-tolerated procedure.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105499"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204390","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":"167PQualitative interviews with caregivers of children aged 4–7 years with Duchenne muscular dystrophy to assess content validity of the proxy-completed DMD-QOL","authors":"A. Pearlmutter ,&nbsp;D. Powell ,&nbsp;D. Carlton ,&nbsp;E. Chen ,&nbsp;K. Gallington ,&nbsp;D. Bacci ,&nbsp;D. Gelhorn ,&nbsp;M. Cho ,&nbsp;D. Dashiell-Aje","doi":"10.1016/j.nmd.2025.105520","DOIUrl":"10.1016/j.nmd.2025.105520","url":null,"abstract":"<div><div>The Duchenne muscular dystrophy quality of life (DMD-QoL) is a 14-item questionnaire designed to assess physical functioning, psychological impact, and social participation among males with Duchenne muscular dystrophy (DMD) that has been validated for use in boys aged 7+ years by proxy report and boys aged 10+ years by self-report. There is currently an evidence gap for use of the proxy-completed DMD-QoL among younger DMD patients. We conducted qualitative concept elicitation/cognitive interviews with caregivers of children under 7 years of age with DMD in the UK and US. The interviews explored the patient experience with DMD and assessed the relevance, comprehensiveness, ease of use, and understandability of the proxy-completed DMD-QoL. Interviews were completed with 7 caregivers (all parents) of children aged 5–7 years with DMD in the UK (n=3) and US (n=4); the mean age at DMD diagnosis was 3.4 years (range: 0–5.3 years). All caregivers (n=7/7) reported that the DMD-QoL instructions were understandable, the recall period was clear, and they were able to answer each item with the response options provided. Frequently endorsed concepts that were relevant for this age group included difficulty getting around (n=7/7), feeling tired (n=6/7), pain (n=6/7), and feeling unhappy (n=6/7). Fewer caregivers endorsed the relevance of psychological impact concepts (eg, he felt embarrassed [n=3/7), he found it hard to talk to people [n=3/7)) or reported they may not be easily attributable to DMD; however, most caregivers anticipated that such concepts would be relevant for their child in the future. Overall caregiver feedback indicated that the proxy-completed DMD-QoL is easy to use, understandable, and face valid for use by caregivers of children aged 4–7 years with DMD. A second phase of interviews should be conducted to further evaluate the measure’s generalizability and accessibility in this age group, including among children aged 4 years with DMD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105520"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204451","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":"192PGNT0004, Genethon's AAV-based gene therapy for Duchenne muscular dystrophy: long-term follow-up of ambulatory boys enrolled in the dose-escalation phase of GNT-016-MDYF","authors":"V. Laugel ,&nbsp;S. De Lucia ,&nbsp;J. Davion ,&nbsp;N. Daniele ,&nbsp;F. Cao ,&nbsp;M. Sanz ,&nbsp;L. BUSCARA ,&nbsp;S. Blaie ,&nbsp;L. Thibaut ,&nbsp;M. Sagot ,&nbsp;A. Riviere ,&nbsp;E. Creoff ,&nbsp;M. Lelait ,&nbsp;A. Valent ,&nbsp;G. Perret ,&nbsp;S. Braun ,&nbsp;F. Muntoni","doi":"10.1016/j.nmd.2025.105545","DOIUrl":"10.1016/j.nmd.2025.105545","url":null,"abstract":"<div><div>GNT0004 is an AAV-8 based gene therapy, containing a shortened functional dystrophin gene (hMD1) with a Spc5.12 promoter, targeting skeletal and cardiac muscles for treating Duchenne muscular dystrophy (DMD). GNT0004 is being evaluated in the international all-in-one (phase 1/2/3) clinical trial GNT-016-MDYF, including a first-in-human dose escalation (Part 1), a placebo-controlled pivotal Phase 3 (Part 2), and a long-term follow-up (Part 3). Ambulatory boys with DMD, aged 6 to 10 years, with a stable or early decline in their North Star Ambulatory Assessment (NSAA) score are included. Participants are on stable corticosteroid treatment and have been followed for at least 6 months in the natural history (NH) study GNT-014-MDYF. Long-term data from Part 1 patients receiving Dose 2 (3 × 10¹³ vg/kg, selected for Part 2) are presented. A comparison with an external control group from the NH study was conducted to explore clinical efficacy. Five patients were enrolled in Part 1, three of whom received Dose 2. At week 8, biopsy results showed a mean of 53% hMD1-positive fibers at Dose 2. A significant decrease in serum creatine kinase (CK) levels was observed post-dose that remains persistently low from week 8 and up to 2 years. At one year, the mean CK level was 5,306 IU/L, representing a mean decrease of -68% compared to baseline (mean: 19,175 IU/L). Clinically, functional outcomes were stable or improving, clearly differentiating from the NH progression across all efficacy parameters (e.g., a delta of 4.7-point on NSAA scale and of 0.1 m/s on the Stride velocity 95th centile (SV95C) at one year). No serious adverse events reported at Dose 2. GNT0004 at Dose 2 was well-tolerated and provided long-term stabilization of the sarcolemma, as evidenced by persistent low levels of CK, with a clear clinical benefit. These effects will need to be confirmed in Part 2 with 64 DMD patients to be enrolled.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105545"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204503","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":"Risdiplam and nusinersen in spinal muscular atrophy: a descriptive real-world study on motor function outcomes in northwestern Iran","authors":"Mohammad Barzegar ,&nbsp;Bita Poorshiri ,&nbsp;Khatereh Rezazadeh ,&nbsp;Vahideh Toopchizadeh ,&nbsp;Shadi Shiva ,&nbsp;Akram Motamedi","doi":"10.1016/j.nmd.2025.106210","DOIUrl":"10.1016/j.nmd.2025.106210","url":null,"abstract":"<div><div>Spinal muscular atrophy (SMA) types 2 and 3 are chronic neuromuscular disorders characterized by progressive motor impairment. Although disease-modifying therapies such as risdiplam and nusinersen have shown clinical efficacy, real-world data in pediatric populations remain limited. This prospective observational study evaluated motor function outcomes in 20 children with SMA (aged 3 to 13 years; 12 with type 2, 8 with type 3) receiving either risdiplam or nusinersen in Northwestern Iran. Motor function was assessed at baseline, 2 weeks, 1 month, and 6 months using the Hammersmith Functional Motor Scale-Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Both treatments were associated with significant improvements in motor function during the 6-month follow-up. In the risdiplam group, HFMSE scores significantly increased at 1 and 6 months, while RULM scores improved at all time points. In the nusinersen group, HFMSE scores improved consistently at all assessments, whereas RULM scores showed minimal change. Nerve conduction parameters remained stable, and no adverse events were reported. These findings suggest that both risdiplam and nusinersen enhance motor function in children with SMA, with risdiplam providing notable benefits in upper limb function. Long-term, comparative studies are warranted to optimize individualized treatment strategies.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"54 ","pages":"Article 106210"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004373","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":"Consensus recommendations and considerations for the delivery and monitoring of gene therapy in patients with Duchenne muscular dystrophy","authors":"Jodi M. Wolff ,&nbsp;Nora Capocci ,&nbsp;Evrim Atas ,&nbsp;Diana X. Bharucha-Goebel ,&nbsp;John F. Brandsema ,&nbsp;Russell J. Butterfield ,&nbsp;Christina B. Chadwick ,&nbsp;Manuela Corti ,&nbsp;Thomas O. Crawford ,&nbsp;Linda Cripe ,&nbsp;John W. Day ,&nbsp;Tina Duong ,&nbsp;Mai K. ElMallah ,&nbsp;Kevin M. Flanigan ,&nbsp;Lindsey A. George ,&nbsp;Natalie L. Goedeker ,&nbsp;Erica Goude ,&nbsp;Sharon Hesterlee ,&nbsp;Brian Lin ,&nbsp;Natalie K. Katz ,&nbsp;Barry J. Byrne","doi":"10.1016/j.nmd.2025.106208","DOIUrl":"10.1016/j.nmd.2025.106208","url":null,"abstract":"<div><div>Gene transfer therapy represents a major advancement in the treatment of patients with Duchenne muscular dystrophy (DMD). As clinical use expands, there is an urgent need for standardized, evidence and practice-informed guidelines to ensure safe and equitable delivery of this and similar products. A group of clinicians and researchers, coordinated by the Muscular Dystrophy Association and Parent Project Muscular Dystrophy, developed these consensus guidelines to outline recommendations for patient selection, institutional readiness, monitoring, and adverse event management, particularly in the first three months after treatment. This document emphasizes the importance of experienced multidisciplinary teams, real-time safety surveillance, and transparent reporting to support patient safety and clinician decision-making after treatment.</div><div>While the Food and Drug Administration has approved only one gene therapy product for the treatment of patients with DMD, these recommendations may potentially apply to other products in clinical development. Currently, significant knowledge gaps remain regarding long-term safety, durability, and optimal timing of dosing, particularly for patients with advanced disease. Researchers do not fully understand how combination therapies and genetic background may impact the response to gene therapy. To address these gaps, ongoing real-world data collection, cross-center collaboration, and flexible adaptation of clinical protocols are essential. While these guidelines are based primarily on clinical expertise rather than well-established evidence, the guideline provides a foundation to support administration of gene therapy for patients with DMD. As the field evolves, continued refinement will be essential to maximize benefit, reduce risk, and inform future standards of care.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"54 ","pages":"Article 106208"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154325","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":"50PInflammatory cells immunophenotyping, MHC1 and type1 interferon proteins expression in myositis and hereditary muscle diseases with inflammatory cell infiltration: a north African study","authors":"E. Farhat ,&nbsp;A. Ben Hmid ,&nbsp;M. Ben Ahmed","doi":"10.1016/j.nmd.2025.105513","DOIUrl":"10.1016/j.nmd.2025.105513","url":null,"abstract":"<div><div>Muscle biopsy (MB) is an important tool to help differentiate autoimmune inflammatory myopathies (AIM) from hereditary muscular diseases (HMD). HMD may sometimes show inflammatory cell infiltration mimicking AIM. The usefulness of immunohistochemical (IHC) stains of the major histocompatibility complex class 1 (MHC1) become controversial, as the possibility of their upregulation in some HMD. More sensitive markers of AIM are recently used such as myxovirus resistance A (MxA) and interferon-stimulated gene 15 (ISG15), a type1 interferon-inductible (IFN1) proteins. This study aims to compare the morphological and the immunophenotype patterns of the inflammatory cells, versus the MHC1 and IFN1 proteins’ expression in different subsets of AIM and HMD. We selected samples of 85 patients diagnosed with AIM including cases with overlap myositis, dermatomyositis, immune-mediated necrotizing myopathy and inclusion body myositis; and HMD including patients with muscular dystrophies and metabolic myopathies. The inclusion criterion was the presence of inflammatory infiltrate on MB. We characterized the IHC expressions of the inflammatory cells (CD4, CD8, CD20, CD68), MHC1, and IFN1-inductible proteins (MxA and ISG15). There was no statistically significant difference in the types of infiltrating cells between the two groups except for the CD68+ T cells, most abundant in the HMD group (p&lt;0,005). MHC1 was expressed in muscle fibers of AIM and HMD without significant difference between the two groups. The sarcoplasmic expressions of MxA and ISG15 were highly and significantly prevalent in DM patients (80%; p&lt;0,005). Our study demonstrated the limitation of inflammatory cells immunophenotyping and the IHC of the MHC1 in the differential diagnosis of AIM and HMD with inflammatory changes. It also enables us to confirm that IFN1-inductible proteins are much accurate IHC markers of AIM especially in the DM subgroup.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105513"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204101","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}