Neuromuscular Disorders最新文献

{"title":"301PPatterns of volume and fat infiltration in skeletal muscle of adults with spinal muscular atrophy","authors":"T. Duong,&nbsp;M. Anna Yao,&nbsp;R. Yoseph Hailu,&nbsp;S. Vogt-Domke,&nbsp;J. Day,&nbsp;N. Hageman","doi":"10.1016/j.nmd.2025.105549","DOIUrl":"10.1016/j.nmd.2025.105549","url":null,"abstract":"<div><div>Spinal muscular atrophy (SMA) is a genetic disorder characterized by protein deficiency affecting lower motor neurons and the neuromuscular junction, leading to muscle weakness and fatigue. Pathologically, muscles exhibit progressive fat infiltration and atrophy. Whole-body MRI is a valuable tool for assessing these changes in vivo. Structural T1 MRI sequences can quantitatively measure fat replacement in skeletal muscle, while fluid-sensitive T2 sequences, such as short tau inversion recovery (STIR), can detect inflammatory changes that precede clinical symptoms and fat infiltration. These imaging techniques can serve as diagnostic biomarkers and monitor disease progression. Recent advancements in artificial intelligence (AI) have enabled reliable automated methods for masking and identifying individual muscles in whole-body MRI, facilitating group-level analysis of muscle volume and fat fraction. Previous studies have highlighted distinct patterns of muscle involvement across different SMA types. This study aims to characterize the neuromuscular pathway structures affected in adults with SMA type 3. We conducted whole-body 3T MRI on six subjects with SMA type 3 (five ambulatory, one non-ambulatory; ages 26-67). Imaging sequences included T1 (2-point) DIXON, T2 STIR, and structural T1/T2 of the brain. An AI-based masking approach (Springbok) was employed to isolate and assess 71 individual muscles across 36 functional groups for muscle volume, fat fraction, and left-right asymmetry. Group-level analysis revealed reduced volumes in hip flexors, hip adductors, knee extensors, and proximal upper extremity muscles, with significant fat infiltration in these areas. Asymmetry levels varied among subjects, with individual muscles exhibiting localized fat infiltration patterns. Notably, atrophy and fat fraction were most pronounced in the hip and knee extensors in the lower extremities, while axial muscles of the trunk and proximal limbs were predominantly affected in the upper extremities. These findings align with previous studies and clinical presentations, suggesting a targeted pathological process affecting specific motor units. This study supports the hypothesis that SMN protein deficiency in SMA selectively impacts certain neuromuscular motor groups, correlating with segmental lower motor neuron weakness observed clinically and in post-mortem analyses. Limitations include the small cohort size and absence of additional imaging modalities. Future research will aim to enhance statistical power and explore central effects on higher structures within the neuromuscular pathway, potentially identifying specific biomarkers or therapeutic targets.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105549"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204117","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":"302PWhole-body fat-referenced MRI measures disease progression in patients with spinal and bulbar muscular atrophy","authors":"M. Karlsson ,&nbsp;P. Widholm ,&nbsp;A. Ahlgren ,&nbsp;P. Hatsis ,&nbsp;C. Gentry ,&nbsp;C. Grunseich ,&nbsp;A. Gharib ,&nbsp;A. Kokkinis ,&nbsp;A. AlQahtani ,&nbsp;P. Fratta ,&nbsp;L. Zampedri ,&nbsp;D. Jayaseelan ,&nbsp;H. McKenzie ,&nbsp;S. Wastling ,&nbsp;M. Katsuno ,&nbsp;S. Yamada ,&nbsp;Y. Kishimoto ,&nbsp;T. Kawase ,&nbsp;T. Taoka ,&nbsp;V. Vigiletta","doi":"10.1016/j.nmd.2025.105550","DOIUrl":"10.1016/j.nmd.2025.105550","url":null,"abstract":"<div><div>More sensitive outcome measures in spinal bulbar muscular atrophy (SBMA) clinical trials are needed. Fat-referenced MRI has been successful in characterizing muscle atrophy and fat replacement in other neuromuscular diseases. We aimed to investigate the ability of fat-referenced MRI to assess changes in muscle composition and track disease progression in SBMA and the association to clinical outcomes. Whole-body Dixon MRI of 25 SBMA patients with mild-to-moderate disease severity were analyzed using AMRA Researcher, quantifying lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) in 38 muscle groups. Muscles were classified as Normal Appearing, Intermediate, or End-Stage based on baseline fat content. Muscle measurements were combined into composites. Responsiveness was assessed using standardized response mean (SRM). Composites were correlated to SBMA functional rating scale (SBMAFRS), modified SBMAFRS (leg and trunk), and 2-minute-walk-test (2MWT) at baseline. The mean±SD age was 57.6±7.1 years, SBMAFRS 40.6±3.9, CAG Repeats 45.3±3.7, BMI 26.3±3.8 kg/m2. Patients had median (min,max) 5 (0,30) Normal Appearing, 26 (8,34) Intermediate, and 2 (0,13) End-Stage muscles. 12-month change in whole-body composite LMV/MFF/MFI was mean±SD (SRM) -4.38±2.48% (-1.76), 2.49±1.38 p.p. (1.81), and 0.79±0.51 p.p. (1.55) respectively (p&lt;0.001). Change in thigh composite was -4.97±3.50% (-1.42), 2.81±1.65 p.p. (1.70), and 1.05±0.76 p.p. (1.38) (p&lt;0.001). There were moderate correlations to SBMAFRS (r: 0.46/-0.41/-0.51), modified SBMAFRS (r: 0.50/-0.63/-0.67), and 2MWT (r: 0.73/-0.53/-0.55). Whole-body MRI captures muscle composition in SBMA patients and shows good responsiveness in describing 12-month natural progression. Baseline MRI assessments reflect disease severity as measured by SBMAFRS and 2MWT.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105550"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204122","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":"WMS 2025 Congress Summary Programme","authors":"","doi":"10.1016/S0960-8966(25)00954-X","DOIUrl":"10.1016/S0960-8966(25)00954-X","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 106227"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204163","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":"WMS 2025 Congress Summary Programme","authors":"","doi":"10.1016/j.nmd.2025.106249","DOIUrl":"10.1016/j.nmd.2025.106249","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 106249"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204177","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":"03INVMyotonic dystrophy type 1: A multisystemic disorder with remarkable clinical variability and burden","authors":"H. Braakman","doi":"10.1016/j.nmd.2025.105459","DOIUrl":"10.1016/j.nmd.2025.105459","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Myotonic dystrophy type 1 (DM1) is a complex, autosomal dominant disorder caused by a CTG repeat expansion in the DMPK gene. Though traditionally classified as a neuromuscular disease, DM1 is fundamentally a multisystemic disorder. It affects numerous organ systems including the heart, lungs, gastrointestinal (GI) tract, endocrine system, eyes, and central nervous system. Symptoms can be broadly divided into those due to skeletal muscle dysfunction—such as myotonia and weakness—and those arising from extra-muscular systems. Importantly, non-muscular manifestations often have a greater impact on daily functioning, independence, and quality of life than muscle symptoms. Recognizing DM1 as a multisystemic disease, rather than a purely neuromuscular one, is essential for effective diagnosis and care. This presentation aims to increase awareness of the broad and often underestimated systemic burden of DM1 and to highlight the need for early recognition, comprehensive screening, and tailored multidisciplinary care across all age groups. DM1 is one of the most variable disorders in medicine, with wide differences in age of onset, symptom severity, and organ involvement—even within the same family. This variability contributes to diagnostic delays and fragmented care. While muscle symptoms are often more visible, it is the gastrointestinal, urological, cognitive-behavioral, and fatigue-related symptoms that most disrupt daily life. These are frequently underdiagnosed, despite being central to patient morbidity. The burden also extends to families, who often provide complex daily care. Cardiac and pulmonary complications are major drivers of mortality in DM1. Conduction defects, arrhythmias, and sudden cardiac death, along with respiratory insufficiency and hypoventilation, pose serious and often under-recognized risks. Systematic screening and timely management of these complications are critical to improve survival. The initial diagnosis of DM1 may be made by a wide range of clinicians, depending on the patient’s presenting symptom: cardiologists, pulmonologists, ophthalmologists, gastroenterologists, neurologists, psychiatrists, or endocrinologists may be involved, as well as pediatricians or clinical geneticists in childhood-onset cases. A key challenge is that DM1 may present through any of its many systemic features, which means that if clinicians do not actively consider a multisystemic diagnosis, it may be overlooked. This presentation will provide an overview of the most burdensome systemic manifestations of DM1, their variability across age groups and individuals, and advocate for a proactive, comprehensive approach to screening, surveillance, and care. DM1 is not just a muscle disease but a multisystemic condition in which non-muscular symptoms often dominate the clinical picture. In particular, cardiac and respiratory complications are key contributors to mortality. The central message is: “What we do not ask, we do not know —and wha","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105459"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204182","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":"02PImmunophenotyping of patients with inclusion body myositis: INSPIRE-IBM study","authors":"P. Farahat,&nbsp;C. Phillips,&nbsp;I. Hernandez,&nbsp;M. Wencel,&nbsp;T. Mozaffar,&nbsp;A. Villalta","doi":"10.1016/j.nmd.2025.105466","DOIUrl":"10.1016/j.nmd.2025.105466","url":null,"abstract":"<div><div>Inclusion Body Myositis (IBM) is a skeletal muscle disorder characterized by severe muscle inflammation and degeneration, leading to functional decline. T cells in IBM patients are skewed towards a Th1 and highly-differentiated phenotype that correlates with disease duration. However, the regulation of this T cell signature with IBM progression remains unclear. The INSPIRE-IBM study is a multicenter longitudinal investigation that enrolled patients ages 40 years or older with clinically defined IBM under the ENMC 2011 criteria. Immunophenotyping of baseline peripheral blood mononuclear cell (PBMC) samples confirmed an elevation of highly-differentiated T cells with a KLRG1+ CD8+ TemRA phenotype. Despite a slight negative correlation between regulatory T cells (Tregs) and KLRG1+ TemRAs, We found a subset of Tregs exhibiting high TIGIT expression. Given that TIGIT suppresses Th1 responses, further studies that define the functional impact of Treg subsets on highly-differentiated T cells may inform immune-modulating therapies to improve IBM outcomes.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105466"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204259","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":"05PConsistent clinical features of anti-Mi-2 myopathy: a Korean retrospective cohort study","authors":"S. Kim ,&nbsp;Y. Choi ,&nbsp;Y. Choi ,&nbsp;W. Kim ,&nbsp;H. Park","doi":"10.1016/j.nmd.2025.105469","DOIUrl":"10.1016/j.nmd.2025.105469","url":null,"abstract":"<div><div>Anti-Mi-2 is a myositis-specific autoantibody associated with a distinct dermatomyositis phenotype. However, its clinical characteristics in Korean patients are not well documented. This study aimed to characterize the clinical features of anti-Mi-2 positive myopathy in a Korean cohort. We conducted a retrospective review of patients diagnosed with inflammatory myopathy at Gangnam Severance Hospital between October 2003 and March 2025. Among 247 patients tested for myositis-specific antibodies using a 16-antibody line blot assay, eleven (4.5%) were positive for anti-Mi-2 antibody (signal intensity ≥2+). Clinical, serological, histopathological, and radiological data were analyzed. The median age at symptom onset was 62.0 years [Interquartile range (IQR): 52.0-69.5]. Among the eleven patients, five were male and six were female. All patients exhibited classic dermatomyositis-type cutaneous features, including heliotrope rash, Gottron's sign, V-sign, and shawl sign. Symmetric proximal limb weakness was observed in 10 patients, though the overall severity was mild. The median MRC sum score was 48.0 [IQR: 47.5–50.5], with 5 patients scoring ≥50, indicating relatively preserved muscle strength in a substantial proportion of this subgroup. Myalgia was reported in five patients, and oropharyngeal involvement was noted in one. No patients showed facial weakness, interstitial lung disease, or coexisting connective tissue disease. Cardiomyopathy and malignancy were identified in two patients each. The median creatine kinase level at diagnosis was 4,183 U/L [IQR: 3,205-5,678]. Muscle biopsies were available for ten patients, revealing necrotic fibers in seven and perifascicular atrophy in four. EMG was performed in eight patients, showing myopathic patterns in five. MRI findings, available in five patients, were consistent with inflammatory myopathy in all cases. In this Korean cohort, anti-Mi-2 positive myopathy showed a consistent clinical phenotype, with classic dermatomyositis-type cutaneous features, relatively preserved muscle strength, and minimal systemic involvement. These findings contribute real-world evidence that may support early recognition and classification of this myositis subtype in clinical settings.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105469"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204261","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":"33PNew insights into the mouse model for Jo-1, PL-7, and PL-12 associated anti-synthetase syndrome","authors":"D. Bachir ,&nbsp;C. Preusse ,&nbsp;S. Lichtenberg ,&nbsp;L. Eigenfeldt ,&nbsp;K. Koch-Hölsken ,&nbsp;V. Umathum ,&nbsp;A. Herrmann ,&nbsp;L. Vinnenberg ,&nbsp;A. Schänzer ,&nbsp;I. Pinal-Fernandez ,&nbsp;A. Mammen ,&nbsp;B. Fassbender ,&nbsp;M. Seifert ,&nbsp;S. Meuth ,&nbsp;W. Stenzel ,&nbsp;T. Ruck","doi":"10.1016/j.nmd.2025.105496","DOIUrl":"10.1016/j.nmd.2025.105496","url":null,"abstract":"<div><div>Anti-synthetase syndrome (ASyS) is an autoimmune condition, characterized by autoantibodies directed against an aminoacyl-tRNA synthetase (anti-ARS). Patients present clinical symptoms such as myositis, interstitial lung disease, Raynaud’s phenomenon, and arthritis. Anti-Jo-1, anti-PL-7 and anti-PL-12 are the most frequent anti-ARS. However, their role in ASyS pathogenesis remains incompletely understood and an animal model could be essential to gain new insights into the underlying pathophysiology. Therefore, aiming to characterize these pathophysiological features, we established and continued the studies on a mouse model for Jo-1, PL-7 and PL-12 associated ASyS. ASyS was induced in NOD.Idd3/5 mice by injection of Jo-1, PL-7 or PL-12 recombinant protein in Complete Freund’s Adjuvant (CFA) in combination with OX86. Controls received CFA and Phosphate Buffered Saline only. Muscle strength was assessed, and the reactivity of autoantibodies was evaluated in the sera of mice. Morphological characteristics of skeletal muscle and lung tissue and the tissue infiltrating immune cells were validated in detail using immunohistochemistry. Immunized mice displayed clinical symptoms including muscle weakness and specific reactivity of autoantibodies in the sera. Quantitative analyses of the muscle tissue revealed immune cells in the epimysium and the adjacent perifascicular area. Immunohistological analyses of lung specimens showed a pronounced peribronchial accumulation of lymphocyte aggregates, including B cells, T cells, and macrophages, within the lung tissue. Pending whole tissue RNA-seq and TCR/BCR sequencing will provide in-depth analysis of these immune cells. We present an update to the established mouse model, which recapitulates features of the human phenotype. The analysis of autoantibody reactivity and histological studies enhances our understanding of the molecular pathogenesis and immune cell involvement, providing new insights into the pathomechanisms of ASyS.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105496"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204340","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":"19PClinico-patho-serological correlation for classification of idiopathic inflammatory myopathies and therapeutic outcomes - a real-world retrospective cohort","authors":"S. Sivaraman Nair,&nbsp;J. George,&nbsp;R. Poyuran,&nbsp;D. Narasimhaiah","doi":"10.1016/j.nmd.2025.105483","DOIUrl":"10.1016/j.nmd.2025.105483","url":null,"abstract":"<div><div>The classification of idiopathic inflammatory myopathies (IIMs) has undergone a paradigm shift with the application of muscle specific antibodies (MSAs) and biology-specific immunohistochemical stains. Many of these techniques are being gradually adopted in developing nations. We aimed to study the spectrum of subtypes in a retrospective cohort of IIMs with specific focus on the roles of clinical, pathological and serological evaluation and the therapeutic choices. We screened the electronic medical records between April 2017 to March 2024 for patients diagnosed as IIM with a follow up of at least one year. Patients where an alternate diagnosis could not be ruled out were excluded. We applied the European Neuromuscular Centre criteria for classification into dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASyS), and sporadic inclusion body myositis (sIBM). Those with a well-defined systemic autoimmune disease were classified as overlap myositis and the rest were labelled unclassified. Descriptive analysis of the clinical, investigational and therapeutic aspects of the subcategories were done. We identified 124 case records of IIM of whom 67 (53.7% females) were included for analysis. The mean age of onset was 42.1 (± 16.9) years with pediatric onset in 7 (10.4%). Symptom duration at presentation was 18.9 (35.3) months. Extramuscular features were seen in 19 (28.4%); 16 (23.9) with cutaneous manifestations, 3 (4.5%) each with arthritis and pulmonary disease and 1 (1.5%) with cardiomyopathy. Four (6%) had association with malignancies. The patient subclassification was DM in 14 (20.9%), IMNM in 11 (16.4%), ASyS in 3 (4.5%), sIBM in 15 (22.4%), and OM in 6 (8.9%) while 18 (26.9) were unclassified. Serology profile was incomplete in 7(38.9%) unclassified. Muscle biopsy was available for 61. Among DM, 6 were Mi2+, 3 NXP2+, and 2 MDA5+. Classical DM muscle pathology was recorded in 6. IMNM has 2 SRP+ and 3 HMGCR+ while ASyS had 2 Jo1+ and 1 PL-7+. Glucocorticoids were given in 97%, oral immunotherapies in 87.9%, and cyclophosphamide or rituximab were given in 25.3%. Excluding sIBM, 15.4% had a favourable immunotherapy response. The immunotherapy response did not differ between unclassified and other groups. Nearly three-fourths of the cohort could be classified into a specific IIM subcategory with judicious application of the criteria. Use of serology and biopsy were suboptimal in seronegative and unclassified groups. Higher therapeutic options were needed in a quarter.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105483"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204343","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":"179PMethodology of the CINRG expanded Duchenne natural history study (eDNHS): assessing disease progression in the era of glucocorticoid and gene therapy treatments","authors":"C. McDonald ,&nbsp;E. Henricson ,&nbsp;T. Duong ,&nbsp;H. Gordish-Dressman ,&nbsp;L. Morgenroth ,&nbsp;CINRG eDNHS Investigators","doi":"10.1016/j.nmd.2025.105532","DOIUrl":"10.1016/j.nmd.2025.105532","url":null,"abstract":"<div><div>The Expanded Duchenne Natural History Study (eDNHS) is a multicenter prospective study aimed at evaluating the long-term progression of Duchenne muscular dystrophy (DMD). The study investigates how evolving clinical care, particularly the increasing use of glucocorticoid therapies and emerging gene repair and gene therapy interventions, influences disease progression in DMD patients. Building upon the original CINRG Duchenne Natural History Study (DNHS), initiated in 2005, the eDNHS includes planned enrollment of up to 500 male participants of any age diagnosed with DMD. Data collection incorporates comprehensive demographic and genetic profiling, physician assessments, and standardized functional evaluations. Key outcomes are measured using tools such as the North Star Ambulatory Assessment (NSAA), Performance of the Upper Limb Module (PUL), timed function tests, pulmonary function tests, and patient-reported outcomes related to function, behavior, and health satisfaction. The study also integrates biomarker discovery efforts. Longitudinal assessments are conducted at baseline, every 6 months through year 3, and annually thereafter for up to 10 years. The eDNHS captures the impact of glucocorticoids and gene therapies on disease progression, providing critical insights into treatment efficacy. It identifies functional milestones and biomarkers that are predictive of long-term outcomes. The study’s longitudinal design allows for the evaluation of the evolving clinical outlook for DMD patients. The eDNHS provides an up-to-date methodology for tracking disease progression in DMD, advancing evolving patient care standards and the development of new therapeutic agents. By incorporating both traditional treatments like glucocorticoids and novel gene therapies, the study supports regulatory approval processes and informs best practices for optimizing clinical care for individuals with DMD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105532"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204350","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}