Journal of neuromuscular diseases最新文献

{"title":"Antisense RNA therapies for muscular dystrophies.","authors":"Virginia Arechavala-Gomeza, Andrea López-Martínez, Annemieke Aartsma-Rus","doi":"10.1177/22143602251324858","DOIUrl":"https://doi.org/10.1177/22143602251324858","url":null,"abstract":"<p><p>Inherited muscular dystrophies are a heterogeneous group of diseases, caused by different types of genetic mutations. RNA therapies, and particularly antisense oligonucleotides, offer a palette of therapeutic strategies to either reduce the production of harmful proteins or to restore or increase protein expression. Consequently, they offer therapeutic promise for multiple forms of muscular dystrophies. This review outlines the different RNA therapy types considered for the treatment of Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy and myotonic dystrophy, emphasizing the strategies used to deliver these therapies to skeletal muscle with a focus on approaches that have reached the clinical trial stage.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251324858"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730432","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":"Automated analysis of quantitative muscle MRI and its reliability in patients with Duchenne muscular dystrophy.","authors":"Sara Nagy, Olga Kubassova, Patricia Hafner, Sabine Schädelin, Simone Schmidt, Michael Sinnreich, Jonas Schröder, Oliver Bieri, Mikael Boesen, Dirk Fischer","doi":"10.1177/22143602251319184","DOIUrl":"https://doi.org/10.1177/22143602251319184","url":null,"abstract":"<p><strong>Background: </strong>Quantitative muscle MRI is one of the most promising biomarkers to detect subclinical disease progression in patients with neuromuscular disorders, including Duchenne muscular dystrophy (DMD). However, its clinical application has been limited partly due to the time-intensive process of manual segmentation.</p><p><strong>Objective: </strong>We present a simple and fast automated approach to obtain quantitative measurement of thigh muscle fat fraction and investigate its reliability in patients with DMD.</p><p><strong>Methods: </strong>Clinical and radiological baseline and 6-month follow-up data of 41 ambulant patients with DMD were analysed retrospectively. Axial 2-point Dixon MR images of all thigh muscles were used to quantify mean fat fraction, while clinical outcomes were measured by the Motor Function Measure (MFM) and its D1 domain. Data obtained by automated segmentation were compared to manual segmentation and correlated with clinical outcomes. Results were also used to compare the statistical power when using automated or manual segmentation.</p><p><strong>Results: </strong>A mean increase of 3.55% in thigh muscle fat fraction at 6-month follow-up could be detected by both methods without any significant difference between them (p=0.437). The automated muscle segmentation method demonstrated a strong correlation with manually segmented data (Pearson's ρ = 0.97). Additionally, there was no statistically significant difference between the automated and manual segmentation methods in their association with clinical progression, as measured by the total MFM score and its D1 domain (p = 0.235 and p = 0.425, respectively).</p><p><strong>Conclusions: </strong>The presented automated segmentation technique is a fast and reliable tool for assessing disease progression, particularly in the early stages of DMD. It is one of the few studies validated using manual segmentation, and with further refinement, it has the potential to become a good surrogate marker for disease progression in various neuromuscular disorders.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251319184"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700566","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":"Erratum to \"Enhancing rehabilitation of neuromuscular diseases through virtual reality and gamification\".","authors":"","doi":"10.1177/22143602251324632","DOIUrl":"10.1177/22143602251324632","url":null,"abstract":"","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251324632"},"PeriodicalIF":3.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634306","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":"A historical perspective on the development of antisense oligonucleotide treatments for Duchenne muscular dystrophy and spinal muscular atrophy.","authors":"Annemieke Aartsma-Rus, Shin'ichi Takeda","doi":"10.1177/22143602251317422","DOIUrl":"https://doi.org/10.1177/22143602251317422","url":null,"abstract":"<p><p>Splice modulating antisense oligonucleotides (ASOs) have been approved for the treatment of spinal muscular atrophy (nusinersen) and Duchenne muscular dystrophy (eteplirsen) since 2016. Nusinersen obtained full approval based on convincing functional evidence in treated patients. The treatment is currently approved in over 40 countries. By contrast, eteplirsen received accelerated approval and functional evidence from clinical trials that treatment slows down disease progression is still lacking. Approval and access is restricted to the USA and several countries in the Middle-East. In this historical perspective we look back to the development paths of these two ASOs focusing on the differences between the approaches, the target tissues and the diseases. Based on this we propose learnings for future development of ASOs for progressive neuromuscular diseases.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251317422"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542393","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":"Prevalence and incidence rates of 17 neuromuscular disorders: An updated review of the literature.","authors":"Johanna Cw Deenen, André Lm Verbeek, Jan Jgm Verschuuren, Baziel Gm van Engelen, Nicol C Voermans","doi":"10.1177/22143602241313118","DOIUrl":"https://doi.org/10.1177/22143602241313118","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological frequency measures serve as reference point for patients, clinicians, researchers, and policymakers. Previously, we published a comprehensive review of the literature with prevalence and incidence rates for thirty neuromuscular disorders frequently encountered in the neuromuscular clinic. No meta-analyses were available at the time.</p><p><strong>Objective: </strong>We included various new studies and meta-analyses that have been published since 2014, we aim to update our previous review.</p><p><strong>Methods: </strong>Pubmed was searched for 'incidence' and 'prevalence' in combination with seventeen acquired and inherited neuromuscular disorders to identify peer-reviewed literature from 1990 to 2023. If multiple prevalence and incidence rates were found, these were summarized by providing the mean, the number of the estimates on which the mean was based and the range of these estimates. Additionally, we searched for meta-analyses to compare the found mean prevalence rates based on the summary of individual studies with the pooled prevalence rates based on the meta-analyses.</p><p><strong>Results: </strong>The mean prevalence estimates for 17 disorders ranged from 0.3/100,000 population for Lambert-Eaton myasthenic syndrome, glycogenosis type V and nemaline myopathy to 20/100,000 for Charcot-Marie-Tooth disease type I. We found annual incidence rates for eight disorders, ranging from 0.3/100,000 population for progressive (spinal) muscular atrophy and facioscapulohumeral muscular atrophy to 1/100,000 for Charcot-Marie-Tooth disease type 1 and myotonic dystrophy type 1. Plotting the mean prevalence estimates from the current study against the pooled prevalence estimates from eight meta-analyses showed reasonable agreement.</p><p><strong>Conclusions: </strong>Epidemiological frequencies about neuromuscular diseases- and in particular data on incidence are scarce. The mean prevalence estimates based on recently published studies on individual cohorts correspond well with the findings from the sparingly performed meta-analyses.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602241313118"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542432","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":"A rare homozygous <i>CAPN3</i> variant with distinct clinical features in unrelated families of Iraqi Jewish descent.","authors":"Nurit Assia Batzir, Naama Orenstein, Yuval Yaron, Alla Kuzminsky, Yoram Nevo, Osnat Konen, Lily Bazak, Gabriel Lidzbarsky, Lina Basel-Salmon, Sharon Aharoni","doi":"10.1177/22143602241301658","DOIUrl":"10.1177/22143602241301658","url":null,"abstract":"<p><p><i>CAPN3</i> encodes a calcium-activated skeletal muscle-specific protease. Pathogenic variants in <i>CAPN3</i> are associated with autosomal recessive and dominant limb-girdle muscular dystrophy. We report on three children and one adult from four unrelated Iraqi Jewish families, who harbor the same homozygous variant in <i>CAPN3</i>, p.Gln123Lys. Patients shared recognizable features of toe-walking and elevated creatine phosphokinase since childhood. The variant affects a conserved protein domain common to the calpain super family and likely represents a founder mutation in individuals of Iraqi Jewish ancestry. Our findings have potential implications on screening in relevant populations, allowing for more prompt diagnoses and future therapies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"279-284"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458275","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":"A novel variant in VMA21 causing adult-onset phenotype of X-linked myopathy with excessive autophagy with cardiac involvement in a Chinese patient.","authors":"Lin Chen, Ming-Juan Fang, Dabing Xu, Yong-Guang Shi, Yong-Zhu Han, Xu-En Yu, Yin Xu","doi":"10.1177/22143602241305510","DOIUrl":"10.1177/22143602241305510","url":null,"abstract":"<p><p>X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive hereditary disorder, characterized by childhood onset weakness of predominantly limb and trunk skeletal muscles due to progressive loss of muscle tissue. Cardiovascular system is clinically spared generally. Here, we report the clinical characteristics, muscle biopsy and genetic findings of one adult-onset individual suffering from XMEA, caused by a novel variant in a Chinese patient. Unusually, the patient developed unexplained hypertension with high left ventricular voltage and cardiac left ventricular hypertrophy at the age of 27. Muscle MRI revealed extensive fat infiltration in the lower extremities involving vastus medialis, vastus lateralis, vastus intermedius, and long head of the biceps femoris, while rectus femoris, gracilis, adductor magnus, semimembranosus, and sartorius muscle relatively preserved. A muscle biopsy indicated numerous cytoplasmic autophagic vacuoles and deposition of complement C5b-9 and also expression of MHC class I. Immunofluorescence staining showed increased immunoreactivity of lysosomal membrane protein LAMP2 and autophagosome protein LC3A/B both localized with cytoplasmic vacuoles, and autophagy carrier protein P62-positive vacuoles accumulated remarkably in the patient's muscle. VMA21 protein levels were lower than controls in skeletal muscle tissue, suggesting a possible pathogenicity related to an alteration of the splicing efficiency in intronic mutation. This is the first report of a Chinese patient with a novel hemizygous intronic c.163 + 3A > G variant in the VMA21 gene, expanding the mutational and phenotypic spectrum of this disease.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"285-292"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458271","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":"Taking ACTION to detect myocarditis related to recombinant gene transfer therapy for Duchenne Muscular Dystrophy; Consensus recommendations for cardiac surveillance.","authors":"Beth D Kaufman, Aravindhan Veerapandiyan, Jonathan H Soslow, Carol Wittlieb-Weber, Paul Esteso, Aaron K Olson, Renata Shih, Neha Bansal, Ashwin Lal, Katheryn Gambetta, Daphne Hsu, Linda Cripe, Chet Villa, Deipanjan Nandi","doi":"10.1177/22143602241303357","DOIUrl":"10.1177/22143602241303357","url":null,"abstract":"<p><strong>Background: </strong>A viral vector recombinant gene transfer therapy (GTT) has recently been approved by the FDA for males of all ages with Duchenne Muscular Dystrophy (DMD) without limitations regarding preexisting cardiac impairment. Acute myocarditis is a potential life-threatening short-term complication that has been reported following GTT. This immune mediated response can range from troponin elevation to rapid cardiovascular compromise and death, particularly in those with abnormal cardiac status at baseline. Early detection of cardiac compromise is essential to optimize outcomes.</p><p><strong>Objectives: </strong>The primary objective of this consensus statement is to advocate for caution with DMD GTT patient selection and to initiate preemptive monitoring for those who may be at increased risk for cardiac adverse events. Secondary objective is to deepen our understanding of short and long-term impact of DMD gene therapies on the heart.</p><p><strong>Methods: </strong>A national learning network of pediatric cardiologists with expertise in DMD developed recommendations for cardiac surveillance of DMD males receiving GTT based on available evidence and expert consensus opinion. A monitoring and treatment plan for standard and high cardiac risk patients was developed.</p><p><strong>Conclusion: </strong>Partnership of cardiologists with GTT prescribers is essential to identify patient-specific considerations that might influence risk for adverse cardiac events and alter post infusion monitoring and management plans. Consistency in cardiac surveillance practices across centers will expedite our knowledge regarding potential short- and long-term cardiac effects of GTT for DMD.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"173-182"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458307","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":"Ultra-Orphan drug development for GNE Myopathy: A synthetic literature review and meta-analysis.","authors":"Naoki Suzuki, Madoka Mori-Yoshimura, Ichizo Nishino, Masashi Aoki","doi":"10.1177/22143602241296226","DOIUrl":"10.1177/22143602241296226","url":null,"abstract":"<p><p>GNE myopathy is an autosomal recessive hereditary muscle disorder that has the following clinical characteristics: develops in early adulthood, gradually progresses from the distal muscles, and is relatively sparing of quadriceps until the advanced stages of the disease. With further progression, patients become non-ambulatory and need a wheelchair. There is growing concern about extra-muscular presentations such as thrombocytopenia, respiratory dysfunction, and sleep apnea syndrome. Pathologically, rimmed vacuoles and tubulofilamentous inclusions are observed in affected muscles. The cause of the disease is thought to be a sialic acid deficiency due to mutations of the <i>GNE</i> gene required for in vivo sialic acid biosynthesis. Sialic acid supplementation to a presymptomatic GNE myopathy mouse model was effective in preventing the development of the disease. Several clinical studies have been conducted to evaluate the safety and efficacy of sialic acid supplementation in humans. Based on the favorable results of these studies, an extended-release aceneuramic acid formulation was approved for treatment of GNE myopathy in Japan in March 2024. It is anticipated that it will be a significant step in the development of an effective treatment for GNE myopathy and other ultra-orphan diseases.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"183-194"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458289","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":"Glycogenosis type XI, a rare association between muscle and skin manifestations - the contribution of proteomics for the understanding of the underlying myopathology.","authors":"Andreas Hentschel, Emmanuelle Lacene, Guy Brochier, Jean-Marc Boisserie, Yves Fromes, Norma Beatriz Romero, Andreas Roos, Teresinha Evangelista","doi":"10.1177/22143602241296248","DOIUrl":"10.1177/22143602241296248","url":null,"abstract":"<p><strong>Background: </strong>Glycogenosis type 11 or deficiency in lactate dehydrogenase A (LDHA) (OMIM: 612933) is an ultra-rare condition of perturbed glycogen metabolism, first described in 1980 in a Japanese patient, and quite rare outside Japan. There are very few cases described in the literature and there is limited awareness of this condition that can easily be misdiagnosed or remain undiagnosed.</p><p><strong>Objective: </strong>To report on an ultra-rare form of glycogenosis stressing the association with cutaneous features and raise awareness for this rare condition. We report a novel pathogenic variant and aim to contribute to the understanding of the myopathophysiological mechanisms of disease by proteomics.</p><p><strong>Methods: </strong>We report the clinical, histopathological, magnetic resonance, genetic and proteomic features of a 19-year-old male of North African background that presented from infancy episodes of muscle pain, contractures and high CK levels immediately after moderate to high-intensity exercise. The patient was followed for several years prior to our observation due to severe acne that involved mostly the back and was resistant to treatment.</p><p><strong>Results: </strong>The phenotype of this patient is similar to the ones previously described with muscle and skin involvement. The MRI functional studies, interrupted at 2'30'' due to muscle pain, allowed us to confirm the presence of a metabolic disturbance of the muscles. The histological features of the muscle were quite subtle consisting mainly in rare subsarcolemmal vacuoles also identified at ultra-structural level. Immunostaining with the antibody targeting LDHA showed intracytoplasmic aggregates of the protein unlike the normal control that presented a diffuse staining. Exome analysis revealed a novel bi-allelic frameshifting deletion in exon 7 of the <i>LDHA</i> gene; c.766_767delGT. Proteomic findings accord with loss of functional LDHA and provide significant insights into the pathobiochemistry of the disease.</p><p><strong>Conclusions: </strong>Our combined data expand the current genetic landscape of LDHA-related disease, confirms the concept of a metabolic-driven vacuolar myopathy and provides insights into the biochemical nature of myopathology.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"271-278"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542413","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}