Journal of neuromuscular diseases最新文献

{"title":"Use of imaging biomarkers and ambulatory functional endpoints in Duchenne muscular dystrophy clinical trials: Systematic review and machine learning-driven trend analysis.","authors":"Matthew Todd, Sanghoon Kang, Shunwen Wu, Devanand Adhin, Deok Yong Yoon, Rebecca Willcocks, Sarah Kim","doi":"10.1177/22143602251360664","DOIUrl":"https://doi.org/10.1177/22143602251360664","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a rare X-linked genetic muscle disorder affecting primarily pediatric males and leading to limited life expectancy. This systematic review of 85 DMD trials and non-interventional studies (2010-2022) evaluated how magnetic resonance imaging biomarkers-particularly fat fraction and T2 relaxation time-are currently being used to quantitatively track disease progression and how their use compares to traditional mobility-based functional endpoints. Imaging biomarker studies lasted on average 4.50 years, approximately 11 months longer than those using only ambulatory functional endpoints. While 93% of biologic intervention trials (n = 28) included ambulatory functional endpoints, only 13.3% (n = 4) incorporated imaging biomarkers. Small molecule trials and natural history studies were the predominant contributors to imaging biomarker use, each comprising 30.4% of such studies. Small molecule trials used imaging biomarkers more frequently than biologic trials, likely because biologics often target dystrophin, an established surrogate biomarker, while small molecules lack regulatory-approved biomarkers. Notably, following the 2018 FDA guidance finalization, we observed a significant decrease in new trials using imaging biomarkers despite earlier regulatory encouragement. This analysis demonstrates that while imaging biomarkers are increasingly used in natural history studies, their integration into interventional trials remains limited. From XGBoost machine learning analysis, trial duration and start year were the strongest predictors of biomarker usage, with a decline observed following the 2018 FDA guidance. Despite their potential to objectively track disease progression, imaging biomarkers have not yet been widely adopted as primary endpoints in therapeutic trials, likely due to regulatory and logistical challenges. Future research should examine whether standardizing imaging protocols or integrating hybrid endpoint models could bridge the regulatory gap currently limiting biomarker adoption in therapeutic trials.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251360664"},"PeriodicalIF":3.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731803","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":"Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.","authors":"Ophélie Vacca, Cathy Nagy, Aurélie Goyenvalle","doi":"10.1177/22143602251360668","DOIUrl":"https://doi.org/10.1177/22143602251360668","url":null,"abstract":"<p><p>Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In addition to the well-known musculoskeletal, cardiac, and respiratory symptoms, DMD also involves significant central nervous system (CNS) manifestations, including cognitive, behavioral, and emotional deficits that profoundly affect patient quality of life. Despite advances in RNA-based therapies targeting muscle symptoms, CNS manifestations remain largely untreated. Preclinical studies in animal models have shown promising results in addressing these deficits through CNS-targeted delivery of antisense oligonucleotides, highlighting the potential of intrathecal and next-generation systemic delivery methods. This review explores the latest advancements in RNA therapeutics for DMD, focusing on overcoming the challenges of CNS delivery to address both muscular and neurological symptoms.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251360668"},"PeriodicalIF":3.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742285","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":"Real-world data on spinal muscular atrophy in Spain: Insights from over 500 individuals in the CuidAME project.","authors":"Cristina Puig-Ram, Sonia Segovia, Rocio Garcia-Uzquiano, Nancy Carolina Ñungo Garzón, Karolina Aragon-Gawinska, Mar García Romero, Jesica María Expósito-Escudero, Laura Carrera-García, Mercedes López-Lobato, Carmen Paradas, Laura González Mera, Mireia Álvarez Molinero, David Gómez Andrés, Esther Toro, Joaquín Alejandro Fernández Ramos, Maria Antonia Grimalt, Laura Toledo Bravo de Laguna, Desire González Barrios, Eduardo F Tizzano, Maria Grazia Cattinari, Julita Medina, Rocío Calvo Medina, Francina Munell, Javier Sotoca, Eduardo Martínez-Salcedo, Antonio Moreno Escribano, Mónica Povedano Panadés, Miguel A Fernández-García, Inmaculada Pitarch-Castellano, Juan F Vázquez-Costa, Daniel Natera-de Benito, Andres Nascimento","doi":"10.1177/22143602251361190","DOIUrl":"https://doi.org/10.1177/22143602251361190","url":null,"abstract":"<p><p>BackgroundThe new treatment paradigm in Spinal Muscular Atrophy (SMA) has introduced novel phenotypes, changes in trajectories and clinical questions not fully addressed in clinical trials. To explore these challenges, several international initiatives have emerged. <i>CuidAME</i> was created as a nationwide clinical network in Spain designed to standardise SMA care, facilitate knowledge sharing, and capture data in a longitudinal comprehensive registry.ObjectiveEvaluating the usefulness of the <i>CuidAME</i> project to capture data in a real-world setting.MethodsThis multicentric cohort study includes individuals with SMA followed at participating hospitals. Clinical examinations and multidisciplinary assessments were performed during routine clinical visits. We present a cross-sectional analysis of the registry population.ResultsAs of February 2025, 543 participants from 25 hospitals were recruited: 12 were presymptomatic, 125 (23%) had SMA type 1, 208 (35%) type 2, 194 (38%) type 3, and 4 (<1%) type 4. Among the cohort, 91% (n = 495) had received at least one disease-modifier treatment, with 17 discontinuations. The registry included 5092 motor assessments, 1565 performed before treatment initiation.Conclusions<i>CuidAME</i> is an academic, longitudinal, real-world data collection project that demonstrated a fast and effective model for implementation facilitating the standardization of clinical practices and outcome measures across Spain. By aligning with core dataset used in other registries and establishing multidisciplinary working groups, the initiative will contribute to sharing knowledge to advance SMA care and improve patient outcomes.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251361190"},"PeriodicalIF":3.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731802","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":"Report on the rare disease consortium Japan inaugural symposium - July 18, 2023, shonan health innovation park, Japan.","authors":"Toshifumi Yokota, Naoto Inukai, Hiroyuki Shibasaki, Harumasa Nakamura, Shinnichi Yokota, Yoshitaka Nakamura, Rikako Yamauchi, Keiko Ishigami, Akitsu Hotta, Hideo Miki, Yoshitsugu Aoki","doi":"10.1177/22143602251356742","DOIUrl":"https://doi.org/10.1177/22143602251356742","url":null,"abstract":"<p><p>The Rare Disease Consortium Japan (RDCJ) is a newly formalized cross-sector initiative launched to address the urgent and growing needs of individuals living with rare diseases in Japan, aiming to support a wide range of rare conditions, including-but not limited to-neuromuscular diseases. RDCJ hosted its inaugural symposium on July 18, 2023, at the Shonan Health Innovation Park. This symposium aimed to address the unique challenges of rare diseases through a collaborative approach involving industry, government, academia, patients, and the community. The event brought together these stakeholders to discuss the current state and future directions of rare disease research and treatment in Japan. The event featured a range of speakers and panel discussions on the state of drug development, patient journeys, and the future of patient-centered healthcare services. Highlights included a keynote on antisense oligonucleotide therapeutics and sessions on patient-centered healthcare, human-centered design in healthcare, and innovative approaches to rare disease treatment. This report provides a detailed overview of the symposium, the key takeaways from each session, and the future directions for RDCJ.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251356742"},"PeriodicalIF":3.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690563","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":"Molecular and genetic characteristics of patients from the National Registry of Duchenne/Becker Muscular Dystrophy in the Russian Federation: Pilot analysis.","authors":"Peter A Sparber, Elena V Zinina, Olga Shchagina, Aleksander V Polyakov, Sergey I Kutsev","doi":"10.1177/22143602251356189","DOIUrl":"https://doi.org/10.1177/22143602251356189","url":null,"abstract":"<p><strong>Background: </strong>There is currently no reliable epidemiological data in the Russian Federation nor data on patient routing and evaluation of the efficacy and feasibility of diagnostic and therapeutic approaches to patients with suspected Duchenne/Becker muscular dystrophy (DMD/BMD).</p><p><strong>Objective: </strong>To record and monitor all patients with DMD/BMD in Russia.</p><p><strong>Methods: </strong>Observational multicenter prospective & retrospective Registry of patients with DMD/BMD.</p><p><strong>Results: </strong>Almost half of the 626 included patients live in the Central and Volga Federal Districts. The most common cause of the disease was large deletions of one or more exons (328 patients, 52.4%). Large duplications were identified in 92 patients (14.7%). Point mutations were identified in 206 patients, 32.9%. Among 448 patients with a known family history, 20% had a first-line relative diagnosed with DMD/BMD. The mean delay in diagnosis (the time from onset to clinically confirmed diagnosis) was 24.3 months.</p><p><strong>Conclusions: </strong>These data demonstrate the preliminary results of the Registry and indicate a considerable delay in diagnosis in Russia.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251356189"},"PeriodicalIF":3.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675010","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":"Pathogenic mechanisms and clinical insights into <i>B3GALNT2</i>-related alpha-dystroglycanopathies.","authors":"Xiaona Fu, Hui Wang, Wenjia Chai, Xiaoyu Chen, Danyu Song, Wei Wang, Jingwei Zhong, Zhimei Liu, Xiao Tong, Hui Xiong, Xiaotun Ren, Jingang Gui","doi":"10.1177/22143602251360270","DOIUrl":"https://doi.org/10.1177/22143602251360270","url":null,"abstract":"<p><p>Background<i>B3GALNT2</i> mutations cause α-dystroglycanopathy (α-DGP), a rare condition characterized by muscular dystrophy, brain malformations, and developmental delay. However, its pathogenic mechanisms remain poorly understood. To date, limited cases have been reported, and the pathogenic mechanisms remain incompletely understood.MethodsClinical and genetic data from 3 newly diagnosed Chinese patients and 28 patients previously diagnosed with <i>B3GALNT2</i>-related α-DGP were analyzed. Using patient-derived fibroblasts, α-dystroglycan (α-DG) glycosylation and laminin-binding capacity were assessed by immunoblotting, laminin overlay and immunofluorescence. <i>B3GALNT2</i> mRNA and protein levels were quantified by real-time PCR and immunoblotting. Enzymatic activity was measured using purified recombinant <i>B3GALNT2</i> proteins. Differentially expressed genes were identified via an mRNA microarray.ResultsAll three patients carried compound heterozygous variants involving one truncating and one missense mutation. Two novel mutations (c.657_658insTT and c.1384T > C) were identified. Functional studies confirmed that the missense mutations (Y436C and C462R) impaired enzymatic activity to 40-50% of wild-type levels, while splice variants caused frameshifts and likely complete loss of protein. Despite partial residual activity, all patients showed severely reduced α-DG glycosylation and loss of laminin binding, consistent with a functional threshold effect. Transcriptomic analysis revealed upregulation of <i>CHST10</i> in two patients.ConclusionsThis study expands the mutational spectrum of <i>B3GALNT2</i>-related α-DGP and provides mechanistic insight into the pathogenicity of novel variants. Our findings support a functional threshold model for B3GALNT2 activity in α-DG glycosylation and suggest CHST10 as a potential transcriptional responder to glycosylation defects. These results deepen the understanding of <i>B3GALNT2</i>-related dystroglycanopathies and may inform future diagnostic and therapeutic strategies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251360270"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642839","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":"<i>DCTN1</i>-associated neurological disorder with symptoms similar to spinal bulbar muscular atrophy.","authors":"Byeonghyeon Lee, Seong Tae Cho, Ryul Kim, Ki Wha Chung, Tae-Jun Kwon, Un-Kyung Kim, Ye-Ri Kim, Byung-Ok Choi, Jin-Sung Park","doi":"10.1177/22143602251352989","DOIUrl":"https://doi.org/10.1177/22143602251352989","url":null,"abstract":"<p><p>Background<i>Dynactin 1</i> (<i>DCTN1</i>) mutations are associated with diverse neurological disorders, including distal hereditary motor neuropathy, Perry syndrome, and amyotrophic lateral sclerosis. This study focused on a family with symptoms resembling spinal and bulbar muscular atrophy, showing severe vocal cord paralysis, to understand <i>DCTN1</i>-related neurological disorders in Koreans.MethodClinical examinations revealed variable phenotypes, such as proximal limb weakness, chronic hypercapnia, and gynecomastia, alongside vocal cord paralysis. Whole-exome sequencing identified a missense mutation, c.1175G > A, in <i>DCTN1</i>. Three more Korean families with the same mutation were analyzed to explore a potential founder effect. Microsatellite analysis indicated a shared haplotype, suggesting a common genetic origin.ResultThis study identified a missense mutation, c.1175G > A, in <i>DCTN1</i> in the initial family with features resembling spinal and bulbar muscular atrophy. The mutation was also present in three other Korean families, indicating a potential founder effect. Microsatellite analysis confirmed a shared haplotype among these families. Meanwhile, the patients also manifested additional clinical features such as peripheral neuropathy and gynecomastia.ConclusionThis study highlights clinical heterogeneity in Korean patients with <i>DCTN1</i>-associated neurological disorders and identifies a potential founder mutation, c.1175G > A, expanding the clinical spectrum of <i>DCTN1</i> mutations with clinical features of spinal bulbar muscular atrophy. Understanding such genetic and clinical diversity is crucial for accurate diagnoses and management, with implications for future research and therapeutic strategies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251352989"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642838","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":"REGISTRE SMA FRANCE: A nationwide observational registry of patients with spinal muscular atrophy in France.","authors":"Lamiae Grimaldi, Rocio Garcia-Uzquiano, Marta Gomez-Garcia de la Banda, Amal Oulhissane-Omar, Celine Tard, Pascale Saugier-Veber, Vincent Laugel, Isabelle Desguerre, Pascal Cintas, Carole Vuillerot, Frederic Audic, Claude Cances, Tanya Stojkovic, Jon Andoni Urtizberea, Shahram Attarian, Juliette Ropars, Susana Quijano-Roy","doi":"10.1177/22143602251353446","DOIUrl":"https://doi.org/10.1177/22143602251353446","url":null,"abstract":"<p><p>BackgroundSpinal muscular atrophy (SMA) is a severe neurodegenerative disease affecting children. Three innovative disease-modifying therapies (DMTs)-nusinersen, risdiplam, and onasemnogene abeparvovec-are available for treatment.ObjectiveTo provide a descriptive overview of patients enrolled in the <i>Registre SMA France</i> until July 22, 2024.Methods<i>Registre SMA France</i> is a multicenter, national observational registry that includes patients with SMA-children and adults, treated or untreated. Data collection began retrospectively in 2016 and prospectively in 2020, with a 10-year follow-up plan. The coordinating center is the neuropediatric department of Garches Hospital (AP-HP), while methodological and, regulatory and operational management, are provided by the Clinical Research Unit of AP-HP Paris-Saclay. Financial support is provided through unrestricted grants from Biogen, Novartis, and Roche. Data on patient characteristics, medical and surgical follow-up, treatments, adverse events, and quality of life are recorded via structured forms, with additional modules developed as required (e.g., hematological monitoring post-gene therapy in 2021). Data quality is ensured through routine checks and periodic monitoring.ResultsBy July 22, 2024, 1299 patients from 59 centers were enrolled (299 SMA1, 502 SMA2, 469 SMA3, 19 SMA4, 10 presymptomatic). Of these, 76.2% received DMT (nusinersen: 46.1%, risdiplam: 23.2%, onasemnogene abeparvovec: 9.2%), with 21.5% undergoing sequential or combination therapy. Major complications included ventilatory support (SMA1: 69.9%, SMA2: 64.5%, SMA3: 18.1%), enteral feeding (SMA1: 56.2%SMA1), and spine surgery (SMA2: 24.5%). Survival was significantly higher in treated SMA1 and SMA2 cases.ConclusionThis registry serves as a key resource for understanding the clinical course and treatment outcomes of SMA in the real world, supporting future research and informing clinical and policy decisions in the era of DMTs.Trial registrationNCT04177134.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251353446"},"PeriodicalIF":3.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584103","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":"Review: Limb-girdle muscular dystrophies (LGMDs) existing registries and natural history studies: Where do we stand?","authors":"Elena Faedo, Iman Tahiri, Christophe Alimi, Hussein Shoaito, Gianmarco Severa, Sophie Olivier, Stephane Degove, Isabelle Richard, Edoardo Malfatti","doi":"10.1177/22143602251355316","DOIUrl":"https://doi.org/10.1177/22143602251355316","url":null,"abstract":"<p><strong>Introduction: </strong>Limb-Girdle Muscular Dystrophies (LGMDs) are heterogeneous inherited disorders with no cure, including 29 recessive (LGMDR) and 5 dominant forms (LGMDD), characterized by proximal muscle weakness. Finding a cure for LGMD is difficult due to the their slow evolution for which comprehensive data collection through registries, network, and natural history studies is pivotal.</p><p><strong>Methods: </strong>We conducted a review following PRISMA guidelines searching in PubMed, Scopus, and Web of Science for articles published between 2000-2025, focusing on LGMD registries, networks, and natural history studies. We included observational studies, cohort designs, and registry-based studies.</p><p><strong>Results: </strong>Among 443 records, 38 studies were included, 10 registries, 4 networks, and 17 natural history studies respectively. Registries varied in scope, with many focused on specific LGMD subtypes. Natural history studies were predominantly subtype-specific, poorly linked to registries. Only 12 studies were connected to registries or networks, and most performed in Europe and North America.</p><p><strong>Discussion: </strong>Registries, networks, and natural history studies showed considerable design variability, leading to challenges with data interoperability and underscoring the need for standardization. Despite regional coverage, low-income countries are underrepresented in the data. The limited linkage between natural history studies and registries presents a missed opportunity to leverage well-characterized cohorts. Many registries and networks remain unpublished, limiting available data for global research.</p><p><strong>Conclusion: </strong>Registries are crucial, benefiting patients, clinicians, researchers, and industries. The scarcity of natural history studies hinders the development of centralized datasets. Standardizing registry design, improving data interoperability, and enhancing patient diversity are critical to boost LGMD research.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251355316"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584104","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":"Sarcoglycanopathies: From clinical diagnosis to new promising therapies.","authors":"Holly Borland, Jordi Diaz-Manera","doi":"10.1177/22143602251324855","DOIUrl":"10.1177/22143602251324855","url":null,"abstract":"<p><p>The sarcoglycanopathies are a severe form of limb girdle muscular dystrophy caused by mutations in the sarcoglycan genes SGCA, SGCB, SGCG, and SGCD, leading to reduced or absent expression of the alpha-, beta-, gamma-, and delta-sarcoglycan proteins respectively. Most patients develop a severe disease starting in the first decade of life that progresses quickly and eventually leads to a loss of ambulation before the age of 20. However, there is a marked heterogeneity in the prognosis, and several patients develop a milder phenotype. The factors correlating with disease progression are not completely known, but recent data suggest that remaining protein expression can be a key factor. The diagnosis is confirmed by genetic studies, which are sometimes not confirmative in the case of identifying variants of unknown significance or just one variant. New tools to understand the potential pathogenesis of missense variants have been developed; these are helping in the diagnosis of these diseases. Additionally, recent data on muscle MRI have revealed a characteristic pattern of involvement that can also support the diagnosis of the disease. In recent years, data coming from international collaborative studies have allowed an understanding of disease progression; however, this is only through retrospective data. There are no prospective studies collecting longitudinal data on skeletal and respiratory muscle function or cardiac structure and function progression over time which is hampering the development of new drugs in the field. Clinical trials with gene therapy are underway or are being designed in some of the subtypes of sarcoglycanopathies to advance therapeutic management.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"463-472"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700577","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}