筋ジストロフィー

INTRODUCTION/AIMS: Due to improvements in clinical care, individuals with Duchenne muscular dystrophy (DMD) are living into adulthood, but little has been published about adults with DMD. We describe key characteristics of adults with DMD using US population-based surveillance data. METHODS: Muscular Dystrophy Surveillance Tracking and Research network (MD STARnet) data were used to describe sociodemographic and clinical characteristics of living and deceased adult males with DMD, born since January 1, 1982, who were ≥ 18 years old at last healthcare visit, using healthcare visit data through 2016. Frequencies and percentages were used to describe the distribution of characteristics, and ages at key milestones were described using medians and interquartile ranges. RESULTS: As of December 31, 2016, of 173 adult males, 61.8% were living. At their last visit, median age was 22.5 years and 35.3% had completed some college. Over 75% were on noninvasive ventilation, over 70% had cardiomyopathy, and 83.8% were prescribed cardiac medications. Corticosteroids were used by 67.1%, including 8.7% as of last clinic visit/death. Public insurance was more common among deceased (66.7%) than living (52.3%). Cough assist was used by 82.2% of living versus 57.6% of deceased individuals. DISCUSSION: Except for cough assist and insurance type, sociodemographic and clinical characteristics were similar between the living and deceased. Low continuation of corticosteroids into adulthood needs interpretation in the context of the study's timeframe. These results can assist clinicians in anticipating the care needs of adults with DMD.

BACKGROUND: Adeno-associated virus (AAV)-mediated mini- and micro-dystrophin gene therapies have emerged as promising treatments for Duchenne muscular dystrophy (DMD), yet their overall efficacy and safety remain uncertain. OBJECTIVE: To systematically evaluate and quantitatively synthesise clinical evidence on the efficacy and safety of AAV-based gene therapies in DMD. METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Five databases were searched from inception to November 2025. Clinical trials reporting functional and/or safety outcomes were included. Random-effects meta-analyses were performed for comparable outcomes. The study protocol was prospectively registered on PROSPERO. RESULTS: Nine studies (six trials; n=218) were included, with four contributing to the meta-analysis. Delandistrogene moxeparvovec improved North Star Ambulatory Assessment (NSAA) scores by +3.08 points at 1 year (95% CI 1.85 to 4.32), with greater effects in 4-5 year-olds (+4.06) than in 6-7 year-olds (+1.01). Improvements from baseline were observed in time to rise (-0.29 s) and four-stair climb (-0.48 s) but not in 10 or 100 m walk/run. Compared with controls, a significant effect was observed only for time to rise (-0.64 s), with no differences in NSAA or other timed tests. Effects were more consistent in younger patients. Fordadistrogene movaparvovec showed smaller effects. Most patients experienced treatment-related adverse events, mainly mild and transient; however, serious events, including hepatotoxicity and rare fatal outcomes, occurred. CONCLUSIONS: AAV-based gene therapies provide modest functional benefits in ambulatory boys with DMD, particularly at younger ages, but carry important safety risks. Larger trials with longer follow-up are needed to clarify long-term efficacy and optimise risk-benefit profiles. PROSPERO REGISTRATION NUMBER: CRD420261293429.

OBJECTIVES: Duchenne muscular dystrophy (DMD) is a genetic disorder that causes those living with the condition to require progressively increasing support needs. This support is often provided by informal carers, usually parents, and can have significant impacts on their well-being. Although some studies have noted positive outcomes as a consequence of caring for someone living with DMD, literature consistently finds poorer well-being outcomes in these carers. Research has supported the need for psychological interventions to be developed and evaluated for improving mental health in these carers. However, little is known about lived-experience perspectives on what qualities of such an intervention are likely to be acceptable to this group. Consequently, we explored lived-experience perspectives on the existing coping strategies and desired qualities of any psychological intervention designed to support mental health in carers of people living with DMD. METHODS: We performed reflexive thematic analysis on transcripts of 17 semi-structured interviews with carers. RESULTS: Six themes regarding existing coping strategies and seven themes regarding desired qualities of psychological support interventions were identified in the data. Existing coping strategies included general lifestyle related factors, emotional and behavioural coping skills, positive perspective takings skills, and social connection. Desired intervention qualities included accessibility issues, accessing quality information, professional support around specific coping strategies and content, engaging families, and supporting carers from the point of diagnosis. CONCLUSIONS: We conclude that carers of people living with DMD require multifaceted psychological support strategies of which direct psychological support may be just one component. PRACTICE IMPLICATIONS: We argue that interventions that integrate our findings regarding lived-experience perspectives and existing evidence-based psychotherapy models may be best placed to effectively support mental health and well-being in these carers.

Detection of matriglycan on α-dystroglycan by immunohistochemistry is one of the essential approaches for studying the mechanisms of functional glycosylation of α-DG, the pathogenesis of dystroglycanopathy, and developing experimental therapies. The limited source of matriglycan-specific antibodies of mouse origin, and their low affinity, pose significant difficulty for evaluating the levels and distribution of matriglycan expression, particularly in diseased mouse models. This study describes an optimized procedure with single ethanol fixation of cryosections that creates the strongest and most consistent membrane signal for matriglycan with the IIH6 C4 antibody. This, together with a reduction in background staining, results in optimal contrast between matriglycan signals and background staining in dystrophic muscle tissues. This procedure increases sensitivity for detecting lower levels of matriglycan in situ, in mouse models, and in human muscle. The optimized method is therefore valuable for evaluating experimental therapies preclinically and in clinical trials for all dystroglycanopathies.

Duchenne muscular dystrophy (DMD) is a devastating X-linked disorder caused by out-of-frame mutations in the DMD gene, most commonly large deletions or duplications, as well as nonsense and splice site mutations, that result in the absence of functional dystrophin protein. These mutations lead to progressive skeletal and cardiac muscle failure. In particular, exon 52 of the DMD gene represents a mutational hotspot in DMD patients. Deletion of exon 52 (DMDΔ52) disrupts the reading frame, leading to premature termination of translation. Here, we used a dual recombinant adeno-associated virus (rAAV) system employing an intein-mediated split strategy to deliver ABE8e using the PAM-less SpRY Cas9 nickase for adenine base editing of splice acceptor sites (SAS) in the dystrophin gene. Targeting the SAS of exon 51 or exon 53 in a DMDΔ52 background aims to induce exon skipping, thereby restoring the open reading frame, in effect converting the severe DMD phenotype into a milder Becker muscular dystrophy (BMD)-like phenotype. We systematically screened sgRNAs in porcine kidney fibroblasts and human embryonic kidney cells (HEK293T), identifying a guide RNA targeting the SAS of exon 53 as the most effective candidate with high on-target editing efficacies and minimal bystander editing. In human DMDΔ52 iPSC-derived cardiomyocytes cultivated as 2D monolayers, high editing efficiencies were achieved with the optimized 1:2 ratio of N-Terminus to C-Terminus. Functional assessment in 3D engineered heart patches revealed a trend toward normalization of the arrhythmic DMD phenotype with an increase in the effective refractory period (ERP) and a reduction in arrhythmic load compared with untreated DMD patches, despite lower editing efficacy in the 3D setting. These findings suggest that even modest levels of base editing-mediated exon skipping may ameliorate the DMD cardiac phenotype toward a BMD-like state, supporting the translational potential of this dual rAAV base editing approach for DMD cardiomyopathy.