Background Spinal muscular atrophy (SMA) is a severe, genetically determined neuromuscular disorder characterised by progressive muscle weakness resulting from motor neuron degeneration. Although therapies such as nusinersen have altered disease trajectories, objective biomarkers for treatment monitoring remain lacking. Neurofilament proteins, particularly phosphorylated neurofilament heavy chain (pNFH), are promising candidates for this role.Objectives To evaluate pNFH levels in cerebrospinal fluid (CSF) and serum as potential biomarkers for monitoring treatment response to nusinersen in paediatric patients with SMA.Methods This two-center observational study involved 56 SMA patients (types I-III) treated with nusinersen and 30 age-matched controls. pNFH concentrations in CSF and serum were measured at predefined intervals using ELISA kits. Motor function was assessed with CHOP INTEND, HFMSE, or MFM scales at baseline and after 3, 6, and 12 months. Mixed linear regression modeling evaluated changes in neurofilament levels and motor function.Results Baseline pNFH levels in both CSF and serum were significantly higher in SMA patients compared to controls. Following nusinersen therapy, pNFH levels decreased significantly in both compartments, especially in the first 6 months. Younger patients had higher initial serum pNFH levels. A significant correlation was found between CSF and serum pNFH concentration. An association between pNFH levels and motor scores was observed.Conclusions pNFH levels in CSF and serum show potential as objective biomarkers for monitoring the initial treatment response in paediatric SMA. Longitudinal changes are more informative than single measurements. Further validation in larger cohorts and using more sensitive methods is warranted.
Background and objective RYR1-related diseases (RYR1-RD) are a group of genetic conditions characterized by early-onset muscle weakness, causing functional impairments. An increasing number of clinical trials is on the horizon. This study aims to improve trial readiness by characterizing the patient perspective on clinical trial participation.Methods In collaboration with RYR1-RD patients and patient representatives we adapted an existing facioscapulohumeral muscular dystrophy (FSHD) survey and conducted the resulting international patient survey in 2025. We used descriptive statistics to analyze the patient characteristics and personal experiences and expectations in clinical trials.Results In total 146 participants (of whom 30 with previous trial experiences), residing mainly in the Netherlands or the United States, completed the survey. Symptoms that caused the greatest difficulties in daily life, including muscle weakness, fatigue, and impaired mobility, were seen as important outcomes for future trials. The possibility to receive the trial drug and results when published were reported as facilitators of trial participation. There was a strong demand for receiving updates on ongoing and upcoming trials. Fear of side effects and travel time were reported as barriers.Conclusion A clear understanding of patients' expectations and preferences is important for relevant future clinical trials to better align with patients' needs.
Background A multidisciplinary team (MDT) care model has been advocated for patients with Duchenne and Becker Muscular dystrophy (DBMD) to provide comprehensive care. We aimed to study the perspectives of parents and/or caregivers of individuals with DBMD on MDT clinic visits. Methods A survey via non-personalized REDCap link was emailed to registered parents/caregivers through the Duchenne Registry provided by Parent Project Muscular Dystrophy (PPMD). The survey contained questions concerning individuals’ demographics, and medical information, as well as knowledge and perspectives on MDT visits. Descriptive and association statistics were utilized. Results Of the 186 respondents, 166 cared for individuals with Duchenne and 20 for Becker. 117 of the respondents noted that their children receive care from one of the PPMD Certified Duchenne Care Centers. Average travel distance to the care site was 228.37 miles. 75% had their visits within 1 day, 19 % had 2 days visit, and 6% had more than 2 days. Majority (89%) preferred to have MDT appointments with all of their care providers at once and 89.4% commented that they had enough time with each of the providers. 77% noted that the duration of MDT visits was just right. 86.1% were satisfied with the care received from MDT visits. Participant comments underscored concerns regarding travel inconveniences, visit duration, standardization of care, and transition of care. Discussion Our findings support continued implementation of MDT care and visits for individuals with DBMD, with an emphasis on optimizing visit efficiency and accommodating patients with complex medical needs.
The 7th Ottawa International Conference on Neuromuscular Disease and Biology was held on September 11-13, 2025, in Ottawa, Canada. The conference brought together international experts in neuromuscular disease, biology and clinical care to provide updates on exciting developments in the field. Topics included novel disease gene identification and characterization, developments in muscle, motor neuron and stem cell biology, characterization of disease pathogenesis and current standards of care, and recent advances in therapy development.
Myotonic Dystrophy type 1 (DM1) is a complex multisystem disorder, and affected children commonly present with gastrointestinal and neurodevelopmental challenges. Despite the high prevalence of these symptoms, their underlying mechanisms remain poorly understood. The gut microbiome is known to be involved in gastrointestinal and neurodevelopmental disorders, and emerging research suggests that it could also play a contributory role in various neuromuscular diseases. However, the gut microbiota of children with DM1 remains unexplored. This pilot study compared gut microbiota profiles of 10 children and one young adult with DM1, to that of their unaffected siblings (n=11). Three-day food records and faecal samples were collected, and bacterial taxa were analysed through 16S rRNA marker-gene sequencing. A within-family paired-sample design accounted for potential confounders, such as diet and lifestyle. Results revealed that overall microbial diversity and community structure were similar between groups. Moreover, participants with DM1 showed a significant lower relative abundance of the bacterial genus Faecalibacterium (mean 4.9% +/- 2.1%) compared to their unaffected siblings (mean 9.1% +/- 4.4%)(p=0.005). This finding should be considered exploratory, as its univariate analysis was uncorrected for multiple testing. Faecalibacterium is a key gut bacterium, and reduced abundance has been reported in several DM1-associated gastrointestinal and neurodevelopmental disorders. Although causality cannot be inferred from this exploratory study the observed reduction may be relevant to gastrointestinal and neurodevelopmental challenges frequently seen in DM1. If larger further studies confirm its role, targeting Faecalibacterium relative abundance could become a potential therapeutic strategy for alleviating gastrointestinal and neurodevelopmental symptoms in DM1.
