Spinal Muscular Atrophy (SMA) type 1 is a severe autosomal recessive neuromuscular disorder caused by SMN1 gene mutations, leading to progressive muscle weakness and respiratory compromise. Without intervention, affected infants can rarely sit independently or live beyond two years of age. The advent of disease-modifying therapies and the timely implementation of physiotherapy have changed the disease trajectory and helped in increased survival. This report describes a two-year and fivemonth-old female child with genetically confirmed SMA type 1 on disease modifying treatment and regular physiotherapy who achieved independent sitting - an uncommon milestone for this phenotype. During hospitalisation for bronchopneumonia at a tertiary care hospital, physiotherapy was continued with chest physiotherapy and truncal activation exercises, progressing to functional strengthening and postural control activities. Functional gains were documented using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) and the Revised Hammersmith Scale for Spinal Muscular Atrophy (RHS-SMA). This case underscores the vital role of structured physiotherapy in translating pharmacological advances into meaningful functional recovery in children with SMA type 1.

Musculoskeletal deformities in children with spinal muscular atrophy: a multicenter cross-sectional study with longitudinal follow-up.

Skeletal muscle in spinal muscular atrophy: Critical insights from pathogenesis to therapeutic strategies.

Workshop report: Findings from the 2025 Italian SMAkers Educational Initiative on SMA management in Italy.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease characterized by muscular atrophy and respiratory and bulbar dysfunction, especially in the most severe phenotypes (SMA type 0 and 1). Swallowing function remains understudied because assessment tools are often unavailable or poorly tolerated by young children. The Iowa Oral Performance Instrument (IOPI), that measures orofacial strength via a small air-filled bulb has recently been evaluated in SMA type 2 and 3 patients. The purpose of this study was to investigate muscle strength of several muscles used during the oral phase of swallowing using IOPI in SMA type 1 children treated with nusinersen compared to healthy controls. In addition, it sought to correlate labial and lingual pressures with known key predictors of phenotype severity (Children's Hospital Of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND], age at first symptoms, SMN2 copy number) and indicators of feeding-nutritional status (p-FOIS (Pediatric Functional Oral Intake Scale)). Combining results from four independent centers, we recruited 22 individuals with a confirmed genetic diagnosis of symptomatic SMA type 1. All patients had been treated with nusinersen for at least 2.5 years and had undergone at least one IOPI measurement at a median age of 5.4 years. IOPI data were compared to age- and gender-matched controls and published normative data when available. Oral pressures were lower in patients than in typically developing children (lips: p < 0.01; tongue: p < 0.001). Weaker labial pressure was significantly correlated with younger age at disease onset (r = 0.66; p = 0.0053), older age at first nusinersen injection (r = -0.52; p = 0.0326), lower body mass index (r = 0.61; p = 0.0149), and worse motor performance as expressed by the CHOP INTEND score (r = 0.60; p = 0.0170). Weaker tongue pressure was significantly correlated with younger age at disease onset (r = 0.49; p = 0.0372) and lower p-FOIS (r = 0.526; p = 0.022). IOPI measurements objectively demonstrate orofacial weakness in this population compared with healthy controls and may serve as a biomarker to monitor the impact of comprehensive management, including disease-modifying therapies, on oral swallowing function in SMA type 1.

Administration of Nusinersen requires repeated lumbar intrathecal access, posing challenges for patients with Spinal Muscular Atrophy (SMA). A purpose-built system may streamline drug delivery. To assess the feasibility and safety of ThecaFlex DRx for intrathecal Nusinersen dosing. We present initial results of a prospective, multicenter investigational device exemption (IDE) study. Patients with SMA who had an indication for intrathecal Nusinersen were enrolled. Primary outcomes were successful system implantation and postoperative infusion. Prespecified safety outcomes consisted of adverse events adjudicated for severity and device or procedure relatedness. Twenty-five subjects underwent device implantation. Median age at implantation was 13.8 years (IQR 10.0-18.0), and 52% were female. Subjects included individuals with SMA types I (16%), II (64%), and III (20%). Implantation was successful in all cases. At the interim data cutoff, median follow-up was 230 days (IQR 76.0-369.0) at which point 23 subjects (92%) had successfully received Nusinersen infusions. Ten patients reached one year of follow-up, and all of them maintained a functional device at this visit. Sixty adverse events occurred in 19 subjects, with 12 events (20%) adjudicated as serious adverse events that were most commonly wound-related or respiratory. At one year, the estimated probability of remaining free from device action was 86.2% (95% CI 0.73-1.00), with two devices requiring explantation due to wound dehiscence and access difficulties, respectively. This interim report supports the feasibility of ThecaFlex DRx for Nusinersen administration, with long-term durability and effectiveness to be defined with longer follow-up.For more information about the PIERRE study (NCT05866419), visit: https://www. gov/study/NCT05866419.

Adult SMA REACH is a Research and Clinical Hub in the UK that established a collaborative clinical network for Spinal Muscular Atrophy (SMA) in 2020 across 19 clinical sites, patient advocacy groups, regulators, and industry. In recent years, the treatment landscape in the SMA setting has rapidly evolved with Nusinersen and Risdiplam receiving conditional approval via a Managed Access Agreement (MAA) in the UK. Here we describe the structure of a Real-World Data (RWD) collection study implemented to collect standardised outcome measures to inform on the natural history of the disease and the impact of novel treatments. The study also reports data to The National Institute for Health and Care Excellence (NICE) and NHS England (NHSE) for the purpose of the MAA's. The Adult SMA REACH database currently contains data from 466 patients and 2255 visits, with more than 8000 functional outcome measure assessments. Adult SMA REACH provides insights into how real-world data can be used to evaluate treatment outcomes in rare diseases, where conducting randomised controlled trials may be difficult. The registry also offers an infrastructure that supports collaborative research and reduces data silos. In this paper we describe the complexity of establishing such a study and clinical network including considerations for adapting this model to other disease areas. Further information on the Adult SMA REACH data collection study and clinical network can be found on the website (https://adultsmareach.co.uk/) and ClinicalTrials.gov (NCT06978985, https://clinicaltrials.gov/study/NCT06978985).

The role of sleep-disordered breathing in adolescents with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder caused by SMN1 mutations, leading to progressive muscle weakness. Although nusinersen improves motor function, its broader impact on daily life remains insufficiently understood. This study explored caregivers' perceptions of nusinersen treatment and identified themes reflecting its influence on everyday functioning. An observational study included 23 children with SMA (10 type 2, 7 type 3, 6 type 1) treated with nusinersen for up to 36 months. The mean age at interview was 6.3 years (SD 2.3). Caregivers completed a semi-structured questionnaire with closed and open-ended items. Narrative responses were analyzed using natural language processing (NLP) and topic modeling to identify recurring patterns. Caregivers reported consistent positive effects. NLP identified three thematic clusters: Functional and Daily Progress (34.9%), Global Improvement and Quality of Life (33.6%), and Hospitalization and Physical Recovery (31.5%). Reported benefits included improved swallowing, easier breathing, fewer hospitalizations, increased independence, and enhanced mood. Families emphasized reduced stress and improved family dynamics. Caregivers perceive nusinersen as providing meaningful improvements in daily functioning beyond motor outcomes. Incorporating caregiver-reported insights through NLP may enrich treatment evaluation and support holistic, patient- and family-centered care in SMA.

Spinal muscular atrophy (SMA) was recently included in the French national newborn screening (NBS) program. The aim of this study was to assess the public health impact and cost-utility of SMA NBS in the French setting. A cost-utility model combining a decision tree with a lifetime state transition model (six health states) was adapted from a previous model. The model simulated a cohort of 700,000 newborns annually, aligned with French birth statistics. Clinical inputs were derived from SMA trials. Cost and utility estimates reflected French healthcare system data and societal burden studies. Analyses were conducted from a societal perspective, with key outcomes including the incremental cost-utility ratio (ICUR), quality-adjusted life years (QALYs), and incremental net monetary benefit (INMB). Deterministic, probabilistic, and scenario analyses were performed. With NBS, 66.5 patients are expected to be treated presymptomatically each year. At age 15years, mortality is reduced to 2% in the NBS arm compared with 26% without screening; 94% of patients will retain the ability to sit or walk versus 38% without NBS. NBS is a dominant strategy versus no NBS, with lower costs (-233.9million [M] euros) and higher QALYs (+1586). The INMB was 265.6M € at a 20,000 €/QALY threshold. Results were robust across all sensitivity and scenario analyses. Key limitations include uncertainty in long-term treatment effects, exclusion of SMA type 0 and 4 from the model, and limited data on long-term outcomes of presymptomatically treated patients. NBS for SMA in France offers significant clinical and economic value, supporting its national implementation.

ABSTRACT Objectives: To examine powered mobility learning in children with spinal muscular atrophy (SMA) type I, involving families and evaluating goal attainment through the use of small, modified electric toy cars in the children’s natural environments. Design: Single-blind pilot intervention study derived from an originally planned wait-list randomized controlled trial. This report includes only the immediate-intervention group that received powered mobility training. Setting: Participants’ natural environments. Participants: Children aged 10 months to 5 years diagnosed with SMA type I, with no previous powered mobility experience. Interventions: Individualized adaptations of electric toy cars, including postural supports and customized control systems. The structured program lasted 12 weeks, with three 30-minute sessions per week. Outcome Measures: Progress in powered mobility use was assessed using the Assessment of Learning Powered Mobility use (ALP). Functional goal achievement was measured with Goal Attainment Scaling (GAS). Results: Of the 16 children enrolled, 9 completed the 12-week intervention. The greatest improvement in ALP phase occurred between weeks 0–4 (88.88%; p = 0.01). Functional goals showed significant improvement at all measured intervals (p < 0.05). Conclusions: A structured powered mobility intervention delivered in natural environments supported mobility learning and functional goal attainment in children with SMA type I.

Nusinersen effectiveness and safety in children with type II/III 5q-spinal muscular atrophy: Second interim analysis from a Chinese disease registry.

A Systematic Review about Neuropathies in Spinal Muscular Atrophy (SMA): Current Insights and Future Directions.

Spinal muscular atrophy (SMA) types III and IV are the most common late-onset forms, and they progress slowly, making the identification of sensitive biomarkers critical. The Motor Unit Number Index (MUNIX) estimates motor unit loss and may complement traditional electrophysiological measurements such as Compound Muscle Action Potential amplitudes (CMAP). However, their respective performances have never been directly compared in adult SMA. In a French multicenter study (NCT04690998), 71 adult patients with SMA and 24 healthy controls underwent clinical and electrophysiological evaluation. MUNIX, CMAP, and Motor Unit Size Index (MUSIX) were recorded in four muscles, and sum scores (SumMUNIX, SumCMAP, SumMUSIX) were calculated. Reliability was assessed using intraclass correlation coefficients (ICCs), and associations with functional outcomes were explored. MUNIX and CMAP effectively distinguished SMA patients from controls, showing strong test - retest reliability. MUNIX showed the highest discriminative performance (AUC = 0.92), while CMAP demonstrated the strongest and most consistent associations with clinical severity. In multivariate analyses, only CMAP remained independently associated with all functional and strength measures, whereas MUNIX and MUSIX lost significance. MUNIX demonstrated the highest discriminative performance among biomarkers for differentiating SMA from controls, indicating early motor unit loss even when CMAP values were within normal limits. However, disease burden and functional impairment were better reflected by CMAP, probably due to it integrating both motor unit loss and reinnervation. The complementary nature of these profiles supports their combined use (concurrent application), and longitudinal studies are warranted to assess their responsiveness in adult SMA as well as their appropriateness for clinical trial settings.

First combined analysis of SMN1, SMN2, and NAIP copy numbers in Moroccan SMA patients and their correlation with disease severity.

285th ENMC international workshop: SMN-associated neurodevelopmental disorder: type 1 spinal muscular atrophy and the brain, 31st January - 2nd February 2025, Hoofddorp, The Netherlands.

Recent disease-modifying treatments have markedly improved the motor prognosis of spinal muscular atrophy, yet the neurocognitive and language outcomes of treated children remain insufficiently characterized. This monocentric observational study included sixteen children with genetically confirmed Spinal muscular atrophy types I-III (10 males; age 2.6-15.4 years; 5 with type I, 5 type II, and 6 type III) treated with at least one disease-modifying therapy and followed at our center. Participants underwent standardized assessments of intellectual abilities, executive functions, social cognition, memory, and language, complemented by parent questionnaires. Data were analyzed descriptively given the small and heterogeneous sample. Intellectual functioning was preserved (mean IQ = 102 ± 4), with no cases of intellectual disability, although 15% showed executive dysfunctions (e.g., inhibition, cognitive flexibility) not perceived by parents. Oral language disorders were found in 73% of individuals, affecting phonology, lexicon, and morphosyntax, and were more frequent in children with more severe motor phenotypes and fewer SMN2 copies. Written language disorders were identified in 29% of individuals, even without major motor impairment. Routine neuropsychological and speech-language assessments should be integrated into multidisciplinary care to enable earlier detection, targeted interventions, and improved long-term outcomes.

Full Paper: https://onlinelibrary.wiley.com/doi/10.1111/dmcn.70112

Spinal muscular atrophy types 2 and 3 encompass a wide spectrum of motor abilities ranging from non-sitting to sitting and walking. This study refines a functional group termed high functioning sitter-standers, positioned between traditional categories, and examined in relation to both the Revised Hammersmith Scale and a World Health Organization motor milestone-based framework. Among 178 participants completing 618 assessments, 109 were classified as type 2, 59 as type 3a, and 10 as type 3b, with ages ranging from 1 to 17.5 years. Twenty-seven non-sitters completed 54 assessments, 110 sitters completed 347, and 50 walkers completed 169, while the high functioning sitter-standers accounted for 48 assessments of 21 individuals. This newly defined group scored significantly lower than walkers and higher than both sitters and non-sitters, highlighting a distinct and measurable functional profile. Although no significant differences in age distribution were observed between the high functioning sitter-standers and walkers or non-sitters, sitters were notably younger. This intermediate phenotype captures patients with partial standing and assisted walking abilities, often overlooked in previous analyses. Recognition of this group is important for understanding emerging functional trajectories in treated spinal muscular atrophy and for informing future outcome measures and quality of life assessments.

Motor unit MRI (MUMRI) non-invasively detects fasciculation, a common symptom of SMA and potential biomarker for clinical trials. We applied MUMRI in ten SMA III patients and ten controls comparing fasciculation rates. Images of the tongue, upper arm, paraspinal and thighs & lower legs were acquired using MUMRI and 3-point Dixon (fat fraction) sequences. Fasciculation rate (cm-3min-1) was significantly higher in SMA than controls for: paraspinal 0.15 ± 0.20 vs. 0.003 ± 0.006, p = 0.001, thighs 1.28 ± 1.76 vs. 0.008 ± 0.005, p = 0.002 and lower legs 0.53 ± 0.85 vs. 0.02 ± 0.02, p = 0.001, but not for the tongue 0.20 ± 0.20 vs. 0.06 ± 0.09, p = 0.082 or upper arm 0.45 ± 0.95 vs. 0.002 ± 0.004, p = 0.014. Fat fraction %, was significantly higher in SMA than controls for: upper arm 35.0 ± 25.4 vs. 4.2 ± 1.1, p<<0.001, paraspinal 41.4 ± 31.0 vs. 7.4 ± 4.5, p = 0.002, thighs 54.8 ± 23.8 vs. 5.7 ± 1.0, p<<0.001 and lower legs 29.6 ± 23.5 vs. 4.4 ± 0.9, p = 0.0003, but not for the tongue 13.9 ± 3.2 vs. 13.0 ± 3.3, p = 0.393. MUMRI is an attractive non-invasive biomarker, which could be used to monitor progression & response in SMA clinical trials.