ArticleBMJ neurology open2021
Persistent neuromuscular junction transmission defects in adults with spinal muscular atrophy treated with nusinersen.
Article in BMJ neurology open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Effectiveness and Safety of Nusinersen and Risdiplam in Spinal Muscular Atrophy: A Systematic Review.Annals of clinical and translational neurology · 2026Pooled it
- Safety, Pharmacokinetics, and Pharmacodynamics of a First-in-Class ClC-1 Inhibitor to Enhance Muscle Excitability: Phase I Randomized Controlled Trial.Clinical pharmacology and therapeutics · 2025Trial
- Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: a randomized, placebo-controlled, crossover phase 2 trial.Journal of neurology · 2022Trial
- Nanotube-Assisted Motor Neuron and Neuromuscular Junction Stabilization in Spinal Muscular Atrophy: A Hypothesis for Adjunctive Therapy.Neurology international · 2026Review
- Haloperidol induces neuroprotection and enhances neuromuscular function in both murine and human models of spinal muscular atrophy.Experimental & molecular medicine · 2026Article
- Astrocyte targeted SMN1 gene therapy and forskolin application improves astrocyte filopodia actin defects and motor neuron synaptic dysfunction in human SMA disease pathology.bioRxiv : the preprint server for biology · 2026Article
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Motor Unit Patterns Correlate With Severity in Symptomatic Patients With Spinal Muscular Atrophy.European journal of neurology · 2025Article
- The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy.Brain pathology (Zurich, Switzerland) · 2025Article
- Neuromuscular transmission deficits in patients with CMT and ClC-1 inhibition in CMT animal models.Annals of clinical and translational neurology · 2025Observational
- Neuromuscular junction dysfunction in Lafora disease.Disease models & mechanisms · 2024Article
- Beyond Motor Neurons in Spinal Muscular Atrophy: A Focus on Neuromuscular Junction.International journal of molecular sciences · 2024Review
- Neurophysiological Characteristics in Type II and Type III 5q Spinal Muscular Atrophy Patients: Impact of Nusinersen Treatment.Drug design, development and therapy · 2024Article
- Fatigue in Spinal Muscular Atrophy: a fundamental open issue.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2024Review
- Biomarkers in 5q-associated spinal muscular atrophy-a narrative review.Journal of neurology · 2023Review
- Neuromuscular junction transmission failure in aging and sarcopenia: The nexus of the neurological and muscular systems.Ageing research reviews · 2023Review
- Neuromuscular junction involvement in inherited motor neuropathies: genetic heterogeneity and effect of oral salbutamol treatment.Journal of neurology · 2023Article
- Article
- Pathophysiology and Management of Fatigue in Neuromuscular Diseases.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSpinal muscular atrophy (SMA) is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. Prior work in models and patients has demonstrated electrophysiological and morphological defects at the neuromuscular junction (NMJ). Therapeutic development has resulted in clinically available therapies to increase SMN protein levels in patients and improve muscle function. Here we aimed to investigate the effect of SMN restoration (via nusinersen) on NMJ transmission in adults with SMA.
methodsParticipants undergoing nusinersen treatment underwent 3 Hz repetitive nerve stimulation (RNS) of the spinal accessory nerve to assess compound muscle action potential amplitude decrement. Maximum voluntary isometric contraction (MVICT), Revised Upper Limb Module (RULM), and 6 min walk test (6MWT) were assessed for correlations with decrement.
resultsData from 13 ambulatory (7 men/6 women, mean age 40±11 years) and 11 non-ambulatory (3 men/8 women, mean age 38±12 years) participants were analysed. Cross-sectional analyses of RNS decrement were similar at 14 months of nusinersen (-14.2%±11.5%, n=17) vs baseline (-11.9%±8.3%, n=15) (unpaired t-test, p=0.5202). Longitudinal comparison of decrement in eight participants showed no change at 14 months (-13.9%±6.7%) vs baseline (-16.9%±13.4%) (paired t-test, p=0.5863). Decrement showed strong correlations with measures of MVICT, RULM and 6MWT but not age or disease duration.
conclusionAdults with SMA had significant NMJ transmission defects that were not corrected with 14 months of nusinersen treatment. NMJ defects were negatively associated with physical function, and thus may represent a promising target for additive or combinatorial treatments.
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Registered trials
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