ArticleNeurobiology of disease2016
The neuromuscular impact of symptomatic SMN restoration in a mouse model of spinal muscular atrophy.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models.Gene therapy · 2022Pooled it
- A dual-action nanoparticle approach for spinal cord injury treatment: ferroptosis inhibition, inflammation control, and Myelin preservation.Journal of nanobiotechnology · 2026Article
- Immaturity of the neuromuscular junction in spinal muscular atrophy mouse models.Frontiers in cellular neuroscience · 2026Review
- Application of Biomarkers in Spinal Muscular Atrophy.International journal of molecular sciences · 2025Review
- The Relevance of Spinal Muscular Atrophy Biomarkers in the Treatment Era.Biomedicines · 2024Review
- Base editing rescue of spinal muscular atrophy in cells and in mice.Science (New York, N.Y.) · 2023Article
- Electrical impedance myography combined with quantitative assessment techniques in paretic muscle of stroke survivors: Insights and challenges.Frontiers in aging neuroscience · 2023Article
- Cell-penetrating peptide-conjugated Morpholino rescues SMA in a symptomatic preclinical model.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice.Neurobiology of disease · 2021Article
- The mitochondrial biogenesis signaling pathway is a potential therapeutic target for myasthenia gravis via energy metabolism (Review).Experimental and therapeutic medicine · 2021Review
- Estimating myofiber cross-sectional area and connective tissue deposition with electrical impedance myography: A study in D2-mdx mice.Muscle & nerve · 2021Article
- In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy.Brain sciences · 2021Review
- Predicting myofiber cross-sectional area and triglyceride content with electrical impedance myography: A study in db/db mice.Muscle & nerve · 2021Article
- Update on Biomarkers in Spinal Muscular Atrophy.Biomarker insights · 2021Review
- Safety, Tolerability, and Effect of Nusinersen Treatment in Ambulatory Adults With 5q-SMA.Frontiers in neurology · 2021Article
- Safety, Tolerability, and Effect of Nusinersen in Non-ambulatory Adults With Spinal Muscular Atrophy.Frontiers in neurology · 2021Article
- RNA in spinal muscular atrophy: therapeutic implications of targeting.Expert opinion on therapeutic targets · 2020Review
- Article
- Hyperexcitability precedes motoneuron loss in theJournal of neurophysiology · 2019Article
- Electrical Impedance Methods in Neuromuscular Assessment: An Overview.Cold Spring Harbor perspectives in medicine · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSignificant advances in the development of SMN-restoring therapeutics have occurred since 2010 when very effective biological treatments were reported in mouse models of spinal muscular atrophy. As these treatments are applied in human clinical trials, there is pressing need to define quantitative assessments of disease progression, treatment stratification, and therapeutic efficacy. The electrophysiological measures Compound Muscle Action Potential and Motor Unit Number Estimation are reliable measures of nerve function. In both the SMN∆7 mouse and a pig model of spinal muscular atrophy, early SMN restoration results in preservation of electrophysiological measures. Currently, clinical trials are underway in patients at post-symptomatic stages of disease progression. In this study, we present results from both early and delayed SMN restoration using clinically-relevant measures including electrical impedance myography, compound muscle action potential, and motor unit number estimation to quantify the efficacy and time-sensitivity of SMN-restoring therapy.
methodsSMA∆7 mice were treated via intracerebroventricular injection with antisense oligonucleotides targeting ISS-N1 to increase SMN protein from the SMN2 gene on postnatal day 2, 4, or 6 and compared with sham-treated spinal muscular atrophy and control mice. Compound muscle action potential and motor unit number estimation of the triceps surae muscles were performed at day 12, 21, and 30 by a single evaluator blinded to genotype and treatment. Similarly, electrical impedance myography was measured on the biceps femoris muscle at 12days for comparison.
resultsElectrophysiological measures and electrical impedance myography detected significant differences at 12days between control and late-treated (4 or 6days) and sham-treated spinal muscular atrophy mice, but not in mice treated at 2days (p<0.01). EIM findings paralleled and correlated with compound muscle action potential and motor unit number estimation (r=0.61 and r=0.50, respectively, p<0.01). Longitudinal measures at 21 and 30days show that symptomatic therapy results in reduced motor unit number estimation associated with delayed normalization of compound muscle action potential.
conclusionsThe incomplete effect of symptomatic treatment is accurately identified by both electrophysiological measures and electrical impedance myography. There is strong correlation between these measures and with weight and righting reflex. This study predicts that measures of compound muscle action potential, motor unit number estimation, and electrical impedance myography are promising biomarkers of treatment stratification and effect for future spinal muscular atrophy trials. The ease of application and simplicity of electrical impedance myography compared with standard electrophysiological measures may be particularly valuable in future pediatric clinical trials.
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