ArticleProceedings of the National Academy of Sciences of the United States of America2015
Systemic, postsymptomatic antisense oligonucleotide rescues motor unit maturation delay in a new mouse model for type II/III spinal muscular atrophy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 of them syntheses 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.
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Who cites it
43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 62 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
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- Cardiac pathology in spinal muscular atrophy: a systematic review.Orphanet journal of rare diseases · 2017Pooled it
- Immaturity of the neuromuscular junction in spinal muscular atrophy mouse models.Frontiers in cellular neuroscience · 2026Review
- The role of vascular pathology in SMA: implications for pathogenesis and treatment.Frontiers in cellular neuroscience · 2026Review
- Systemic mRNA-LNP administration in fetuses improves survival in a mouse model of spinal muscular atrophy.Molecular therapy. Methods & clinical development · 2025Article
- Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy.Science translational medicine · 2025Article
- Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.Cell reports. Medicine · 2024Article
- Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation.Nature neuroscience · 2024Article
- Differential impact on motor unit characteristics across severities of adult spinal muscular atrophy.Annals of clinical and translational neurology · 2023Article
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- Clinical implications of tristetraprolin (TTP) modulation in the treatment of inflammatory diseases.Pharmacology & therapeutics · 2022Review
- Motor unit recovery following Smn restoration in mouse models of spinal muscular atrophy.Human molecular genetics · 2022Article
- Motor defects in a Drosophila model for spinal muscular atrophy result from SMN depletion during early neurogenesis.PLoS genetics · 2022Article
- Emerging concepts underlying selective neuromuscular dysfunction in infantile-onset spinal muscular atrophy.Neural regeneration research · 2021Review
- Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Antisense Drugs Make Sense for Neurological Diseases.Annual review of pharmacology and toxicology · 2021Review
- Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral to Neuromuscular Junction Reinnervation after Nerve Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- RNA in spinal muscular atrophy: therapeutic implications of targeting.Expert opinion on therapeutic targets · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Clinical presentation of spinal muscular atrophy (SMA) ranges from a neonatal-onset, very severe disease to an adult-onset, milder form. SMA is caused by the mutation of the Survival Motor Neuron 1 (SMN1) gene, and prognosis inversely correlates with the number of copies of the SMN2 gene, a human-specific homolog of SMN1. Despite progress in identifying potential therapies for the treatment of SMA, many questions remain including how late after onset treatments can still be effective and what the target tissues should be. These questions can be addressed in part with preclinical animal models; however, modeling the array of SMA severities in the mouse, which lacks SMN2, has proven challenging. We created a new mouse model for the intermediate forms of SMA presenting with a delay in neuromuscular junction maturation and a decrease in the number of functional motor units, all relevant to the clinical presentation of the disease. Using this new model, in combination with clinical electrophysiology methods, we found that administering systemically SMN-restoring antisense oligonucleotides (ASOs) at the age of onset can extend survival and rescue the neurological phenotypes. Furthermore, these effects were also achieved by administration of the ASOs late after onset, independent of the restoration of SMN in the spinal cord. Thus, by adding to the limited repertoire of existing mouse models for type II/III SMA, we demonstrate that ASO therapy can be effective even when administered after onset of the neurological symptoms, in young adult mice, and without being delivered into the central nervous system.
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