ArticleHuman molecular genetics2015
Repeated low doses of morpholino antisense oligomer: an intermediate mouse model of spinal muscular atrophy to explore the window of therapeutic response.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 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
- The role of vascular pathology in SMA: implications for pathogenesis and treatment.Frontiers in cellular neuroscience · 2026Review
- Therapeutic strategies for spinal muscular atrophy: the history and future perspective.Frontiers in human neuroscience · 2026Review
- Morpholino-Mediated Exon Inclusion for Spinal Muscular Atrophy (SMA).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.Cell reports. Medicine · 2024Article
- Impact of Disease Severity and Disease-Modifying Therapies on Myostatin Levels in SMA Patients.International journal of molecular sciences · 2024Article
- Innovating spinal muscular atrophy models in the therapeutic era.Disease models & mechanisms · 2023Article
- Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect.The Journal of clinical investigation · 2022Article
- Motor defects in a Drosophila model for spinal muscular atrophy result from SMN depletion during early neurogenesis.PLoS genetics · 2022Article
- The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy.Annals of clinical and translational neurology · 2021Article
- Short-duration splice promoting compound enables a tunable mouse model of spinal muscular atrophy.Life science alliance · 2021Article
- RNA in spinal muscular atrophy: therapeutic implications of targeting.Expert opinion on therapeutic targets · 2020Review
- Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy.Journal of cachexia, sarcopenia and muscle · 2020Article
- Motor transmission defects with sex differences in a new mouse model of mild spinal muscular atrophy.EBioMedicine · 2020Article
- Comparison of the efficacy of MOE and PMO modifications of systemic antisense oligonucleotides in a severe SMA mouse model.Nucleic acids research · 2020Article
- AAV9-Stathmin1 gene delivery improves disease phenotype in an intermediate mouse model of spinal muscular atrophy.Human molecular genetics · 2019Article
- NCALD Antisense Oligonucleotide Therapy in Addition to Nusinersen further Ameliorates Spinal Muscular Atrophy in Mice.American journal of human genetics · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The human SMN2 transgenic mice are well-established models of spinal muscular atrophy (SMA). While the severe type I mouse model has a rapidly progressive condition mimicking type I SMA in humans, the mild type III mice do not faithfully recapitulate chronic SMA variants affecting children. A SMA mouse model that clinically mimics the features of type II and III SMA in human is therefore needed. In this study, we generated intermediately affected SMA mice by delivering low-dose morpholino oligomer (PMO25) into the existing severe SMA mice. We show that a single low-dose administration of PMO25 moderately extended the survival of severe type I SMA mice. The neuromuscular pathology is also modestly but significantly improved in these mice. A second administration of PMO25 at postnatal day 5 (PND5) demonstrated an additive effect on survival. Additional systemic administration of low-dose PMO25 at 2-week intervals suppressed the occurrence of distal necrosis beyond postnatal day 100, and induced more complete phenotypic rescue than a single bolus high-dose injection at PND0. Our study demonstrates that survival of motor neuron (SMN) is required early at a critical threshold to prevent symptoms and suggests that subsequent systemic administration of low-dose PMO25 in SMA mice can provide therapeutic benefit and phenotypic rescue, presumably via peripheral SMN restoration. Our work also provides additional insight into the time window of response to administration of antisense oligonucleotides to SMA mice with an intermediate phenotype. This information is crucial at a time when a number of therapeutic interventions are in clinical trials in SMA patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.