ArticleHuman molecular genetics2014
Defining the therapeutic window in a severe animal model of spinal muscular atrophy.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 3 of them syntheses that pooled it.
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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, 3 syntheses or guidelines pooled it.
- 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
- Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy.Pediatric pulmonology · 2019Trial
- Maternal-Fetal Administration of Risdiplam Partially Rescues the SMNΔ7 Mouse Model of Spinal Muscular Atrophy.Annals of neurology · 2026Article
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Disease-Modifying Therapies in Spinal Muscular Atrophy: Neurodevelopmental and Behavioral Outcomes in the Treatment Era.Advances in therapy · 2026Review
- Single-dose GC101 gene therapy for spinal muscular atrophy types II and III: an open-label single-arm study.World journal of pediatrics : WJP · 2025Article
- Base editing of trinucleotide repeats that cause Huntington's disease and Friedreich's ataxia reduces somatic repeat expansions in patient cells and in mice.Nature genetics · 2025Article
- IL-1ra and CCL5, but not IL-10, are promising targets for treating SMA astrocyte-driven pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Morpholino-Mediated Exon Inclusion for Spinal Muscular Atrophy (SMA).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Base editing rescue of spinal muscular atrophy in cells and in mice.Science (New York, N.Y.) · 2023Article
- Motor unit recovery following Smn restoration in mouse models of spinal muscular atrophy.Human molecular genetics · 2022Article
- Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders.Neurological research and practice · 2022Review
- Defining the optimal dose and therapeutic window in SMA with respiratory distress type I model mice, FVB/NJ-Molecular therapy. Methods & clinical development · 2021Article
- Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice.Neurobiology of disease · 2021Article
- Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool,Human gene therapy · 2021Article
- Short-duration splice promoting compound enables a tunable mouse model of spinal muscular atrophy.Life science alliance · 2021Article
- Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord.Frontiers in molecular neuroscience · 2021Review
- AAV9-DOK7 gene therapy reduces disease severity in SmnBiochemical and biophysical research communications · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of a single gene, Survival Motor Neuron-1 (SMN1). Administration of a self-complementary Adeno-Associated Virus vector expressing full-length SMN cDNA (scAAV-SMN) has proven an effective means to rescue the SMA phenotype in SMA mice, either by intravenous (IV) or intracerebroventricular (ICV) administration at very early time points. We have recently shown that ICV delivery of scAAV9-SMN is more effective than a similar dose of vector administered via an IV injection, thereby providing an important mechanism to examine a timeline for rescuing the disease and determining the therapeutic window in a severe model of SMA. In this report, we utilized a relatively severe mouse model of SMA, SMNΔ7. Animals were injected with scAAV9-SMN vector via ICV injection on a single day, from P2 through P8. At each delivery point from P2 through P8, scAAV9-SMN decreased disease severity. A near complete rescue was obtained following P2 injection while a P8 injection produced a ∼ 40% extension in survival. Analysis of the underlying neuromuscular junction (NMJ) pathology revealed that late-stage delivery of the vector failed to provide protection from NMJ defects despite robust SMN expression in the central nervous system. While our study demonstrates that a maximal benefit is obtained when treatment is delivered during pre-symptomatic stages, significant therapeutic benefit can still be achieved after the onset of disease symptoms.
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