ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03381729 (Phase I, Open-Label, Dose Comparison Study of AVXS-101 for Sitting But Non-ambulatory Patients With Spinal Muscular Atrophy), which is not on this map. Cited by 192 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Phase I, Open-Label, Dose Comparison Study of AVXS-101 for Sitting But Non-ambulatory Patients With Spinal Muscular Atrophy
Who cites it
192 citing papers in PubMed, 3 syntheses or guidelines pooled it, 273 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
- Biologic Therapies for Alleviating Neurodegeneration in Lysosomal Storage Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Next generation AAV-F capsid gene therapy rescues disease pathology in a model of pyruvate dehydrogenase complex deficiency.Molecular therapy. Advances · 2026Article
- Antisense oligonucleotide treatment following viral delivery of artificial SOD1-targeting miRNA shows improved efficacy in SOD1-G93A mice.Molecular therapy. Advances · 2026Article
- Neonatal expression of human FMRP isoform corrects cortical deficits and improves behavior in a mouse model of fragile X syndrome.Molecular therapy. Nucleic acids · 2026Article
- Lack of sensorimotor toxicity when using the clinical SMN expression cassette in scAAV9.Nature neuroscience · 2026Article
- Article
- Distribution of transgene in the rodent choroid plexus after intracerebroventricular injection of adeno-associated virus.Fluids and barriers of the CNS · 2026Article
- Differential expression of monoclonal antibody in rat brain following systemic and local administration of AAV.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Safety considerations of gene-based therapies for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Review
- Preclinical evaluation of INS1201 AAV9-micro-dystrophin via CSF administration as a potential therapy for Duchenne muscular dystrophy.Molecular therapy. Advances · 2026Article
- Comparison of AAV9-driven motor neuron transduction following different CNS-directed delivery methods in mice.Scientific reports · 2026Article
- Article
- Survival motor neuron protein-independent amelioration of spinal muscular atrophy by pharmacological inhibition of c-Jun-NHBrain communications · 2026Article
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Systemic mRNA-LNP administration in fetuses improves survival in a mouse model of spinal muscular atrophy.Molecular therapy. Methods & clinical development · 2025Article
- Advances and Challenges in Adeno-Associated Virus Gene Therapy Applications of Localized Delivery Strategies.Current medical science · 2025Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is the most frequent lethal genetic neurodegenerative disorder in infants. The disease is caused by low abundance of the survival of motor neuron (SMN) protein leading to motor neuron degeneration and progressive paralysis. We previously demonstrated that a single intravenous injection (IV) of self-complementary adeno-associated virus-9 carrying the human SMN cDNA (scAAV9-SMN) resulted in widespread transgene expression in spinal cord motor neurons in SMA mice as well as nonhuman primates and complete rescue of the disease phenotype in mice. Here, we evaluated the dosing and efficacy of scAAV9-SMN delivered directly to the cerebral spinal fluid (CSF) via single injection. We found widespread transgene expression throughout the spinal cord in mice and nonhuman primates when using a 10 times lower dose compared to the IV application. Interestingly, in nonhuman primates, lower doses than in mice can be used for similar motor neuron targeting efficiency. Moreover, the transduction efficacy is further improved when subjects are kept in the Trendelenburg position to facilitate spreading of the vector. We present a detailed analysis of transduction levels throughout the brain, brainstem, and spinal cord of nonhuman primates, providing new guidance for translation toward therapy for a wide range of neurodegenerative disorders.
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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.