ArticleMolecular therapy. Methods & clinical development2021
Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease.
Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04833907 (Phase 1/2, Open Label, Sequential Cohort Study of a Single Intracranial Dose of AVASPA Gene Therapy for Treatment of Children With Typical Canavan Disease), which is not on this map. Cited by 32 papers, 1 of them a synthesis 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 1/2, Open Label, Sequential Cohort Study of a Single Intracranial Dose of AVASPA Gene Therapy for Treatment of Children With Typical Canavan Disease
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders-Implications for Individuals with Rett Syndrome: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Oligodendrocyte-targeted adeno-associated virus gene therapy for Canavan disease in children: a phase 1/2 trial.Nature medicine · 2025Trial
- From neuronal marker to metabolic mediator: Expanding the functional landscape of N-acetylaspartate in the central nervous system and the periphery.Neural regeneration research · 2026Article
- An AAV vector for glial cells.Nature biotechnology · 2026Article
- Targeting UBE3A and downstream estrogen receptor-β signaling to restore oligodendroglial homeostasis in Angelman syndrome.bioRxiv : the preprint server for biology · 2026Article
- An improved method for high-purity isolation of oligodendrocytes from neonatal and adult mouse brain.iScience · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025Review
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Selective RNAi silencing of Schwann cell Piezo1 alleviates mechanical hypersensitization following peripheral nerve injury.Molecular therapy. Methods & clinical development · 2025Article
- Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
- Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease.PLoS biology · 2024Article
- Neurosurgical gene therapy for central nervous system diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Quantification of N-acetyl-l-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease.Molecular genetics and metabolism · 2024Article
- In vivo base editing of a pathogenic Eif2b5 variant improves vanishing white matter phenotypes in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Cellular and molecular mechanisms of aspartoacylase and its role in Canavan disease.Cell & bioscience · 2024Review
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Gene and Cellular Therapies for Leukodystrophies.Pharmaceutics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent advances in adeno-associated viral (AAV) capsid variants with novel oligotropism require validation in models of disease in order to be viable candidates for white matter disease gene therapy. We present here an assessment of the biodistribution, tropism, and efficacy of a novel AAV capsid variant (AAV/ Olig001) in a model of Canavan disease. We first define a combination of dose and route of administration of an AAV/Olig001-GFP reporter conducive to widespread CNS oligodendrocyte transduction in acutely symptomatic animals that model the Canavan brain at time of diagnosis. Administration of AAV/Olig001-GFP resulted in >70% oligotropism in all regions of interest except the cerebellum without the need for lineage-specific expression elements. Intracerebroventricular infusion into the cerebrospinal fluid (CSF) was identified as the most appropriate route of administration and employed for delivery of an AAV/Olig001 vector to reconstitute oligodendroglial aspartoacylase (ASPA) in adult Canavan mice, which resulted in a dose-dependent rescue of ASPA activity, motor function, and a near-total reduction in vacuolation. A head-to-head efficacy comparison with astrogliotropic AAV9 highlighted a significant advantage conferred by oligotropic AAV/Olig001 that was independent of overall transduction efficiency. These results support the continued development of AAV/Olig001 for advancement to clinical application to white matter disease.
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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.