ArticleNeurobiology of disease2016
N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase.
Article in Neurobiology of disease, 2016. 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 33 papers.
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
33 citing papers in PubMed, 41 citations in OpenAlex.
- Oligodendrocyte-targeted adeno-associated virus gene therapy for Canavan disease in children: a phase 1/2 trial.Nature medicine · 2025Trial
- N-Acetylaspartate Synthesis as a Thermodynamic Relief Mechanism for Mitochondrial Aspartate Aminotransferase.bioRxiv : the preprint server for biology · 2026Article
- The Emerging Role of N-Acetylaspartate in Cancer.International journal of molecular sciences · 2026Review
- Monocarboxylate transporter 2 regulates maintenance of myelin and axonal integrity by oligodendrocytes.Nature communications · 2026Article
- Aspartate-Glutamate Carrier 1 (International journal of molecular sciences · 2026Review
- Neuroglial Pathophysiology of Leukodystrophies.Advances in neurobiology · 2025Review
- Impact of Histone Acetyltransferases and Histone Deacetylases on Adult Brain Myelin Plasticity.Results and problems in cell differentiation · 2025Review
- Review
- 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
- Repurposing Ketamine in the Therapy of Depression and Depression-Related Disorders: Recent Advances and Future Potential.Aging and disease · 2024Review
- Cellular and molecular mechanisms of aspartoacylase and its role in Canavan disease.Cell & bioscience · 2024Review
- Parallel Metabolomics and Lipidomics of a PSMA/GCPII Deficient Mouse Model Reveal Alteration of NAAG Levels and Brain Lipid Composition.ACS chemical neuroscience · 2024Article
- Developing Hypoimmunogenic Human iPSC-Derived Oligodendrocyte Progenitor Cells as an Off-The-Shelf Cell Therapy for Myelin Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Therapeutic development for Canavan disease using patient iPSCs introduced with the wild-typeiScience · 2022Article
- Phosphoproteomic profiling of the hippocampus of offspring rats exposed to prenatal stress.Brain and behavior · 2021Article
- Transcriptomic profiling of high- and low-spiking regions reveals novel epileptogenic mechanisms in focal cortical dysplasia type II patients.Molecular brain · 2021Article
- Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease.Molecular therapy. Methods & clinical development · 2021Article
- Diagnostic Approach to Macrocephaly in Children.Frontiers in pediatrics · 2021Review
- Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair.Frontiers in cellular neuroscience · 2021Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
Breakdown of neuro-glial N-acetyl-aspartate (NAA) metabolism results in the failure of developmental myelination, manifest in the congenital pediatric leukodystrophy Canavan disease caused by mutations to the sole NAA catabolizing enzyme aspartoacylase. Canavan disease is a major point of focus for efforts to define NAA function, with available evidence suggesting NAA serves as an acetyl donor for fatty acid synthesis during myelination. Elevated NAA is a diagnostic hallmark of Canavan disease, which contrasts with a broad spectrum of alternative neurodegenerative contexts in which levels of NAA are inversely proportional to pathological progression. Recently generated data in the nur7 mouse model of Canavan disease suggests loss of aspartoacylase function results in compromised energetic integrity prior to oligodendrocyte death, abnormalities in myelin content, spongiform degeneration, and motor deficit. The present study utilized a next-generation "oligotropic" adeno-associated virus vector (AAV-Olig001) to quantitatively assess the impact of aspartoacylase reconstitution on developmental myelination. AAV-Olig001-aspartoacylase promoted normalization of NAA, increased bioavailable acetyl-CoA, and restored energetic balance within a window of postnatal development preceding gross histopathology and deteriorating motor function. Long-term effects included increased oligodendrocyte numbers, a global increase in myelination, reversal of vacuolation, and rescue of motor function. Effects on brain energy observed following AAV-Olig001-aspartoacylase gene therapy are shown to be consistent with a metabolic profile observed in mild cases of Canavan disease, implicating NAA in the maintenance of energetic integrity during myelination via oligodendroglial aspartoacylase.
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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.