ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
rAAV Gene Therapy in a Canavan's Disease Mouse Model Reveals Immune Impairments and an Extended Pathology Beyond the Central Nervous System.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- An improved method for high-purity isolation of oligodendrocytes from neonatal and adult mouse brain.iScience · 2026Article
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Adeno-associated virus vector delivery to the brain: Technology advancements and clinical applications.Advanced drug delivery reviews · 2024Review
- Myelin lesion in the aspartoacylase (Aspa) knockout rat, an animal model for Canavan disease.Experimental animals · 2024Article
- Comprehensive Study on Mineral Processing Methods and Mineral Technical Economics of Manganese Ore in Chongqing Chengkou.ACS omega · 2024Article
- Therapeutic development for Canavan disease using patient iPSCs introduced with the wild-typeiScience · 2022Article
- Dual-function AAV gene therapy reverses late-stage Canavan disease pathology in mice.Frontiers in molecular neuroscience · 2022Article
- Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases.Frontiers in molecular neuroscience · 2022Review
- Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease.Molecular therapy. Methods & clinical development · 2021Article
- Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair.Frontiers in cellular neuroscience · 2021Review
- Nucleic Acid-Based Therapeutics in Orphan Neurological Disorders: Recent Developments.Frontiers in molecular biosciences · 2021Review
- Cell-Based Therapy for Canavan Disease Using Human iPSC-Derived NPCs and OPCs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Pathophysiology and Treatment of Canavan Disease.Neurochemical research · 2020Article
- Gene Delivery to Nonhuman Primate Preimplantation Embryos Using Recombinant Adeno-Associated Virus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- Intravenous Infusion of AAV for Widespread Gene Delivery to the Nervous System.Methods in molecular biology (Clifton, N.J.) · 2019Article
- A Rationally Engineered Capsid Variant of AAV9 for Systemic CNS-Directed and Peripheral Tissue-Detargeted Gene Delivery in Neonates.Molecular therapy. Methods & clinical development · 2018Article
- Brain Nat8l Knockdown Suppresses Spongiform Leukodystrophy in an Aspartoacylase-Deficient Canavan Disease Mouse Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy.Acta neuropathologica · 2018Article
- RedirectingJCI insight · 2017Article
- Increasing N-acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the CNS Pathologies of Canavan Disease.Frontiers in molecular neuroscience · 2017Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Aspartoacylase (AspA) gene mutations cause the pediatric lethal neurodegenerative Canavan disease (CD). There is emerging promise of successful gene therapy for CD using recombinant adeno-associated viruses (rAAVs). Here, we report an intracerebroventricularly delivered AspA gene therapy regime using three serotypes of rAAVs at a 20-fold reduced dose than previously described in AspA(-/-) mice, a bona-fide mouse model of CD. Interestingly, central nervous system (CNS)-restricted therapy prolonged survival over systemic therapy in CD mice but failed to sustain motor functions seen in systemically treated mice. Importantly, we reveal through histological and functional examination of untreated CD mice that AspA deficiency in peripheral tissues causes morphological and functional abnormalities in this heretofore CNS-defined disorder. We demonstrate for the first time that AspA deficiency, possibly through excessive N-acetyl aspartic acid accumulation, elicits both a peripheral and CNS immune response in CD mice. Our data establish a role for peripheral tissues in CD pathology and serve to aid the development of more efficacious and sustained gene therapy for this 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.