ArticleHuman gene therapy2012
Correction of brain oligodendrocytes by AAVrh.10 intracerebral gene therapy in metachromatic leukodystrophy mice.
Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01801709 (A Phase I/II, Open Labeled, Monocentric Study of Direct Intracranial Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human ARSA cDNA to Children With Metachromatic Leukodystrophy.), which is not on this map. Cited by 47 papers.
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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.
A Phase I/II, Open Labeled, Monocentric Study of Direct Intracranial Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human ARSA cDNA to Children With Metachromatic Leukodystrophy.
Who cites it
47 citing papers in PubMed, 90 citations in OpenAlex.
- Intrathecal delivery of AAVrh10-mHexa combined with anti-inflammatory treatment reduces neuropathological markers and extends the lifespan of mice with early-onset Tay-Sachs disease.Metabolic brain disease · 2026Article
- Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025Review
- Advances in AAV-mediated gene replacement therapy for pediatric monogenic neurological disorders.Molecular therapy. Methods & clinical development · 2024Review
- 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
- Dose-response evaluation of intravenous gene therapy in a symptomatic mouse model of metachromatic leukodystrophy.Molecular therapy. Methods & clinical development · 2024Article
- Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs.International journal of molecular sciences · 2023Article
- Single Systemic Administration of a Gene Therapy Leading to Disease Treatment in Metachromatic LeukodystrophyThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Review
- Gene Therapy of Sphingolipid Metabolic Disorders.International journal of molecular sciences · 2023Review
- Gene therapy for lysosomal storage diseases: Current clinical trial prospects.Frontiers in genetics · 2023Review
- Mammalian Sulfatases: Biochemistry, Disease Manifestation, and Therapy.International journal of molecular sciences · 2022Review
- Treatment of adult metachromatic leukodystrophy model mice using intrathecal administration of type 9 AAV vector encoding arylsulfatase A.Scientific reports · 2021Article
- Safety of Direct Intraparenchymal AAVrh.10-Mediated Central Nervous System Gene Therapy for Metachromatic Leukodystrophy.Human gene therapy · 2021Article
- Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development.Biomolecules · 2021Review
- Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord.Frontiers in molecular neuroscience · 2021Review
- Delivery Platforms for CRISPR/Cas9 Genome Editing of Glial Cells in the Central Nervous System.Frontiers in genome editing · 2021Review
- Clinical Trials for Gene Therapy in Lysosomal Diseases With CNS Involvement.Frontiers in molecular biosciences · 2021Review
- Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice.Frontiers in molecular neuroscience · 2021Article
- Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair.Frontiers in cellular neuroscience · 2021Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder characterized by accumulation of sulfatides in glial cells and neurons, the result of an inherited deficiency of arylsulfatase A (ARSA; EC 3.1.6.8) and myelin degeneration in the central and peripheral nervous systems. No effective treatment is currently available for the most frequent late infantile (LI) form of MLD, which results in rapid neurological degradation and early death after the onset of clinical manifestations. To potentially arrest or reverse disease progression, ARSA enzyme must be rapidly delivered to brain oligodendrocytes of patients with LI MLD. We previously showed that brain gene therapy with adeno-associated virus serotype 5 (AAV5) driving the expression of human ARSA cDNA under the control of the murine phosphoglycerate kinase (PGK) promoter alleviated most long-term disease manifestations in MLD mice. Herein, we evaluated the short-term effects of AAVrh.10 driving the expression of human ARSA cDNA under the control of the cytomegalovirus/β-actin hybrid (CAG/cu) promoter in 8-month-old MLD mice that already show marked sulfatide accumulation and brain pathology. Within 2 months, and in contrast to results with the AAV5-PGK-ARSA vector, a single intrastriatal injection of AAVrh.10cuARSA resulted in correction of brain sulfatide storage, accumulation of specific sulfatide species in oligodendrocytes, and associated brain pathology in the injected hemisphere. Better potency of the AAVrh.10cuARSA vector was mediated by higher neuronal and oligodendrocyte transduction, axonal transport of the AAVrh.10 vector and ARSA enzyme, as well as higher CAG/cu promoter driven expression of ARSA enzyme. These results strongly support the use of AAVrh.10cuARSA vector for intracerebral gene therapy in rapidly progressing early-onset forms of MLD.
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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.