ArticleThe Journal of clinical investigation2006
Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01560182 (A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Treatment of Metachromatic Leukodystrophy), which is not on this map. Cited by 121 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.
A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Treatment of Metachromatic Leukodystrophy
Who cites it
121 citing papers in PubMed, 224 citations in OpenAlex.
- Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.Lancet (London, England) · 2022Trial
- Edited HSPCs rescue frataxin deficiency and inflammation-driven multisystemic pathology in Friedreich's ataxia mice.The Journal of clinical investigation · 2026Article
- Microglial clonal dynamics and the impact of clonal hematopoiesis in autologously transplanted rhesus macaques.Cell reports · 2026Article
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Mapping Lysosomal Storage Disorders with Neurological Features by Cellular Pathways: Towards Precision Medicine.Current issues in molecular biology · 2025Review
- Article
- Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025Review
- Hematopoietic stem cell gene therapy of neurometabolic lysosomal storage diseases.Brain & development · 2025Review
- Metachromatic Leukodystrophy: New Therapy Advancements and Emerging Research Directions.Neurology · 2025Review
- Effective gene therapy for metachromatic leukodystrophy achieved with minimal lentiviral genomic integrations.Molecular therapy. Nucleic acids · 2025Article
- Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: a long-term follow-up pilot study.Protein & cell · 2025Article
- Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.Antioxidants & redox signaling · 2024Review
- Review
- Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice.Nature communications · 2024Article
- Therapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer's disease mouse model.Nature communications · 2024Article
- Hematopoietic stem cell gene therapy to halt neurodegeneration.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
- Novel strategies in Parkinson's disease treatment: a review.Frontiers in molecular neuroscience · 2024Review
- Sustained long-term disease correction in a murine model of MPSII following stem cell gene therapy.Molecular therapy. Methods & clinical development · 2023Article
- Donor bone marrow-derived macrophage engraftment into the central nervous system of patients following allogeneic transplantation.Blood advances · 2023Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 3 countries.
Funding
Abstract
Metachromatic leukodystrophy (MLD) is a demyelinating lysosomal storage disorder for which new treatments are urgently needed. We previously showed that transplantation of gene-corrected hematopoietic stem progenitor cells (HSPCs) in presymptomatic myeloablated MLD mice prevented disease manifestations. Here we show that HSC gene therapy can reverse neurological deficits and neuropathological damage in affected mice, thus correcting an overt neurological disease. The efficacy of gene therapy was dependent on and proportional to arylsulfatase A (ARSA) overexpression in the microglia progeny of transplanted HSPCs. We demonstrate a widespread enzyme distribution from these cells through the CNS and a robust cross-correction of neurons and glia in vivo. Conversely, a peripheral source of enzyme, established by transplanting ARSA-overexpressing hepatocytes from transgenic donors, failed to effectively deliver the enzyme to the CNS. These results indicate that the recruitment of gene-modified, enzyme-overexpressing microglia makes the enzyme bioavailable to the brain and makes therapeutic efficacy and disease correction attainable. Overall, our data provide a strong rationale for implementing HSPC gene therapy in MLD patients.
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What OpenQuestion holds
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.