ArticleThe Journal of clinical investigation2004
Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells.
Article in The Journal of clinical investigation, 2004. 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 141 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
141 citing papers in PubMed, 262 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
- Unlocking the curative potential of gene transfer and editing for hematopoietic disorders.Experimental hematology · 2026Review
- Development and characterization of a model of mucopolysaccharidosis type IVA for evaluating therapies targeting bone disease.Disease models & mechanisms · 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
- Neonatal gene therapy effectively prevents disease manifestations in a murine model of Mucopolysaccharidosis type I.Molecular therapy. Methods & clinical development · 2025Article
- 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
- Exploring tumor-associated macrophages in glioblastoma: from diversity to therapy.NPJ precision oncology · 2025Review
- Donor insertion into CX3CR1 allows epigenetic modulation of a constitutive promoter on hematopoietic stem cells and its activation upon myeloid differentiation.Nucleic acids research · 2025Article
- Effective gene therapy for metachromatic leukodystrophy achieved with minimal lentiviral genomic integrations.Molecular therapy. Nucleic acids · 2025Article
- Microglia and macrophages in glioblastoma: landscapes and treatment directions.Molecular oncology · 2024Review
- Hematopoietic stem cell gene therapy improves outcomes in a clinically relevant mouse model of multiple sulfatase deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- AMolecular therapy. Methods & clinical development · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Hematopoietic stem cell gene therapy to halt neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- The molecular determinants of microglial developmental dynamics.Nature reviews. Neuroscience · 2024Review
- Macrophage transplantation rescues RNASET2-deficient leukodystrophy by replacing deficient microglia in a zebrafish model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- A review of animal models utilized in preclinical studies of approved gene therapy products: trends and insights.Laboratory animal research · 2024Review
- Current and Future Perspective in Hematopoietic Stem Progenitor Cell-gene Therapy for Inborn Errors of Metabolism.HemaSphere · 2023Article
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Gene-based delivery can establish a sustained supply of therapeutic proteins within the nervous system. For diseases characterized by extensive CNS and peripheral nervous system (PNS) involvement, widespread distribution of the exogenous gene may be required, a challenge to in vivo gene transfer strategies. Here, using lentiviral vectors (LVs), we efficiently transduced hematopoietic stem cells (HSCs) ex vivo and evaluated the potential of their progeny to target therapeutic genes to the CNS and PNS of transplanted mice and correct a neurodegenerative disorder, metachromatic leukodystrophy (MLD). We proved extensive repopulation of CNS microglia and PNS endoneurial macrophages by transgene-expressing cells. Intriguingly, recruitment of these HSC-derived cells was faster and more robust in MLD mice. By transplanting HSCs transduced with the arylsulfatase A gene, we fully reconstituted enzyme activity in the hematopoietic system of MLD mice and prevented the development of motor conduction impairment, learning and coordination deficits, and neuropathological abnormalities typical of the disease. Remarkably, ex vivo gene therapy had a significantly higher therapeutic impact than WT HSC transplantation, indicating a critical role for enzyme overexpression in the HSC progeny. These results indicate that transplantation of LV-transduced autologous HSCs represents a potentially efficacious therapeutic strategy for MLD and possibly other neurodegenerative disorders.
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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.