ArticleGene therapy2002
Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations.
Article in Gene therapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 79 citations in OpenAlex.
- Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs.International journal of molecular sciences · 2023Article
- Therapeutic effects of stem cells in different body systems, a novel method that is yet to gain trust: A comprehensive review.Bosnian journal of basic medical sciences · 2021Review
- Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development.Biomolecules · 2021Review
- Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.Frontiers in medicine · 2020Review
- Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective.Orphanet journal of rare diseases · 2019Review
- TSEN54 missense variant in Standard Schnauzers with leukodystrophy.PLoS genetics · 2019Article
- Long-Term Persistence of Anti-HIV Broadly Neutralizing Antibody-Secreting Hematopoietic Cells in Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Gene therapy for metachromatic leukodystrophy.Journal of neuroscience research · 2016Review
- Review
- Developing therapeutic approaches for metachromatic leukodystrophy.Drug design, development and therapy · 2013Review
- The myelin mutants as models to study myelin repair in the leukodystrophies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2011Review
- Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Non-inhibitory antibodies impede lysosomal storage reduction during enzyme replacement therapy of a lysosomal storage disease.Journal of molecular medicine (Berlin, Germany) · 2008Article
- Enzyme, cell and gene-based therapies for metachromatic leukodystrophy.Journal of inherited metabolic disease · 2007Review
- Partial cure of established disease in an animal model of metachromatic leukodystrophy after intracerebral adeno-associated virus-mediated gene transfer.Gene therapy · 2007Article
- Embryonic stem cell-based reduction of central nervous system sulfatide storage in an animal model of metachromatic leukodystrophy.Gene therapy · 2006Article
- Modest phenotypic improvements in ASA-deficient mice with only one UDP-galactose:ceramide-galactosyltransferase gene.Lipids in health and disease · 2006Article
- Future perspectives for glycolipid research in medicine.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2003Review
- Gene therapy: prospects for glycolipid storage diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2003Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arylsulfatase A (ASA) knockout mice represent an animal model for the lysosomal storage disease metachromatic leukodystrophy (MLD). Stem cell gene therapy with bone marrow overexpressing the human ASA cDNA from a retroviral vector resulted in the expression of high enzyme levels in various tissues. Treatment partially reduces sulfatide storage in livers exceeding 18 ng ASA/mg tissue, while complete reduction was observed in livers exceeding 50 ng ASA/mg tissue. This corresponds to about 80% and 200% of normal enzyme activity. Similar values seem to apply for kidney. A partial correction of the lipid metabolism was detectable in the brain where the galactoerebroside/sulfatide ratio, which is diminished in ASA-deficient mice, increased upon treatment. This partial correction was accompanied by amelioration of neuropathology; axonal cross-sectional areas, which are reduced in deficient mice, were significantly increased in the saphenic and sciatic nerve but not in the optic nerve. Behavioral tests suggest some improvement of neuromotor abilities. The gene transfer did not delay the degeneration occurring in the acoustic ganglion of ASA-deficient animals. The limited success of the therapy appears to be due to the requirement of unexpected high levels of ASA for correction of the metabolic defect.
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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.