ReviewJournal of inherited metabolic disease1998
Metachromatic leukodystrophy: molecular genetics and an animal model.
Review in Journal of inherited metabolic disease, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 75 citations in OpenAlex.
- Gene therapy for lysosomal storage diseases: Current clinical trial prospects.Frontiers in genetics · 2023Review
- Generation and characterization of motor neuron progenitors and motor neurons using metachromatic leukodystrophy-induced pluripotent stem cells.Molecular genetics and metabolism reports · 2022Article
- Lipidomic analysis identifies age-disease-related changes and potential new biomarkers in brain-derived extracellular vesicles from metachromatic leukodystrophy mice.Lipids in health and disease · 2022Article
- Rare Diseases in Glycosphingolipid Metabolism.Advances in experimental medicine and biology · 2022Article
- Safety of Direct Intraparenchymal AAVrh.10-Mediated Central Nervous System Gene Therapy for Metachromatic Leukodystrophy.Human gene therapy · 2021Article
- Synaptic Function and Dysfunction in Lysosomal Storage Diseases.Frontiers in cellular neuroscience · 2021Article
- Deregulation of signalling in genetic conditions affecting the lysosomal metabolism of cholesterol and galactosyl-sphingolipids.Neurobiology of disease · 2020Review
- Human iPSC-based models highlight defective glial and neuronal differentiation from neural progenitor cells in metachromatic leukodystrophy.Cell death & disease · 2018Article
- Generation of Human Induced Pluripotent Stem Cell-Derived Bona Fide Neural Stem Cells for Ex Vivo Gene Therapy of Metachromatic Leukodystrophy.Stem cells translational medicine · 2017Article
- Gene therapy for metachromatic leukodystrophy.Journal of neuroscience research · 2016Review
- A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease.Disease models & mechanisms · 2016Article
- In Vivo NMR Studies of the Brain with Hereditary or Acquired Metabolic Disorders.Neurochemical research · 2015Review
- Accumulation of lysosulfatide in the brain of arylsulfatase A-deficient mice.Lipids in health and disease · 2011Article
- Establishment of an improved mouse model for infantile neuroaxonal dystrophy that shows early disease onset and bears a point mutation in Pla2g6.The American journal of pathology · 2009Article
- Cell-surface arylsulfatase A and B on sinusoidal endothelial cells, hepatocytes, and Kupffer cells in mammalian livers.Medical molecular morphology · 2009Article
- Sulfatide storage in neurons causes hyperexcitability and axonal degeneration in a mouse model of metachromatic leukodystrophy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007Article
- Enzyme, cell and gene-based therapies for metachromatic leukodystrophy.Journal of inherited metabolic disease · 2007Review
- Modest phenotypic improvements in ASA-deficient mice with only one UDP-galactose:ceramide-galactosyltransferase gene.Lipids in health and disease · 2006Article
- Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestations.Gene therapy · 2002Article
- The role and metabolism of sulfatide in the nervous system.Molecular neurobiologyReview
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (ASA; EC 3.1.6.8). Deficiency of this enzyme causes intralysosomal storage of the sphingolipid cerebroside sulphate. This lipid is abundant in myelin and it may thus not be surprising that storage mainly affects oligodendrocytes. Patients suffer from a progressive demyelination causing various neurological symptoms. The disease is fatal and treatment is not available. The human ASA gene has been cloned and more than 40 mutations have been analysed that cause metachromatic leukodystrophy. Few of these alleles are frequent among patients, whereas most mutant alleles have only been found in single families. Since MLD has only been described in humans and no naturally occurring animal model has been described, ASA-deficient mice have been generated by homologous recombination. The ASA knockout mice are unable to degrade sulphatide and store the lipid intralysosomally. The pattern of lipid storage in neuronal and non-neuronal tissues resembles that described for patients. In the nervous system, lipid storage is found in oligodendrocytes, astrocytes and some neurons. Animals display an astrogliosis and a decreased average axonal diameter. Purkinje cells and Bergmann glia of the cerebellum are morphologically aberrant. Demyelination is seen in the acoustic ganglion and occurs between the ages of 6 and 12 months. The animals are deaf at this age and display various neuromotor abnormalities. However, compared to humans the mice have a surprisingly mild phenotype, since they have a normal life span and do not develop widespread demyelination. ASA-deficient mice have been transplanted with bone marrow, which was transduced with a retroviral vector expressing arylsulphatase A. The majority of transplanted animals display sustained expression of arylsulphatase A from the retroviral construct up to 5 months after transplantation. However, preliminary data suggest that this therapeutic approach does not reduce storage material.
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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.