ArticleAnnals of clinical and translational neurology2020
Metachromatic leukodystrophy and transplantation: remyelination, no cross-correction.
Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 80 citations in OpenAlex.
- Effects of sulfatide on peripheral nerves in metachromatic leukodystrophy.Annals of clinical and translational neurology · 2024Trial
- Proteasome inhibitors rescue hypomyelination in iPSC based model of HIKESHI-associated leukodystrophy.Journal of translational medicine · 2026Article
- 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
- Bone marrow transplantation reverses metabolic alterations in multiple sulfatase deficiency: a case series.Communications medicine · 2025Article
- Human iPSC-derived myelinating organoids and globoid cells to study Krabbe Disease.bioRxiv : the preprint server for biology · 2024Article
- CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice.Nature communications · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Progressive demyelinating polyneuropathy after hematopoietic cell transplantation in metachromatic leukodystrophy: a case series.Journal of neurology · 2024Article
- Stem Cell Therapy and Thiamine Deficiency-Induced Brain Damage.Neurochemical research · 2024Review
- Human post-mortem organotypic brain slice cultures: a tool to study pathomechanisms and test therapies.Acta neuropathologica communications · 2024Article
- Allogeneic hematopoietic cell transplantation for adult metachromatic leukodystrophy: a case series.Blood advances · 2024Article
- Article
- Inventory of current practices regarding hematopoietic stem cell transplantation in metachromatic leukodystrophy in Europe and neighboring countries.Orphanet journal of rare diseases · 2024Article
- Article
- Gene and Cellular Therapies for Leukodystrophies.Pharmaceutics · 2023Review
- Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy.Annals of clinical and translational neurology · 2023Article
- A Rare Case of Hypomyelinating Leukodystrophy and Its Management: A Case Report and Literature Review.Cureus · 2023Article
- Recognizing early MRI signs (or their absence) is crucial in diagnosing metachromatic leukodystrophy.Annals of clinical and translational neurology · 2022Article
- High-throughput analysis of hematopoietic stem cell engraftment after intravenous and intracerebroventricular dosing.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveIn metachromatic leukodystrophy, a lysosomal storage disorder due to decreased arylsulfatase A activity, hematopoietic stem cell transplantation may stop brain demyelination and allow remyelination, thereby halting white matter degeneration. This is the first study to define the effects and therapeutic mechanisms of hematopoietic stem cell transplantation on brain tissue of transplanted metachromatic leukodystrophy patients.
methodsAutopsy brain tissue was obtained from eight (two transplanted and six nontransplanted) metachromatic leukodystrophy patients, and two age-matched controls. We examined the presence of donor cells by immunohistochemistry and microscopy. In addition, we assessed myelin content, oligodendrocyte numbers, and macrophage phenotypes. An unpaired t-test, linear regression or the nonparametric Mann-Whitney U-test was performed to evaluate differences between the transplanted, nontransplanted, and control group.
resultsIn brain tissue of transplanted patients, we found metabolically competent donor macrophages expressing arylsulfatase A distributed throughout the entire white matter. Compared to nontransplanted patients, these macrophages preferentially expressed markers of alternatively activated, anti-inflammatory cells that may support oligodendrocyte survival and differentiation. Additionally, transplanted patients showed higher numbers of oligodendrocytes and evidence for remyelination. Contrary to the current hypothesis on therapeutic mechanism of hematopoietic cell transplantation in metachromatic leukodystrophy, we detected no enzymatic cross-correction to resident astrocytes and oligodendrocytes.
interpretationIn conclusion, donor macrophages are able to digest accumulated sulfatides and may play a neuroprotective role for resident oligodendrocytes, thereby enabling remyelination, albeit without evidence of cross-correction of oligo- and astroglia. These results emphasize the importance of immunomodulation in addition to the metabolic correction, which might be exploited for improved outcomes.
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