ArticleJournal of molecular medicine (Berlin, Germany)2008
Non-inhibitory antibodies impede lysosomal storage reduction during enzyme replacement therapy of a lysosomal storage disease.
Article in Journal of molecular medicine (Berlin, Germany), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Hematopoietic stem cell gene therapy of neurometabolic lysosomal storage diseases.Brain & development · 2025Review
- Dose-intensive therapy (DIT) for infantile Pompe disease: A pilot study.Molecular genetics and metabolism reports · 2025Article
- Engineered arylsulfatase A with increased activity, stability and brain delivery for therapy of metachromatic leukodystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Oral immunotherapy tolerizes mice to enzyme replacement therapy for Morquio A syndrome.The Journal of clinical investigation · 2020Article
- Immune Modulation for Enzyme Replacement Therapy in A Female Patient With Hunter Syndrome.Frontiers in immunology · 2020Article
- Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.Advanced drug delivery reviews · 2017Review
- Correlation between urinary GAG and anti-idursulfase ERT neutralizing antibodies during treatment with NICIT immune tolerance regimen: A case report.Molecular genetics and metabolism · 2017Article
- Gene therapy for lysosomal storage disorders: recent advances for metachromatic leukodystrophy and mucopolysaccaridosis I.Journal of inherited metabolic disease · 2017Review
- Continual Low-Dose Infusion of Sulfamidase Is Superior to Intermittent High-Dose Delivery in Ameliorating Neuropathology in the MPS IIIA Mouse Brain.JIMD reports · 2016Article
- Targeted gene transfer into ependymal cells through intraventricular injection of AAV1 vector and long-term enzyme replacement via the CSF.Scientific reports · 2014Article
- Comparison of five peptide vectors for improved brain delivery of the lysosomal enzyme arylsulfatase A.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Comparative binding, endocytosis, and biodistribution of antibodies and antibody-coated carriers for targeted delivery of lysosomal enzymes to ICAM-1 versus transferrin receptor.Journal of inherited metabolic disease · 2013Article
- Systemic delivery of scAAV9 in fetal macaques facilitates neuronal transduction of the central and peripheral nervous systems.Gene therapy · 2013Article
- Strategies for delivery of therapeutics into the central nervous system for treatment of lysosomal storage disorders.Drug delivery and translational research · 2012Article
- Heparin cofactor II-thrombin complex and dermatan sulphate:chondroitin sulphate ratio are biomarkers of short- and long-term treatment effects in mucopolysaccharide diseases.Journal of inherited metabolic disease · 2011Article
- Saposin B-dependent reconstitution of arylsulfatase A activity in vitro and in cell culture models of metachromatic leukodystrophy.The Journal of biological chemistry · 2009Article
- 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
- New biotechnological and nanomedicine strategies for treatment of lysosomal storage disorders.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enzyme replacement therapy is a treatment option for several lysosomal storage disorders. We reported previously that treatment of a knockout mouse model of the sphingolipid storage disease metachromatic leukodystrophy (MLD) by intravenous injection of recombinant human arylsulfatase A (rhASA) reduces sulfatide storage and improves nervous system pathology and function. Here, we show that treated mice can develop anti-rhASA antibodies, which impede sulfatide clearance without inhibiting enzyme activity. The neutralizing effect of antibodies was reproduced in cell culture models of MLD by demonstrating that mouse immune serum reduces the ability of rhASA to clear sulfatide from cultured ASA-deficient Schwann and kidney cells. We show that reduced clearance is due to an antibody-mediated blockade of mannose 6-phosphate receptor-dependent enzyme uptake, retargeting of rhASA from sulfatide-storing cells to macrophages, intracellular misrouting of rhASA, and reduction of enzyme stability. Induction of immunotolerance to rhASA by transgenic expression of an active site mutant of human ASA restores sulfatide clearance in mice. The data indicate that the influence of non-inhibitory antibodies must be more intensively considered in evaluating the therapeutic efficacy of enzyme replacement in lysosomal storage disorders in general and in patients without cross-reacting material specifically.
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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.