ArticleProceedings of the National Academy of Sciences of the United States of America2005
Overcoming the blood-brain barrier with high-dose enzyme replacement therapy in murine mucopolysaccharidosis VII.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Population Pharmacokinetic/Pharmacodynamic Modeling of Therapeutic Enzymes in Lysosomal Storage Diseases.Clinical pharmacokinetics · 2026Pooled it
- Rescue of neurologic disease in mucopolysaccharidosis type II mice via AAV-mediated liver delivery of brain-penetrating iduronate-2-sulfatase.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Small fibre neuropathy in Fabry disease: a human-derived neuronalBrain communications · 2024Article
- Hematopoietic stem cell gene therapy ameliorates CNS involvement in murine model of GM1-gangliosidosis.Molecular therapy. Methods & clinical development · 2022Article
- Timing is everything: Clinical courses of Hunter syndrome associated with age at initiation of therapy in a sibling pair.Molecular genetics and metabolism reports · 2022Article
- Brain Microglial Activation Increased in Glucocerebrosidase (GBA) Mutation Carriers without Parkinson's disease.Movement disorders : official journal of the Movement Disorder Society · 2021Article
- Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement.Biomolecules · 2021Review
- Intravenous delivery for treatment of mucopolysaccharidosis type I: A comparison of AAV serotypes 9 and rh10.Molecular genetics and metabolism reports · 2020Article
- A Highly Efficacious PS Gene Editing System Corrects Metabolic and Neurological Complications of Mucopolysaccharidosis Type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- A novel gene editing system to treat both Tay-Sachs and Sandhoff diseases.Gene therapy · 2020Article
- Targeted enzyme delivery systems in lysosomal disorders: an innovative form of therapy for mucopolysaccharidosis.Cellular and molecular life sciences : CMLS · 2019Review
- ZFN-Mediated In Vivo Genome Editing Corrects Murine Hurler Syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Alpha-Mannosidosis: Therapeutic Strategies.International journal of molecular sciences · 2018Review
- RTB lectin-mediated delivery of lysosomal α-l-iduronidase mitigates disease manifestations systemically including the central nervous system.Molecular genetics and metabolism · 2018Article
- Leaf-Encapsulated Vaccines: Agroinfiltration and Transient Expression of the AntigenJournal of immunology research · 2018Article
- Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.Advanced drug delivery reviews · 2017Review
- Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Inflammation-associated extracellular β-glucuronidase alters cellular responses to the chemical carcinogen benzo[a]pyrene.Archives of toxicology · 2016Article
- CNS-directed gene therapy for the treatment of neurologic and somatic mucopolysaccharidosis type II (Hunter syndrome).JCI insight · 2016Article
- Clinical course of sly syndrome (mucopolysaccharidosis type VII).Journal of medical genetics · 2016Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Enzyme replacement therapy (ERT) effectively reverses storage in several lysosomal storage diseases. However, improvement in brain is limited by the blood-brain barrier except in the newborn period. In this study, we asked whether this barrier could be overcome by higher doses of enzyme than are used in conventional trials. We measured the distribution of recombinant human beta-glucuronidase (hGUS) and reduction in storage by weekly doses of 0.3-40 mg/kg administered i.v. over 1-13 weeks to mucopolysaccharidosis type VII mice immunotolerant to recombinant hGUS. Mice given up to 5 mg/kg enzyme weekly over 3 weeks had moderate reduction in meningeal storage but no change in neo-cortical neurons. Mice given 20-40 mg/kg three times over 1 week showed no reduction in storage in any area of the CNS except the meninges. In contrast, mice receiving 4 mg/kg per week for 13 weeks showed clearance not only in meninges but also in parietal neocortical and hippocampal neurons and glia. Mice given 20 mg/kg once weekly for 4 weeks also had decreased neuronal, glial, and meningeal storage and averaged 2.5% of wild-type hGUS activity in brain. These results indicate that therapeutic enzyme can be delivered across the blood-brain barrier in the adult mucopolysaccharidosis type VII mouse if administered at higher doses than are used in conventional ERT trials and if the larger dose of enzyme is administered over a sufficient period. These results may have important implications for ERT for lysosomal storage diseases with CNS involvement.
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