ArticleProceedings of the National Academy of Sciences of the United States of America2008
Chemically modified beta-glucuronidase crosses blood-brain barrier and clears neuronal storage in murine mucopolysaccharidosis VII.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study.Journal of inherited metabolic disease · 2013Trial
- 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
- Review
- Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- A universal GlycoDesign for lysosomal replacement enzymes to improve circulation time and biodistribution.Frontiers in bioengineering and biotechnology · 2023Article
- Identification of a novel fusion Iduronidase with improved activity in the cardiovascular system.Molecular genetics and metabolism reports · 2022Article
- Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain.AAPS PharmSciTech · 2021Review
- Exploiting the Potential ofBiomedicines · 2021Review
- Intravenous delivery of a chemically modified sulfamidase efficiently reduces heparan sulfate storage and brain pathology in mucopolysaccharidosis IIIA mice.Molecular genetics and metabolism reports · 2019Article
- Enzyme replacement therapy for mucopolysaccharidoses; past, present, and future.Journal of human genetics · 2019Review
- An Engineered Galactosylceramidase Construct Improves AAV Gene Therapy for Krabbe Disease in Twitcher Mice.Human gene therapy · 2019Article
- The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells.Nature communications · 2019Article
- Neuromuscular degeneration and locomotor deficit in aDisease models & mechanisms · 2018Article
- An improved purification method for the lysosomal storage disease protein β-glucuronidase produced in CHO cells.Protein expression and purification · 2017Article
- Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives.Advanced drug delivery reviews · 2017Review
- Induced pluripotent stem cell models of lysosomal storage disorders.Disease models & mechanisms · 2017Review
- Drug delivery in overcoming the blood-brain barrier: role of nasal mucosal grafting.Drug design, development and therapy · 2017Review
- New therapeutic approaches for Krabbe disease: The potential of pharmacological chaperones.Journal of neuroscience research · 2016Review
- From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery.Nature reviews. Drug discovery · 2016Review
- Chronic enzyme replacement therapy ameliorates neuropathology in alpha-mannosidosis mice.Annals of clinical and translational neurology · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Enzyme replacement therapy has been used successfully in many lysosomal storage diseases. However, correction of brain storage has been limited by the inability of infused enzyme to cross the blood-brain barrier. The newborn mouse is an exception because recombinant enzyme is delivered to neonatal brain after mannose 6-phosphate receptor-mediated transcytosis. Access to this route is very limited after 2 weeks of age. Recently, several studies showed that multiple infusions of high doses of enzyme partially cleared storage in adult brain. These results raised the question of whether correction of brain storage by repeated high doses of enzyme depends on mannose 6-phosphate receptor-mediated uptake or whether enzyme gains access to brain storage by another route when brain capillaries are exposed to prolonged, high levels of circulating enzyme. To address this question, we used an enzyme whose carbohydrate-dependent receptor-mediated uptake was inactivated by chemical modification. Treatment of human beta-glucuronidase (GUS) with sodium metaperiodate followed by sodium borohydride reduction (PerT-GUS) eliminated uptake by mannose 6-phosphate and mannose receptors in cultured cells and dramatically slowed its plasma clearance from a t(1/2) of <10 min to 18 h. Surprisingly, PerT-GUS infused weekly for 12 weeks was more effective in clearing central nervous system storage than native GUS at the same dose. In fact, PerT-GUS resulted in almost complete reversal of storage in neocortical and hippocampal neurons. This enhanced correction of neuronal storage by long-circulating enzyme, which targets no known receptor, suggests a delivery system across the blood-brain barrier that might be exploited therapeutically.
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