ArticleProceedings of the National Academy of Sciences of the United States of America2006
Enzyme therapy in mannose receptor-null mucopolysaccharidosis VII mice defines roles for the mannose 6-phosphate and mannose receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Systematic Review of Genetic Substrate Reduction Therapy in Lysosomal Storage Diseases: Opportunities, Challenges and Delivery Systems.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Pooled it
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- AAV-based gene therapy with modified HEXB confers lasting therapeutic benefits in GM2 gangliosidosis models.Cell reports. Medicine · 2026Article
- N-glycan-modified α-L-iduronidase produced by transgenic silkworms ameliorates clinical signs in a Japanese macaque with mucopolysaccharidosis I.Communications medicine · 2025Article
- Development of Oligomeric Mannose-6-phosphonate Conjugates for Targeted Protein Degradation.ACS medicinal chemistry letters · 2023Article
- Review
- Development of Lanzyme as the Potential Enzyme Replacement Therapy Drug for Fabry Disease.Biomolecules · 2022Article
- Identification of a novel fusion Iduronidase with improved activity in the cardiovascular system.Molecular genetics and metabolism reports · 2022Article
- Early enzyme replacement therapy prevents dental and craniofacial abnormalities in a mouse model of mucopolysaccharidosis type VI.Frontiers in physiology · 2022Article
- A kaleidoscopic view of extracellular vesicles in lysosomal storage disorders.Extracellular vesicles and circulating nucleic acids · 2022Review
- Therapeutic Approaches in Lysosomal Storage Diseases.Biomolecules · 2021Review
- Chemoenzymatic glycan-selective remodeling of a therapeutic lysosomal enzyme with high-affinity M6P-glycan ligands. Enzyme substrate specificity is the name of the game.Chemical science · 2021Article
- Migalastat Tissue Distribution: Extrapolation From Mice to Humans Using Pharmacokinetic Modeling and Comparison With Agalsidase Beta Tissue Distribution in Mice.Clinical pharmacology in drug development · 2021Article
- Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders.Journal of extracellular vesicles · 2021Article
- Article
- Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases.Frontiers in veterinary science · 2020Review
- The glycosylation design space for recombinant lysosomal replacement enzymes produced in CHO cells.Nature communications · 2019Article
- RTB lectin-mediated delivery of lysosomal α-l-iduronidase mitigates disease manifestations systemically including the central nervous system.Molecular genetics and metabolism · 2018Article
- Pathogenesis and treatment of spine disease in the mucopolysaccharidoses.Molecular genetics and metabolism · 2016Review
- Mannose receptor-mediated delivery of moss-made α-galactosidase A efficiently corrects enzyme deficiency in Fabry mice.Journal of inherited metabolic disease · 2016Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Enzyme replacement therapy (ERT) is available for several lysosomal storage diseases. Except for Gaucher disease, for which an enzyme with exposed mannosyl residues targets mannose receptors (MR) on macrophages, ERT targets primarily the mannose 6-phosphate receptor (MPR). Most recombinant lysosomal enzymes contain oligosaccharides with both terminal mannosyl and mannose 6-phosphate residues. Effective MPR-mediated delivery may be compromised by rapid clearance of infused enzyme by the MR on fixed tissue macrophages, especially Kupffer cells. To evaluate the impact of this obstacle to ERT, we introduced the MR-null mutation onto the mucopolysaccharidosis type VII (MPS VII) background and produced doubly deficient MR-/- MPS VII mice. The availability of both MR+/+ and MR-/- mice allowed us to study the effects of eliminating the MR on MR- and MPR-mediated plasma clearance and tissue distribution of infused phosphorylated (P) and nonphosphorylated (NP) forms of human beta-glucuronidase (GUS). In MR+/+ MPS VII mice, the MR clearance system predominated at doses up to 6.4 mg/kg P-GUS. Genetically eliminating the MR slowed plasma clearance of both P- and NP-GUS and enhanced the effectiveness of P-GUS in clearing storage in kidney, bone, and retina. Saturating the MR clearance system by high doses of enzyme also improved targeting to MPR-containing tissues such as muscle, kidney, heart, and hepatocytes. Although ablating the MR clearance system genetically is not practical clinically, blocking the MR-mediated clearance system with high doses of enzyme is feasible. This approach delivers a larger fraction of enzyme to MPR-expressing tissues, thus enhancing the effectiveness of MPR-targeted ERT.
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