ArticleThe Biochemical journal2014
Insulin-like growth factor II peptide fusion enables uptake and lysosomal delivery of α-N-acetylglucosaminidase to mucopolysaccharidosis type IIIB fibroblasts.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 36 citations in OpenAlex.
- A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B.The Journal of clinical investigation · 2023Trial
- Reduced heparan sulfate levels in cerebrospinal fluid reflect brain neuron correction in Sanfilippo B mice.The Journal of clinical investigation · 2025Article
- Molecular therapy and nucleic acid adeno-associated virus-based gene therapy delivering combinations of two growth-associated genes to MPS IVA mice.Molecular therapy. Nucleic acids · 2024Article
- Current Concepts in the Management of Sanfilippo Syndrome (MPS III): A Narrative Review.Cureus · 2024Review
- Disease correction in mucopolysaccharidosis type IIIB mice by intraparenchymal or cisternal delivery of a capsid modified AAV8 codon-optimized NAGLU vector.Human molecular genetics · 2023Article
- Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys.Toxicology reports · 2023Article
- Brain transplantation of genetically corrected Sanfilippo type B neural stem cells induces partial cross-correction of the disease.Molecular therapy. Methods & clinical development · 2022Article
- Tralesinidase Alfa Enzyme Replacement Therapy Prevents Disease Manifestations in a Canine Model of Mucopolysaccharidosis Type IIIB.The Journal of pharmacology and experimental therapeutics · 2022Article
- Heparan Sulfate, Mucopolysaccharidosis IIIB and Sulfur Metabolism Disorders.Antioxidants (Basel, Switzerland) · 2022Review
- Delivering gene therapy for mucopolysaccharide diseases.Frontiers in molecular biosciences · 2022Review
- Biochemical evaluation of intracerebroventricular rhNAGLU-IGF2 enzyme replacement therapy in neonatal mice with Sanfilippo B syndrome.Molecular genetics and metabolism · 2021Article
- Two Distinct Lysosomal Targeting Strategies Afford Trojan Horse Antibodies With Pan-Filovirus Activity.Frontiers in immunology · 2021Article
- Novel therapies for mucopolysaccharidosis type III.Journal of inherited metabolic disease · 2021Review
- A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise.Medical research archives · 2020Article
- Enzyme replacement therapy for mucopolysaccharidoses; past, present, and future.Journal of human genetics · 2019Review
- Differential Uptake of NAGLU-IGF2 and Unmodified NAGLU in Cellular Models of Sanfilippo Syndrome Type B.Molecular therapy. Methods & clinical development · 2019Article
- Review
- Genetically Corrected iPSC-Derived Neural Stem Cell Grafts Deliver Enzyme Replacement to Affect CNS Disease in Sanfilippo B Mice.Molecular therapy. Methods & clinical development · 2018Article
- Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.EMBO molecular medicine · 2018Article
- How close are we to therapies for Sanfilippo disease?Metabolic brain disease · 2018Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Enzyme replacement therapy for MPS IIIB (mucopolysaccharidosis type IIIB; also known as Sanfilippo B syndrome) has been hindered by inadequate mannose 6 phosphorylation and cellular uptake of rhNAGLU (recombinant human α-N-acetylglucosaminidase). We expressed and characterized a modified rhNAGLU fused to the receptor-binding motif of IGF-II (insulin-like growth factor 2) (rhNAGLU-IGF-II) to enhance its ability to enter cells using the cation-independent mannose 6-phosphate receptor, which is also the receptor for IGF-II (at a different binding site). RhNAGLU-IGF-II was stably expressed in CHO (Chinese-hamster ovary) cells, secreted and purified to apparent homogeneity. The Km and pH optimum of the fusion enzyme was similar to those reported for rhNAGLU. Both intracellular uptake and confocal microscopy suggested that MPS IIIB fibroblasts readily take up the fusion enzyme via receptor-mediated endocytosis that was inhibited significantly (P<0.001) by the monomeric IGF-II peptide. Glycosaminoglycan storage was reduced by 60% (P<0.001) to near background levels in MPS IIIB cells after treatment with rhNAGLU-IGF-II, with half-maximal correction at concentrations of 3-12 pM. A similar cellular uptake mechanism via the IGF-II receptor was also demonstrated in two different brain tumour-derived cell lines. Fusion of rhNAGLU to IGF-II enhanced its cellular uptake while maintaining enzymatic activity, supporting its potential as a therapeutic candidate for treating MPS IIIB.
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Registered trials
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