Biodistribution, Kinetics, and Efficacy of Highly Phosphorylated and Non-phosphorylated β-Glucuronidase in the Murine Model of Mucopolysaccharidosis VII

Sands, Mark S.; Vogler, Carole; Ohlemiller, Kevin K.; Roberts, Marie S.; Grubb, Jeffrey H.; Levy, Beth; Sly, William S.

doi:10.1074/jbc.m107778200

Cited by 69 publications

(65 citation statements)

References 36 publications

(28 reference statements)

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“…We speculated that M6P͞IGF2R could be the BBB transporter for P-GUS because M6P͞IGF2R is important in the uptake of P-GUS by peripheral tissues (15) and it had been demonstrated on bovine and rodent brain capillaries (31,32). In this study, we found that both P-GUS and M6P inhibited the transport of 131 I-P-GUS across the BBB in 2-day-old mice in a dose-dependent manner.…”

Section: Discussionsupporting

confidence: 49%

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Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier

Urayama

Grubb

Sly

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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146

138

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Mucopolysaccharidosis type VII is a lysosomal storage disorder resulting from inherited deficiency of ␤-glucuronidase (GUS). Mucopolysaccharidosis type VII is characterized by glycosaminoglycan storage in most tissues, including brain. In these disorders, enzyme delivery across the blood-brain barrier (BBB) is the main obstacle to correction of lysosomal storage in the CNS. Prior studies suggested mouse brain is accessible to GUS in the first 2 weeks of life but not later. To explore a possible role for the mannose 6-phosphate͞insulin-like growth factor II receptor in GUS transport across the BBB in neonatal mice, we compared brain uptake of phosphorylated GUS (P-GUS) and nonphosphorylated GUS (NP-GUS) in newborn and adult mice. 131 I-P-GUS was transported across the BBB after i.v. injection in 2-day-old mice. The brain influx rate (Kin) of 131 I-P-GUS in 2-day-old mice was 0.21 l͞g⅐min and decreased with age. By 7 weeks of age, transport of 131 I-P-GUS was not significant. Capillary depletion revealed that 62% of the 131 I-P-GUS in brain was in brain parenchyma in 2-day-old mice. In addition, uptake of 131 I-P-GUS into brain was significantly reduced by coinjection of unlabeled P-GUS or M6P in a dose-dependent manner. In contrast, the Kin of 131 I-NP-GUS (0.04 l͞g⅐min) was significantly lower than 131 I-P-GUS in 2-day-old mice. Transcardiac brain perfusion confirmed that neither 131 I-P-GUS nor 131 I-NP-GUS crossed the BBB in adult mice. These results indicate that 131 I-P-GUS transport into brain parenchyma in early postnatal life is mediated by the mannose 6-phosphate͞insulin-like growth factor II receptor. This receptor-mediated transport is not observed in adult mice.␤-glucuronidase ͉ mannose 6-phosphate͞insulin-like growth factor II receptor ͉ central nervous system ͉ lysosomal storage disease ͉ phosphorylated ␤-glucuronidase

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Section: Discussionsupporting

confidence: 49%

“…15. NP-GUS was purified from media from virus-infected Sf21 insect cells by anti-human GUS monoclonal antibody Affi-Gel 10 affinity column chromatography by the same procedure used for P-GUS.…”

Section: Methodsmentioning

confidence: 99%

Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier

Urayama

Grubb

Sly

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

146

138

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“…We have reported that infused, phosphorylated native mGUS was distributed much more broadly than nonphosphorylated mGUS, which targets nearly exclusively to reticuloendothelial macrophages (11). Fig.…”

Section: Comparison Of the Tissue Distribution Of Native And Modifiedmentioning

confidence: 99%

“…Each of these enzymes is effective in reversing lysosomal storage in many tissues in animal disease models. The requirement of Man6-P on enzymes for delivery to nonreticuloendothelial system (RES) cells has been demonstrated directly in the murine model of MPS VII (11). Recombinant ␣-galactosidase A (16) and ␣-L-iduronidase (14) are now approved for treatment of Fabry disease and MPS I in humans.…”

mentioning

confidence: 99%

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Glycosylation-independent targeting enhances enzyme delivery to lysosomes and decreases storage in mucopolysaccharidosis type VII mice

LeBowitz

Grubb

Maga

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Enzyme-replacement therapy is an established means of treating lysosomal storage diseases. Infused therapeutic enzymes are targeted to lysosomes of affected cells by interactions with cellsurface receptors that recognize carbohydrate moieties, such as mannose and mannose 6-phosphate, on the enzymes. We have tested an alternative, peptide-based targeting system for delivery of enzymes to lysosomes in a murine mucopolysaccharidosis type VII (MPS VII) model. This strategy depends on the interaction of a fragment of insulin-like growth factor II (IGF-II), with the IGF-II binding site on the bifunctional, IGF-II cation-independent mannose 6-phosphate receptor. A chimeric protein containing a portion of mature human IGF-II fused to the C terminus of human ␤-glucuronidase was taken up by MPS VII fibroblasts in a mannose 6-phosphate-independent manner, and its uptake was inhibited by the addition of IGF-II. Furthermore, the tagged enzyme was delivered effectively to clinically significant tissues in MPS VII mice and was effective in reversing the storage pathology. The tagged enzyme was able to reduce storage in glomerular podocytes and osteoblasts at a dose at which untagged enzyme was much less effective. This peptide-based, glycosylation-independent lysosomal targeting system may enhance enzyme-replacement therapy for certain human lysosomal storage diseases.␤-glucuronidase ͉ IGF-II͞Man6-P receptor ͉ receptor-mediated endocytosis ͉ enzyme-replacement therapy ͉ lysosomal storage disease

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Evaluation of peer-group support and problem-solving training in the treatment of adolescents with type 1 diabetes

Løding

Wold

Skavhaug

et al. 2007

European Diabetes Nursing

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Aim: The aim of this study was to describe the elements and results of peer-group support and problem-solving training in the treatment of adolescents with type 1 diabetes and their parents. The hypothesis was that the intervention would improve HbA 1c and enable the adolescents to take responsibility in managing their diabetes. Method: A total of 60 adolescents with type 1 diabetes, aged 13-18 years, and their parents, were invited to participate in this study. They were recruited from outpatient clinics in two centres in Norway, and 19 adolescents agreed to participate. Both adolescents and parents completed self-report questionnaires pre-treatment, during treatment, post-treatment and at one year follow up. In addition HbA 1c values were obtained five times from the adolescents' medical records over the same time period. Results:The results indicated that peer-group support and problem-solving training is a suitable intervention in the treatment of adolescents with type 1 diabetes. In terms of metabolic control there was a significant decrease in HbA 1c in girls (p=0.039). Conclusion:The intervention was peer-oriented and psycho-educative, and encouraged collaboration between the paediatric diabetes clinic and the psychiatric department in the treatment for adolescents with diabetes and their parents. This collaboration was of great importance for the quality of the study and added valuable knowledge and experience to the diabetes multidisciplinary team.Eur Diabetes Nursing 2007; 4(1): 28-33.

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Biodistribution, Kinetics, and Efficacy of Highly Phosphorylated and Non-phosphorylated β-Glucuronidase in the Murine Model of Mucopolysaccharidosis VII

Cited by 69 publications

References 36 publications

Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier

Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier

Glycosylation-independent targeting enhances enzyme delivery to lysosomes and decreases storage in mucopolysaccharidosis type VII mice

Evaluation of peer-group support and problem-solving training in the treatment of adolescents with type 1 diabetes

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