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  • Intravenous administration of phosphorylated acid alpha-glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice.

Intravenous administration of phosphorylated acid alpha-glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice.

The Journal of clinical investigation (1991-02-01)
A T Van der Ploeg, M A Kroos, R Willemsen, N H Brons, A J Reuser
ABSTRACT

The lysosomal storage disorder glycogenosis type II is caused by acid alpha-glucosidase deficiency. In this study we have investigated the possible applicability of mannose 6-phosphate receptor-mediated enzyme replacement therapy to correct the enzyme deficiency in the most affected tissues. Bovine testes acid alpha-glucosidase containing phosphorylated mannose residues was intravenously administered to mice and found to be taken up by heart (70% increase of activity) and skeletal muscle (43% increase); the major target organs. The uptake of nonphosphorylated human placenta acid alpha-glucosidase by heart and skeletal muscle appeared to be significantly less efficient, whereas uptake of dephosphorylated bovine testes enzyme was not detectable. The phosphorylated bovine testes acid alpha-glucosidase remained present in mouse skeletal muscle up to 9-15 d after administration, with a half-life of 2-4 d. Besides being measured in skeletal muscle and heart, uptake of phosphorylated bovine testes and nonphosphorylated human placenta acid alpha-glucosidase was measured in several other organs, but not in brain. The increase of acid alpha-glucosidase activity was highest in liver and spleen. We concluded that application of mannose 6-phosphate receptor-mediated enzyme replacement therapy may offer new perspectives for treatment of glycogenesis type II.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
D-(+)-Mannose, BioUltra, ≥99.5% (sum of enantiomers, HPLC)
Millipore
D-(+)-Mannose, ≥99.0% (sum of enantiomers, HPLC), suitable for microbiology
Millipore
D-(+)-Mannose, suitable for microbiology, ≥99%
Sigma-Aldrich
D-(+)-Mannose, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
D-(+)-Mannose, wood, ≥99%