Breakdown of lysosomal glycogen in cultured fibroblasts from glycogenosis type II patients after uptake of acid α-glucosidase

Cardiac evaluation in children and adults with Pompe disease sharing the common c.−32-13T>G genotype rarely reveals abnormalities

“…This may be due to differences in storage capacity and metabolism of heart and skeletal muscle [35]. The more abundant presence of cytoplasmic glycogen in skeletal muscle fibers compared to cardiomyocytes may lead to more extensive lysosomal glycogen accumulation in the skeletal muscles through autophagy, resulting in more muscle fiber damage [36,37].…”

Rat Heart Perfusion as Model System for Enzyme Replacement Therapy in Glycogenosis Type II

“…This figure compares to the efficiency of mannose 6-phosphate receptor-mediated uptake of bovine testis and human urine acid a-glucosidases by cultured fibroblasts and muscle cells. The recovery of these enzymes, added directly to the culture medium, was approximately 4% (7,25). By contrast, the uptake of human placental acid a-glucosidase, not recognized by this receptor, was much less (0.04%) (25).…”

“…In late onset juvenile and adult variants, skeletal muscle weakness is usually the only clinical symptom, and respiratory failure is the major cause of death. The severity of symptoms appears to correlate closely with the extent of lysosoma1 glycogen storage and the level of residual acid a-glucosidase activity (5)(6)(7)(8).…”

“…In previous studies, we have investigated the basic requirements for treatment of glycogenosis type I1 by receptor-mediated enzyme therapy (7,8,25,26). We demonstrated that mannose.…”

Enzyme therapy for Pompe disease: from science to industrial enterprise

“…To this end, muscle biopsies of patients were dissociated with collagenase and trypsin, and myoblasts (satellite cells) were taken into culture. It turned out no problem to correct the lysosomal glycogen storage in these cells by addition of M6P-containing acid AGLU to the culture medium [32,33,34]. Herewith, the first requirements were fulfilled, but the experimental set-up does not mimic the reality in detail.…”