calcimycin and Glycogen-Storage-Disease-Type-II

Pompe disease is caused by a deficiency in the lysosomal enzyme α-glucosidase, and this leads to glycogen accumulation in the autolysosomes of patient cells. Glycogen storage material is exocytosed at a basal rate in cultured Pompe cells, with one study showing up to 80% is released under specific culture conditions. Critically, exocytosis induction may reduce glycogen storage in Pompe patients, providing the basis for a therapeutic strategy whereby stored glycogen is redirected to an extracellular location and subsequently degraded by circulating amylases. The focus of the current study was to identify compounds capable of inducing rapid glycogen exocytosis in cultured Pompe cells. Here, calcimycin, lysophosphatidylcholine and α-l-iduronidase each significantly increased glycogen exocytosis compared to vehicle-treated controls. The most effective compound, calcimycin, induced exocytosis through a Ca

Topics: Calcimycin; Cells, Cultured; Drug Evaluation, Preclinical; Exocytosis; Fibroblasts; Glycogen; Glycogen Storage Disease Type II; Humans; Iduronidase; Lysophosphatidylcholines; Lysosomes; Phagosomes; Pharmaceutical Vehicles