Deconstructing Pompe disease by analyzing single muscle fibers: to see a world in a grain of sand..

Journal Article (Journal Article)

Autophagy is a major pathway for delivery of proteins and organelles to lysosomes where they are degraded and recycled. We have previously shown excessive autophagy in a mouse model of Pompe disease (glycogen storage disease type II), a devastating myopathy caused by a deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase. The autophagic buildup constituted a major pathological component in skeletal muscle and interfered with delivery of the therapeutic enzyme. To assess the role of autophagy in the pathogenesis of the human disease, we have analyzed vesicles of the lysosomal-degradative pathway in isolated single muscle fibers from Pompe patients. Human myofibers showed abundant autophagosome formation and areas of autophagic buildup of a wide range of sizes. In patients, as in the mouse model, the enormous autophagic buildup causes greater skeletal muscle damage than the enlarged, glycogenfilled lysosomes outside the autophagic regions. Clearing or preventing autophagic buildup seems, therefore, a necessary target of Pompe disease therapy.

Full Text

Duke Authors

Cited Authors

  • Raben, N; Takikita, S; Pittis, MG; Bembi, B; Marie, SKN; Roberts, A; Page, L; Kishnani, PS; Schoser, BGH; Chien, Y-H; Ralston, E; Nagaraju, K; Plotz, PH

Published Date

  • 2007

Published In

Volume / Issue

  • 3 / 6

Start / End Page

  • 546 - 552

PubMed ID

  • 17592248

International Standard Serial Number (ISSN)

  • 1554-8627

Digital Object Identifier (DOI)

  • 10.4161/auto.4591


  • eng

Conference Location

  • United States