Impaired autophagy contributes to muscle atrophy in glycogen storage disease type II patients

Anna Chiara Nascimbeni, Marina Fanin, Eva Masiero, Corrado Angelini, Marco Sandri

Research output: Contribution to journalArticlepeer-review


The autophagy-lysosome system is essential for muscle cell homeostasis and its dysfunction has been linked to muscle disorders that are typically distinguished by massive autophagic buildup. Among them, glycogen storage disease type II (GSDII) is characterized by the presence of large glycogen-filled lysosomes in the skeletal muscle, due to a defect in the lysosomal enzyme acid α-glucosidase (GAA). The accumulation of autophagosomes is believed to be detrimental for myofiber function. However, the role of autophagy in the pathogenesis of GSDII is still unclear. To address this issue we monitored autophagy in muscle biopsies and myotubes of early and late-onset GSDII patients at different time points of disease progression. Moreover we also analyzed muscles from patients treated with enzyme replacement therapy (ERT). Our data suggest that autophagy is a protective mechanism that is required for myofiber survival in late-onset forms of GSDII. Importantly, our findings suggest that a normal autophagy flux is important for a correct maturation of GAA and for the uptake of recombinant human GAA. In conclusion, autophagy failure plays an important role in GSDII disease progression, and the development of new drugs to restore the autophagic flux should be considered to improve ERT efficacy.

Original languageEnglish
Pages (from-to)1697-1700
Number of pages4
Issue number11
Publication statusPublished - Nov 2012


  • Atrophy
  • Autophagy
  • Glycogen storage disease type II
  • MURF-1
  • Muscle wasting
  • Pompe disease

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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