Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder - Murine Pompe disease

Nina Raben, Cynthia Schreiner, Rebecca Baum, Shoichi Takikita, Sengen Xu, Tao Xie, Rachel Myerowitz, Masaaki Komatsu, Jack H. Van Der Meulen, Kanneboyina Nagaraju, Evelyn Ralston, Paul H. Plotz

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


Autophagy, an intracellular system for delivering portions of cytoplasm and damaged organelles to lysosomes for degradation/recycling, plays a role in many physiological processes and is disturbed in many diseases. We recently provided evidence for the role of autophagy in Pompe disease, a lysosomal storage disorder in which acid alpha-glucosidase, the enzyme involved in the breakdown of glycogen, is deficient or absent. Clinically the disease manifests as a cardiac and skeletal muscle myopathy. The current enzyme replacement therapy (ERT) clears lysosomal glycogen effectively from the heart but less so from skeletal muscle. In our Pompe model, the poor muscle response to therapy is associated with the presence of pools of autophagic debris. To clear the fibers of the autophagic debris, we have generated a Pompe model in which an autophagy gene, Atg7, is inactivated in muscle. Suppression of autophagy alone reduced the glycogen level by 50-60%. Following ERT, muscle glycogen was reduced to normal levels, an outcome not observed in Pompe mice with genetically intact autophagy. The suppression of autophagy, which has proven successful in the Pompe model, is a novel therapeutic approach that may be useful in other diseases with disturbed autophagy.

Original languageEnglish (US)
Pages (from-to)1078-1089
Number of pages12
Issue number8
StatePublished - Nov 16 2010
Externally publishedYes


  • Atg7
  • Enzyme replacement therapy
  • Lysosomal glycogen storage
  • Myopathy
  • Pompe disease

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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