Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

Mol Genet Metab. 2016 Sep;119(1-2):115-23. doi: 10.1016/j.ymgme.2016.05.013. Epub 2016 May 19.


Background: Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined.

Methods: This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments.

Results: Sixteen patients completed the study. After 6months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6months. A majority of patients showed improvements on functional assessments after 6months of treatment. All treatment-related adverse events were mild or moderate.

Conclusions: This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease.

Trial registration: NCT01288027.

Keywords: Alglucosidase alfa; Enzyme replacement therapy; Functional effects; Glycogen; Histopathology; Late-onset Pompe disease; Muscle pathology; Pompe disease.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Biopsy
  • Enzyme Replacement Therapy*
  • Female
  • Glycogen / isolation & purification
  • Glycogen / metabolism
  • Glycogen Storage Disease Type II / diagnostic imaging
  • Glycogen Storage Disease Type II / drug therapy*
  • Glycogen Storage Disease Type II / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Physical Therapy Modalities
  • Treatment Outcome
  • alpha-Glucosidases / administration & dosage*
  • alpha-Glucosidases / genetics


  • Glycogen
  • GAA protein, human
  • alpha-Glucosidases

Associated data