A chaperone enhances blood α-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy

Mol Ther. 2014 Nov;22(11):2004-12. doi: 10.1038/mt.2014.138. Epub 2014 Jul 23.


Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / pharmacology
  • Adolescent
  • Adult
  • Animals
  • Child
  • Child, Preschool
  • Disease Models, Animal
  • Dried Blood Spot Testing
  • Drug Synergism
  • Enzyme Replacement Therapy / methods
  • Enzyme Stability
  • Female
  • Glycogen Storage Disease Type II / blood*
  • Glycogen Storage Disease Type II / drug therapy*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Young Adult
  • alpha-Glucosidases / blood
  • alpha-Glucosidases / pharmacology*
  • alpha-Glucosidases / therapeutic use


  • Glycoside Hydrolase Inhibitors
  • 1-Deoxynojirimycin
  • miglustat
  • GAA protein, human
  • alpha-Glucosidases