The pharmacological chaperone N-butyldeoxynojirimycin enhances enzyme replacement therapy in Pompe disease fibroblasts

Mol Ther. 2009 Jun;17(6):964-71. doi: 10.1038/mt.2009.53. Epub 2009 Mar 17.


In spite of the progress in the treatment of lysosomal storage diseases (LSDs), in some of these disorders the available therapies show limited efficacy and a need exists to identify novel therapeutic strategies. We studied the combination of enzyme replacement and enzyme enhancement by pharmacological chaperones in Pompe disease (PD), a metabolic myopathy caused by the deficiency of the lysosomal acid alpha-glucosidase. We showed that coincubation of Pompe fibroblasts with recombinant human alpha-glucosidase and the chaperone N-butyldeoxynojirimycin (NB-DNJ) resulted in more efficient correction of enzyme activity. The chaperone improved alpha-glucosidase delivery to lysosomes, enhanced enzyme maturation, and increased enzyme stability. Improved enzyme correction was also found in vivo in a mouse model of PD treated with coadministration of single infusions of recombinant human alpha-glucosidase and oral NB-DNJ. The enhancing effect of chaperones on recombinant enzymes was also observed in fibroblasts from another lysosomal disease, Fabry disease, treated with recombinant alpha-galactosidase A and the specific chaperone 1-deoxygalactonojirimycin (DGJ). These results have important clinical implications, as they demonstrate synergy between pharmacological chaperones and enzyme replacement. A synergistic effect of these treatments may result particularly useful in patients responding poorly to therapy and in tissues in which sufficient enzyme levels are difficult to obtain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / pharmacology
  • 1-Deoxynojirimycin / therapeutic use
  • Animals
  • Biological Transport / drug effects
  • Blotting, Western
  • Cell Line
  • Drug Stability
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Fibroblasts / drug effects*
  • Fibroblasts / pathology
  • Glycogen Storage Disease Type II / drug therapy*
  • Humans
  • Lysosomes / metabolism
  • Mice
  • Microscopy, Confocal
  • alpha-Galactosidase / administration & dosage
  • alpha-Galactosidase / metabolism
  • alpha-Galactosidase / pharmacology
  • alpha-Galactosidase / therapeutic use


  • Enzyme Inhibitors
  • 1-Deoxynojirimycin
  • miglustat
  • alpha-Galactosidase