Enzyme replacement therapy for lysosomal storage diseases

Curr Opin Pediatr. 2011 Dec;23(6):588-93. doi: 10.1097/MOP.0b013e32834c20d9.


Purpose of review: Enzyme replacement therapy (ERT) for type 1 Gaucher has been highly successful. ERT is now available for other lysosomal storage disorders (LSDs) but none of these highly expensive treatments has had the same efficacy. This review explores why these newer treatments have failed to live up to expectations and how future products might be made more effective.

Recent findings: In Gaucher, the target cells for ERT are macrophages, which are efficiently accessed by intravenously injected recombinant enzyme. The target tissues in other LSDs receive much lower doses of enzyme and intravenous ERT does not enter the brain at all. Uptake of recombinant enzyme is via the mannose-6-phosphate receptor (M6PR). Recent work has looked at improving the efficiency of enzyme delivery to tissues by altering both the ligand on the infused enzyme and the expression of the M6PR on cells. For delivery to the central nervous system, intrathecal routes of administration have been explored.

Summary: Work in tissue culture and in animal models has shown increased efficiency of enzyme delivery and clinical trials of second-generation products and novel delivery systems are now underway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Replacement Therapy / methods*
  • Enzyme Therapy*
  • Enzymes / administration & dosage
  • Enzymes / pharmacokinetics
  • Humans
  • Injections, Intravenous
  • Lysosomal Storage Diseases / drug therapy*
  • Lysosomal Storage Diseases / enzymology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use


  • Enzymes
  • Recombinant Proteins