Delivery of lysosomal enzymes for therapeutic use: glucocerebrosidase as an example.
Enzyme therapies for lysosomal storage diseases have developed over the past decade into the standard-of-care for affected patients. Such therapy for Gaucher disease has been the prototype, using natural source or recombinant forms of human acid beta-glucosidase (GCase). In Gaucher disease, macrophages are the repository for the pathological lipid and the target for delivery of GCase. The macrophage mannose receptor provides a Trojan horse for intracellular delivery of intravenously administered GCase (man-GCase) with mannosyl-terminated oligosaccharide chains. Passage through several hostile compartments (e.g., plasma) leads to inefficient delivery of man-GCase to macrophage lysosomes. However, regular infusions of man-GCase re-establishes health in affected patients. Similar results are being obtained in several other lysosomal storage diseases. Evolving gene and chaperone approaches provide alternative treatment strategies.
Grabowski
Gregory A
GA
The Division and Programme in Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. greg.grabowski@cchmc.org
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005776:Gaucher Disease / Q000188:drug therapy / Q000201:enzymology; D005962:Glucosylceramidase / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy / Q000201:enzymology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use
D011994:Recombinant Proteins; D005962:Glucosylceramidase