Enzyme replacement with recombinant beta-glucuronidase in the newborn mucopolysaccharidosis type VII mouse.
beta-Glucuronidase injected i.v. into newborn mucopolysaccharidosis VII mice was cleared from the circulation in less than 1 h and taken up by tissues in a distribution corresponding to the location of the mannose 6-phosphate receptor. One h after a 3.5-mg/kg beta-glucuronidase injection, beta-glucuronidase levels were equal to or greater than normal in every organ examined with the exception of the brain, where 31% normal activity was present. Enzyme was detectable histochemically in the major sites of pathology for mucopolysaccharidosis VII including bone, brain, heart, and fixed tissue macrophages. The half-life of recombinant beta-glucuronidase activity in various organs of injected mucopolysaccharidosis VII mice was 1.5 to 4.5 d. These studies show that recombinant beta-glucuronidase administered to newborn mice reaches the sites of clinically important storage in murine mucopolysaccharidosis VII.
Vogler
C
C
Department of Pathology, St. Louis University School of Medicine, Missouri 63104.
Sands
M
M
Higgins
A
A
Levy
B
B
Grubb
J
J
Birkenmeier
E H
EH
Sly
W S
WS
D000818:Animals; D000831:Animals, Newborn; D005966:Glucuronidase / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006651:Histocytochemistry; D007275:Injections, Intravenous; D051379:Mice; D008817:Mice, Mutant Strains; D016538:Mucopolysaccharidosis VII / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
D011994:Recombinant Proteins; D005966:Glucuronidase