ENZYME REPLACEMENT WITH RECOMBINANT BETA-GLUCURONIDASE IN THE NEWBORNMUCOPOLYSACCHARIDOSIS TYPE-VII MOUSE

Beta-Glucuronidase injected i.v. into newborn mucopolysaccharidosis VI I 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 mann ose 6-phosphate receptor. One h after a 3.5-mg/kg beta-glucuronidase i njection, beta-glucuronidase levels were equal to or greater than norm al 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 b one, brain, heart, and fixed tissue macrophages. The half-life of reco mbinant beta-glucuronidase activity in various organs of injected muco polysaccharidosis VII mice was 1.5 to 4.5 d. These studies show that r ecombinant beta-glucuronidase administered to newborn mice reaches the sites of clinically important storage in murine mucopolysaccharidosis VII.