ENZYME REPLACEMENT WITH RECOMBINANT BETA-GLUCURONIDASE IN MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII - IMPACT OF THERAPY DURING THE FIRST 6 WEEKS OF LIFE ON SUBSEQUENT LYSOSOMAL STORAGE, GROWTH, AND SURVIVAL

Treatment of mucopolysaccharidosis type VII (MPS VII) mice with recomb inant mouse beta-glucuronidase injections has been shown to deliver en zyme to most tissues and to reduce lysosomal storage during the first 6 wk of life. Here we determine the effect of enzyme therapy limited t o the first 6 wk of life on survival and growth and follow the subsequ ent accumulation of lysosomal storage after beta-glucuronidase treatme nt is discontinued, MPS VII mice received 28,000 U of beta-glucuronida se i.v. at weekly intervals from birth to 6 wk of life and were killed at intervals up to 1 y after the last injection. By 29 d after the la st enzyme injection, lysosomal storage in bone was no different in amo unt than that seen in untreated MPS VII mice, By 85 d, the fixed tissu e macrophage system, meninges, and brain glia had also accumulated sto rage comparable to that seen in untreated controls, One year after tre atment, lysosomal storage was similar to that of untreated MPS VII mic e in all sites except cortical that were not killed earlier, Lived lon ger, were larger, and had milder facial and skeletal deformities than untreated MPS VII mice. These data show that enzyme replacement therap y in MPS VII mice during the first 6 wk of life improves survival and growth. After treatment is discontinued, storage accumulates slowly in he brain and more rapidly in the fixed tissue macrophage system, Whet her therapy continued later in life can further improve survival and g rowth remains to be established.