ENZYME REPLACEMENT THERAPY FOR MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII

Recombinant mouse beta-glucuronidase administered intravenously to new born mice with mucopolysaccharidosis type VII (RIPS VII) is rapidly cl eared from the circulation and localized in many tissues. Here we dete rmine the tissue distribution of injected enzyme and describe its effe cts on the histopathology in 6-wk-old MPS VII mice that received eithe r one injection of 28,000 U recombinant beta-glucuronidase at 5 wk of age or received six injections of 28,000 U given at weekly intervals b eginning at birth. These mice were compared with untreated 6-wk-old RI PS VII mice. The single injection decreased lysosomal distention in th e fi?red tissue macrophage system. MPS VII mice that received multiple injections had 27.8, 3.5, and 3.3% of normal le,els of beta-glucuroni dase in liver, spleen, and kidney, respectively. Brain had detectable beta-glucuronidase, ranging from 2.0-12.1% of normal. Secondary elevat ions of alpha-galactosidase and beta-hexosaminidase in brain, spleen, liver, and kidney were decreased compared with untreated MPS VII mice. Although no improvement was observed in chondrocytes, glia, and some neurons, the skeleton had less clinical and pathological evidence of d isease and the brain had reduced lysosomal storage in meninges and sel ected neuronal groups. These data show that recombinant beta-glucuroni dase treatment begun in newborn MPS VII mice provides enzyme to most t issues and significantly reduces or prevents the accumulation of lysos omal storage during the first 6 wk of life. Whether therapy begun late r in life ran achieve this level of correction remains to be establish ed.