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| ENZYME REPLACEMENT THERAPY FOR MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII |
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| Author(s): SANDS MS, VOGLER C, KYLE JW, GRUBB JH, LEVY B, GALVIN N, SLY WS, BIRKENMEIER EH |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 93 Issue: 6 Pages: 2324-2331 Published: JUN 1994 |
| Times Cited: 141 References: 35 |
| Abstract: Recombinant mouse beta-glucuronidase administered intravenously to newborn mice with mucopolysaccharidosis type VII (RIPS VII) is rapidly cleared from the circulation and localized in many tissues. Here we determine the tissue distribution of injected enzyme and describe its effects on the histopathology in 6-wk-old MPS VII mice that received either 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 beginning at birth. These mice were compared with untreated 6-wk-old RIPS VII mice. The single injection decreased lysosomal distention in the 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-glucuronidase in liver, spleen, and kidney, respectively. Brain had detectable beta-glucuronidase, ranging from 2.0-12.1% of normal. Secondary elevations 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 disease and the brain had reduced lysosomal storage in meninges and selected neuronal groups. These data show that recombinant beta-glucuronidase treatment begun in newborn MPS VII mice provides enzyme to most tissues and significantly reduces or prevents the accumulation of lysosomal storage during the first 6 wk of life. Whether therapy begun later in life ran achieve this level of correction remains to be established. |
| Document Type: Article |
| Language: English |
Addresses:
1. JACKSON LAB, BAR HARBOR, ME 04609 USA
2. ST LOUIS UNIV, SCH MED, DEPT PATHOL, ST LOUIS, MO 63104 USA
3. ST LOUIS UNIV, SCH MED, EA DOISY DEPT BIOCHEM & MOLEC BIOL, ST LOUIS, MO 63104 USA
4. UNIV CHICAGO, DEPT MED CARDIOL, CHICAGO, IL 60637 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: NP577 |
| ISSN: 0021-9738 |
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