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https://hdl.handle.net/2440/73457
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Type: | Journal article |
Title: | Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats |
Author: | Auclair, D. Finnie, J. Walkley, S. White, J. Nielsen, T. Fuller, M. Cheng, A. O'Neill, C. Hopwood, J. |
Citation: | Pediatric Research, 2012; 71(1):39-45 |
Publisher: | Int Pediatric Research Foundation Inc |
Issue Date: | 2012 |
ISSN: | 0031-3998 1530-0447 |
Statement of Responsibility: | Dyane Auclair, John Finnie, Steven U. Walkley, Joleen White, Timothy Nielsen, Maria Fuller, Alphonsus Cheng, Charles A. O'Neill and John J. Hopwood |
Abstract: | <h4>Introduction</h4>Mucopolysaccharidosis VI (MPS-VI) is caused by a deficiency in N-acetylgalactosamine-4-sulfatase activity, resulting in lysosomal accumulation of partially degraded glycosaminoglycans (GAGs). Compressive myelopathy in early-onset MPS-VI patients has been partly attributed to thickening of the dura mater following engorgement with GAG. In this study, we therefore tested whether the dural abnormalities could be prevented in a feline model of the disorder.<h4>Results</h4>All intrathecal injections (IT-INJs) were well tolerated. MPS-VI cats treated with IT-INJ of recombinant human N-acetylgalactosamine-4-sulfatase (rhASB) exhibited reduced vacuolation in the dural fibroblasts, diminished levels of sulfated-N-acetylhexosamine (HNAc(+S)) in the cerebrospinal fluid (CSF) and no hind-limb paresis. Serum anti-rhASB antibodies remained low in MPS-VI cats treated with intravenous enzyme replacement therapy (IV-ERT) and increased slightly in normal cats treated with IT-INJ of rhASB alone. Anti-rhASB antibodies in CSF remained undetectable.<h4>Discussion</h4>These data indicate that repeated IT-INJ of rhASB can safely prevent GAG storage in MPS-VI dura.<h4>Methods</h4>Cats were assigned to three groups: (i) receiving weekly IV-ERT of rhASB from birth plus six monthly IT-INJs of rhASB from age 2 months; (ii) receiving six monthly IT-INJs of vehicle; or (iii) untreated. Additional normal cats received five fortnightly IT-INJs of rhASB or vehicle alone. |
Keywords: | Dura Mater Animals Cats Humans Mucopolysaccharidosis VI Disease Models, Animal N-Acetylgalactosamine-4-Sulfatase Glycosaminoglycans Recombinant Proteins Treatment Outcome Injections, Spinal |
Rights: | Copyright © 2012 International Pediatric Research Foundation, Inc. |
DOI: | 10.1038/pr.2011.13 |
Published version: | http://dx.doi.org/10.1038/pr.2011.13 |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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