Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

Dyane Auclair, John Finnie, Steven U. Walkley, Joleen White, Timothy Nielsen, Maria Fuller, Alphonsus Cheng, Charles A. O'Neill, John J. Hopwood

Research output: Contribution to journalArticle

27 Scopus citations


Introduction: 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. Results: 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. Discussion: These data indicate that repeated IT-INJ of rhASB can safely prevent GAG storage in MPS-VI dura.Methods: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.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalPediatric Research
Issue number1
Publication statusPublished - Jan 1 2012
Externally publishedYes


ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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