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https://hdl.handle.net/2440/23251
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Type: | Journal article |
Title: | Validation of a heparan sulfate-derived disaccharide as a marker of accumulation in murine mucopolysaccharidosis type IIIA |
Author: | King, B. Savas, P. Fuller, M. Hopwood, J. Hemsley, K. |
Citation: | Molecular Genetics and Metabolism, 2006; 87(2):107-112 |
Publisher: | Academic Press Inc Elsevier Science |
Issue Date: | 2006 |
ISSN: | 1096-7192 1096-7206 |
Abstract: | Mucopolysaccharidosis type IIIA (MPS IIIA) is a neurodegenerative lysosomal storage disorder resulting from sulfamidase deficiency, which leads to accumulation of heparan sulfate within lysosomes. We have determined the time-course of accumulation of a disaccharide [hexosamine-N-sulfate[alpha-1,4]hexuronic acid; HNS-UA] marker of heparan sulfate storage within the brain, liver, and spleen of a naturally occurring mouse model of MPS IIIA. HNS-UA is detectable in the brain of affected mice on the day of birth, when it is significantly increased compared to normal control mice. As mice age, this compound steadily accumulates until a plateau is reached at approximately 20-weeks. A similar rate of accumulation of HNS-UA is seen in the liver and spleen of affected mice. Intracerebral delivery of recombinant human sulfamidase reduced the amount of HNS-UA present in segments of the brain receiving the correcting enzyme, thus demonstrating the effectiveness of enzyme replacement therapy within the central nervous system of affected mice. This finding therefore provides evidence for the use of the disaccharide HNS-UA to monitor the effect of therapies for this condition in humans, when treatment strategies are devised. |
Keywords: | lysosomal storage disorder heparan sulfate electrospray-ionization tandem mass spectrometry oligosaccharides mucopolysaccharidosis type IIIA mouse sulfamidase |
DOI: | 10.1016/j.ymgme.2005.09.026 |
Published version: | http://dx.doi.org/10.1016/j.ymgme.2005.09.026 |
Appears in Collections: | Aurora harvest 2 Paediatrics publications |
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