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Inhibition of glycosaminoglycan synthesis using rhodamine B in a mouse model of mucopolysaccharidosis type IIIA

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dc.contributor.authorDerrick Roberts, A.
dc.contributor.authorThomas, B.
dc.contributor.authorWilkinson, A.
dc.contributor.authorFletcher, J.
dc.contributor.authorByers, S.
dc.date.issued2006
dc.description.abstractReduction of an enzyme activity required for the lysosomal degradation of glycosaminoglycan (gag) chains will result in a mucopolysaccharidosis (MPS) disorder. Substrate deprivation therapy (SDT), a potential therapy option for MPS with residual enzyme activity, aims to reduce the synthesis of gag chains, the natural substrate for the deficient enzyme. Reduced substrate levels would balance the reduced level of enzyme in patient cells, resulting in normalized gag turnover. Rhodamine B, a nonspecific inhibitor, reduced gag synthesis in a range of normal and MPS cells and also decreased lysosomal storage of gag in MPS VI (72%) and MPS IIIA (60%) cells. Body weight gain of male MPS IIIA mice treated with 1 mg/kg rhodamine B was reduced compared with untreated MPS IIIA mice and was indistinguishable from that of normal mice. Liver size, total gag content, and lysosomal gag was reduced in treated MPS IIIA animals as was urinary gag excretion. Lysosomal gag content in the brain was also reduced by treatment. The alteration in MPS IIIA clinical pathology by rhodamine B, combined with the observation that treatment had no effect on the health of normal animals, demonstrates the potential for SDT in general as a therapy for MPS disorders.
dc.identifier.citationPediatric Research, 2006; 60(3):309-314
dc.identifier.doi10.1203/01.pdr.0000233037.00707.da
dc.identifier.issn0031-3998
dc.identifier.issn1530-0447
dc.identifier.orcidByers, S. [0000-0001-5576-3636]
dc.identifier.urihttp://hdl.handle.net/2440/23280
dc.language.isoen
dc.publisherInt Pediatric Research Foundation Inc
dc.source.urihttps://doi.org/10.1203/01.pdr.0000233037.00707.da
dc.subjectLiver
dc.subjectBrain
dc.subjectCells, Cultured
dc.subjectAnimals
dc.subjectMice
dc.subjectMucopolysaccharidosis III
dc.subjectDisease Models, Animal
dc.subjectWeight Gain
dc.subjectRhodamines
dc.subjectGlycosaminoglycans
dc.subjectOrgan Size
dc.subjectMale
dc.titleInhibition of glycosaminoglycan synthesis using rhodamine B in a mouse model of mucopolysaccharidosis type IIIA
dc.typeJournal article
pubs.publication-statusPublished

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