Abstract |
MPS IIIA is a lysosomal storage disorder caused by mutations in the sulphamidase gene, resulting in the accumulation of heparan sulphate glycosaminoglycans (HS GAGs). Symptoms predominantly manifest in the CNS and there is no current therapy that effectively addresses neuropathology in MPS IIIA patients. Recent studies in MPS IIIA mice have shown that rhodamine B substrate deprivation therapy (SDT) (also termed substrate reduction therapy/SRT) inhibits GAG biosynthesis and, improves both somatic and CNS disease pathology. Acute overexposure to high doses of rhodamine B results in liver toxicity and is detrimental to reproductive ability. However, the long-term effects of decreasing GAG synthesis, at the low dose sufficient to alter neurological function are unknown. A trans-generational study was therefore initiated to evaluate the continuous exposure of rhodamine B treatment in MPS IIIA mice over 4 generations, including treatment during pregnancy. No alterations in litter size, liver histology or liver function were observed. Overall, there are no long-term issues with the administration of rhodamine B at the low dose tested and no adverse effects were noted during pregnancy in mice.
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Authors | Ainslie L K Roberts, Janice M Fletcher, Lynette Moore, Sharon Byers |
Journal | Molecular genetics and metabolism
(Mol Genet Metab)
2010 Oct-Nov
Vol. 101
Issue 2-3
Pg. 208-13
ISSN: 1096-7206 [Electronic] United States |
PMID | 20650670
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Glycosaminoglycans
- Rhodamines
- rhodamine B
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Topics |
- Animals
- Disease Models, Animal
- Female
- Glycosaminoglycans
(antagonists & inhibitors, biosynthesis)
- Litter Size
(drug effects)
- Liver
(drug effects, pathology, physiology)
- Mice
- Mucopolysaccharidosis III
(genetics, physiopathology)
- Pregnancy
- Rhodamines
(therapeutic use)
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