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• W2021995424 abstract "Mucopolysaccharidoses (MPS) are severe inherited metabolic disorders from the group of lysosomal storage diseases. They are caused by deficiency in the activity of enzymes involved in the degradation of glycosaminoglycans (GAGs) and resultant accumulation of these compounds in the cells of patients. Although enzyme replacement therapy has become available for some MPS types (MPS I, MPS II and MPS VI), this treatment is not efficient when neurological symptoms occur, especially in MPS III (Sanfilippo disease). Recent studies indicated that substrate reduction therapy (SRT) may be an effective option for the treatment of neurodegenerative lysosomal storage diseases, including MPS III. However, previous attempts to SRT for MPS III focused on the use of non-specific inhibitors of GAG synthesis. Thus, we aimed to use the small interfering RNA (siRNA) procedure to control expression of particular genes, whose products are involved in GAG synthesis. In this report we show that, in MPS IIIA fibroblasts, we were able to reduce mRNA levels of four genes, XYLT1, XYLT2, GALTI and GALTII, whose products are involved in GAG synthesis. This decrease in levels of transcripts corresponded to a decrease in levels of proteins encoded by them. Moreover, efficiency of GAG production in these fibroblasts was considerably reduced after treatment of the cells with siRNA. These results indicate that efficient reduction of GAG synthesis may be achieved by the use of siRNA." @default.
• W2021995424 created "2016-06-24" @default.
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• W2021995424 date "2009-08-19" @default.
• W2021995424 modified "2023-10-17" @default.
• W2021995424 title "Impairment of glycosaminoglycan synthesis in mucopolysaccharidosis type IIIA cells by using siRNA: a potential therapeutic approach for Sanfilippo disease" @default.
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• W2021995424 doi "https://doi.org/10.1038/ejhg.2009.144" @default.
• W2021995424 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2987185" @default.
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