Abstract
Mucopolysaccharidoses (MPS) are severe, inherited metabolic disorders caused by storage of glycosaminoglycans (GAGs). Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is described as severe neurological type of MPS, characterized by rapid deterioration of brain functions. No therapy for Sanfilippo disease is approved to date, however, a specific substrate reduction therapy (SRT), called gene expression-targeted isoflavone therapy (GET IT), has been used as an experimental therapy. In this report, we describe effects of treatment of six Sanfilippo disease patients with GET IT, in which the dose of genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), an active compound of GET IT present in the soy isoflavone extract, has been increased to 10, and then to 15 mg/kg/day, contrary to the previously reported dose of 5 mg/kg/day. By measuring levels of urinary GAGs and assessing hair dysmorphology as biomarkers, and by considering clinical symptoms of patients, we obtained results suggesting that elevated doses of genistein may improve efficacy of GET IT for Sanfilippo disease.
Competing interests: None declared.
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Acknowledgments
This research was supported by Ministry of Sciences and Higher Education of Poland (project grant no. N N301 668540 to GW), and was operated within the Foundation for Polish Science Team Programme co-financed by the EU European Regional Development Fund (grant no. TEAM/2008-2/7 to GW). A support from Polish MPS Society is greatly acknowledged.
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Communicated by: Verena Peters.
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Malinová, V., Węgrzyn, G., Narajczyk, M. (2011). The Use of Elevated Doses of Genistein-Rich Soy Extract in the Gene Expression-Targeted Isoflavone Therapy for Sanfilippo Disease Patients. In: JIMD Reports - Case and Research Reports, 2012/2. JIMD Reports, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_87
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DOI: https://doi.org/10.1007/8904_2011_87
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