The Use of Elevated Doses of Genistein-Rich Soy Extract in the Gene Expression-Targeted Isoflavone Therapy for Sanfilippo Disease Patients

  • Věra Malinová
  • Grzegorz Węgrzyn
  • Magdalena NarajczykEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 5)


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.


Mucopolysaccharidosis Type Substrate Reduction Therapy Elevated Dose Inherited Metabolic Disorder Hair Morphology 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



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.


  1. Arfi A, Richard M, Gandolphe C, Scherman D (2010) Storage correction in cells of patients suffering from mucopolysaccharidoses types IIIA and VII after treatment with genistein and other isoflavones. J Inherit Metab Dis 33:61–67PubMedCrossRefGoogle Scholar
  2. Beck M (2007) Mucopolysaccharidoses: clinical features and management. In: vom Dahl S, Wendel U, Strohmeyer G (eds) Genetic metabolic disorders: management, costs and sociomedical aspects.. Deutscher Arzte-Verlag, Cologne, pp 13–18Google Scholar
  3. de Ruijter J, Valstar MJ, Wijburg FA (2011) Mucopolysaccharidosis type III (Sanfilippo syndrome): emerging treatment strategies. Curr Pharm Biotechnol 12(6):923–930PubMedCrossRefGoogle Scholar
  4. Delgadillo V, del Mar O’Callaghan M, Artuch R, Montero R, Pineda M (2011) Genistein supplementation in patients affected by Sanfilippo disease. J Inherit Metab Dis 34(5):1039–1044, doi: 10.1007/s10545-011-9342-4
  5. Friso A, Tomanin R, Salvalaio M, Scarpa M (2010) Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type II. Br J Pharmacol 159:1082–1091PubMedCrossRefGoogle Scholar
  6. Kloska A, Jakóbkiewicz-Banecka J, Narajczyk M, Banecka-Majkutewicz Z, Węgrzyn G (2011) Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses. Metab Brain Dis 26:1–8PubMedCrossRefGoogle Scholar
  7. Malinowska M, Jakóbkiewicz-Banecka J, Kloska A, Tylki-Szymańska A, Czartoryska B, Piotrowska E, Wegrzyn A, Wegrzyn G (2008) Abnormalities in the hair morphology of patients with some but not all types of mucopolysaccharidoses. Eur J Pediatr 167:203–209PubMedCrossRefGoogle Scholar
  8. Malinowska M, Wilkinson FL, Bennett W et al (2009) Genistein reduces lysosomal storage in peripheral tissues of mucopolysaccharide IIIB mice. Mol Genet Metab 98:235–242PubMedCrossRefGoogle Scholar
  9. Malinowska M, Wilkinson FL, Langford-Smith KJ et al (2010) Genistein improves neuropathology and corrects behaviour in a mouse model of neurodegenerative metabolic disease. PLoS One 5:e14192PubMedCrossRefGoogle Scholar
  10. Marucha J, Tylki-Szymańska A, Jakóbkiewicz-Banecka J, Piotrowska E, Kloska A, Czartoryska B, Węgrzyn G (2011) Improvement in the range of joint motion in seven patients with mucopolysaccharidosis type II during experimental gene expression-targeted isoflavone therapy (GET IT). Am J Med Genet A 155A(9):2257–2262Google Scholar
  11. Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill Co., New York, pp 3421–3452Google Scholar
  12. Piotrowska E, Jakobkiewicz-Banecka J, Baranska S et al (2006) Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur J Hum Genet 14:846–852PubMedCrossRefGoogle Scholar
  13. Piotrowska E, Jakobkiewicz-Banecka J, Tylki-Szymanska A et al (2008) Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients. Curr Ther Res Clin Exp 63:166–179CrossRefGoogle Scholar
  14. Piotrowska E, Jakóbkiewicz-Banecka J, Wegrzyn G (2010) Different amounts of isoflavones in various commercially available soy extracts in the light of gene expression-targeted isoflavone therapy. Phytother Res 24(Suppl 1):S109–S113PubMedCrossRefGoogle Scholar
  15. Piotrowska E, Jakobkiewicz-Banecka J, Maryniak A, Tylki-Szymanska A, Puk E, Liberek A, Wegrzyn A, Czartoryska B, Slominska-Wojewodzka M, Wegrzyn G (2011) Two-year follow-up of Sanfilippo Disease patients treated with a genistein-rich isoflavone extract: Assessment of effects on cognitive functions and general status of patients. Med Sci Monit 17:CR196–CR202PubMedCrossRefGoogle Scholar
  16. Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA (2008) Sanfilippo syndrome: a mini-review. J Inherit Metab Dis 31:240–252PubMedCrossRefGoogle Scholar
  17. Wegrzyn G, Jakóbkiewicz-Banecka J, Narajczyk M, Wiśniewski A, Piotrowska E, Gabig-Cimińska M, Kloska A, Słomińska-Wojewódzka M, Korzon-Burakowska A, Węgrzyn A (2010a) Why are behaviors of children suffering from various neuronopathic types of mucopolysaccharidoses different. Med Hypoth 75:605–609CrossRefGoogle Scholar
  18. Wegrzyn G, Jakóbkiewicz-Banecka J, Gabig-Cimińska M, Piotrowska E, Narajczyk M, Kloska A, Malinowska M, Dziedzic D, Gołebiewska I, Moskot M, Wegrzyn A (2010b) Genistein: a natural isoflavone with a potential for treatment of genetic diseases. Biochem Soc Trans 38:695–701PubMedCrossRefGoogle Scholar

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© SSIEM and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Věra Malinová
    • 1
  • Grzegorz Węgrzyn
    • 2
  • Magdalena Narajczyk
    • 3
    Email author
  1. 1.Department of Pediatrics and Adolescent MedicineCharles UniversityPraha 2Czech Republic
  2. 2.Department of Molecular BiologyUniversity of GdańskGdańskPoland
  3. 3.Laboratory of Electron MicroscopyUniversity of GdańskGdańskPoland

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