title: Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients.
abstract: BACKGROUND
  Mucopolysaccharidoses (MPSs) are a group of severe metabolic disorders caused by deficiencies in enzymes involved in the degradation of glycosaminoglycans (GAGs)-long chains of sugar carbohydrates in cells that help build bone, cartilage, tendons, corneas, skin, and connective tissue. Although enzyme replacement therapy has become available for the treatment of some types of MPS, effective treatment of neurodegenerative forms of MPS has yet to be determined. Recently, genistein (4',5,7-trihydroxyisoflavone), a specific inhibitor of protein tyrosine kinase, has been found to inhibit GAG synthesis and to reduce GAG concentrations in cultures of fibroblasts of MPS patients. Therefore, a potential substrate reduction therapy has been proposed.
  
  
  OBJECTIVE
  The aim of this study was to examine urinary GAG concentration, hair morphology, and cognitive function in patients receiving genistin treatment for Sanfilippo syndrome (MPS type III).
  
  
  METHODS
  Patients aged 3 to 14 years with a biochemically confirmed diagnosis of MPS IIIA or MPS IIIB were eligible to enroll in this open-label, pilot study. Genistin-rich soy isoflavone extract 5 mg/kg/d was administered PO for 12 months. Urinary GAG concentration, hair morphology,and cognitive function (measured using a modified version of the Brief Assessment Examination [BAE] and parent observations)were measured at baseline and after 12 months of treatment.
  
  
  RESULTS
  Ten patients (6 girls, 4 boys; mean age, 8 years [range,3\2-14 years];mean weight, 28 kg [range, 17\2-43 kg]) were included in the study. All patients had Sanfilippo syndrome; 5 patients had MPS IIIA and 5 had MPS IIIB. After 1 year, statistically significant improvement was found in urinary GAG concentration, hair morphology, and cognitive function. Urinary GAG concentration decreased significantly in all 5 patients with MPS IIIA and in 2 patients with MPS IIIB (P = 0.028). Hair morphology improved significantly in all 5 MPS IIIA patients and in 3 MPS IIIB patients (P = 0.012). A significant increase in the BAE score (by 2-6 points) was noted in 8 patients, while the scores of 2 patients did not change after 12 months of treatment (P = 0.012). No adverse events (AEs) considered related to treatment were reported. Moreover, no AEs not related to the treatment (apart from classical symptoms of MPS III) were noted.
  
  
  CONCLUSIONS
  This pilot study found some improvements in GAG concentration, hair morphology, and cognitive function in these pediatric patients with Sanfilippo syndrome treated with genistin-rich soy isoflavone extract for 1 year. Clinical trials are needed to evaluate the efficacy and safety of this potential treatment.
authors.affiliation: Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Piotrowska
authors.affiliation: Department of Molecular Biology, University of Gdansk, Gdansk, Poland ; Laboratory of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Gdansk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakóbkiewicz-Banecka
authors.affiliation: The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymanska
authors.affiliation: Department of Pediatrics, Children's Gastroenterology and Oncology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Liberek
authors.affiliation: The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Maryniak
authors.affiliation: Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
authors.forename: Marcelina
authors.initials: M
authors.lastname: Malinowska
authors.affiliation: Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Czartoryska
authors.affiliation: Biofarm, Poznan, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Puk
authors.affiliation: Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kloska
authors.affiliation: Department of Nephrology, Transplantation, and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Liberek
authors.affiliation: Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Baranska
authors.affiliation: Laboratory of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Gdansk, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Wegrzyn
authors.affiliation: Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wegrzyn
keywords: gene expression; genistein; genistin; mucopolysaccharidosis; substrate reduction therapy