title: Genistein in Sanfilippo disease: a randomized controlled crossover trial.
abstract: OBJECTIVE
  Sanfilippo disease (mucopolysaccharidosis type III [MPS III]) is a rare neurodegenerative metabolic disease caused by a deficiency of 1 of the 4 enzymes involved in the degradation of heparan sulfate (HS), a glycosaminoglycan (GAG). Genistein has been proposed as potential therapy but its efficacy remains uncertain. We aimed to determine the efficacy of genistein in MPS III.
  
  
  METHODS
  Thirty patients were enrolled. Effects of genistein were determined in a randomized, crossover, placebo-controlled intervention with a genistein-rich soy isoflavone extract (10mg/kg/day of genistein) followed by an open-label extension study for patients who were on genistein during the last part of the crossover.
  
  
  RESULTS
  Genistein resulted in a significant decrease in urinary excretion of total GAGs (p = 0.02, slope -0.68 mg GAGs/mmol creatinine/mo) and in plasma concentrations of HS (p = 0.01, slope -15.85 ng HS/ml/mo). No effects on total behavior scores or on hair morphology were observed. Parents or caregivers could not predict correctly during which period of the crossover a patient was on genistein.
  
  
  CONCLUSIONS
  Genistein at 10mg/kg/day effectively reduces urinary excretion of GAGs and plasma HS concentration in patients with MPS III. However, the absolute reduction in GAGs and in HS is small and values after 12 months of treatment remain within the range as observed in untreated patients. No clinical efficacy was detected. Substantially higher doses of genistein might be more effective as suggested by recent studies in animal models.
authors.affiliation: Department of Pediatrics and Amsterdam Lysosome Centre Sphinx, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: de Ruijter
authors.forename: Marlies J
authors.initials: MJ
authors.lastname: Valstar
authors.forename: Magdalena
authors.initials: M
authors.lastname: Narajczyk
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wegrzyn
authors.forename: Wim
authors.initials: W
authors.lastname: Kulik
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Ijlst
authors.forename: Tom
authors.initials: T
authors.lastname: Wagemans
authors.forename: Willem M
authors.initials: WM
authors.lastname: van der Wal
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D019833:Genistein / Q000627:therapeutic use*; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009084:Mucopolysaccharidosis III / Q000188:drug therapy* / Q000652:urine; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D019833:Genistein