title: Evaluation of miglustat treatment in patients with type III mucopolysaccharidosis: a randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of oral miglustat treatment in patients with mucopolysaccharidosis type III. The primary outcome was efficacy with improvement or stabilization in at least two domains of Vineland Adaptative Behavior Scales at 6 months. The secondary outcome measured the evolution of other cognitive tests at 12 months. The safety and tolerability were assessed throughout the study.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, monocenter, institutional, phase IIb to III study. In case of efficacy at 6 months, the study would go on for another 6 months on an open design with all patients receiving miglustat. In the absence of efficacy at 6 months, the trial had to be continued for 6 more months with the initial design.
  
  
  RESULTS
  After 6 months, efficacy was not superior in patients with miglustat. The independent review board confirmed continuing the study until 12 months.
  
  
  CONCLUSIONS
  Miglustat treatment was not associated with any improvement/stabilization in behavior problems in patients with mucopolysaccharidosis type III. Miglustat has an acceptable safety profile. However, the study has confirmed that miglustat is able to pass through the blood-brain barrier without significantly decreasing ganglioside levels.
authors.affiliation: Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de Référence des Maladies Héréditaires du Métabolisme, Bron, France. nathalie.guffon-fouilhoux@chu-lyon.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bin-Dorel
authors.forename: Evelyne
authors.initials: E
authors.lastname: Decullier
authors.forename: Carole
authors.initials: C
authors.lastname: Paillet
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guitton
authors.forename: Alain
authors.initials: A
authors.lastname: Fouilhoux
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D005260:Female; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009084:Mucopolysaccharidosis III / Q000188:drug therapy*; D009483:Neuropsychological Tests; D012893:Sleep Wake Disorders / Q000188:drug therapy; D000520:alpha-Glucosidases / Q000134:cerebrospinal fluid
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat; D000520:alpha-Glucosidases