title: 24 month-treatment with miglustat of three patients with Niemann-Pick disease type C: follow up using brain spectroscopy.
abstract: Niemann-Pick C (NPC) is a fatal progressive neurolipidosis. Miglustat, an inhibitor of glycosphingolipid synthesis, has been proposed to treat patients but questions remain regarding its efficacy. A major problem has been the lack of suitable objective efficacy endpoints. Three adults with NPC were treated with miglustat for 24 months. Efficacy of treatment was assessed clinically and using brain magnetic resonance spectroscopy. All patients reported mild clinical improvement or stabilization. Furthermore, a sustained decrease in the choline/creatine ratio was observed in all three patients over time. Although these preliminary results require confirmation on a larger cohort of patients, they suggest that miglustat has some beneficial effect on brain dysfunction in NPC and that MRS could be used routinely as a non invasive surrogate marker of treatment efficacy.
authors.affiliation: Department of Neuroradiology and Center for NeuroImaging Research-CENIR , Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Galanaud
authors.forename: Ayman
authors.initials: A
authors.lastname: Tourbah
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehéricy
authors.forename: Nathalie
authors.initials: N
authors.lastname: Leveque
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Heron
authors.forename: Thierry
authors.initials: T
authors.lastname: Billette de Villemeur
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.forename: François
authors.initials: F
authors.lastname: Feillet
authors.forename: Nicole
authors.initials: N
authors.lastname: Baumann
authors.forename: Marie T
authors.initials: MT
authors.lastname: Vanier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sedel
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000378:metabolism; D015331:Cohort Studies; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D017485:1-Deoxynojirimycin; C059896:miglustat; D003401:Creatine; D002794:Choline