title: Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long-term data from a clinical trial.
abstract: A randomized, controlled trial of miglustat indicated that miglustat (Zavesca) stabilized neurological disease over 12 months in adult and juvenile patients with Niemann-Pick disease type C (NP-C). We report data from a non-controlled, open-label extension to this initial randomized trial. All patients completing the randomized trial were allowed to continue treatment in a 12-month, non-controlled open-label extension. Those completing 12 months of extension therapy could continue further on miglustat in a 'continued extension' phase. From a total of 29 patients in the randomized phase (mean [+/-SD] age 24.6+/-9.1 ears; 52% female), 21 completed 12 months of therapy with miglustat (17 of whom received miglustat in the initial randomized phase, and four in the extension phase), and 15 patients (all from the miglustat-randomized group) completed 24 months on miglustat. Mean horizontal saccadic eye movement velocity (HSEM-alpha) indicated improvement in the 12-month miglustat group, and stabilization in the 24-month group; swallowing was improved or stable in 86% and in up to 93%, respectively. Ambulation was stabilized in both the 12- and 24-month groups. In an exploratory disease stability analysis of prospective data on key parameters of disease progression (HSEM-alpha, swallowing, ambulation and cognition), 13/19 (68%) patients receiving >or= 12 months' miglustat therapy had stable disease. Among all patients receiving >or= 1 dose of miglustat (n=28), the most frequent adverse events were diarrhoea, weight decrease, flatulence and tremor. Overall, these data suggest that long-term miglustat therapy stabilizes neurological disease and is well tolerated in adult and juvenile patients with NP-C.
authors.affiliation: Willink Biochemical Genetics Unit, Department of Genetic Medicine, St. Mary's Hospital, Manchester, UK. ed.wraith@cmft.nhs.uk
authors.forename: James E
authors.initials: JE
authors.lastname: Wraith
authors.forename: Darleen
authors.initials: D
authors.lastname: Vecchio
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jacklin
authors.forename: Larry
authors.initials: L
authors.lastname: Abel
authors.forename: Harbajan
authors.initials: H
authors.lastname: Chadha-Boreham
authors.forename: Cécile
authors.initials: C
authors.lastname: Luzy
authors.forename: Ruben
authors.initials: R
authors.lastname: Giorgino
authors.forename: Marc C
authors.initials: MC
authors.lastname: Patterson
mesh_terms: D017485:1-Deoxynojirimycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D002648:Child; D003679:Deglutition / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006801:Humans; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy*; D016138:Walking; D015431:Weight Loss
chemical_list: D017485:1-Deoxynojirimycin; C059896:miglustat