Efficacy of miglustat in Niemann-Pick C disease: a single centre experience

Mol Genet Metab. 2013 Nov;110(3):329-35. doi: 10.1016/j.ymgme.2013.07.019. Epub 2013 Aug 7.

Abstract

Niemann-Pick disease type C (NPC) is a lysosomal storage disease characterized by progressive neurological degeneration. Miglustat is the first approved specific therapy and its efficacy in stabilizing or slowing disease progression has been demonstrated in previous studies. We evaluated data from 10 NPC patients treated with Miglustat in a single study centre. All disease manifestations were assessed and patients were stratified according to age at onset of neurological symptoms. Neurological data were recorded by using a modified version of the NP-C disability scale; a "composite score" and a "mean annual change" were calculated to evaluate disease progression. We observed a mean annual change of the composite score of 0.04 in our cohort, indicating slower progression of neurological symptoms if compared with the natural history of the disease. The evidence of slower disease evolution in patients treated with Miglustat suits with previous data and here it is also emphasized by the comparison between disease progression in two early-infantile onset patients receiving different Miglustat dosages. Evaluation of the mean annual change for individual subgroups of patients evidenced minor values in juvenile patients, highlighting better response in such class of patients. Among individual neurological parameters, swallowing showed the minor mean annual change (0.02), indicating better response to therapy. We underline the importance of using a standardized disability scale to quantify and compare neurological features and their evolution over time.

Keywords: BS; CS; Disability scale; Dysphagia; ER; Epilepsy; LE/L; Mean annual change; Miglustat; NPC; Niemann–Pick disease type C; Niemann–Pick type C; body surface; composite score; endoplasmic reticulum; late endosomes/lysosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / administration & dosage
  • 1-Deoxynojirimycin / adverse effects
  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / therapeutic use
  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • Delayed Diagnosis
  • Disabled Persons
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Glycoside Hydrolase Inhibitors
  • Humans
  • Male
  • Niemann-Pick Disease, Type C / diagnosis
  • Niemann-Pick Disease, Type C / drug therapy*
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • 1-Deoxynojirimycin
  • miglustat