Miglustat in Niemann-Pick disease type C patients: a review

Orphanet J Rare Dis. 2018 Aug 15;13(1):140. doi: 10.1186/s13023-018-0844-0.


Objective: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive, neurodegenerative disease associated with a wide variety of progressive neurological manifestations. Miglustat is indicated for the treatment of progressive neurological manifestations in both adults and children. Since approval in 2009 there has been a vast growth in clinical experience with miglustat. The effectiveness of miglustat has been assessed using a range of measures.

Methods: Comprehensive review of published data from studies of cellular neuropathological markers and structural neurological indices in the brain, clinical impairment/disability, specific clinical neurological manifestations, and patient survival.

Results: Cranial diffusion tensor imaging and magnetic resonance spectroscopy studies have shown reduced levels of choline (a neurodegeneration marker), and choline/N-acetyl aspartate ratio (indicating increased neuronal viability) in the brain during up to 5 years of miglustat therapy, as well as a slowing of reductions in fractional anisotropy (an axonal/myelin integrity marker). A 2-year immunoassay study showed significant reductions in CSF-calbindin during treatment, indicating reduced cerebellar Purkinje cell loss. Magnetic resonance imaging studies have demonstrated a protective effect of miglustat on cerebellar and subcortical structure that correlated with clinical symptom severity. Numerous cohort studies assessing core neurological manifestations (impaired ambulation, manipulation, speech, swallowing, other) using NP-C disability scales indicate neurological stabilization over 2-8 years, with a trend for greater benefits in patients with older (non-infantile) age at neurological onset. A randomized controlled trial and several cohort studies have reported improvements or stabilization of saccadic eye movements during 1-5 years of therapy. Swallowing was also shown to improve/remain stable during the randomized trial (up to 2 years), as well as in long-term observational cohorts (up to 6 years). A meta-analysis of dysphagia - a potent risk factor for aspiration pneumonia and premature death in NP-C - demonstrated a survival benefit with miglustat due to improved/stabilized swallowing function.

Conclusions: The effects of miglustat on neurological NP-C manifestations has been assessed using a range of approaches, with benefits ranging from cellular changes in the brain through to visible clinical improvements and improved survival.

Keywords: Biomarker; Efficacy; Miglustat; Niemann-Pick disease type C.

Publication types

  • Review

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives
  • 1-Deoxynojirimycin / therapeutic use
  • Biomarkers / metabolism
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Niemann-Pick Disease, Type C / drug therapy*
  • Niemann-Pick Disease, Type C / metabolism
  • Niemann-Pick Disease, Type C / mortality
  • Niemann-Pick Disease, Type C / pathology
  • Treatment Outcome


  • Biomarkers
  • Enzyme Inhibitors
  • 1-Deoxynojirimycin
  • miglustat