Long-term efficacy of miglustat in paediatric patients with Niemann-Pick disease type C.

Abstract

Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease characterized by progressive neurological manifestations. Oral miglustat was first approved for the treatment of children and adults with NP-C in Europe in 2009. There are still relatively few published data on the long-term efficacy and safety of miglustat in patients with NP-C in clinical practice. We report the effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five children. Overall, 3/5 patients displayed progressive dysphagia before starting miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age at treatment start was 11.6 years, and the median (range) duration of therapy so far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but therapy was interrupted for 1-3 months at least once in all patients due to supply issues. Swallowing function was stabilised during miglustat therapy, with no significant increase in Han dysphagia scale or aspiration-penetration index scores among four evaluable patients (p > 0.05). Scores on the mini-mental state examination indicated an improvement in cognitive function during the first 3-6 months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory function remained stable for at least the first 2 years of treatment in most patients, but there was a trend towards deterioration thereafter, possibly related to treatment interruptions. The safety/tolerability profile of miglustat was similar to previous clinical studies, although reports of gastrointestinal disturbances were rare. Overall, miglustat appeared to stabilise key parameters of neurological disease progression.

• Authors: Y H Chien, S F Peng, C C Yang, N C Lee, L K Tsai, A C Huang, S C Su, C C Tseng, W L Hwu
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 36 Issue 1 Pg. 129-37 (Jan 2013) ISSN: 1573-2665 [Electronic] United States
• PMID: 22476655 (Publication Type: Journal Article)

Chemical References

• 1-Deoxynojirimycin
• miglustat

Topics

• 1-Deoxynojirimycin (administration & dosage, adverse effects, analogs & derivatives)
• Child
• Child, Preschool
• Cognition (drug effects)
• Deglutition (drug effects)
• Disease Progression
• Drug Administration Schedule
• Female
• Humans
• Male
• Nervous System Diseases (drug therapy)
• Niemann-Pick Disease, Type C (drug therapy)
• Time
• Treatment Outcome