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.

Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker

“…Pre-BMT sampling and analysis in this study was performed prior to conditioning with immunosuppressive drugs. She initially made a good recovery; however, donor chimerism developed after the initial response (reduced MEFL value), and she clinirate of disease progression in NPC1 patients (5,(12)(13)(14). Patients in whom pre-post analysis was performed exhibited the most marked decrease in storage, relative to the chronically miglustat treated group, which was relatively stable at the initiation of the study.…”

Niemann-Pick C disease and mobilization of lysosomal cholesterol by cyclodextrin

“…Similarly, in Npc1 Ϫ / Ϫ mice, miglustat reduced ganglioside storage in LEs/Ls. In addition, miglustat modestly extended life span of ( 87 ) and produced some neurological improvements in NPC patients (152)(153)(154)(155)(156). However, the mechanism underlying these clinical improvements is not clear because reduction of gangliosides in LEs/Ls of NPC-defi cient mice does not appear to be benefi cial (93)(94)(95).…”

Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C

“…The clinical experience of long-term miglustat treatment in children before 16 years of age is still limited in previous studies [7-13] since some of these described single cases or small series of children with heterogeneous conditions, treated for variable periods [7,9,11,13]. …”