Table 3 Summary of randomised and non-randomised studies with information on the effects of miglustat on dysphagia

OGT-918-007[25]

12-month randomised, controlled Phase II study comparing miglustat with standard (symptomatic) therapy

Main study: miglustat 200 mg t.i.d. (n = 20) vs. standard care (n = 9)

Main study: male and female adults and juveniles (aged ≥12 years)

Ability to swallow different foods (5 mL of water, 1 teaspoon of puree, 1 teaspoon of soft lumps, or a third of a cookie)

Improved ability to swallow water in 6 patients (30%), puree in 3 patients (15%), soft lumps in 3 patients (15%), and a third of a cookie in 7 patients (35%) after 12 months of miglustat therapy

Sub-study: miglustat 200 mg t.i.d adjusted for BSA (n = 12)

Sub study: male and female children aged 4–11 years

Assessed at 6 and 12 months or withdrawal/follow-up

Over 80% of children had normal swallowing at baseline

OGT-918-007 ext (a)[27]

Prospective, non-controlled, 12-month extension to OGT-918-007

Miglustat 200 mg t.i.d.

Male and female adults and juveniles (aged ≥12 years) who received miglustat (n = 17) or standard care (n = 8) for 12 months

Swallowing assessment (as above) at 12 and 24 months and last visit

Swallowing improved/stable (vs. baseline) in 86% of patients completing 12 months, and 79–93% of those completing 24 months on miglustat

OGT-918-007 ext (b)[26]

Prospective, non-controlled, 12-month extension to OGT-918-007 sub-study

Miglustat 200 mg t.i.d adjusted for BSA

Male and female children aged 4–11 years who underwent 12 months of miglustat therapy (n = 10)

Swallowing assessment (as above) at 12 and 24 months and last visit

Nine patients (90%) had normal swallowing function at both baseline and Month 24

NP-C retrospective Stage 1 survey[70]

Retrospective, multicentre observational cohort study

Adults ≥18 years (n = 14): miglustat 200 mg t.i.d.

Patients previously or currently treated with miglustat in clinical practice settings

Dysphagia subscale of NP-C disability scale[12]

Continuous deterioration prior to initiation of miglustat therapy

Juveniles 12–17 years (n = 13): miglustat 200 mg t.i.d.

Similar proportions of patients in each swallowing disability category at treatment start and last post-treatment assessment (stabilisation)

Paediatrics ≤12 years (n = 34): miglustat adjusted for BSA

Spanish/Portuguese paediatric cohort study[11]

Multicentre observational chart review

Miglustat 200 mg t.i.d. adjusted for BSA in symptomatic patients (n = 16)

Male and female paediatric patients treated in Spain and Portugal

Dysphagia subscale of a modified NP-C disability scale[11]

Stable neurological manifestations (including swallowing) in juvenile-onset patients

Symptomatic therapy in 1 asymptomatic patient

Smaller therapeutic benefits in younger-onset patients with greater disease severity at baseline

Italian case series[18]

Longitudinal case series of Italian patients

Miglustat 250–300 mg/mq/day in three divided doses for up to 4 years

Male and female patients treated for ≥3 years, with swallowing function assessed by VFSS (n = 4)

VFSS

Improved swallowing in patients with dysphagia/aspiration at baseline (n = 3)

No deterioration in the patient with normal swallowing at baseline

Taiwanese data[29]

Longitudinal case reports

Miglustat 200 mg t.i.d. adjusted for BSA for 1 year

Young male patients, 1 with severe swallowing impairment and 1 with impaired language/speech, who underwent serial VFSS

VFSS

Patient 1: substantially improved swallowing function after 6 months

Patient 2: normal swallowing before and throughout therapy