Table 2 Summary of adult and across-ages cohorts
From: Miglustat in Niemann-Pick disease type C patients: a review
Study / ref | Design | Pts / controls (N) | Mean (range) pt agea | Biomarkers and surrogate biomarkers | Median (range) treatment duration | Reported treatment effects |
|---|---|---|---|---|---|---|
Patterson et al. (2007) [56] | 12-mo prospective multicentre Phase II RCT | JUV and A/A pts. (N = 29) | Miglustat pts. 25 (12–42) yrs. Std care: 23 (13–32) yrs | • HSEM-α/HSEM-β • Swallowing • SAI • Hearing | Adol/adults 1 (0.5–1.2) yr Children 1 (0.2–1.1) yr | • Stabilised SEM, swallowing, SAI • Disease progression stable in 80% pts |
Pineda et al. (2009) [42] | Retrospective multicentre observational study | EI, LI, JUV, A/A pts. (N = 66) | 10 (0–32) yrs | • NP-C disability scale • Disability score | 1.5 (0.1–4.5) yrs | • Stabilised disability scores • Stabilised cerebral hypometabolism • Greater benefits in LI and JUV vs. EI pts |
Wraith et al. (2009) [114] | Post hoc analysis from Phase II RCT | LI, JUV, A/A pts. (N = 29) | A/A: 23 (NR) yrs LI/JUV: 7 (NR) yrs | • Disease stability | 1.0 (NR) yr | • Stabilisation in 21/29 (72%) pts. overall • Stabilisation in 8/10 (80%) children |
Galanaud et al. (2009) [79] | Single-centre case series with 24-mo follow up | A/A pts. (N = 3) | 17 (16–19) yrs | • MRI • MRS | 2.0 (NR) yrs | • Clinical improvement or stabilization • Sustained improvement in Cho/Cr ratio |
Wraith et al. (2010) [43] | 12-mo open-label extension and continued extension of Phase II RCT | A/A pts. (N = 21) | 25 (12–42) yrs | • HSEM-α • Swallowing • SAI • Cog. function (MMSE) | 1.9 (0.1–2.0) yrs | • Stabilised HSEM-α, ambulation and swallowing |
Walterfang et al. (2012) [121] | Systematic literature review and longitudinal meta-analysis | EI, LI, JUV and A/A pts. (N = 97) | NR | • Survival • Dysphagia | NR | • Potential survival benefit • Survival related to reduced dysphagia |
Fecarotta et al. (2015) [48] | Prospective open-label multicentre observational study | EI, LI, JUV, A/A pts. (N = 25) | 13 (< 1–44) yrs | • Disability scale • Clinical swallowing studies • Developmental delay • Cog. impairment | 5.9 (4.0–8.0) yrs | • Stabilised/improved neurological manifestations • Greater benefits with earlier treatment |
Bowman et al. (2015) [57] | Prospective open-label single-centre observational study | A/A pts. vs. healthy controls (N = 26) | 28 (14–47) yrs | • MRI • HSEM-α, HSG • Disability scale • Ataxia (BARS) | 2.8 (NR) yrs | • Protective effect on cerebellar Purkinje neurones • Benefits in key brain regions |
Patterson et al. (2015) [46] | Registry-based multicentre observational study | EI, LI, JUV, A/A pts. (N = 92) | 10 (< 1–45) yrs | • Disability scale | 3.9b (1.1–9.8) yrs | • Reduced disease progression • Greater benefits in older pts |
Sedel et al. (2016) [80] | Prospective open-label multicentre observational study | JUV and A/A pts. (N = 16) | 17 (9–32) yrs | • Disability scale • MRS | 1.6 (0.5–8) yrs | • Improved Cho/NAA ratio • Reduced disease progression |
Lau et al. (2016) [88] | Prospective, open-label single-centre observational study | EI, LI, JUV, A/A pts. (N = 39) | 11 (1–22) yrs | • NNSS • DTI | NR | • Lower NNSS severity scores across a range of cerebellar DTI measures |
Bradbury et al. (2016) [67] | Prospective open-label single-centre observational study | EI, LI, JUV, A/A pts. (N = 36) | 11 (2–51) yrs | • CSF calbindin • NNSS | NR (0.5–1.25) yrs | • Reduced CSF calbindin vs. controls |
Masingue et al. (2017) [58] | Retrospective open-label single-centre observational study | A/A pts. vs. healthy controls (N = 26) | MRI: 18 (5–56) yrs DTI: 16 (5–30) yrs | • Disability scale • MRI • DTI | 5.0b (1.0–9.0) yrs | • Improved FA in some brain regions • Clinical and MRI metrics not correlated |
Heitz et al. (2017) [111] | Retrospective open-label single-centre observational study | A/A pts. (N = 21) | 35 (NR) yrs | • Cog. function (MMSE/FAB) • Disability scale | 1.5 (NR) yrs | • Stable neuropsychological scores |