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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
  1. aAge at disease onset or diagnosis; bmean duration; A/A adolescent/adult onset, BARS Brief ataxia rating scale, Cho choline, ChT chitotriosidase, Cr creatine, CSF cerebrospinal fluid, DTI diffusion tension imaging, EI early-infantile, FA fractional anisotropy, FAB frontal assessment battery, HSEM horizontal saccadic eye movements, HSG horizontal saccadic gain, JUV juvenile, LI late infantile, MMSE mini-mental state examination, MRI magnetic resonance imaging, MRS magnetic resonance spectroscopy, NAA N-acetyl aspartate, NNSS NIH neurological severity scale, NR not reported, pt./pts. patient(s), RCT randomised controlled trial, SAI standard ambulation index