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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