Journal article
Disease Progression in CMT related to MPZ Mutations: A Longitudinal Study
Annals of neurology, Vol.93(3), pp.563-576
03/2023
DOI: 10.1002/ana.26518
PMCID: PMC9977145
PMID: 36203352
Abstract
OBJECTIVE The paucity of longitudinal natural history studies in MPZ-neuropathy remains a barrier to clinical trials. We have completed a longitudinal natural history study in patients with MPZ-neuropathies across 13 sites of the Inherited Neuropathy Consortium. METHODS Change in Charcot Marie Tooth Examination scores (CMTES) and Rasch modified CMTES (CMTES-R) scores were evaluated using longitudinal regression over a 5-year period in subjects with MPZ-neuropathy. Data from 139 patients with MPZ-neuropathy were examined. RESULTS The average baseline CMTES and CMTES-R scores were 10.84 (SD 6.0, range 0 - 28) and 14.60 (SD= 7.56, range 0 - 32), respectively. A mixed regression model showed significant change in CMTES at years 2-5 [mean change from baseline of 0.87 points at 2 years (p=0.008)]. Subgroup analysis revealed greater change in CMTES at 2 years in subjects with axonal as compared to demyelinating neuropathy [mean change of 1.30 points, (p=0.016) versus 0.06 points, (p=0.889)]. Patients with a moderate baseline neuropathy severity also showed more notable change, by estimate, than those with mild or severe neuropathy [mean 2 year change of 1.14 for baseline CMTES 8-14 (p=0.025), versus -0.03 for baseline CMTES 0-7 (p=0.958) and 0.25 for baseline CMTES ≥15 (p=0.6897)]. The progression in patients harboring specific MPZ mutations was highly variable. INTERPRETATION CMTES scores are sensitive to change over time in adult patients with axonal but not demyelinating forms of MPZ-neuropathy. Change in CMTES was greatest in patients with moderate baseline disease severity. These findings will inform future clinical trials of MPZ-neuropathies. This article is protected by copyright. All rights reserved.
Details
- Title: Subtitle
- Disease Progression in CMT related to MPZ Mutations: A Longitudinal Study
- Creators
- Vera FridmanStefan SillauJacob BockhorstKaitlin SmithIsabella MoroniEmanuela PaglianoChiara PisciottaGuiseppe PiscosquitoMatilde LauráFrancesco MuntoniChelsea BaconShawna FeelyTiffany GriderLaurie GutmannRosemary ShyJanel WilcoxDavid N HerrmannJun LiSindhu RamchandrenCharlotte J SumnerThomas E LloydJohn DayCarly E SiskindSabrina W YumReza SadjadiRichard S FinkelSteven S SchererDavide PareysonMary M ReillyMichael E Shy
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.93(3), pp.563-576
- DOI
- 10.1002/ana.26518
- PMID
- 36203352
- PMCID
- PMC9977145
- NLM abbreviation
- Ann Neurol
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Grant note
- DOI: 10.13039/100014926, name: Acceleron; DOI: 10.13039/100018748, name: Argenx; DOI: 10.13039/501100002426, name: Fondazione Telethon, award: UILDM; DOI: 10.13039/100002108, name: Friedreich's Ataxia Research Alliance; DOI: 10.13039/501100000265, name: Medical Research Council; DOI: 10.13039/100005202, name: Muscular Dystrophy Association; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: 1R01DK115687‐03, 5K23DK118202‐02; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: 2U54NS065712‐07, 5U01NS109403‐03, U54 NS0657, U54 NS065712; DOI: 10.13039/100004337, name: Roche; DOI: 10.13039/100018556, name: Voyager Therapeutics; DOI: 10.13039/100010269, name: Wellcome Trust
- Language
- English
- Electronic publication date
- 10/06/2022
- Date published
- 03/2023
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984306260102771
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