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Disease Progression in Charcot-Marie-Tooth Disease Related to MPZ Mutations: A Longitudinal Study
Vera Fridman1, Stefan Sillau1, Jacob Bockhorst1
1Department of Neurology, University of Colorado Denver, Aurora, CO, USA.
Annals of Neurology
|October 7, 2022
Summary
Longitudinal natural history studies of MPZ neuropathy are crucial for clinical trials. The Charcot-Marie-Tooth Examination Score (CMTES) showed significant change over 5 years, particularly in axonal forms and moderate severity cases.
Area of Science:
- Neurology
- Clinical Neuroscience
- Genetics
Background:
- Longitudinal natural history studies are essential for advancing clinical trials in MPZ neuropathy.
- Paucity of such studies has historically hindered therapeutic development.
- The Inherited Neuropathies Consortium conducted a multi-site study to address this gap.
Purpose of the Study:
- To evaluate the longitudinal changes in MPZ neuropathy using the Charcot-Marie-Tooth Examination Score (CMTES) and its Rasch-modified version (CMTES-R).
- To assess the sensitivity of CMTES to disease progression over a 5-year period in patients with MPZ neuropathy.
- To identify patient subgroups, such as those with axonal vs. demyelinating forms or varying baseline severity, that exhibit more pronounced changes.
Main Methods:
- A longitudinal natural history study involving 139 patients with MPZ neuropathy across 13 sites.
- Utilized longitudinal regression analysis to evaluate changes in CMTES and CMTES-R over a 5-year timeframe.
- Conducted subgroup analyses based on neuropathy type (axonal vs. demyelinating) and baseline disease severity.
Main Results:
- A significant change in CMTES was observed from year 2 to year 5 (mean change of 0.87 points at 2 years, p=0.008).
- Axonal MPZ neuropathies showed a greater change in CMTES at 2 years compared to demyelinating forms (1.30 points vs. 0.06 points).
- Patients with moderate baseline neuropathy severity (CMTES 8-14) exhibited the most notable change over 2 years (1.14 points).
Conclusions:
- The Charcot-Marie-Tooth Examination Score (CMTES) is a sensitive measure for detecting changes over time in adult patients with axonal MPZ neuropathy, but not typically in demyelinating forms.
- Disease progression, as measured by CMTES, is most pronounced in individuals with moderate baseline disease severity.
- These findings provide valuable insights for the design and stratification of future clinical trials targeting MPZ neuropathies.
