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Remyelination varies between and within lesions in multiple sclerosis following bexarotene
J William L Brown1,2,3, Ferran Prados2,4,5, Daniel R Altmann6
1Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Annals of Clinical and Translational Neurology
|September 18, 2022
Summary
Bexarotene treatment showed remyelination effects in multiple sclerosis (MS) gray matter lesions, particularly in outer regions. White matter lesion remyelination varied by location and baseline abnormality, suggesting future trials should focus on gray matter measures.
Area of Science:
- Neuroscience
- Radiology
- Clinical Trials
Background:
- Chronic demyelination in multiple sclerosis (MS) leads to axonal loss and progressive disability.
- Enhancing remyelination offers a potential strategy to slow or reverse MS-related disability.
Purpose of the Study:
- To explore factors influencing bexarotene treatment response in MS lesions, specifically location and baseline abnormality.
- To determine if remyelination effects vary by tissue type (gray matter vs. white matter) and proximity to cerebrospinal fluid (CSF).
Main Methods:
- Exploratory analysis of bexarotene versus placebo trial data in 49 MS patients.
- Assessment of treatment effects using magnetisation transfer ratio (MTR) changes at whole lesion, component, and voxel levels.
- Analysis of lesion location (tissue type, CSF proximity) and baseline MTR/T1 values.
Main Results:
- Significant bexarotene treatment effects were observed in gray matter (GM) lesions but not white matter (WM) lesions at the whole lesion level.
- Voxel-level analysis revealed treatment effects in WM lesions with the lowest baseline MTR.
- Treatment effects showed gradients in both WM and cortical gray matter (CGM) lesions, decreasing near CSF spaces.
- Larger treatment effects were noted in the outer and surrounding components of GM lesions compared to their inner cores.
Conclusions:
- Remyelination efficacy varies significantly within and between MS lesions.
- Gray matter lesions exhibit a greater remyelination response compared to white matter lesions.
- Future remyelination trials could benefit from focusing on whole GM lesion measures, which require less complex analysis and smaller sample sizes than WM lesion voxel-level analyses.
