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Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Altmann, Daniel R 

Abstract

OBJECTIVE: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis. While the primary MRI outcome was negative, there was converging neurophysiological and MRI evidence of efficacy. Multiple factors influence lesion remyelination. In this study we undertook a systematic exploratory analysis to determine whether treatment response - measured by change in magnetisation transfer ratio - is influenced by location (tissue type and proximity to CSF) or the degree of abnormality (using baseline magnetisation transfer ratio and T1 values). METHODS: We examined treatment effects at the whole lesion level, the lesion component level (core, rim and perilesional tissues) and at the individual lesion voxel level. RESULTS: At the whole lesion level, significant treatment effects were seen in GM but not WM lesions. Voxel-level analyses detected significant treatment effects in WM lesion voxels with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesional voxels, suggesting that treatment effects were lower near CSF spaces. Finally, larger treatment effects were seen in the outer and surrounding components of GM lesions compared to inner cores. INTERPRETATION: Remyelination varies markedly within and between lesions. The greater remyelinating effect in GM lesions is congruent with neuropathological observations. For future remyelination trials, whole GM lesion measures require less complex post-processing compared to WM lesions (which require voxel level analyses) and markedly reduce sample sizes.

Description

Funder: MS Society of the United Kingdom


Funder: NIHR UCLH Biomedical Research Centre


Funder: UCL


Funder: University College London


Funder: NIHR


Funder: Thorne Family Foundation


Funder: Adeslon Medical Research Foundation

Keywords

Bexarotene, Brain, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Remyelination

Journal Title

Ann Clin Transl Neurol

Conference Name

Journal ISSN

2328-9503
2328-9503

Volume Title

9

Publisher

Wiley
Sponsorship
Wellcome Trust (105924/Z/14/Z)
Wellcome Trust (105924/Z/14/Z)
Wellcome Trust (105924/Z/14/A)
Wellcome Trust (105924/Z/14/A)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (MR/N013255/1)