Here are additional results from a study with Bexarotene, which suggest some success. However, the trial is viewed as a failure. This is because the intended outcome aim wasn’t seen. You have to define this before the trialfinshes to stop you picking and choosing the positive outcome. However, it bodes better for the next study. However, Bexarotene is unlikely to be developed because it induces poorly tolerated side effects
Brown JWL, Prados F, Altmann DR, Kanber B, Stutters J, Cunniffe NG, Jones JL, Georgieva ZG, Needham EJ, Daruwalla C, Wheeler-Kingshott CG, Connick P, Chandran S, Franklin R, MacManus D, Samson R, Coles A, Chard D. Remyelination varies between and within lesions in multiple sclerosis following bexarotene. Ann Clin Transl Neurol. 2022 Sep 17. doi: 10.1002/acn3.51662.
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….Analyses detected significant treatment effects in WM lesions with the lowest baseline MTR, and uncovered gradients of treatment effect in both WM and CGM lesions, 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 and markedly reduce sample sizes.