Serum neurofilament light chain levels suggest neuroprotection following bexarotene-induced remyelination in people with relapsing remitting multiple sclerosis

BACKGROUND: Remyelination offers a potential neuroprotective strategy in multiple sclerosis (MS). In the Cambridge Centre of Myelin Repair One (CCMR-One) trial, bexarotene, an RXR agonist, promoted remyelination in people with MS, evidenced through a reduction in the latency of the full-field visual evoked potential (VEP). However, it remained uncertain whether bexarotene additionally promoted neuroprotection. METHODS: We conducted a sub-study of the Cambridge-based (n = 31) participants of the CCMR-One trial. Participants were aged 18-50 years, had baseline EDSS 0-6.0 and had been stable on dimethyl fumarate for at least 6 months. Consenting participants contributed serum samples at baseline and month 6, which were analysed for neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total Tau protein (Tau), and C-terminal hydrolase L1 (UCHL1). The change in serum biomarker values and their associations with changes in VEP latency were assessed using linear models adjusted for age, sex, EDSS, disease duration and baseline biomarker levels. RESULTS: 27 participants consented to provide blood samples (15 bexarotene, 12 placebo). There were no significant differences in biomarker change between these groups. However, a significant interaction was observed between treatment group and sNfL change (p = 0.001) among those with prolonged baseline VEP latency (≥118 ms). In the bexarotene group, latency improvement was associated with a reduction in sNfL (β = 23.4 ms per logpg/mL decrease; 95 % CI 11.1 to 36.2); this relationship was not seen in the placebo group. CONCLUSIONS: Bexarotene-induced remyelination was associated with reduced sNfL in individuals with prior demyelination, suggesting a potential neuroprotective effect.