Clinical Trials & Remyelination
(Cunniffe Group)
Our research mission focusses on preventing and reversing disability in people living with multiple sclerosis. We lead groundbreaking research in the field of remyelination, dedicated to repairing the nervous system and improving the lives of individuals affected by demyelinating disorders. We therefore conduct drug trials of remyelination-promoting drugs, and conduct clinical studies to better understand the reasons people with MS fail to repair the damage done by the disease.
Meet the Group
Learn a little more about each member of the Remyelination group by clicking on their profile picture below.
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Publications
The Lancet Neurology
Volume 20, Issue 9, September 2021
Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study
Preliminary research has suggested that agonists of the retinoic acid receptor RXR-gamma may promote remyelination, making them a potential therapeutic target for multiple sclerosis. Bexarotene, a non-selective RXR agonist that is approved for the treatment of cutaneous T-cell lymphoma (CTCL), was evaluated in a clinical trial involving 52 participants with relapsing-remitting multiple sclerosis (RRMS) to assess its safety and efficacy. The primary safety outcomes were the number of adverse events and withdrawals attributable to bexarotene, while the primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio (MTR). All participants receiving bexarotene developed central hyperthyroidism, and most also experienced hypertriglyceridaemia, indicating poor tolerability. Furthermore, there was no significant difference in MTR between the bexarotene and placebo groups, demonstrating a lack of efficacy. Based on these findings, bexarotene is not recommended for the treatment of multiple sclerosis due to its poor tolerability and failure to achieve its primary efficacy outcome.
Multiple Sclerosis and Related Disorders
Volume 103, November 2025
Serum neurofilament light chain levels suggest neuroprotection following bexarotene-induced remyelination in people with relapsing remitting multiple sclerosis
Although the CCMR-One trial highlighted that treatment with bexarotene promoted remyelination in people living with multiple sclerosis, it was unclear whether there was an added neuroprotective benefit. To investigate this, a biomarker sub-study was performed, where serum neurofilament light chain (sNfL), glial fibrillary acidic protein (GFAP), total tau and C-terminal hydrolase L1 (UCHL1) were measured at baseline and 6 months in 27 participants (15 from the bexarotene arm, 12 from the placebo arm). While no overall differences in biomarker changes were observed between the bexarotene and placebo groups, a significant relationship emerged in participants with evidence of prior demyelination, defined by prolonged baseline VEP latency. In this subgroup, improvements in VEP latency following bexarotene treatment were associated with reductions in sNfL, whereas no such association was seen with placebo. From these findings, we concluded that bexarotene-induced remyelination was associated with reduced sNfL in individuals with prior demyelination, suggesting a potential neuroprotective effect.
Multiple Sclerosis Journal
Volume 30, Issue 8, July 2024
Bexarotene leads to durable improvements in visual evoked potential latency: A follow-up study of the Cambridge Centre for Myelin Repair One trial
The Cambridge Centre for Myelin Repair One (CCMR-One) trial previously demonstrated that 6 months of bexarotene treatment reduced visual evoked potential (VEP) latency in people with relapsing-remitting multiple sclerosis, consistent with remyelination. Although multiple studies have now shown remyelination is possible, the long-term impacts of a relatively short dosing protocol are unclear. In this follow-up study, 20 participants (12 originally assigned to bexarotene and 8 to placebo) were followed up on average 27 months after their involvement in the trial and underwent full-field VEP and clinical assessments. The results showed a sustained and significant decrease in P100 latency in the bexarotene group compared with placebo. From these findings, we concluded that there were durable improvements in VEP latency, suggesting long-term benefits from exposure to a remyelinating drug.
Trials
Volume 26, Article 562, December 2025
The Cambridge Centre for Myelin Repair trial Two (CCMR Two): a trial protocol for a phase 2a, randomised, double-blind, placebo-controlled clinical trial of the ability of the combination of metformin and clemastine to promote remyelination in people with relapsing-remitting multiple sclerosis already on disease-modifying therapy
The Cambridge Centre for Myelin Repair Two (CCMR-Two) trial was designed to evaluate whether the combination of metformin and clemastine can enhance remyelination in people with relapsing-remitting multiple sclerosis. Building on preclinical evidence that metformin restores the responsiveness of ageing oligodendrocyte progenitor cells to pro-remyelinating signals, this study combines metformin with clemastine, a drug previously shown to promote oligodendrocyte differentiation. In this randomised, placebo-controlled trial, 70 participants with chronic stable optic neuropathy received either active treatment or placebo for 24 weeks. The primary endpoint was change in visual evoked potential (VEP) P100 latency, a sensitive measure of myelin repair, with secondary outcomes including multifocal VEP and lesion magnetisation transfer ratio (MTR). The study was designed to detect both functional and structural evidence of remyelination within a feasible single-centre clinical trial framework. This article outlines the full protocol used for the trial.
Click on the paper titles below to view the key publications to which members of the Clinical Trials and Remyelination group have contributed.
Visual outcome measures in clinical trials of remyelinating drugs
Remyelination varies between and within lesions in multiple sclerosis following bexarotene
Seeing is believing: Identifying remyelination in the central nervous system
Remyelination in humans due to a retinoid-X receptor agonist is age-dependent
Promoting remyelination in multiple sclerosis
Books
Carpenter’s neurophysiology: a conceptual approach (6th ed.)