Evidence of Remyelination Seen in People with MS Receiving Combination Therapy
Combined treatment with metformin, a biguanide used to treat diabetes mellitus type 2, and clemastine, a antihistamine, may promote myelin repair in people with multiple sclerosis, according to results of the phase 2 CCMR-Two clinical trial (NCT05131828) presented at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The data demonstrated statistically significant improvements in biomarkers of remyelination associated with the combined therapy, although there was no evidence of improvement in visual function or disability within the study period. The authors note that the results support longer-term participant follow-up and subsequent studies to assess potential long-term benefits.
CCMR-Two, conducted at the University of Cambridge, included 67 participants with relapsing-remitting MS who had stable disease on a disease-modifying therapy, were randomized to receive metformin 1 g + clemastine 5.46 mg twice daily or placebo, and completed 6 months of treatment. Eligible participants were aged 25 to 50 years, had an Expanded Disability Status Scale (EDSS) score of ≤6.0, and evidence of chronic optic neuropathy. The primary end point was change in visual evoked potential (VEP) latency, with secondary outcomes including multifocal VEP and MRI-based assessments of lesion characteristics. A lower VEP latency value indicates quicker electrical signal transmission, suggesting remyelination.
Key results included the following:
- Active combination therapy was associated with a 1.2 ms reduction in average VEP latency compared with placebo.
- No significant differences were observed in measures of disability, visual function, or overall MRI outcomes.
- MRI analyses showed evidence that remyelination was more likely for lesions with less severe myelin damage.
- Safety was consistent with known profiles of both drugs; 3 participants discontinued due to sedation or consent withdrawal, and common adverse events included fatigue, sedation, and gastrointestinal symptoms.
Sources: Cunniffe NG, Riboni-Verri G, McMurran C, et al. Evaluating the remyelinating efficacy and safety of the combination of metformin and clemastine in people with relapsing remitting multiple sclerosis (CCMR-Two CCMR-Two): a randomised, placebo-controlled, double-blind, phase 2 clinical trial. Abstract presented at: ECTRIMS 2025; September 26, 2025; Barcelona, Spain. Scientific Session 17. Abstract Number 152/O133. https://distribute.congrex.com/from.storage?image=rqetJOF1YXChDh_STAPoNnO6APeYzzgPQ8C4nePGLLAZp9mv8VNxL9zwlyGAqKB30
Wexler M. ECTRIMS 2025: drug combo shows promise for myelin repair in trial. Multiple Sclerosis News Today. Published September 30, 2025. Accessed October 2, 2025. https://multiplesclerosisnewstoday.com/ectrims/2025/09/30/ectrims-2025-drug-combo-shows-promise-myelin-repair/