Myelin Repair Research in MS: Lessons From Clinical Trials and the Road Ahead

Although advances in disease-modifying therapies (DMTs) have substantially improved the management of multiple sclerosis (MS), preventing inflammatory disease activity and addressing long-term disability progression remain distinct challenges. Remyelination represents an important area of ongoing research, with the potential to restore damaged nerve fibers and help preserve neurological function. Over the past decade, several proof-of-concept clinical trials have investigated approaches to promoting myelin repair in people with MS, providing early evidence that the process may be achievable in humans.

Despite encouraging findings, translating biological evidence of remyelination into meaningful clinical benefits remains a major challenge. Investigators continue to evaluate how best to measure treatment effects, identify patients most likely to benefit, and determine how long participants need to be followed to capture meaningful outcomes. These considerations are particularly important given that some measures of myelin repair may demonstrate changes over relatively short periods, while the potential clinical benefits of neuroprotection may take years to emerge.

At the 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto2026), held October 21-23 in Toronto, Canada,NeurologyLive spoke with Nick Cunniffe, MD, PHD, assistant professor and consultant neurologist at the University of Cambridge in the United Kingdom, about lessons from the past decade of myelin repair trials in MS. In the interview, Cunniffe discusses the challenges of measuring remyelination, considerations for clinical trial design and participant selection, and emerging approaches that could improve the development of remyelinating therapies over the next several years.

NeurologyLive: Could you provide an overview of your talk and some of the key lessons learned from proof-of-concept clinical trials investigating myelin repair in MS?

Nick Cunniffe, MD, PHD: My talk was about the different proof-of-concept clinical trials. Essentially, I'm discussing a series of reflections on the last decade of myelin repair trials that have been conducted. These include not just the 2 trials that I conducted in Cambridge, but also the key lessons that emerge when you consider all of the different trials undertaken to date.

What I try to present in my talk is a series of key lessons and reflections on what's been done to date, what we've done well, and what we could try to improve in the future.

What have been some of the biggest challenges in demonstrating myelin repair in people with MS through these clinical trials?

The first thing I would really emphasize is that we should be encouraged by the trials undertaken so far because we've now seen across several clinical trials that myelin repair in people with MS is achievable. However, we have to stay grounded because we haven't yet seen a real clinical impact from these treatments.

One of the main challenges is measurement. What we're trying to do at the moment is demonstrate that our drugs are having a biological effect over short-duration trials. The ways we can do that are either by deploying a test of nerve function, such as looking at the latency of the visual evoked potential (VEP), because as you promote myelin repair, that latency gets shorter.

Alternatively, you can look at a test of nerve structure, such as applying a myelin-sensitive MRI sequence. Those approaches have been used with varying degrees of success over the last 10 years.The challenge is translating those findings into a clinically important and meaningful impact for our patients and trial participants. While we've seen signals on those early measures, translating that into long-term benefit is the next step we need to make.

Based on the trials conducted to date, what have you learned about clinical trial design, particularly regarding outcome measures, participant selection, and the timing of assessments?

There are 3 key lessons that I discuss in my talk. The first is around outcome measures, which we've already discussed. I think the key thing we've learned is that visual outcome measures are highly sensitive to detecting a remyelination effect over a short-duration trial. Leading the way at the moment appears to be the change in full-field VEP latency, because that has shown statistically significant effects across clinical trials to date.

The second key lesson pertaining to clinical trial design is participant selection. This is important because a remyelinating treatment requires abundant axons, or nerve fibers, that are there and ready to be repaired. In more advanced MS, more nerve fibers have degenerated because they've been left without myelin for too long.

That's not to say our drugs won't work in people with progressive or more advanced MS, but they probably won't be as effective or as easy to measure. One reflection I have from conducting proof-of-concept trials is that the effect is most likely greatest and easier to measure in people early in their MS journey. Perhaps that's the first cohort we should be testing to get a go/no-go signal for a drug and determine whether it promotes a benefit before extending it to those people whose need is greatest, where the drug may not be as effective but could still be meaningful.

The third point, in addition to outcome measure and participant selection, comes down to when we measure the benefit to someone. The key consideration there is duration because what we're trying to promote is axonal protection, and that emerges over years, not short periods of months.I think it'simportant that when we conduct these trials, if they are short in duration, we capture that long-term information 3 to 5 years later. Alternatively, being bold and conducting longer-term trials will be important as well.

Looking ahead, what developments in myelin repair research are you most excited about, and where do you see the field heading over the next several years?

I think the reason I'm excited is that we're seeing consistent signals from several different trials that remyelination in people is achievable. So far, we're doing the best we can with repurposed medications, or drugs that were designed for other reasons but that we think are important for stimulating oligodendrocyte precursor cells (OPCs) to make more of themselves and promote myelin repair.

As I said, that has been successful to date. I think what's going to be important going forward is using novel drugs that have been targeted specifically for this process, which may be more potent while also being tolerable and safe. In terms of where things might go next, I'm really excited to see novel drugs coming through.

I'm also really excited by some of the work around new and novel outcome measures. We may have more sensitive electrophysiological measures of myelin repair, as well as other biomarkers, including blood biomarkers. Being able to detect signatures of myelin repair occurring in the brain through the blood in the periphery would be a fantastic advance.

Improving myelin imaging is also important. Being able to stratify MS lesions according to how amenable they are to repair, and using that as a way of quantifying myelin recovery, could be important. I think that's how we're going to conduct better trials with more potent drugs. 

Ultimately, it's about demonstrating the long-term benefits of a remyelinating drug. That's the thing I'm most excited about.

Is there anything else about the future of myelin repair research or its potential role in MS treatment that you would like clinicians to take away?

I think it's an exciting time to be working in myelin repair research because we're getting some positive signals from clinical trials. We're also at this exciting stage where we're testing new drugs with better outcome measures and looking at the long term, with the ultimate goal of scaling these approaches to people affected by MS.

The key unmet need for people with MS is, of course, drugs that can delay or prevent disability progression. I absolutely feel that remyelinating therapy is going to be part of that strategy. It would be great if we had optimized disease-modifying treatments and neuroprotective treatments starting to emerge alongside our remyelinating therapies.I think it's an exciting time to be part of myelin repair research, and the next 5 to 10 years will be really exciting.

Transcript edited for clarity. For more MSToronto coverage, click here.