Headlining Current Advances and Challenges in Multiple Sclerosis Care

The treatment landscape for multiple sclerosis (MS) has changed considerably over the past several decades, with the availability of high-efficacy disease-modifying therapies (DMTs) allowing clinicians to better control inflammatory disease activity and reduce relapses. Despite these advances, significant unmet needs remain, particularly in progressive MS and the development of treatments capable of preventing or reversing neurological damage. As a result, improving the ability to identify and monitor disease progression has become an important focus of ongoing research and clinical care.

Advances in imaging and blood-based biomarkers are also providing clinicians with additional tools to evaluate disease activity and treatment response. Although MRI remains the primary imaging tool for monitoring MS, biomarkers such as neurofilament light (NfL) are becoming more accessible, while glial fibrillary acidic protein (GFAP) is being investigated for its potential to better reflect disease progression. At the same time, emerging therapeutic approaches, including Bruton tyrosine kinase (BTK) inhibitors, are generating interest for their potential to target mechanisms of disease activity within the central nervous system.

At the 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto2026), held October 21-23, NeurologyLive spoke with Robert Bermel, MD, director of the Mellen Center for Multiple Sclerosis at Cleveland Clinic, about the current state of MS treatment and the challenges that remain in managing long-term disease progression. In this Q&A, Bermel discusses considerations when selecting DMTs, the limitations of current monitoring approaches, advances in biomarkers, and emerging therapies that may help address some of the remaining unmet needs in MS care.

NeurologyLive: Could you provide an overview of the current MS treatment landscape and how the approach to managing the disease has evolved in recent years?

Robert Bermel, MD: We're doing amazing things in MS. Right now, we have the ability to control the inflammatory component of the disease and the relapsing component better than we ever have before, and in a very safe way. That's largely been the product of high-efficacy therapies, such as B-cell-depleting therapies and others that we have access to.

For patients with MS these days, it's a dramatically different landscape than it was 10 to 20 years ago. This dawn of high-efficacy therapies has been exciting. That being said, we still have an incredible unmet need in progressive MS. Of course, trying to restore neurological function or repair damage would be the holy grail of neurological research.

When clinicians are considering placing patients on a DMT, what factors should they assess before selecting a treatment?

Every patient is an individual, and everyone is affected differently by MS. MS is also a very heterogeneous disease, so these conversations deserve a one-on-one approach between a patient and their provider.

Providers should be considering things like how long the patient has had the disease, how old they are, how active the disease has been, and what else is going on in the patient's life. Do they have other medical comorbidities? Is pregnancy on the horizon? Is this someone in their childbearing years? All of these things should play a very prominent role in the selection of a disease-modifying therapy.

What would you say are some of the biggest remaining challenges in MS care today, particularly when it comes to managing disease progression?

We do a wonderful job preventing new lesions, preventing MS relapses, and controlling the inflammatory biology. But despite that, I still walk into many exam rooms in my clinic and tell a patient, "Hey, good news, your MRI is stable." And they sort of stare back at me and say, "Well, if that's the case, then why am I getting worse?"

We have a couple of big unmet needs. One is better monitoring of patients. MRI has been the standard way to monitor patients, but our standard MRI sequences, at least the ones we use clinically, clearly don't have correlates that track in real time with progression.We would love either an imaging biomarker or a blood biomarker that would help us identify markers of progression in MS. That's the first need: the ability to monitor people a little more closely.

The neurological examination is not very sensitive for monitoring progression, either.Some clinical testing can help us monitor patients. This often comes in the form of quantitative testing, such as timed 6-minute walk tests, timed 25-foot walk tests, and 9-hole peg tests. Quantitatively monitoring our patients can help us assess whether they are stable or progressing over time.

Then we need therapeutic options to meet that need. We're hopeful that if we can monitor patients and identify who might be a candidate for clinical trials and eventually treatments, we can address that need with therapies that target different mechanisms and do so safely to stop the progression of disability. We would love to get to a point where we're reversing that disability with myelination or repair therapies. I think that's further on the horizon, but it's what we're all trying to get to.

How are advances in biomarkers, imaging, and other assessment tools changing the way clinicians evaluate disease activity and treatment response in MS?

MRI is definitely the most used biomarker. It's an imaging biomarker that's used around the world to monitor patients with MS. We monitor new T2 lesion formation and gadolinium-enhancing lesion formation, both in our clinical trials and in our patients.

However, a new liquid biomarker called neurofilament light [chain] (NfL) is becoming much more widely available and accessible to patients. It's a measure of nerve cell breakdown that can happen for any reason. In MS, one of the major reasons neurofilament levels go up is inflammatory disease activity.

We can monitor the blood biomarker NfL, which is now available in almost all hospital systems, to evaluate our patients for recent disease activity. The blood test essentially measures back 3 months. You could conceivably obtain this measure more frequently in patients or in settings where it's difficult to obtain an MRI, and it could give you an idea about inflammatory disease activity. 

We're looking for blood biomarkers that track with progressive MS, or what we call progression independent of relapse activity. That's been more elusive. One candidate on the near-term horizon is GFAP, which is being investigated for its potential to relate better to rates of progression in real time.

Looking ahead over the next 3 to 5 years, what emerging research or therapeutic developments are you most excited about?

At MSToronto2026, we've just heard exciting results about a class of compounds that I think are on the near-term horizon for MS: BTK inhibitors, or Bruton tyrosine kinase inhibitors.They're oral therapies that modulate the immune system without depleting cells.

Additionally, they have a mechanism of action that, because they're small molecules and because of the doses being used for MS, allows them to penetrate the central nervous system. They might have new ways to modulate parts of the immune system that were previously off-limits to us or that we couldn't reach with peripheral B-cell-depleting therapies.

BTK inhibitors are particularly exciting because they can access that compartment of immune cells, including microglia and CNS-resident B cells, that we've not been able to touch before.

We're hopeful that this will influence progression. At least with the first few BTK inhibitors we've seen that the clinical trial results do look like they have beneficial effects on both relapsing biology and disease disability progression. That's very encouraging, and we're hopeful that we're going to get access to those therapies for use in clinical patients.

Is there anything else about the current research landscape or clinical management of MS that you would like clinicians to take away?

I would say that the MS community is really a trailblazing community for therapeutics in neurological disease. I think the constituents of this community, including neurologists and patients around the world, have led to an incredible evolution of developments.

We're hopeful that what we've learned about how to bring a community together, develop phase II outcome measures for trials, and test new therapies in MS can translate into other neurological diseases. We would love for disease-modifying therapies in Parkinson disease, for instance, and better disease-modifying therapies in Alzheimer disease to come about because of that progress.

Being an MS neurologist these days is somewhat gratifying because you can honestly sit in a room with a patient and, in good conscience, tell them, "We're not going to let you end up in a wheelchair." I think that's largely the result of clinical trials and the betterunderstanding of the disease process that we've gained over the last 30 years.

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