From new treatment targets and trial designs to broader inclusion and predictive biomarkers, MS research is entering a new era focused on progression, precision, and quality of life.
For many years, the research discussion about multiple sclerosis (MS) centered on two numbers: how often relapses happen, and what shows up on MRI scans.
Those markers helped clinicians track disease activity and guided how treatment decisions were made. But for a large share of people living with MS, those numbers never fully captured the daily reality — especially the subtle, steady changes that can add up over time.
Today, research teams are asking different questions. How can progression be slowed even when relapses aren’t happening? What tools can better predict future MS activity? How can studies reflect the diversity of people living with MS — including older adults, those with higher levels of disability, different ethnic and racial groups, and women’s health needs across menopause, pregnancy, and the postpartum period?
That broader focus isn’t an abstract shift. It’s aimed at the things that matter most to daily life: preserving independence, protecting cognition and function, and improving overall quality of life.
In practical terms, that means care tailored to the individual — less about counting new lesions, and more about sustaining what people can do, how they feel, and how they thrive. In terms of the ongoing focus of MS research efforts around the world, it also means earlier diagnosis, more inclusive study designs, and new endpoints that track function and progression over time.
In this issue of InforMS, we’ll explore some of the efforts leading us in this direction, and real-world examples of what this shift means. We’ll also take a look at how this applies at the grassroots level, through the lens of research at the Rocky Mountain MS Center at University of Colorado. And we’ll talk to a participant in recent research studies to see what taking an active role in furthering MS science can look like from a patient’s perspective.
How and Why MS Research is Evolving
Tracking relapses and MRI activity are still important components of MS care, and they’re not going anywhere any time soon. But what’s new is the growing understanding that they don’t always tell the whole story — particularly for people whose disability accumulates slowly.
Researchers now refer to Progression Independent of Relapse Activity (PIRA): the gradual worsening that happens even without acute attacks. PIRA acknowledges the reality many people describe — fewer flare-ups, yet more difficulty with walking distance, hand dexterity, or mental stamina over the years. PIRA was developed to look at progression within clinical trials, and it is helping us to understand the contribution of progression to the disability accumulation that occurs in patients with MS.
PIRA also helps illustrate the adapting understanding of MS as a spectrum, rather than a collection of distinct disease states. We’ve traditionally referred to MS as a series of types — relapsing-remitting, primary-progressive, or secondary-progressive forms — but we’re moving toward thinking of it as a spectrum of manifestations of the same disease, changing from person to person and over time.
That shift in focus isn’t just reshaping how we talk about MS – it’s having a real impact on the way MS studies are designed. More and more, studies are looking at functional measures that reflect a patient’s daily life.
One notable example is a study called ORATORIO-HAND, which emphasized upper limb function — something that’s been often overlooked in other studies. The study showed that ocrelizumab (branded Ocrevus) significantly slowed disability progression and the worsening of hand and arm function, compared to a placebo.
In the past, such studies commonly relied solely on the Expanded Disability Status Scale (EDSS) – a 1 to 10 scale that measures walking, speed and balance. Of course, hand and arm ability can be just as critical to independence as walking, so researchers added a 9-Hole Peg test to measure hand dexterity.
This shift in focus may seem minor, but it represents researchers looking more holistically at the impacts of MS disease modifying therapies and the experience of those living with the disease.
Other endpoints appearing more often include timed walking tests, other dexterity tests, patient-reported outcomes (fatigue, cognition, mood), and tests that combine several of these measures. This broader toolkit helps researchers measure what matters — and helps people with MS and their care teams make decisions based on function and quality of life, not just MRI activity and relapses.
Who Gets Studied Is Changing: Older Adults, Higher Disability, Racial and Ethnic Diversity, and Real-World Needs
A major concern in MS research has been whether study participants look like the real community. Historically, many trials enrolled younger adults with lower disability. That is slowly changing.
Studies like ORATORIO-HAND, mentioned above, included study participants up to 65 years of age, and people who scored up to 8.0 on the EDSS scale, indicating they were already experiencing significant disability and could be almost entirely dependent on a wheelchair. Both of these populations represent people who’ve not always been included in similar studies in the past.
CHIMES is a study that was specifically deisgned to evaluate the efficacy and safety of ocrelizumab in Black and Hispanic/Latino people with MS. The study results, reported in “Analysis of Efficacy and Safety Data from Black/African American and Hispanic/Latino People with Relapsing MS” (Neurology, April 9, 2024), were consistent with prior studies, but were still significant in that these groups were underrepresented in prior studies.
Another study was aimed specifically at measuring a particular DMT’s impact on older adults living with MS. “Real-world Experience with Cladribine Tablets in the MSBase Registry” (Neurology, April 13, 2021) looked at people over the age of 50. Cladribine (branded Mavenclad) was shown to have low average relapse and disability progression rates in this older population, representing people who’ve typically been left out of such research.
Limiting studies by age – for example, the once-common practice of only including participants up to age 55 – leaves a gap in real-world data, and can make it hard for doctors and their older patients to make informed treatment decisions. Results from studies like this cladribine study can give critical insights into what might be the best path forward for older adults. For context, the average age of a patient with MS at the Rocky Mountain MS Center at CU is just under 50 years old.
Late-Onset MS: Tailoring Treatment to the Over-50 Experience
Another longstanding gap involves late-onset MS — people whose first symptoms appear at age 50 or later. MS often presents differently in those who are diagnosed later in life: they can experience lower relapse rates, slower MRI activity, and more steady progression compared to younger onset. That often changes the risk–benefit equation for therapies, especially when age-related comorbidities come into play.
“Effectiveness of disease-modifying therapies in patients with late-onset relapsing-remitting MS” (Neurology, Aug. 26, 2025) is one study that looked specifically at late-onset groups. Analyses have suggested that disease-modifying therapies (DMTs) can reduce relapse risk and MRI activity in people who’ve developed MS later in life, even though the effect on disability progression may be more modest than in younger patients.
Clinically, that means treatment decisions may prioritize safety, tolerability, and quality of life alongside efficacy, and that rehabilitation, fall prevention, and cognitive support take on a larger role.
A related question many older adults ask is whether to continue therapy after years of stability. While individual decisions vary, ongoing work on discontinuation in older populations — including the Rocky Mountain MS Center-led DISCO-MS study (see “The Evolving Research of Discontinuing DMTs” in this issue of InforMS) — emphasizes weighing relapse risk, MRI activity, and disease trajectory. The key takeaway is that treatment plans should be tailored to each individual, and adapt over time — sometimes continuing, sometimes deescalating, and sometimes pausing under close monitoring.
Women’s Health: Menopause, Pregnancy, and the Postpartum Period
For years, questions about how life stages affect MS — especially menopause and pregnancy — didn’t have clear answers. That’s changing, thanks to new research that helps guide real-world decisions.
Many people wonder whether menopause accelerates MS. The largest study to date, “Menopause Impact on Multiple Sclerosis Disability Progression” (JAMA Neurology, Sept. 29, 2025), offers some reassurance: researchers found no direct link between menopause and faster disability progression. In other words, changes that happen around age 50 seem more related to natural aging and disease duration than to menopause itself.
That said, menopause can still bring challenges — like sleep disruption, hot flashes, and mood changes — that affect quality of life. Addressing these symptoms matters, even if they don’t drive MS progression. Talk with your care team about strategies for sleep, hormone management, and mental health support during this transition.
Family planning often raises tough questions that aren’t always answered in routine clinical trials. Recent Phase IV studies — MINORE, looking at infants exposure to ocrelizumab during pregnancy, and SOPRANINO, looking at exposure through breastmilk — provide encouraging news. Results showed minimal transfer to infants, no impact on infant immune function, and normal vaccine responses in infants.
While these findings are reassuring, decisions still need to be considered individually. Timing treatment around conception, coordinating with obstetric care, and monitoring infants remain essential steps. But the growing evidence base means families can make choices with more confidence and less uncertainty.
Predicting Future Disability: Imaging, Biomarkers, and Functional Tests
It wasn’t always the case, but we’ve now known for a long time that early and effective treatment is ideal in MS. Research is moving toward developing tools to predict future disability, in the hopes of giving clinicians and patients a chance to act even sooner.
From advanced imaging techniques to blood-based biomarkers and practical functional tests, these innovations aim to make MS care more proactive and personalized. Some of the tools leading this charge include:
- Paramagnetic rim lesions (PRLs), sometimes called iron rim lesions, are MRI features that may reflect chronic active plaques with smoldering inflammation. Updated diagnostic thinking highlighted at ECTRIMS and in clinical reporting suggests PRLs, the central vein sign, and kappa free light chains may support earlier and more accurate diagnosis for some patients, while also informing risk stratification. These markers were added to the new diagnostic criteria that were recently published.
- Grey matter atrophy measured on MRIs correlates with cognitive change and may forecast PIRA, according to findings published in “Gray matter atrophy predicts Progression Independent of Relapse Activity [PIRA]” (Multiple Sclerosis Journal, ECTRIMS 2025 Supplement, P1937, Sept. 23, 2025). Researchers concluded that PIRA events were common within the first five years after a demyelinating event is seen on MRI, and that neurodegeneration is a key contributor to early disability accumulation in MS.
- Functional tests such as the Six-Minute Walk Test, dexterity tests and others help show the real life experience of people living with MS. These practical tools used in routine visits can track mobility, hand function, and day-to-day performance, allowing your MS care team to see what’s really impacting your life, rather than relying on annual MRI reports.
- Biomarkers in blood (such as neurofilament light chain, or NfL) can serve as indicators of axonal damage, and if they’re shown to be reliable, could make simple blood tests an important part of diagnosing and managing MS. NfL measurement is being integrated into studies and observational cohorts to monitor activity and guide treatment decisions.
Taken together, these tools aim to anticipate where MS is heading for a given person. The real promise is better timing — earlier treatment, targeted rehabilitation, and brain health strategies (sleep, exercise, stress management) that can cushion the path and build resilience long before disability begins to set in.
What’s Next: Repair and Remyelination
Beyond slowing MS, researchers are beginning to take aim at repair — especially remyelination, the process of restoring the myelin that insulates nerve fibers. A Cambridge University study called CCMR-Two combines clemastine (an antihistamine) with metformin (a diabetes medicine) to target mechanisms that could accelerate myelin repair. Early results are promising, suggesting improved nerve conduction after several months in people with relapsing MS. However, patients weren’t able to notice a clinical improvement. This remains experimental and requires a lot more study before practical applications are developed.
Studies like CCMR-Two have a long way to go, but signal a future where the goals of MS care include restoring function, not only preventing loss.
Conclusion: Precision, Progression, and Real Life Impact
MS research is changing in ways that put patients closer to the forefront than ever before. The focus is shifting from counting relapses to slowing progression, from narrow trial groups to inclusive designs, and from reacting to predicting.
For people living with MS, these advances are not just scientific milestones — they’re practical steps toward protecting independence, sustaining function, and living well. Evidence-based hope means more choices, better timing, and care that sees the whole person. That is the horizon the MS community is pushing toward, one careful study and one daily choice at a time.
