DMTs are necessary, even transformative. They are just not enough.

Why MS care needs a prevention revolution — and why now.

She had done everything right.

Diagnosed with relapsing-remitting MS in her late thirties, she started a disease-modifying therapy promptly and stayed on it. Over the years she moved to a more potent agent, and by the time I saw her in clinic in her mid-fifties, her inflammation was well-controlled. No recent relapses, stable MRI. On paper, a treatment success.

But she wasn’t doing well.

Over the previous two years she had developed progressive cognitive difficulties: word-finding problems, memory lapses, trouble concentrating at work. She had recently quit her job because of it. She also carried a longstanding diagnosis of obstructive sleep apnea that had never been treated, and she had been pre-diabetic for years, a fact that had never quite made it to the center of her MS care. Every visit, she would come back to the same question: her inflammation is controlled. So why is she declining?

Around the same time, her younger sister came to see me. She was 47, had been noticing progressive imbalance and leg weakness for a little over a year, and after a full workup was diagnosed with primary progressive MS. She started on a DMT. As the two of them processed the diagnosis together, they asked the question I imagine many siblings in this situation ask: *could this have been prevented?*

I didn’t have a satisfying answer. But I’m increasingly convinced that we need one and that finding it requires us to rethink what MS care actually is.

The Treatment Decade Has Been Remarkable. And It Has Exposed a Gap.

The past twenty years have delivered a genuine revolution in MS therapeutics. We now have more than twenty approved disease-modifying therapies. The most effective among them reduce relapse rates so significantly that people can now expect to live free of disease activity. For many people living with MS, especially those diagnosed early and started on high-efficacy treatment promptly, the prognosis has changed substantially.

And yet. Disability still accumulates. Cognitive decline still happens, often insidiously, even in people whose MRIs look stable. Quality of life remains significantly impaired for a large proportion of the MS population. And we do not prevent a single case of MS.

The reason, I think, is that we have built an extraordinarily sophisticated system for suppressing one dimension of MS pathology, inflammatory lesion activity, while leaving much of the rest of the disease largely unaddressed. Disease-modifying therapy is necessary, even transformative. For most people living with MS, it should be non-negotiable. But it is only part of the equation. The rest — lifestyle, comorbidities, sleep, mental health — we have treated as someone else’s problem, or no one’s problem, or a problem to be handled later.

That gap between what our best therapies achieve and what our patients actually need is where preventive neurology begins.

What Preventive Neurology Actually Means

The term sounds like it might refer to prevention in the colloquial sense, eating well, exercising, the kind of advice that gets dismissed as obvious or insufficient. It is something more specific and more ambitious than that.

Preventive neurology is the systematic application of evidence-based risk reduction strategies across the full arc of neurological disease before it starts, after diagnosis, and throughout the disease course. It encompasses three distinct tiers.

Primary prevention means preventing MS onset itself: identifying and modifying the risk factors that cause the disease to develop in the first place. This is the newest and perhaps most exciting frontier. The science here has moved rapidly recently. We now know that Epstein-Barr virus infection is essentially a prerequisite for MS, that obesity in adolescence and low vitamin D levels are causally implicated, that smoking meaningfully increases risk. We have the first clinical trials testing whether pharmacological intervention in people with early radiological abnormalities, before any clinical event, can delay or prevent the disease. The possibility of actually preventing MS, which would have seemed fanciful a decade ago, is now a legitimate scientific goal.

Secondary prevention means intervening early after diagnosis to decrease the risk of progression, preserve function, and improve quality of life through means that go beyond DMTs. This includes lifestyle interventions, such as exercise, sleep, diet, smoking cessation that have stronger evidence behind them than most clinicians appreciate. It includes aggressive management of comorbidities like hypertension, diabetes, and depression, which independently accelerate disability in ways that DMTs do not address. It includes treatment of obstructive sleep apnea, which mediates a substantial fraction of cognitive impairment in people living with MS. It is, in short, the comprehensive care that the first patient I described deserved and largely didn’t receive.

Tertiary prevention means minimizing disability and maximizing function in established disease. Cognitive rehabilitation, fall prevention, fatigue management, mental health support. This is not giving up. It is recognizing that there is always something meaningful to preserve or recover, and that the goal of MS care is a full and engaged life, not just a stable MRI.

Why This Conversation Is Happening Now

Several things have converged to bring preventive neurology to the center of MS discourse.

The science has matured. The causal role of EBV in MS confirmed by a landmark 2022 study following over ten million US military personnel has opened the door to genuine primary prevention strategies, including vaccine development.[1] Mendelian randomization studies have strengthened the causal case for vitamin D, obesity, and smoking as MS risk factors, not merely correlates. Large long-term cohort studies have quantified the impact of lifestyle factors on disability trajectories in ways that are clinically meaningful. One recent Swedish study found that high levels of physical activity were associated with a 36% reduction in the risk of confirmed disability worsening over 15 years.[2] Numbers like that are not background noise. They belong in the clinic.

The treatment landscape has also created a new urgency. Precisely because we have become so effective at controlling inflammation, we are now watching a different phenomenon more clearly: disability that accumulates in the absence of clinical relapses, driven by compartmentalized CNS inflammation, neurodegeneration, and the compounding effect of untreated comorbidities. Addressing this, what we now call progression independent of relapse activity, or PIRA, requires tools that go beyond our current DMT armamentarium.

Many people living with MS have been watching the development of BTK inhibitors, a new class of drugs designed to cross the blood-brain barrier and target precisely the smoldering neuroinflammation thought to drive progression, with real hope. That hope has been met with real frustration. Tolebrutinib, the furthest along of the class, showed a meaningful reduction in disability progression in clinical trials, but received a complete response letter from the FDA in December 2025, citing safety and efficacy concerns. Other agents in the class are still in development, and the biology remains compelling but no approved therapy targeting PIRA exists today, and the path to one has proven longer and harder than many anticipated. For people living with progressive disease who have been waiting, that is genuinely difficult news. The feeling of watching the clock while the regulatory process runs its course, of wanting to act but being told there is nothing yet to act on, is one I hear in clinic regularly.

It is partly that frustration that makes preventive neurology so important right now. Because while the pipeline evolves, the evidence for lifestyle interventions, comorbidity management, and behavioral strategies is already here. Exercise, sleep, metabolic health, mental health — these are not consolation prizes. They target overlapping biology. They are actionable today. And for people who want to do something meaningful for their health rather than wait passively, they represent a real and evidence-based way to take control.

And practically speaking, the people most affected by MS are asking for exactly this. They want to be active participants in their own disease management. They want to know what they can do. For too long, our answer has been inadequate: take your medication, come back in six months.

What This Series Is About

Over the next three weeks, I’ll be exploring the prevention revolution in MS in depth.

We’ll look at the primary prevention evidence: what we actually know about preventing MS onset, what the EBV science means for families, and where the most promising clinical trials are heading. We’ll dig into secondary prevention: the lifestyle and comorbidity evidence that should be reshaping how we practice MS neurology right now. And we’ll examine what it takes to actually implement preventive care at scale: what a working model looks like, what the barriers are, and what the field needs to prioritize in the decade ahead.

My aim is to make this series useful for everyone who cares about the future of MS whether you are living with the disease, caring for someone who is, working in the MS space in industry or advocacy, or practicing as a clinician. The evidence belongs to all of you. So does the conversation about what to do with it.

Because one thing I am certain of, after years in this field and after caring for patients like the two sisters I described at the start: the status quo is not good enough. We can do more. The science says we can. The question is whether we will build the care model to make it real.

I believe we will. This series is my attempt to help move that forward.

Next week: Can MS actually be prevented? The evidence on EBV, smoking, vitamin D, obesity — and the challenges of designing trials targeting MS before it starts.

[1] Kjetil Bjornevik et al., Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science375,296-301(2022).DOI:10.1126/science.abj8222

[2] Hedström AK, Olsson T, Piehl F, et al., Beneficial impact of physical activity on multiple sclerosis disability progression. Journal of Neurology, Neurosurgery & Psychiatry 2026;97:209-216. 10.1136/jnnp-2025-336738