"Foamy" Immune Cells May Be Making Multiple Sclerosis Worse

Introduction: a discovery that reshapes how we see multiple sclerosis

A Dutch team uncovers an unsuspected mechanism

A team of researchers in the Netherlands, bringing together the Netherlands Institute for Neuroscience, Leiden University, and Utrecht University, has just published a study in the journal Nature Neuroscience that could upend our understanding of progressive multiple sclerosis. Led by researcher Daan van der Vliet, the scientists identified, in post-mortem brain tissue from patients with secondary progressive MS, an abundance of particular immune cells loaded with fat, which they describe as "foamy" because of their appearance under the microscope.

This discovery, published on May 21, 2026, and bearing the number DOI 10.1038/s41593-026-02302-3, offers a solid lead for explaining why some patients see their disease progress much faster than others, a question that has largely eluded neurologists despite decades of research into this autoimmune disease of the central nervous system.

Why this research deserves attention

Multiple sclerosis affects millions of people worldwide and remains one of the leading causes of neurological disability among young adults. Yet one of the great clinical frustrations of this disease remains the unpredictability of its course: some patients maintain a relatively stable quality of life for decades, while others rapidly slide into progressive disability without medicine being able to clearly explain this divergence.

It is precisely this puzzle that the study by van der Vliet and colleagues attempts to solve, drawing on a multi-omic analysis combining lipidomics, transcriptomics, proteomics, and histology on samples from 250 donors with MS, a sample size that lends notable statistical robustness to the conclusions presented.

What is a "foamy" microglial cell

The normal role of microglia in the brain

To understand this discovery, one must first grasp the role of microglial cells, specialized immune cells residing in the brain and spinal cord. Normally, these cells act as cleanup crews: they clear away cellular debris and remnants of damaged myelin, and actively help repair nerve tissue after injury, an essential protective role for maintaining the health of the central nervous system.

In patients with multiple sclerosis, however, researchers observed that these microglial cells can undergo a radical transformation, absorbing such a large amount of damaged myelin that they end up loaded with lipid droplets, giving them that characteristic "foamy" look observed under the microscope by van der Vliet's team.

A cleanup system that becomes overwhelmed

According to the lead researcher's explanation, these cells "are probably trying to do something good: clean up the damage," but they end up overwhelmed by the amount of material to process, an overload phenomenon that compromises their lysosomes' ability to properly digest debris accumulated over time in active lesions.

This functional overload gradually turns cells that were initially protective into potential drivers of chronic inflammation, a reversal of role that could explain why certain brain lesions keep expanding in some patients instead of healing normally, thereby contributing to the disease's gradual worsening.

The findings of the study published in Nature Neuroscience

A clear correlation with disease severity

The study's central finding is unambiguous: patients showing a high proportion of lesions containing foamy cells experienced, significantly more often, a more severe course of their disease over their lifetime. "We found that patients with a large number of these foamy microglia more frequently had a more severe disease course," explained Daan van der Vliet in a statement from the research institute.

This correlation was established through analysis of 250 donors with MS, where the proportion of lesions containing foamy cells was directly associated with faster progression toward higher disability scores, while lesions lacking this cell type were not associated with rapid disease progression.

A distinct molecular signature identified

Beyond the microscopic observation, the research team identified a precise biochemical signature associated with these lesions: an accumulation of cholesterol esters, bismonoacylglycerophosphates, and above all oxylipins, lipid molecules involved in regulating inflammation and cell-to-cell communication, without, however, showing the classic markers of acute pro-inflammatory activity.

Notably, these lesions also showed increased B-cell infiltration and elevated levels of immunoglobulin G1, suggesting a complex interaction between the innate immunity represented by microglia and adaptive immunity, opening new lines of inquiry into the combined mechanisms involved in MS progression.

MAGL, the enzyme identified as a potential therapeutic target

A key enzyme in lipid metabolism

One of the most promising contributions of this research lies in the identification of monoacylglycerol lipase, better known by its acronym MAGL, an enzyme strongly present in lesions containing foamy cells. This enzyme plays a central role in breaking down lipid molecules into oxylipins, the very molecules researchers found in elevated concentrations in the damaged brain regions of the patients studied.

By identifying this enzyme as a central biochemical actor in the disease process, the team led by Mario van der Stelt, senior lead author of the study and a researcher at Leiden University, opened up a concrete therapeutic path: pharmacologically blocking this enzyme's activity to interrupt the harmful cycle observed in the most severe lesions.

Encouraging results in an animal model

To test this hypothesis, researchers administered a MAGL inhibitor in a mouse model of demyelination, observing signs of neurological repair that are not normally seen in this type of experimental model. This inhibition promoted lesion recovery and reduced microgliosis, meaning the excessive proliferation of microglial cells in damaged brain regions.

These preclinical results, though carried out in mice and not directly transferable to humans, provide important mechanistic support for a phase 2 clinical trial already underway, involving the molecule RO7268489, a MAGL inhibitor being tested in combination with ocrelizumab in patients with progressive forms of MS, under the identifier NCT07282574.

Toward new biomarkers in cerebrospinal fluid

A non-invasive diagnostic lead under study

Another notable advance from this research: the researchers discovered that oxylipin levels measured in patients' cerebrospinal fluid closely correlated with the proportion of foamy lesions present in their brain. This correlation opens the possibility, still to be confirmed by further studies, of using these molecules as biomarkers that could identify, earlier on, patients at risk of rapid progression.

Such a biomarker, if clinically validated, would represent a considerable advance for day-to-day neurological practice, potentially allowing treatments to be adjusted in a more personalized way, even before obvious clinical signs of worsening appear in the patient concerned.

The methodological limits to keep in mind

It should be noted, however, that this correlation, while encouraging, remains at this stage an observation drawn from a specific cohort and requires validation in independent prospective studies before it can be incorporated into the routine clinical practice of neurologists treating patients with progressive MS.

The authors themselves point out, in the publication in Nature Neuroscience, that more work will be needed to determine whether this potential biomarker holds up reliably across different patient populations and different stages of the disease, a methodological caution that speaks to the team's scientific rigor.

What this means for patients with progressive MS

A disease that remains hard to predict day to day

For people living with secondary progressive multiple sclerosis, uncertainty about how their disease will evolve remains one of the heaviest psychological burdens to carry. This new research, while offering no immediate answer, provides a conceptual framework that could eventually help clinicians better anticipate each patient's individual trajectory.

Patient advocacy groups, notably through outlets like Multiple Sclerosis News Today, welcomed this publication, while reminding their readers that no treatment based on this discovery is yet available in routine clinical practice, an essential nuance to avoid any premature false hope among patients already worn down by the disease.

The importance of basic research in chronic diseases

This study also illustrates the crucial importance of basic research in understanding chronic neurological diseases. Without years of methodical work devoted to precisely mapping the cellular and molecular mechanisms of MS, such a precise discovery about the role of foamy cells simply would not have been possible.

Continued funding for basic research, often less publicized than late-stage clinical trials, nonetheless remains the essential foundation on which all future therapeutic advances rest for diseases as complex as multiple sclerosis.

The broader context of multiple sclerosis research

Other recent discoveries that converge

This discovery about foamy cells fits into a particularly active research landscape around progressive multiple sclerosis. Other teams have recently identified radial glial cells associated with the disease, showing signs of premature senescence and heightened reactivity to inflammatory signals, notably interferon, according to work published in the journal Neuron.

Researchers at the University of Geneva, working with teams in Munich, also demonstrated in mice that synapse loss linked to gray-matter inflammation could be reversible, opening another therapeutic avenue complementary to the one explored by van der Vliet's team.

A convergence of leads that fuels measured hope

This accumulation of complementary discoveries, each shedding light on a different aspect of the mechanisms behind progressive MS, is gradually painting a fuller picture of this complex disease, in which several pathological pathways appear to interact simultaneously to determine each patient's clinical trajectory.

This convergence of results coming from several independent laboratories across Europe strengthens the overall scientific credibility of these research leads, each contributing an additional piece to a biological puzzle the international neurological community has been trying to solve for decades.

The stakes of funding and international scientific collaboration

A study made possible by multi-institutional collaboration

Carrying out this study required mobilizing an extensive team, involving researchers from the Netherlands Institute for Neuroscience, Leiden University, Utrecht University, as well as industry partners like Roche, several of whose researchers are among the publication's co-authors, illustrating the growing importance of partnerships between academia and the pharmaceutical industry in modern neurological research.

This collaboration made it possible to combine complementary expertise in lipidomics, neuropathology, and pharmacology, an increasingly necessary multidisciplinary approach for unpacking diseases as complex as multiple sclerosis, where no single discipline can claim to provide a complete answer on its own.

Access to post-mortem brain tissue, an underappreciated challenge

An often-overlooked aspect of this kind of research concerns access to post-mortem brain tissue from MS patients, made possible through specialized brain banks, in this case that of the Netherlands Institute for Neuroscience, which depend entirely on the generosity of donors who agreed during their lifetime to donate their brain tissue to scientific research after death.

Without the generosity of several hundred families and patients, a study involving 250 donors simply could not have happened, an important reminder of the human and altruistic dimension underlying every major scientific advance in the field of neurological disease.

Current MS treatments and their limits against progressive forms

Real progress against relapsing-remitting forms

It's worth remembering that pharmaceutical research over the past twenty years has enabled considerable advances in treating relapsing-remitting forms of multiple sclerosis, with disease-modifying treatments able to significantly reduce the frequency of inflammatory flare-ups in many patients around the world.

However, these same treatments remain largely insufficient against progressive forms of the disease, where classic inflammation gives way to more insidious neurodegenerative mechanisms that are harder to target pharmacologically, which explains the urgency of discoveries like the one about foamy cells in filling this persistent therapeutic gap.

Why the MAGL lead is drawing particular industry interest

It is precisely this therapeutic gap that explains the interest shown by pharmaceutical companies like Roche in the MAGL inhibition lead, an entirely different mechanism of action from the classic immunosuppressants used until now, potentially offering a new therapeutic class for patients who, until now, had very few effective options against the progression of their disability.

The phase 2 clinical trial currently underway with the molecule RO7268489 thus represents a crucial test to determine whether the promise observed in the lab and in animals will actually translate into a measurable clinical benefit for human patients with progressive MS.

The ethical questions raised by post-mortem tissue research

Consent and the dignity of donors

Research on post-mortem brain tissue naturally raises important ethical questions, notably around the informed consent given by patients during their lifetime, and how these donations are handled with dignity and respect by the research institutions entrusted with them, an issue that brain banks like the one in the Netherlands take very seriously in their protocols.

These ethical questions, though rarely at the center of media coverage of this kind of scientific discovery, deserve to be raised regularly to ensure that the legitimate race for therapeutic advances never comes at the expense of the respect owed to people who have donated their bodies to science.

The transparency owed to donor families

The institutions responsible for these tissue banks also bear a responsibility to maintain transparent communication with donor families about how these donations are used, particularly when major discoveries like this one are published in journals as prestigious as Nature Neuroscience.

This transparency helps maintain public trust in scientific research, an essential factor for ensuring the continued supply of brain tissue donations needed to sustain this kind of basic research into neurodegenerative diseases.

Outlook for the next five years of research

Toward more targeted clinical trials

The researchers involved in this study anticipate that the next five years will see the emergence of increasingly targeted clinical trials, drawing on a fine-grained understanding of the lipid mechanisms involved in MS progression, rather than continuing to test generic therapeutic approaches across the entire patient population without regard for individual biological profile.

This precision medicine approach applied to neurology could, if it materializes, profoundly transform how neurologists approach treating progressive multiple sclerosis, selecting treatments based on each patient's specific molecular profile rather than a one-size-fits-all approach.

Measured hope for a therapeutic paradigm shift

If the ongoing clinical trials confirm the preclinical results obtained with MAGL inhibition, this discovery could mark the beginning of a paradigm shift in treating progressive forms of MS, a disease for which effective therapeutic options have remained desperately limited for decades.

Patience will be required, however, as medical research rarely follows a straight, fast path, and patients with progressive MS will likely have to wait several more years before seeing this fundamental discovery translate concretely into new therapeutic options available in the clinic.

What this discovery reveals about the complexity of the human brain

A brain immune system still poorly understood

Beyond its direct clinical implications for multiple sclerosis, this study illustrates just how incompletely the brain's immune system is still understood by modern science, despite decades of research in neuroimmunology. Every new discovery, like this one about foamy microglial cells, reveals an additional layer of complexity that calls for scientific humility.

This humility is, moreover, shared by the researchers themselves, who readily acknowledge that their work probably opens up more new questions than it definitively resolves, an admission of scientific transparency that speaks to the rigor of their methodological approach.

An invitation to keep exploring science

This discovery is, above all, an invitation to continue exploring the human brain, an organ whose fundamental mechanisms are, even in 2026, still being uncovered, a reminder that even in a field as well-studied as neuroimmunology, there remains enormously more for the international scientific community to learn.

This humility in the face of the complexity of living systems should, in my view, encourage policymakers and funding bodies to keep investing heavily in basic neuroscience research, rather than exclusively favoring immediate clinical results at the expense of a deeper mechanistic understanding of disease.

Reactions from the international scientific community

A favorable reception in neuroimmunology circles

The publication of this study in Nature Neuroscience received a largely favorable reception within the international scientific community specializing in neuroimmunology, with several researchers publicly praising the methodological rigor of the multi-omic approach used by the van der Vliet and van der Stelt team.

Institutions such as the UC Davis Institute for Psychedelics and Neurotherapeutics notably relayed this discovery to their professional networks, underscoring the importance of this advance for the overall understanding of progression mechanisms in chronic neurodegenerative diseases, well beyond the specific context of multiple sclerosis.

Calls for replication in other cohorts

As is systematically the case for any major scientific discovery, several voices within the community are now calling for these results to be replicated in other patient cohorts, ideally from other regions of the world, to confirm that the observations made in this Dutch cohort generalize well to the global population living with progressive MS.

This demand for scientific replication, far from being a criticism of the original study, is instead a normal and necessary step in a rigorous scientific process, ensuring that future therapeutic decisions rest on sufficiently solid and generalizable empirical grounds.

Implications for other neurodegenerative diseases

A mechanism potentially transferable to other conditions

Beyond the specific case of multiple sclerosis, the researchers suggest that this mechanism of foamy microglial cells could also play a role in other neurodegenerative diseases characterized by an accumulation of lipid debris in the brain, notably certain forms of dementia or chronic neuroinflammatory diseases still poorly understood by the medical community.

This hypothesis, still largely speculative at this stage, nonetheless opens up a potentially fruitful research field for the entire domain of neuroscience, where understanding cellular lipid mechanisms could become a cross-cutting research theme applicable to several distinct diseases of the central nervous system.

A call for caution against hasty extrapolation

The researchers themselves, however, warn against any hasty extrapolation of their results to other diseases, noting that each neurodegenerative condition has its own specific mechanisms and that multiple sclerosis shows distinct immunological features that don't necessarily carry over to other, different clinical contexts.

This scientific caution, far from being a weakness, is actually a methodological strength that distinguishes rigorous research from sensationalist scientific communication, a balance that van der Vliet's team seems to have managed to maintain throughout this publication.

Conclusion: a measured glimmer of hope for MS patients

A fundamental advance, not yet a treatment

This discovery of foamy microglial cells represents an important fundamental scientific advance in understanding progressive multiple sclerosis, without, at this stage, constituting an available treatment for patients living with this disease today. The distinction between a fundamental discovery and immediate clinical application remains essential to avoid any misinformation or premature false hope.

The ongoing phase 2 clinical trial with the MAGL inhibitor, the molecule RO7268489, represents the logical next step in determining whether this mechanistic lead will actually translate into a tangible clinical benefit, a process that will still take several years before delivering definitive, clinically usable results.

Why this research deserves close attention

Despite these necessary caveats, this research deserves to be followed closely by everyone interested in the future of multiple sclerosis treatment, because it perfectly illustrates how meticulous basic research can, with time and the necessary patience, open therapeutic doors that seemed inaccessible just a few years earlier.

For patients with progressive MS and their loved ones, this discovery offers, at the very least, a legitimate reason to hope, while also reminding us that the path to new, effective treatments remains long, demanding, and marked by scientific uncertainties that it would be dishonest to minimize.

By Maxime Marquette, columnist

Columnist's transparency note

Who I am and my limits

I am a generalist columnist, not a neurologist or a neuroimmunology researcher. My analysis of this study relies on a careful reading of the original scientific publication in Nature Neuroscience, as well as on several specialized journalistic and institutional outlets that detailed its methodology and results. I have no medical training, and I strive to translate this research for a general audience with the greatest possible rigor, without ever claiming an expertise I do not have.

My method and my acknowledged biases

My method is to cross-reference the original scientific publication with journalistic sources specializing in health and neuroscience before formulating my editorial commentary. My only acknowledged bias here is a preference for scientific caution: I would always rather underpromise than oversell a discovery, particularly when it concerns patients living with a chronic disease as burdensome as multiple sclerosis.

Sources

Primary sources

ScienceDaily, these fat-laden brain cells could worsen multiple sclerosis — June 29, 2026

PubMed, Foamy microglia link oxylipins to disease progression in multiple sclerosis — May 21, 2026

Leiden University Scholarly Publications, full publication in Nature Neuroscience — May 21, 2026

Secondary sources

Multiple Sclerosis News Today, abnormal fat buildup in immune cells may worsen progressive MS — June 2, 2026

Institute for Chemical Neuroscience, foamy microglial cells linked to more severe multiple sclerosis — May 21, 2026

University of Geneva, repairing synapses to fight multiple sclerosis