# "Foamy" Immune Cells May Be Making Multiple Sclerosis Worse

> A team of researchers in the Netherlands, bringing together the Netherlands Institute for Neuroscience, Leiden University, and Utrecht University, has just published

- Author: Maxime Marquette
- Publisher: MadMax (https://mad-max.co)
- Section: Column
- Published: 2026-07-05
- Canonical URL: https://mad-max.co/en/article/des-cellules-immunitaires-spumeuses-aggraveraient-la-sclerose-en-plaques

## Key takeaways

- Researchers led by Daan van der Vliet analyzed post-mortem brain tissue from 250 MS donors, finding that patients with many lesions containing foamy microglia more often had severe disease courses.
- The cells appear to absorb large amounts of damaged myelin, become overwhelmed, and turn from protective into drivers of chronic inflammation.
- Lesions showed a distinct lipid signature, including elevated oxylipins, along with increased B-cell infiltration.
- The team identified the enzyme MAGL as a potential target; a MAGL inhibitor promoted repair in a mouse model, and a phase 2 trial (RO7268489 with ocrelizumab) is underway.
- Oxylipin levels in cerebrospinal fluid correlated with foamy lesion burden, a possible biomarker that still needs independent validation.

## 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.

*As a columnist, I'm no neurologist, but I recognize when a scientific study has the potential to change an entire clinical trajectory. This discovery of **foamy cells** strikes me as exactly that kind of moment, where a meticulous microscopic observation suddenly opens a therapeutic door that had seemed closed for years.*

## 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.

*This image of well-meaning cells that end up turning against the very organism they're supposed to protect strikes me for its biological irony. It's a reminder that the human body, even in its most sophisticated defense mechanisms, remains vulnerable to its own excesses of zeal.*

## 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.

*This level of molecular precision impresses me, even though I must humbly admit that oxylipin biochemistry is well beyond my skills as a generalist columnist. What I take away is the methodological rigor deployed to establish such a solid link between a cellular observation and a concrete clinical prognosis.*

## 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 pre**clinical** 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**.

*I remain cautious about the enthusiasm this kind of discovery naturally sparks. A positive result in mice never guarantees success in humans, and I'd rather emphasize this cloud of uncertainty than sell people living with this disease a false hope of an imminent cure.*

## 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.

*This caution displayed by the researchers themselves reassures me about the quality of this study. Too often, promising discoveries are oversold in press releases before they've even been confirmed, and I want to commend here a piece of scientific communication that stays measured about its own results.*

## 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**.

*I want to use this column to underline a point close to my heart: basic research never makes headlines the way clinical trials do, and yet without it, no promising **clinical trial** would ever come to exist. This patient, painstaking work deserves to be recognized for what it's worth.*

## 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.

*What strikes me when looking at all these converging lines of research is the gradual maturing of the scientific field devoted to multiple sclerosis. We're moving from a broad, fuzzy understanding of the disease to an increasingly precise map of its cellular mechanisms, which hints at increasingly targeted treatments down the road.*

## 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.

*I want to salute here, with particular sincerity, the generosity of these hundreds of donors and their families. Without this often quiet, little-publicized act, none of the scientific advances being discussed today would be possible. It's a form of altruism that deserves to be told as much as the science itself.*

## 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**.

*I'm keeping measured hope about this phase 2 clinical trial. The history of medical research is littered with mechanisms that showed great promise in the lab but never delivered on their promise in humans, and I'd rather stay honest with readers than give in to surface-level optimism.*

## 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**.

*This ethical dimension strikes me as too often overlooked in media coverage of scientific advances. We celebrate the discovery, but sometimes forget to mention the respect owed to the people who make it possible. I think it's my duty as a columnist to point that out, even briefly.*

## 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.

*I choose to end this section on a note of measured hope rather than excitement. Precision medicine is a fascinating horizon, but I refuse to promise patients an imminent therapeutic revolution when clinical reality still demands years of rigorous validation.*

## 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.

*This reflection on scientific humility strikes me as the most important lesson to take from this column. The further science advances, the more it reveals the scope of what remains to be discovered, and I find that perspective both dizzying and deeply energizing.*

## 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.

*I particularly appreciate this culture of scientific replication, which contrasts with the media temptation to treat every new study as definitive truth. Science advances through the careful accumulation of evidence, not isolated dramatic announcements, and that's a nuance I want to pass on to my readers.*

## 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.

*I find it refreshing to see researchers resist the temptation to overstate the reach of their own work. This intellectual rigor, which refuses easy shortcuts to other diseases without solid evidence, is exactly the kind of scientific posture I want to highlight in my columns.*

## 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.

*I close this column with the conviction that science, even when slow and uncertain, always ends up moving forward. This discovery of foamy cells won't cure anyone tomorrow morning, but it brings a little closer the day when progressive multiple sclerosis stops being a sentence with no recourse.*

**By Maxime Marquette, columnist**

## Columnist's transparency note

### Editorial stance

I am not a journalist but a **columnist and analyst**. My expertise lies in observing and analysing the geopolitical, economic and strategic dynamics that shape our world. My work is to take political strategies apart, to understand global economic movements, to put the decisions of international actors in context and to offer analytical perspectives on the changes that are redefining our societies.

I do not claim the cold objectivity of traditional journalism, which stops at reporting facts. **I claim analytical clarity**, rigorous interpretation and a deep understanding of the complex issues that concern us all. My role is to give meaning to the facts, to place them in their historical and strategic context, and to offer a critical reading of events.

### Method and sources

This text keeps the basic distinction between **verified facts and interpretive analysis**. The rule never changes: a factual claim is published only when a verifiable source supports it, and the sources this article actually used are listed under **Sources**, never here.

**Primary source families** used by the publication, when the story has them: official statements from governments and international institutions, public statements by political leaders, reports from intergovernmental organisations, dispatches from recognised international news agencies.

**Secondary source families**: specialised publications, internationally recognised news media, analyses from established research institutions, reports from industry organisations.

When an article cites statistical, economic or geopolitical data, it comes from the institutions that produce it (intergovernmental organisations, central banks, national statistics offices), and the exact institution is named under **Sources**.

### Nature of the analysis

The analyses, interpretations and perspectives in the analytical sections of this article are a **critical, contextual synthesis** based on the information available, the trends observed and the expert comments cited in the sources consulted.

My role is to interpret these facts, to set them in the context of today's geopolitical and economic dynamics, and to give them a coherent meaning within the larger story of the changes shaping our time. These analyses reflect expertise built through continuous observation of international affairs and an understanding of the strategic mechanisms that drive global actors.

This article describes a documented state of affairs on its publication date, not a prediction: later developments may shift its outlook. No update is promised in advance; when an article is corrected or completed, the change is dated in the text.

## 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

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Source: Maxime Marquette, MadMax. When citing, name the author and link https://mad-max.co/en/article/des-cellules-immunitaires-spumeuses-aggraveraient-la-sclerose-en-plaques