Researchers have discovered why multiple sclerosis ravages some patients while others live with milder symptoms for years. The answer appears to lie in immune cells that become dangerously overloaded with fat inside the brain.
Scientists at the Netherlands Institute for Neuroscience, working alongside colleagues from Leiden and Utrecht universities, found that MS patients with rapid disease progression harbor unusually high numbers of these bloated immune cells, known as foamy microglia. The cells are so packed with fat droplets they take on a distinctive bubbly appearance under a microscope.
"We found that patients with large numbers of these foamy microglia had a more severe disease course more frequently," says Daan van der Vliet, who led the research.
MS attacks myelin, the fatty insulation that wraps around nerve fibers in the brain and spinal cord. As this protective coating deteriorates, patients develop walking difficulties, vision problems, and other neurological damage. The disease's unpredictability has long puzzled researchers: some people decline rapidly into disability while others remain relatively stable for decades.
The research team examined brain tissue from 28 deceased MS patients, using advanced molecular techniques to analyze gene activity, proteins, and fat profiles within diseased lesions. What emerged was a picture of immune system failure.
Microglia normally function as the brain's cleanup crew, removing debris and supporting tissue repair. In MS, these cells attempt to clear away damaged myelin fragments but eventually become overwhelmed by the sheer volume of material flooding in.
"These cells are probably trying to do something good: clearing up damage," Van der Vliet explains. "But they become overloaded, so to speak. As a result, they can no longer effectively contribute to repair."
When microglia fail, the consequences cascade. Areas containing foamy microglia showed enriched levels of specific fats associated with persistent inflammation. This suggests the disease involves far more than simple inflammation running amok.
"It does not appear to be simply about the inflammatory response alone," Van der Vliet says. "These cells are probably attempting to clear damage and promote repair, but that process fails, worsens inflammation, and counteracts recovery."
The discovery opens concrete new avenues for treatment. Researchers found evidence that certain fats linked to foamy microglia may appear in cerebrospinal fluid, the fluid surrounding the brain and spinal cord. If validated in future studies, these fat molecules could become biomarkers that identify which patients will experience rapid decline, allowing doctors to tailor treatment plans accordingly.
Several experimental therapies targeting fat metabolism are already in clinical trials, developed in partnership with pharmaceutical company Roche. The new research provides a biological rationale for why these approaches might work.
The achievement also highlights how modern neuroscience depends on merging cutting-edge lab technology with carefully preserved human tissue samples. Van der Vliet notes that sophisticated gene-sequencing and protein-mapping tools reveal little without connection to actual disease pathology.
"Today we have incredibly sophisticated techniques that can map the brain in great detail," he says. "The technologies are fantastic, but they tell you relatively little if you cannot connect them to pathology in brain tissue."
Author Jessica Williams: "Finding foamy microglia as a driver of severe MS could finally explain why the disease hits some patients like a wrecking ball while others get a reprieve."
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