Researchers have identified a population of lipid-filled immune cells that may help explain why some multiple sclerosis (MS) lesions continue to grow and drive disability in patients with progressive disease.
The study, published in Nature Neuroscience, analyzed postmortem brain tissue from patients with secondary progressive MS using a combination of molecular and histological techniques to better understand the biology of chronic brain lesions.
Although disease-modifying therapies can reduce relapses in early MS, treatment options for progressive disease remain limited. One reason is that chronic lesions can continue to expand, causing ongoing damage to nerve tissue.
The researchers found that lesions containing "foamy" microglia – immune cells filled with lipids – were linked to faster disease progression. Patients with more of these lesions reached disability milestones sooner than those with fewer foamy lesions. In contrast, patients with more remyelinated lesions tended to experience slower disease progression.
Further analysis showed that the foamy microglia had abnormal lipid metabolism and signs of impaired waste processing within the cell. The lesions also showed increased immune activity, but not the type of inflammation typically seen in active MS lesions. According to the researchers, this suggests that chronic active lesions represent a distinct disease process.
The team also identified monoacylglycerol lipase (MAGL), an enzyme involved in lipid metabolism, as a possible therapeutic target. In a mouse model of demyelination, blocking MAGL reduced immune cell activation, improved removal of myelin debris, and promoted tissue repair.
The researchers also measured lipid molecules known as oxylipins in cerebrospinal fluid. Several of these molecules were associated with the number of foamy lesions in the brain, suggesting they could eventually serve as biomarkers of chronic lesion activity. However, further studies in living patients will be needed to confirm their clinical value.
The authors noted that the study was based on postmortem tissue, meaning it provides a snapshot of disease rather than showing how lesions change over time.
The findings highlight the value of combining histopathology with molecular profiling to better understand progressive MS. They also suggest that identifying lipid-filled microglia and related molecular markers could improve future approaches to diagnosing and monitoring chronic active lesions.
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