MS Biomarker Finding Could Lead to Personalized Treatment Approaches

Researchers from the Netherlands Institute for Neuroscience (NIN), in collaboration with the University of Münster (Germany) and the University of Turku (Finland), have discovered a novel biomarker for severe multiple sclerosis (MS). This research will contribute to our understanding of the molecular processes involved in progressive MS, and may aid in allocation of patients to novel therapies.

Multiple Sclerosis (MS) is a chronic disease in which the immune system mistakenly attacks the central nervous system and removes myelin from nerves. As a result, individuals with MS may experience a wide range of neurological symptoms, including difficulties with walking, speech, and vision.

New therapies that delay disability accumulation in subsets of patients are currently under development. There is therefore a substantial need for biomarkers to identify people with progressive MS eligible for these therapies.

A new lesion type

Since each patient undergoes a different disease trajectory, neurologists Joost Smolders (Erasmus MC/NIN) and Luisa Klotz (University of Münster) assessed the clinical course of all MS from brain donors from the Netherlands Brain Bank. They identified 29 donors who had undergone rapid disability accumulation and 33 donors who had undergone the slowest disability accumulation. Then, neuropathologist Tanja Kuhlmann (University of Münster) looked at tissues of these brain donors with areas of removed myelin, also known as demyelinating MS lesions, to study any potential differences. [YC1]

“We identified striking differences between the two groups”, Smolders explains. “More than half[LL2]  of the rapid cases had MS lesions with a particularly thick rim of immune active cells around demyelinating lesions, while only one of the slow cases had such a rim”. After a more detailed analysis, they concluded that the lesions could be classified as ‘broad rim lesions’, a novel lesion-type.

Potential therapeutic targets

While first discovered in post-mortem donated brain tissue, broad rim lesions can be identified in living people with MS as well on specific PET-MRI scans. This was demonstrated by Laura Airas (Turku PET Centre in Finland), who also found a link between the presence of these lesions to a swifter accumulation of disability. These findings suggest that this biomarker could give more precise predictions of prognosis to progressive MS patients and aid in the process of allocating optimal novel therapies.

In the same publication, the researchers identified unique molecular changes in broad rim lesions, which could be prime targets to slow down the disability accumulations in rapid progressing patients. Further studies will show if there is a direct relationship between the presence of these lesions and the response of people with MS to novel therapies.

Reference: Klotz L, Smolders J, Lehto J, et al. Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis. Nat Med. 2025. doi: 10.1038/s41591-025-03625-7

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