Why Does MS Progress Differently in Patients?

In a new publication, first authors Lukas Lütje and Alida Chen from the Huitinga group analysed pathological, clinical, and genetic data from 287 people with MS who donated their brain to the Netherlands Brain Bank. It is the largest well-characterised MS pathology cohort currently available.

The researchers examined whether people with MS show distinct patterns of brain damage and repair. They focused on four pathological characteristics: inflammation around blood vessels, clusters of immune cells in the brain, the presence of broad rim lesions, and the brain’s ability to repair myelin-the protective coating around nerve fibres.

“MS is not one single disease process,” says Aletta van den Bosch. “Different inflammatory and repair mechanisms dominate in different people, helping explain why the disease can follow very different paths.”

Finding patterns

The team found that these four pathological characteristics were associated with different patterns of lesion activity, tissue repair, and disease severity. For example, people with broad rim lesions were more likely to have a more severe disease course, while those with poor capacity for myelin repair had more chronic tissue damage.

Genetic variants known to increase the risk of developing MS were more common in people with inflammation around blood vessels and clusters of the brain’s immune cells, suggesting that genetic background contributes to the inflammatory processes occurring in the brain. Another genetic variant, previously associated with faster disease progression, was more frequently observed in people with broad rim lesions.

By combining pathology, genetics and clinical information, the researchers were able to identify donor-specific pathological features that help explain why MS differs so much between individuals

Although this is fundamental research, it provides a basis for understanding why MS differs so much between individuals. The next step is to find biomarkers that can detect these biological patterns in people living with MS. Such biomarkers could help monitor disease processes over time and ultimately support more personalised treatment strategies.

“Understanding which biological processes are driving disease in each individual will be key to developing more personalised treatments,” the researchers conclude.