Marker of latent brain inflammation in multiple sclerosis has been discovered

One of the main problems with multiple sclerosis remains the inability to accurately determine in which patients the disease is actually progressing. This makes it difficult to choose a therapy and reduces the effectiveness of clinical trials of new drugs.

Multiple sclerosis is one of the most common neurological diseases in Canada, with thousands of people diagnosed every year. In about a part of patients, the disease initially proceeds in a progressive form, in which the symptoms slowly but steadily worsen. In others, the disease begins with a remitting course, but over time it can also progress to a progressive stage.

Modern drugs are able to act on recurrent forms of the disease, reducing the activity of the immune system. However, there are still very few effective treatments for advanced multiple sclerosis. One of the reasons for this, according to the researchers, was the lack of an adequate experimental model that reproduces real changes in the patients’ brains.

To solve this problem, scientists have developed a new mouse model that mimics damage to the gray matter of the brain, a characteristic feature of progressive multiple sclerosis. A key element of this process turned out to be inflammation in the membranes of the brain surrounding the brain and spinal cord. During the experiments, the researchers recorded a sharp increase in the level of CXCL13 and a simultaneous decrease in BAFF, two molecules that play an important role in immune responses.

When the animals were treated with drugs of the BTK inhibitor class, which are already being tested in clinical trials, inflammation decreased, and the ratio of CXCL13 and BAFF approached normal. This suggested that it is their ratio that can serve as a marker of pathological inflammation in the brain.

To test this hypothesis, the researchers analyzed brain tissue samples from deceased patients with multiple sclerosis, as well as the cerebrospinal fluid of people living with this diagnosis. In both cases, a high CXCL13 score relative to BAFF was associated with more pronounced inflammation and signs of disease progression.

The authors believe that the lack of an easy way to detect such inflammation could be the reason for the mixed results of clinical trials of BTK inhibitors. The studies could include patients for whom these drugs were not initially suitable, which is why the potential effect of therapy was blurred.

According to scientists, the use of a new biomarker can change the approach to the treatment of multiple sclerosis, making it more accurate and personalized. In the future, the team plans to test whether this indicator can be used to identify patients with early signs of disease progression and select the most effective therapy in advance.