A University of Toronto–led study has identified a potential biomarker associated with disease progression in multiple sclerosis (MS), which may help determine which patients are most likely to benefit from emerging therapies. The findings, published in Nature Immunology, were validated in both animal models and human samples.
The researchers identified a biomarker linked to “compartmentalized inflammation” in the central nervous system—a pathological feature strongly associated with MS progression. According to senior author Jen Gommerman, professor and chair of immunology at the Temerty Faculty of Medicine, this inflammatory process has been difficult to detect, making it challenging to distinguish patients with progressive disease from those who are stable.
Canada has one of the highest MS prevalence rates worldwide, with more than 4,300 new diagnoses annually. Approximately 10% of individuals are diagnosed initially with progressive MS, while many others transition from relapsing-remitting MS to a progressive form characterized by gradual neurological decline and disability.
While effective immunomodulatory therapies exist for relapsing-remitting MS, treatment options for progressive MS remain limited. Co-lead author Valeria Ramaglia of the Krembil Brain Institute noted that prior to this study, researchers lacked an experimental model that accurately reproduced the pathology of progressive MS.
To address this gap, the team developed a novel mouse model that replicates grey matter damage and leptomeningeal inflammation—key features of progressive MS. Using this model, researchers observed a dramatic increase in the immune signal CXCL13 alongside reduced levels of BAFF. Treatment with BTK inhibitors restored these markers to levels seen in healthy controls, leading the team to propose the CXCL13-to-BAFF ratio as a surrogate biomarker for disease-driving inflammation.
Validation studies in postmortem brain tissue and cerebrospinal fluid from people with MS showed that higher CXCL13-to-BAFF ratios correlated with increased compartmentalized inflammation, supporting the biomarker’s relevance in humans.
