Biological Mechanisms of MS Progression

In this episode, panelists investigate the distinct and overlapping biological pathways driving both relapsing and progressive forms of multiple sclerosis. They explain that relapsing disease activity primarily involves pro-inflammatory B cells and T cells crossing the blood-brain barrier, resulting in focal central nervous system lesions observed as clinical relapses or new MRI findings. The conversation then shifts to the drivers of progression, highlighting the recent understanding of chronic active lesions, “smoldering” or persistent areas of inflammation marked by activated microglia and iron deposition, which contribute to ongoing tissue damage and gradual disability. The panel delves into additional progressive mechanisms, including meningeal follicle formation, subpial demyelination, cortical and gray matter atrophy, diffuse microglial activity, and neurodegeneration related to aging. Acknowledging the current gaps and complexities in fully elucidating progressive disease biology, panelists emphasize that ongoing research continues to shape how clinical progression is understood and managed.