Mechanisms of complement dysregulation in MS
Complement dysregulation is a central driver of neuroinflammation, demyelination, and axonal damage in multiple sclerosis.
Compartmentalized central nervous system inflammation in multiple sclerosis is sustained by microglial C1q and astrocytic C3 signaling within meningeal and cortical niches.
Complement profiling, particularly in cerebrospinal fluid, enables patient stratification and correlates with disease activity and progression in multiple sclerosis.
Complement inhibitors targeting C5, C3, C1q, and C5aR1 have achieved clinical success in related neuroinflammatory and neurodegenerative diseases but remain unexplored in multiple sclerosis.
Brain-penetrant small-molecule inhibitors of factor B, factor D, and C5aR1 represent promising candidates for next generation, pathway-selective multiple sclerosis therapies.
https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(26)00039-8
