Neurodegeneration and inflammation in MS

In multiple sclerosis (MS), neurodegeneration contributes to axon loss and irreversible disability, but the degree to which neurodegeneration is a consequence of inflammatory mechanisms is unknown. Urgent need exists in all forms of MS, but especially in progressive MS, for therapies that preserve the integrity and function of CNS tissue in the face of a partially controlled chronic disease. It is likely that agents envisioned to fulfill that role (primary neuroprotective therapies) will act via a mechanism outside immune modulation. In analogous terms, the CNS could be likened to a home that we aim to protect from storm damage. Immune-modulating therapies are the equivalent of a weather machine that prevents the storm from ever brewing, and in that way provide indirect neuroprotection. Primary neuroprotection would be achieved by another mechanism, something akin to installing storm shutters or reinforcing the structure of a home to help it weather the years. The concern in MS is that ongoing neurodegeneration may occur even in the absence of detectable active inflammation, compelling a need for primary neuroprotective therapies that utilize novel mechanisms of action.