Protecting axons in multiple sclerosis

Abstract

Typically patients with multiple sclerosis (MS) experience acute episodes of neurological dysfunction, which recover followed, at a later stage, by slow and insidious accumulation of disability (disease progression). Disease progression reflects axon damage and loss within the central nervous system. However, the precise mechanism of axon injury in MS is not clear. Inflammation occurring during acute relapses undoubtedly causes some degree of acute axon damage, but epidemiological data and treatment studies have suggested that inflammation alone is not the sole cause of axonopathy. Indeed, there appears to be dissociation between inflammation and disease progression once a certain level of clinical disability has been reached because immune suppression in patients who have established disease progression does not halt the slow decrease of function. The slow and insidious loss of neurological function that occurs during the progressive phase of the disease implies a degenerative process. Whether axon drop-out occurs at these later stages because of previous inflammatory damage to axons; because of low grade inflammation causing damage to already vulnerable demyelinated axons; because of loss of trophic environment for axons to survive; or as part of a completely independent neurodegenerative process is not clear. Understanding disease mechanisms involved in the axonopathy of MS allows for the development of rational therapies for disease progression.