Emerging therapies to target CNS pathophysiology in multiple sclerosis.

The rapidly evolving therapeutic landscape of multiple sclerosis (MS) has contributed to paradigm shifts in our understanding of the biological mechanisms that contribute to CNS injury and in treatment philosophies. Opportunities remain to further improve treatment of relapsing-remitting MS, but two major therapeutic gaps are the limiting of progressive disease mechanisms and the repair of CNS injury. In this Review, we provide an overview of selected emerging therapies that predominantly target processes within the CNS that are thought to be involved in limiting non-relapsing, progressive disease injury or promoting tissue repair. Among these, we consider agents that modulate adaptive and innate CNS-compartmentalized inflammation, which can be mediated by infiltrating immune cells and/or resident CNS cells, including microglia and astrocytes. We also discuss agents that target degenerative disease mechanisms, agents that might confer neuroprotection, and agents that create a more favourable environment for or actively contribute to oligodendrocyte precursor cell differentiation, remyelination and axonal regeneration. We focus on agents that are novel for MS, that are known to or are presumed to penetrate the CNS, and that have already entered early stages of development in MS clinical trials.