Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies.

Progressive forms of multiple sclerosis (MS) include primary progressive MS (PPMS) and secondary progressive MS (SPMS). Unlike relapsing-remitting MS (RRMS), progressive MS is recognized by relentless progression with accumulating disability, rare to no relapses nor new activity on MRIs. Clinically, neurologic worsening in MS can occur in the relapsing-remitting (RRMS) phase of disease due to incomplete recovery from neuroinflammatory relapses. However, a progressive disease course is the dominant factor related to accumulating disability. There is persistent central nervous system (CNS) compartmentalized inflammation, mitochondrial dysfunction and altered immune responses. Unlike in RRMS, the efficacy of disease modifying agents (DMA) in progressive MS has been limited, highlighting the need for novel therapeutic approaches that address both inflammation and neurodegeneration. This article explores current management of progressive MS, and future directions in targeting the unique pathophysiology of this complex disease.