Evolving targeted biologics against T cells, cytokines, and intracellular immune targets for multiple sclerosis with implications in other autoimmune neurologic diseases.

Over the last three decades, immunotherapies targeting T cells, cytokines, and intracellular molecules have been explored extensively in clinical trials in multiple sclerosis (MS). These studies resulted in the approval of several therapies for the treatment of relapsing-remitting MS, and secondary and primary progressive MS. However, many treatment approaches were unsuccessful but provided important insights into pathomechanisms driving disease activity and progression in MS. Additional treatment strategies are currently evaluated in phase II and III trials in MS and are likely to improve the treatment of relapsing and progressive MS in the future. Some of the established treatment strategies in MS paved the way for the development of treatment strategies in other autoimmune diseases of the central nervous system, in particular neuromyelitis optica spectrum disorders (NMOSD) and myelin-oligodendrocyte glycoprotein-associated disorders. As a result, the first drugs for the treatment of NMOSD were recently approved and are now available to alter the course of this disease. Overall, T cell and cytokine-targeting treatment approaches have proven less successful in neuroinflammatory diseases than strategies targeting B cells. A better understanding of the pathomechanisms underlying MS and related diseases will facilitate the successful development of specific therapies targeting T cells, cytokines, and intracellular molecules in the future.