Bruton’s Tyrosine Kinase Inhibitors for Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with a chronic and often progressive disease course. The current disease-modifying treatments (DMTs) limit disease progression primarily by controlling immune cell activity in the peripheral blood or inhibiting their migration from the periphery into the CNS. However, approved therapies are less effective at slowing disability accumulation in patients with MS, and new therapies are needed to target CNS immunopathology, which is a key driver of disability progression in MS. Bruton’s tyrosine kinase (BTK) is an intracellular signalling molecule involved in the regulation of maturation, survival, migration and activation of B cells and microglia, therefore BTK inhibitors target both adaptive and innate mechanisms that contribute to the immunopathology of MS on both sides of the blood-brain barrier. This article reviews the preclinical researches and therapeutic roles of Bruton's tyrosine kinase inhibitors as promising DMTs to target cells of the adaptive and innate immune system outside and within the CNS in the MS.