Inhibition of Bruton´s tyrosine kinase as a novel therapeutic approach in multiple sclerosis

Introduction: B cells have increasingly come under the spotlight as mediators of inflammatory central nervous system (CNS) demyelinating diseases such as multiple sclerosis (MS). B cell depletion via the targeting of the surface molecule CD20 has proven to be highly effective, however, continuous absence of an integral component of the immune system may cause safety concerns over time. Declining humoral competence and potential immune system impairments are key issues and moreover, unselective removal of B cells reduces immune system control functions which should preferably be maintained in inflammatory CNS disease. Areas covered: This paper illuminates the novel approach of specific interference with B cell signaling by targeting Bruton´s tyrosine kinase (BTK). We discuss the role of BTK within the B cell receptor (BCR) signaling cascade and BTK inhibition as a promising strategy to control inflammatory CNS disease which crucially excludes immune-cell depletion. We searched PubMed or clinicaltrials.gov for the terms 'BTK inhibition' or 'Bruton´s Tyrosine Kinase' or 'anti-CD20' and 'Multiple Sclerosis' Expert opinion: BTK inhibition has shown effectiveness in preclinical models of CNS disease and MS clinical trials. Further studies are necessary to differentiate this approach from B cell depletion and to position it in the armamentarium of therapeutics.

Keywords: BTKi; Bruton´s tyrosine kinase; evobrutinib; experimental autoimmune encephalomyelitis; ibrutinib; multiple sclerosis.