Inhibition of Bruton's tyrosine kinase interferes with pathogenic B-cell development in inflammatory CNS demyelinating disease.

ABSTRACT: Anti-CD20-mediated B-cell depletion effectively reduces acute multiple sclerosis (MS) flares. Recent data shows that antibody-mediated extinction of B cells as a lasting immune suppression, harbors the risk of developing humoral deficiencies over time. Accordingly, more selective, durable and reversible B-cell-directed MS therapies are needed. We here tested inhibition of Bruton's tyrosine kinase (BTK), an enzyme centrally involved in B-cell receptor signaling, as the most promising approach in this direction. Using mouse models of MS, we determined that evobrutinib, the first BTK inhibiting molecule being developed, dose-dependently inhibited antigen-triggered activation and maturation of B cells as well as their release of pro-inflammatory cytokines. Most importantly, evobrutinib treatme

SUBMITTER: Torke S 

PROVIDER: S-EPMC7498502 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature