Bruton's tyrosine kinase as a promising therapeutic target for multiple sclerosis

Expert Opin Ther Targets. 2023 Apr-May;27(4-5):347-359. doi: 10.1080/14728222.2023.2218615. Epub 2023 Jun 5.

Abstract

Introduction: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). Although there are several disease-modifying therapies that can effectively manage MS relapses, the treatment of chronic progressive MS remains a difficult task. CNS-compartmentalized inflammation plays a primary role in progressive MS, especially by activated microglia. In this context, Bruton's tyrosine kinase (BTK) inhibition may be a promising therapeutic approach, as the enzyme is centrally involved in the activation of B cells as well as myeloid cells, such as macrophages and microglia.

Areas covered: This paper discusses a novel and promising approach for MS treatment. We discuss the factors assumed to promote progression in MS and how this process could be counteracted by BTK inhibition, as well as summarize all available clinical data on the usefulness of this therapeutic approach for halting MS progression.

Expert opinion: Current therapeutic approaches in MS are effective for treating relapses but fail to halt progression of the disease. This reflects the emerging concept that the underlying pathophysiology of chronic progressive MS differs from that of relapsing-remitting MS. Understanding the CNS intrinsic process in more detail provides novel therapeutic targets, and one of these may be the inhibition of the enzyme BTK.

Keywords: Bruton’s tyrosine kinase; Btki; evobrutinib; experimental autoimmune encephalomyelitis; microglia; multiple sclerosis.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • B-Lymphocytes
  • Humans
  • Inflammation / drug therapy
  • Macrophages
  • Multiple Sclerosis* / drug therapy
  • Protein Kinase Inhibitors / pharmacology

Substances

  • Agammaglobulinaemia Tyrosine Kinase
  • Protein Kinase Inhibitors