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Current Neurology and Neuroscience Reports
Published in: Current Neurology and Neuroscience Reports 11/2022

27-10-2022 | Multiple Sclerosis | Demyelinating Disorders (J. Bernard and M. Cameron, Section Editors)

Bruton’s Tyrosine Kinase Inhibition in Multiple Sclerosis

Authors: Raphael Schneider, Jiwon Oh

Published in: Current Neurology and Neuroscience Reports | Issue 11/2022

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Abstract

Purpose of Review

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 dampening immune cell activity in the peripheral blood or hindering their migration from the periphery into the CNS. New therapies are needed to target CNS immunopathology, which is a key driver of disability progression in MS. This article reviews Bruton’s Tyrosine Kinase Inhibitors (BTKIs), a new class of experimental therapy that is being intensely evaluated in MS. We focus on the potential peripheral and central mechanisms of action of BTKIs and their use in recent clinical trials in MS.

Recent Findings

There is evidence that some BTKIs cross the blood–brain barrier and may be superior to currently available DMTs at dampening the chronic neuroinflammatory processes compartmentalized within the CNS that contribute to progressive worsening in people withMS (pwMS). Recently, evobrutinib and tolebrutinib have shown efficacy in phase II clinical trials, and there are numerous ongoing phase III clinical trials of various BTKIs in relapsing and progressive forms of MS. Results from these clinical trials will be essential to understand the efficacy and safety of BTKIs across the spectrum of MS and keydifferences between specific BTKIs when treating pwMS.

Summary

Inhibition of BTK has emerged as an attractive strategy to target cells of the adaptive and innate immune system outside and within the CNS. BTKIs carry great therapeutic potential across the MS spectrum, where key pathobiology aspects seem confined to the CNS compartment.
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Metadata
Title
Bruton’s Tyrosine Kinase Inhibition in Multiple Sclerosis
Authors
Raphael Schneider
Jiwon Oh
Publication date
27-10-2022
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 11/2022
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-022-01229-z

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