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

被引:7
|
作者
Saberi, Darius [1 ,2 ]
Geladaris, Anastasia [2 ,3 ]
Dybowski, Sarah [3 ]
Weber, Martin S. [1 ,2 ,3 ,4 ]
机构
[1] Univ Med Ctr, Dept Neurol, Gottingen, Germany
[2] Fraunhofer Inst Translat Med & Pharmacol, Dept Translat Neuroinflammat & Automated Microscop, Gottingen, Germany
[3] Univ Med Ctr, Inst Neuropathol, Gottingen, Germany
[4] Georg August Univ, Univ Med Ctr, Dept Neuropathol, Dept Neurol, Robert Koch Str 40, D-37099 Gottingen, Germany
关键词
Bruton's tyrosine kinase; Btki; evobrutinib; experimental autoimmune encephalomyelitis; multiple sclerosis; microglia; BTK INHIBITOR; OCRELIZUMAB; EFFICACY; BRAIN; MITOXANTRONE; INFLAMMATION; PROGRESSION; MECHANISMS; ASSOCIATE; MIGRATION;
D O I
10.1080/14728222.2023.2218615
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
IntroductionMultiple 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 coveredThis 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 opinionCurrent 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.
引用
收藏
页码:347 / 359
页数:13
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