Shulga Olga, Chabanova Anna, Kotsiuba Oleksandra
Volyn Regional Clinical Hospital, Lutsk, Ukraine.
Department of Clinical Medicine, Lesia Ukrainka Volyn National University, Ukraine.
Postep Psychiatr Neurol. 2023 Mar;32(1):23-30. doi: 10.5114/ppn.2023.126319. Epub 2023 Mar 30.
In this review, we have highlighted a new class of drugs, Bruton's tyrosine kinase (BTK) inhibitors, and summarized the results of recent clinical trials in the treatment of multiple sclerosis.
Multiple sclerosis (MS) is considered an autoimmune disease of the central nervous system, in which B-lymphocytes and myeloid cells, such as macrophages and microglia, play an important role in the pathogenesis. B-cells induce pathological processes by presenting autoantigens to T-lymphocytes, secreting pro-inflammatory cytokines, and forming ectopic lymphoid follicle-shaped clusters. Accordingly, the activation of microglia contributes to the development of chronic inflammation due to the production of chemokines, cytokines, reactive oxygen, and nitrogen species. BTK is an enzyme important in the activation and function of both B-lymphocytes and microglia. The demand for highly effective and well-tolerated drugs still remains at all stages of MS despite the availability of a number of effective drugs against the disease. Thus, in recent years BTK inhibitors have been the newest approach in the treatment of MS, since they affect the leading links of the pathogenesis of this disease and are able to pass through the blood-brain barrier.
The study of new mechanisms of the development of MS continues in combination with the elaboration of new treatment methods, i.e., Bruton's tyrosine kinase inhibitors. The review provided the analysis of core studies evaluating the safety and efficacy of these drugs. In the future, positive results of these studies will be able to greatly expand the therapy for various forms of MS.
在本综述中，我们重点介绍了一类新型药物——布鲁顿酪氨酸激酶（BTK）抑制剂，并总结了其治疗多发性硬化症的近期临床试验结果。
多发性硬化症（MS）被认为是一种中枢神经系统自身免疫性疾病，其中B淋巴细胞和髓样细胞，如巨噬细胞和小胶质细胞，在发病机制中起重要作用。B细胞通过向T淋巴细胞呈递自身抗原、分泌促炎细胞因子以及形成异位淋巴滤泡样簇来诱导病理过程。因此，小胶质细胞的激活由于趋化因子、细胞因子、活性氧和氮物种的产生而导致慢性炎症的发展。BTK是一种对B淋巴细胞和小胶质细胞的激活及功能都很重要的酶。尽管有多种针对该疾病的有效药物，但在MS的各个阶段，对高效且耐受性良好的药物的需求仍然存在。因此，近年来BTK抑制剂一直是治疗MS的最新方法，因为它们影响该疾病发病机制的主要环节，并且能够穿过血脑屏障。
MS发病新机制的研究与新治疗方法（即布鲁顿酪氨酸激酶抑制剂）的研发相结合仍在继续。本综述对评估这些药物安全性和有效性的核心研究进行了分析。未来，这些研究的积极结果将能够极大地扩展对各种形式MS的治疗。
