Bruton's tyrosine kinase inhibitors in the treatment of multiple sclerosis.

Olga Shulga, Anna Chabanova, Oleksandra Kotsiuba
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引用次数: 2

Abstract

Purpose: 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.

Views: 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.

Conclusions: 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.

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布鲁顿酪氨酸激酶抑制剂治疗多发性硬化症。
目的:在这篇综述中,我们重点介绍了一类新的药物,布鲁顿酪氨酸激酶(BTK)抑制剂,并总结了最近治疗多发性硬化症的临床试验结果。观点:多发性硬化症(Multiple sclerosis, MS)被认为是一种中枢神经系统自身免疫性疾病,其中b淋巴细胞和髓系细胞如巨噬细胞和小胶质细胞在发病中起重要作用。b细胞通过向t淋巴细胞呈递自身抗原、分泌促炎细胞因子和形成异位淋巴滤泡状簇来诱导病理过程。因此,由于趋化因子、细胞因子、活性氧和氮的产生,小胶质细胞的激活有助于慢性炎症的发展。BTK在b淋巴细胞和小胶质细胞的激活和功能中都是一种重要的酶。尽管有许多有效的药物可以治疗多发性硬化症,但对高效和耐受性良好的药物的需求仍然存在于多发性硬化症的各个阶段。因此,近年来BTK抑制剂已成为治疗MS的最新途径,因为它们影响了该疾病发病机制的主要环节,并且能够穿过血脑屏障。结论:MS发展新机制的研究仍在继续,同时新的治疗方法如布鲁顿酪氨酸激酶抑制剂的研究也在继续。本综述分析了评价这些药物安全性和有效性的核心研究。在未来,这些研究的积极结果将能够大大扩展治疗各种形式的MS。
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