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2 型慢性炎症性疾病:靶点、疗法和未满足的需求。

Type 2 chronic inflammatory diseases: targets, therapies and unmet needs.

机构信息

Institute of Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.

出版信息

Nat Rev Drug Discov. 2023 Sep;22(9):743-767. doi: 10.1038/s41573-023-00750-1. Epub 2023 Aug 1.

Abstract

Over the past two decades, significant progress in understanding of the pathogenesis of type 2 chronic inflammatory diseases has enabled the identification of compounds for more than 20 novel targets, which are approved or at various stages of development, finally facilitating a more targeted approach for the treatment of these disorders. Most of these newly identified pathogenic drivers of type 2 inflammation and their corresponding treatments are related to mast cells, eosinophils, T cells, B cells, epithelial cells and sensory nerves. Epithelial barrier defects and dysbiotic microbiomes represent exciting future drug targets for chronic type 2 inflammatory conditions. Here, we review common targets, current treatments and emerging therapies for the treatment of five major type 2 chronic inflammatory diseases - atopic dermatitis, chronic prurigo, chronic urticaria, asthma and chronic rhinosinusitis with nasal polyps - with a high need for targeted therapies. Unmet needs and future directions in the field are discussed.

摘要

在过去的二十年中,人们对 2 型慢性炎症性疾病发病机制的理解取得了重大进展,这使得能够鉴定出 20 多种新型靶点的化合物,这些化合物已获得批准或处于不同的开发阶段,最终为这些疾病的治疗提供了更有针对性的方法。这些新发现的 2 型炎症的发病机制驱动因素及其相应的治疗方法大多数与肥大细胞、嗜酸性粒细胞、T 细胞、B 细胞、上皮细胞和感觉神经有关。上皮屏障缺陷和微生物组失调代表了慢性 2 型炎症性疾病的令人兴奋的未来药物靶点。在这里,我们回顾了五种主要的 2 型慢性炎症性疾病——特应性皮炎、慢性痒疹、慢性荨麻疹、哮喘和伴有鼻息肉的慢性鼻-鼻窦炎——的常见靶点、现有治疗方法和新兴治疗方法,这些疾病都非常需要靶向治疗。讨论了该领域的未满足需求和未来方向。

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