Emerging therapeutic targets in systemic sclerosis

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Abstract

Systemic sclerosis is an autoimmune connective tissue disease which is characterised by vascular perturbations, inflammation, and fibrosis. Although huge progress recently into the underlying molecular pathways that are perturbed in the disease, currently no therapy exists that targets the fibrosis element of the disease and consequently there is a huge unmet medical need. Emerging studies reveal new dimensions of complexity, and multiple aberrant pathways have been uncovered that have shed light on disturbed signalling in the disease, primarily in inflammatory pathways that can be targeted with repurposed drugs. Pre-clinical animal models using these inhibitors have yielded proof of concept for targeting these signalling systems and progressing to clinical trials. This review will examine the recent evidence of new perturbed pathways in SSc and how these can be targeted with new or repurposed drugs to target a currently intractable disease.

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系统性硬化症的新治疗靶点
摘要 系统性硬化症是一种自身免疫性结缔组织疾病,其特点是血管紊乱、炎症和纤维化。尽管最近在研究该病的潜在分子通路方面取得了巨大进展,但目前还没有针对该病纤维化因素的疗法,因此存在着巨大的未满足医疗需求。新的研究揭示了复杂性的新层面,发现了多种异常途径,揭示了疾病中紊乱的信号传导,主要是炎症途径,这些途径可以用重新设计的药物进行靶向治疗。使用这些抑制剂的临床前动物模型已经证明了靶向这些信号系统的概念,并已进入临床试验阶段。本综述将探讨最近有关 SSc 中新的紊乱通路的证据,以及如何利用新药或重新设计的药物来靶向治疗这种目前难以治愈的疾病。
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