Department of Biosciences, Durham University, South Road, Durham, UK.
J Mol Med (Berl). 2024 Apr;102(4):465-478. doi: 10.1007/s00109-024-02424-w. Epub 2024 Feb 22.
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.
系统性硬化症是一种自身免疫性结缔组织疾病,其特征为血管功能紊乱、炎症和纤维化。尽管最近在疾病中受干扰的潜在分子途径方面取得了巨大进展,但目前尚无针对疾病纤维化成分的治疗方法,因此存在巨大的未满足的医疗需求。新兴研究揭示了新的复杂性维度,已经发现了多个异常途径,这些途径阐明了疾病中信号转导的紊乱,主要是在炎症途径中,可以用重新利用的药物进行靶向治疗。使用这些抑制剂的临床前动物模型为靶向这些信号系统并推进临床试验提供了概念验证。本综述将探讨 SSc 中最近发现的新受干扰途径,以及如何使用新的或重新利用的药物靶向这些途径,以治疗目前难以治疗的疾病。