Inflammation across tissues: can shared cell biology help design smarter trials?
Inflammation across tissues: can shared cell biology help design smarter trials?
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DOI：
10.1038/s41584-023-01007-2
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发表时间：
2023-09-04
影响因子：
33.7
通讯作者：
Buckley, Christopher Dominic
中科院分区：
文献类型：
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作者：
Hosack, Tom;Thomas, Tom;Buckley, Christopher Dominic
免疫介导的炎症性疾病（IMIDs）造成了巨大的全球疾病负担和相关的卫生保健费用。传统的研究和服务提供模式将其管理局限于以器官为基础的医学学科。在一个器官患病的患者通常会同时累及另一个器官，这表明有共同的致病途径。此外，不同的IMIDs通常使用相同的药物（包括糖皮质激素、免疫调节剂和生物制剂）治疗。解开这些疾病的细胞基础仍然是一项重大挑战，这使我们不禁要问，如果这些疾病有如此多的共同点，为什么没有以一种共同的方式对它们进行研究。以组织为基础的对炎症的细胞理解可能为跨疾病、跨学科的篮子试验（针对两种或多种疾病测试一种药物）铺平道路，以降低IMIDs早期药物开发失败的风险。这种新方法将能够在人类跨疾病转化研究中快速评估新治疗剂的疗效。免疫介导的炎症性疾病在发病机制和治疗方面的相似性表明，它们可以在篮子试验中一起进行研究，以减少早期药物开发失败的风险，并促进罕见病的研究。
Immune-mediated inflammatory diseases (IMIDs) are responsible for substantial global disease burden and associated health-care costs. Traditional models of research and service delivery silo their management within organ-based medical disciplines. Very often patients with disease in one organ have comorbid involvement in another, suggesting shared pathogenic pathways. Moreover, different IMIDs are often treated with the same drugs (including glucocorticoids, immunoregulators and biologics). Unlocking the cellular basis of these diseases remains a major challenge, leading us to ask why, if these diseases have so much in common, they are not investigated in a common manner. A tissue-based, cellular understanding of inflammation might pave the way for cross-disease, cross-discipline basket trials (testing one drug across two or more diseases) to reduce the risk of failure of early-phase drug development in IMIDs. This new approach will enable rapid assessment of the efficacy of new therapeutic agents in cross-disease translational research in humans.Similarities in the pathogenesis and treatment of immune-mediated inflammatory diseases suggest that they can be investigated together in basket trials, to reduce the risk of failure of early-phase drug development and to facilitate the study of rare diseases.