AMPEL BioSolutions and RILITE Research Institute, Charlottesville, VA, USA.
Nat Rev Rheumatol. 2020 Jan;16(1):32-52. doi: 10.1038/s41584-019-0337-0. Epub 2019 Dec 12.
The past century has been characterized by intensive efforts, within both academia and the pharmaceutical industry, to introduce new treatments to individuals with rheumatic autoimmune inflammatory diseases (RAIDs), often by 'borrowing' treatments already employed in one RAID or previously used in an entirely different disease, a concept known as drug repurposing. However, despite sharing some clinical manifestations and immune dysregulation, disease pathogenesis and phenotype vary greatly among RAIDs, and limited understanding of their aetiology has made repurposing drugs for RAIDs challenging. Nevertheless, the past century has been characterized by different 'waves' of repurposing. Early drug repurposing occurred in academia and was based on serendipitous observations or perceived disease similarity, often driven by the availability and popularity of drug classes. Since the 1990s, most biologic therapies have been developed for one or several RAIDs and then tested among the others, with varying levels of success. The past two decades have seen data-driven repurposing characterized by signature-based approaches that rely on molecular biology and genomics. Additionally, many data-driven strategies employ computational modelling and machine learning to integrate multiple sources of data. Together, these repurposing periods have led to advances in the treatment for many RAIDs.
过去一个世纪，学术界和制药行业都在不遗余力地努力为风湿性自身免疫性炎症性疾病（RAIDs）患者引入新的治疗方法，通常是通过“借鉴”一种 RAID 中已有的治疗方法或以前用于完全不同疾病的治疗方法，这一概念被称为药物再利用。然而，尽管 RAIDs 具有一些共同的临床表现和免疫失调，但它们的发病机制和表型差异很大，对其病因的有限认识使得 RAIDs 的药物再利用具有挑战性。尽管如此，过去一个世纪一直以不同的“浪潮”的药物再利用为特征。早期的药物再利用发生在学术界，是基于偶然的观察或对疾病相似性的感知，通常是由药物类别的可用性和流行度驱动的。自 20 世纪 90 年代以来，大多数生物疗法都是为一种或几种 RAIDs 开发的，然后在其他 RAIDs 中进行测试，取得了不同程度的成功。过去二十年出现了以基于特征的方法为特征的数据驱动药物再利用，这些方法依赖于分子生物学和基因组学。此外，许多数据驱动策略采用计算模型和机器学习来整合多种数据源。这些药物再利用时期共同推动了许多 RAIDs 的治疗进展。
