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药物再利用治疗肾小球疾病:未充分利用的资源。

Drug repurposing for glomerular diseases: an underutilized resource.

机构信息

Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.

Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, Queensland, Australia.

出版信息

Nat Rev Nephrol. 2024 Nov;20(11):707-721. doi: 10.1038/s41581-024-00864-8. Epub 2024 Jul 31.

DOI:10.1038/s41581-024-00864-8
PMID:39085415
Abstract

Drug repurposing in glomerular disease can deliver opportunities for steroid-free regimens, enable personalized multi-target options for resistant or relapsing disease and enhance treatment options for understudied populations (for example, children) and in resource-limited settings. Identification of drug-repurposing candidates can be data driven, which utilizes existing data on disease pathobiology, drug features and clinical outcomes, or experimental, which involves high-throughput drug screens. Information from databases of approved drugs, clinical trials and PubMed registries suggests that at least 96 drugs on the market cover 49 targets with immunosuppressive potential that could be candidates for drug repurposing in glomerular disease. Furthermore, evidence to support drug repurposing is available for 191 immune drug target-glomerular disease pairs. Non-immunological drug repurposing includes strategies to reduce haemodynamic overload, podocyte injury and kidney fibrosis. Recommended strategies to expand drug-repurposing capacity in glomerular disease include enriching drug databases with glomeruli-specific information, enhancing the accessibility of primary clinical trial data, biomarker discovery to improve participant selection into clinical trials and improve surrogate outcomes and initiatives to reduce patent, regulatory and organizational hurdles.

摘要

肾小球疾病的药物再利用可为无激素治疗方案提供机会,为耐药或复发疾病提供个性化的多靶点选择,并为研究不足的人群(例如儿童)和资源有限的环境增强治疗选择。药物再利用候选药物的鉴定可以是基于数据的,利用疾病病理生物学、药物特征和临床结果的现有数据,也可以是基于实验的,涉及高通量药物筛选。来自已批准药物数据库、临床试验和 PubMed 登记处的信息表明,市场上至少有 96 种药物针对 49 个具有免疫抑制潜力的靶点,这些靶点可能成为肾小球疾病药物再利用的候选药物。此外,有 191 个免疫药物靶点-肾小球疾病对支持药物再利用的证据。非免疫性药物再利用包括减轻血液动力学过载、足细胞损伤和肾脏纤维化的策略。扩大肾小球疾病药物再利用能力的推荐策略包括用肾小球特异性信息丰富药物数据库,提高主要临床试验数据的可及性,发现生物标志物以改善临床试验中患者的选择,并改善替代终点和减少专利、监管和组织障碍的举措。

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