慢性阻塞性肺疾病动物模型及其在药物发现和开发中的作用:综述

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Maria Gabriella Matera, Luigino Calzetta, Barbara Rinaldi, Vito de Novellis, Clive P Page, Peter J Barnes, Mario Cazzola
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引用次数: 0

摘要

为了了解慢性阻塞性肺病的机制,发现和测试新药,实验动物是必不可少的。然而,与人类疾病相关的复杂变化很难在动物模型中完全复制。涵盖领域:本综述回顾了最近关于COPD动物模型的文献及其对药物发现和开发的意义。专家意见:动物模型的最新进展包括引入转基因小鼠,这些小鼠更容易出现copd相关特征,如肺气肿,以及暴露于香烟烟雾以外的相关环境因素(如生物质烟雾和其他空气污染物)的动物。此外,其他动物物种,包括斑马鱼、猪、雪貂和非人类灵长类动物,也越来越多地被用于了解人类COPD。此外,三维类器官和人源化小鼠模型正在成为在更类似人类的模型中评估新疗法的技术。然而,尽管有一些显著的进展,迄今为止还没有一个模型完全捕捉到COPD患者观察到的异质性和进展。因此,需要进一步的研究来开发改进的模型,在实验动物中加入人源化元素,从而更好地预测临床治疗反应,并加速这种使人衰弱的疾病的新治疗方法的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Animal models of chronic obstructive pulmonary disease and their role in drug discovery and development: a critical review.

Introduction: The use of laboratory animals is essential to understand the mechanisms underlying COPD and to discover and evaluate new drugs. However, the complex changes associated with the disease in humans are difficult to fully replicate in animal models.

Areas covered: This review examines the most recent literature on animal models of COPD and their implications for drug discovery and development.

Expert opinion: Recent advances in animal models include the introduction of transgenic mice with an increased propensity to develop COPD-associated features, such as emphysema, and animals exposed to relevant environmental agents other than cigarette smoke, in particular biomass smoke and other air pollutants. Other animal species, including zebrafish, pigs, ferrets and non-human primates, are also increasingly being used to gain insights into human COPD. Furthermore, three-dimensional organoids and humanized mouse models are emerging as technologies for evaluating novel therapeutics in more human-like models. However, despite these advances, no model has yet fully captured the heterogeneity and progression of COPD as observed in humans. Therefore, further research is needed to develop improved models incorporating humanized elements in experimental animals, that may better predict therapeutic responses in clinic settings and accelerate the development of new treatments for this debilitating disease.

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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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