Use of animal models in IPF research

被引:75
|
作者
Carrington, R. [1 ,2 ]
Jordan, S. [2 ]
Pitchford, S. C. [1 ]
Page, C. P. [1 ]
机构
[1] Kings Coll London, Inst Pharmaceut Sci, Sackler Inst Pulm Pharmacol, London SE1 9NH, England
[2] Envigo CRS, Dept Pharmacol, Woolley Rd, Huntingdon PE28 4HS, Cambs, England
关键词
Animal models; IPF; Preclinical; INDUCED PULMONARY-FIBROSIS; INDUCED LUNG FIBROSIS; COUGH REFLEX; BLEOMYCIN; INJURY; MOUSE; MICE; PATHOGENESIS; INHIBITOR; RAT;
D O I
10.1016/j.pupt.2018.07.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a poor prognosis and limited treatment options. Many compounds have shown efficacy in preclinical models of this condition, but only pirfenidone and nintedanib have been approved for clinical use. It is widely accepted that the current animal models of IPF need to be improved and in this review we have critically evaluated the current state of play of preclinical models of IPF and discuss the challenges facing this field. The popular model of a single intratracheal (I.T.) administration of bleomycin could be adapted to provide a more progressive fibrosis as is thought to occur in humans. Furthermore, currently the majority of new drugs are investigated in preclinical models of IPF are dosed using a prophylactic dosing regimen, whereas patients are almost always treated after the fibrosis is well established. Using a therapeutic dosing regimen in preclinical models would be a better way to establish potential efficacy of new drugs. The most popular endpoints examined in pre-clinical models of IPF are histological scoring and lung collagen content. However in IPF patients imaging and lung function tests are more commonly used as end points. We propose that examining more clinically relevant endpoints in pre-clinical models could also provide give a better indication of a compound's potential efficacy on endpoints measured in patients.
引用
收藏
页码:73 / 78
页数:6
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