An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis

被引:279
作者
Jenkins, R. Gisli
Moore, Bethany B.
Chambers, Rachel C.
Eickelberg, Oliver
Konigshoff, Melanie
Kolb, Martin
Laurent, Geoffrey J.
Nanthakumar, Carmel B.
Olman, Mitchell A.
Pardo, Annie
Selman, Moises
Sheppard, Dean
Sime, Patricia J.
Tager, Andrew M.
Tatler, Amanda L.
Thannickal, Victor J.
White, Eric S.
机构
[1] University of Michigan, 4053 BSRB, 109 Zina Pitcher Place, Ann Arbor, 48109-2200, MI
基金
英国医学研究理事会;
关键词
ENDOPLASMIC-RETICULUM STRESS; USUAL INTERSTITIAL PNEUMONIA; MICRO-COMPUTED TOMOGRAPHY; INDUCED LUNG FIBROSIS; TGF-BETA ACTIVATION; COLLAGEN PRODUCTION; MOUSE MODELS; MURINE LUNG; CFTR GENE; PIRFENIDONE;
D O I
10.1165/rcmb.2017-0096ST
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Numerous compounds have shown efficacy in limiting development of pulmonary fibrosis using animal models, yet few of these compounds have replicated these beneficial effects in clinical trials. Given the challenges associated with performing clinical trials in patients with idiopathic pulmonary fibrosis (IPF), it is imperative that preclinical data packages be robust in their analyses and interpretations to have the best chance of selecting promising drug candidates to advance to clinical trials. The American Thoracic Society has convened a group of experts in lung fibrosis to discuss and formalize recommendations for preclinical assessment of antifibrotic compounds. The panel considered three major themes (choice of animal, practical considerations of fibrosis modeling, and fibrotic endpoints for evaluation). Recognizing the need for practical considerations, we have taken a pragmatic approach. The consensus view is that use of the murine intratracheal bleomycin model in animals of both genders, using hydroxyproline measurements for collagen accumulation along with histologic assessments, is the best-characterized animal model available for preclinical testing. Testing of antifibrotic compounds in this model is recommended to occur after the acute inflammatory phase has subsided (generally after Day 7). Robust analyses may also include confirmatory studies in human IPF specimens and validation of results in a second system using in vivo or in vitro approaches. The panel also strongly encourages the publication of negative results to inform the lung fibrosis community. These recommendations are for preclinical therapeutic evaluation only and are not intended to dissuade development of emerging technologies to better understand IPF pathogenesis.
引用
收藏
页码:667 / 679
页数:13
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