医学
临床前试验
特发性肺纤维化
任天堂
临床试验
吡非尼酮
纤维化
临床前研究
动物模型
肺纤维化
羟脯氨酸
博莱霉素
重症监护医学
病理
限制
肺
医学物理学
内科学
机械工程
化疗
工程类
作者
Gisli Jenkins,Bethany B. Moore,Rachel C. Chambers,Oliver Eickelberg,Mélanie Königshoff,Martin Kolb,Geoffrey J. Laurent,Carmel B. Nanthakumar,Mitchell A. Olman,Annie Pardo,Moisés Selman,Dean Sheppard,Patricia J. Sime,Andrew M. Tager,Amanda L. Tatler,Victor J. Thannickal,Eric S. White
标识
DOI:10.1165/rcmb.2017-0096st
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.
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