An official American Thoracic Society workshop report: use of animal models for the preclinical assessment of potential therapies for pulmonary fibrosis

RG Jenkins, BB Moore, RC Chambers… - American journal of …, 2017 - atsjournals.org
RG Jenkins, BB Moore, RC Chambers, O Eickelberg, M Königshoff, M Kolb, GJ Laurent…
American journal of respiratory cell and molecular biology, 2017atsjournals.org
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 …
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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