Mouse Models of Lung Fibrosis.
The drug discovery pipeline, from discovery of therapeutic targets through preclinical and clinical development phases, to an approved product by health authorities, is a time-consuming and costly process, where a lead candidates' success at reaching the final stage is rare. Although the time from discovery to final approval has been reduced over the last decade, there is still potential to further optimize and streamline the evaluation process of each candidate as it moves through the different development phases. In this book chapter, we describe our preclinical strategies and overall decision-making process designed to evaluate the tolerability and efficacy of therapeutic candidates suitable for patients diagnosed with fibrotic lung disease. We also describe the benefits of conducting preliminary discovery trials, to aid in the selection of suitable primary and secondary outcomes to be further evaluated and assessed in subsequent internal and external validation studies. We outline all relevant research methodologies and protocols routinely performed by our research group and hope that these strategies and protocols will be a useful guide for biomedical and translational researchers aiming to develop safe and beneficial therapies for patients with fibrotic lung disease.
['Mekhael|Olivia|O|', 'Naiel|Safaa|S|', 'Vierhout|Megan|M|', 'Hayat|Aaron I|AI|', 'Revill|Spencer D|SD|', 'Abed|Soumeya|S|', 'Inman|Mark D|MD|', 'Kolb|Martin R J|MRJ|', 'Ask|Kjetil|K|']
D000818:Animals D001761:Bleomycin D019295:Computational Biology D003657:Decision Making D004195:Disease Models, Animal D004353:Drug Evaluation, Preclinical D005786:Gene Expression Regulation D053263:Gene Regulatory Networks D006801:Humans D051379:Mice D008810:Mice, Inbred C57BL D011658:Pulmonary Fibrosis
Lung Antifibrotic agents Bleomycin Collagen deposition Cytokines Experimental models of pulmonary fibrosis Myofibroblast Primary/secondary endpoints Pulmonary fibrosis Smooth muscle actin Target engagement