Sabina Antonela Antoniu1, Martin Rj Kolb. 1. Assistant Lecturer, 'Gr T Popa' University of Medicine and Pharmacy Iaşi, Pulmonary Disease University Hospital, Department of Internal Medicine-Pulmonary Disease, 30 Dr I Cihac Street, 700115 Iasi, Romania.
Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease with high morbidity and mortality for which current medications are not effective. Therefore, identification of potential therapies is of paramount importance. The preclinical evaluation of novel compounds in animal models represents a critical step in drug development. OBJECTIVE: To describe features and limitations of common animal models of pulmonary fibrosis and discuss relevant preclinical and clinical data on novel potential IPF therapies. METHODS: Review of the existing literature on such models with a special focus on the bleomycin model and its usefulness for the IPF preclinical drug testing. CONCLUSIONS: The model of bleomycin-induced pulmonary fibrosis has the advantages of being well established, reproducible and both time- and cost-efficient. However, it has major limitations as it only mimics some features of human IPF. Most importantly, it is initiated by acute lung injury and is at least partially reversible, which is strikingly different from IPF. The failure in establishing effective IPF therapies despite strong efforts in the last decade is partly attributable to our uncritical trust in the models of lung fibrosis and the false belief that they truly reflect what is going on in human disease.
BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a disease with high morbidity and mortality for which current medications are not effective. Therefore, identification of potential therapies is of paramount importance. The preclinical evaluation of novel compounds in animal models represents a critical step in drug development. OBJECTIVE: To describe features and limitations of common animal models of pulmonary fibrosis and discuss relevant preclinical and clinical data on novel potential IPF therapies. METHODS: Review of the existing literature on such models with a special focus on the bleomycin model and its usefulness for the IPF preclinical drug testing. CONCLUSIONS: The model of bleomycin-induced pulmonary fibrosis has the advantages of being well established, reproducible and both time- and cost-efficient. However, it has major limitations as it only mimics some features of human IPF. Most importantly, it is initiated by acute lung injury and is at least partially reversible, which is strikingly different from IPF. The failure in establishing effective IPF therapies despite strong efforts in the last decade is partly attributable to our uncritical trust in the models of lung fibrosis and the false belief that they truly reflect what is going on in human disease.
Authors: Jun Tashiro; Gustavo A Rubio; Andrew H Limper; Kurt Williams; Sharon J Elliot; Ioanna Ninou; Vassilis Aidinis; Argyrios Tzouvelekis; Marilyn K Glassberg Journal: Front Med (Lausanne) Date: 2017-07-28