Airway disease: the use of large animal models for drug discovery

Abstract

Large animal models have contributed to our current understanding of respiratory pathophysiology and the effects of pulmonary disease modifying drugs. For drug development, the benefit of using large animals over smaller animal species is primarily due to the greater similarity between humans and equivalent sized animals in terms of gross anatomy, morphometry, structure and physiology of their respiratory systems. Thus, when appropriate lung structure and function are required for correctly assessing the efficacy of novel drugs, large animals can play an important role in the development of these drugs to combat respiratory disease. The most widely used and best characterised large animal for drug development has been the sheep model of asthma. Recently, large animal models for chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) have been reported but thus far have not been used extensively for drug development. Some important limitations of using large animals are the large costs associated with this type of research, as well as the poorer understanding of disease mechanisms in these species relative to rodents. In this review we discuss the extent of correlations between preclinical testing performed in large animal models and the initial indication of clinical efficacy in ongoing clinical trials.