The Use of Mouse Asthma Models to Successfully Discover and Develop Novel Drugs

The past 20 years have seen a proliferation of scientific data on the pathophysiology of asthma. Most of these data were generated in mice using tool reagents, gene-deficient or transgenic animals. In contrast, studies on disease pathogenesis in patients are scarce. Previously, a good novel antiasthma target for drug development was one that abrogated asthma in mice when it was knocked out, neutralized or induced asthma when it was overexpressed. This type of approach led to many drug candidates that worked in mice but unfortunately failed in patients, thereby demonstrating that the results of experiments in mice are not always predictive of clinical efficacy. Currently, there is active debate about the use of mouse models in drug discovery. In this review, we summarize the obstacles and challenges faced when using experimental mouse models of asthma in drug discovery. We propose that the initial selection of a novel drug target begins with defining the unmet medical need and specific patient population, followed by a thorough evaluation of available human data, and, only then, well-planned and executed mouse asthma experiments. Using this approach, we argue that mouse models lend support for the target when the models are tailored for the specific asthma patient population, and that targeted, reliable, and predictive mouse models can indeed improve and accelerate the drug discovery process.
Int Arch Allergy Immunol 2017;173:61-70

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