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Genetics and Environment: Their Influence on Rational Drug Therapy for Asthma

Custovic A, Simpson A.

RDD Europe 2011. Volume 1, 2011: 1-10.

Abstract:

Despite considerable effort by the pharmaceutical industry and academia to develop novel therapeutic agents, little has changed in the approach to asthma management in the last five decades, and inhaled corticosteroids remain the cornerstone of treatment. One of the problems in the search for novel targets is the relatively poor understanding of the mechanisms underlying asthma. This is due in part to phenotypic heterogeneity and poor phenotype definition, and to the existence of numerous gene-environment interactions. This makes reproducible studies aiming to understand the mechanisms of asthma extremely difficult (if not impossible). The first step towards better understanding of asthma is to accept that it is not a single disease entity, but a conglomerate of several distinct diseases presenting with similar symptoms. “Phenotypes” of asthma can be re-defined using rich data sets, through the fusion of computational thinking and novel mathematical approaches with genetics, biomedical and environmental science. These novel phenotypes may better reflect the different underlying pathophysiological processes and molecular pathways underpinning each of the diseases in the “asthma” syndrome, and may be more relevant for genetic and environmental association studies. This strategy may lead to the development of methods for prevention and new drugs for treatment of different “asthmas” that are genotype and phenotype-specific, and identification of target molecules for drug discovery.