Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. By using the latest pharmacology techniques in human fresh tissues from the target patient population, combined with genomics and clinical metadata associated with each individual, an improved understanding of the link between genetics and inter-individual drug responses emerges.

Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD) or inflammatory bowel disease (IBD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung or gastrointestinal tissue as the test system.  In order to assess patient variation and responsiveness to both ‘standard of care’ and potential novel therapies, the reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy.  The individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness and demonstrate the combined power of pharmacology and genomics during pre-clinical development.

Within the COPD cohort (n=25 donors), a total of 30 SNPs corresponding to 23 genes were found to be tentatively associated with response to roflumilast plus fluticasone. Several of these genes have already been identified as being associated with COPD or other pulmonary diseases and include; HEY1, SMAD3, BARD1 and FOXP1.