Personalized Medicine In Translation

Welcome to Personalized Medicine In Translation (PERMIT)

Personalized medicine is both an emerging discipline and a destination. The goal of PERMIT – the ITMAT center for PERsonalized Medicine In Translation (PERMIT) – is to shorten its path and accelerate its arrival. A major current focus of the PERMIT program is to integrate the efforts of ITMAT and the CTSA with those of the NHLBI supported Personalized NSAID Therapeutics Consortium, a group of roughly 40 investigators from diverse backgrounds focused on the integration of data drawn from experiments in 5 model systems, yeast and mammalian cells, zebrafish, mice and humans, to develop predictive paradigms around analgesic efficacy and cardiovascular risk of nonsteroidal anti-inflammatory drugs (NSAIDs) that will then be tested at scale.

The consortium plans to compare the effects of two pharmacological probes – celecoxib and naproxen – that favor inhibition of Prostaglandin G/H synthase -2 or COX-2 and COX-1 respectively across these systems. Outputs will include genomic, epigenomic, proteomic , lipidomic, imaging, metabolomic and microbiomic (GEPLIMM) data. Novel tools will be developed to integrate data such that they can be analyzed for differential systems perturbation across a range of concentrations of the pharmacological probes, adjusting for drug exposure and variables such as timing of drug administration and gender. Observational studies, linking data from electronic medical records to genomic and biomarker based evidence of variability of drug response will be used to generate hypotheses which will be tested a priori in the model systems which include deep phenotyping studies in humans. Ultimately, systems approaches will be utilized to develop hypotheses to be tested prospectively in controlled trials at scale to attempt to refine prediction of efficacy and risk beyond the current approach based on the "art" of medicine.

In its current configuration, PERMIT represents an example where the NCATS supported CTSA adds value by expanding the scope of an initiative stemming from another NIH institute, in this case NHLBI. NHLBI has a primary interest in the prediction of cardiovascular risk from NSAIDs, whereas this is logically linked to the prediction of efficacy – in this case analgesic efficacy. It is hoped that the lessons learned from the 10 year PENTACON program can then be exported to parsing variability in drug response to establishing a science base for the prediction of efficacy and risk from other commonly used drug classes beyond NSAIDs.