Consomic rat panels for pharmacogenomic studies and target identification

DESCRIPTION (provided by applicant): PhysioGenix plans to commercialize a rat discovery platform that markedly accelerates the deployment of genetic tools for drug development by Pharma. While genetics can offer pharmaceutical companies a powerful discovery tool, this strategy has not been widely adopted because traditional methods are too slow. The consomic rat panels are validated as a strategy for pharmaceutical researchers to discover new therapeutics targets and treatments for common human diseases, like hypertension and the associated cardiovascular and renal diseases, in a parallel fashion never before available to the industry. The consomic technology is a fast way (6-9 months) to go from mapping disease quantitative trait loci to identifying a handful of targets while enabling parallel functional studies in rats. No other genetic technology is close to this pace. The consomic technology we plan to commercialize is comprised of two complete rat panels each having 22 chromosomal substitution strains. Since the introgressed chromosomes come from a ?normal? strain superimposed upon a ?diseased? genome background, curing a disease phenotype provides a bioassay to screen for protective genes that can lead to the discovery of new therapeutic targets. To date, consomic rats have been successfully used in academia to identify chromosomes that cure salt-sensitive hypertension, global ischemia and end-stage renal disease. The goal of this Fast-Track application is to support PhysioGenix?s efforts to move the consomic rat panels from the academic sector into Pharma?s preclinical drug development programs. In Phase I studies, we will complete the transfer and re-derivation of one consomic panel (SS.BN) to our commercial breeder, mine the PhysGen database for clinically relevant phenotypes and characterize the progenitor strains (FHH, SS and BN) for neuropsychiatric disorders (e.g. immobility for depression and open-field activity monitoring for hyperactivity). We will also combine the PhysGen data into more usable datasets for our Pharma clients, as well as providing internal leads for PhysioGenix scientists. In Phase II, PhysioGenix will finish cleaning up the second consomic panel (FHH.BN), measure phenotypic traits for neuropsychiatric disorders in both consomic panels and extend the technology to new applications, like pharmacogenomics. In this latter case, we will perform testing with tacrine (a commonly used Alzheimer?s medication with hepatotoxic side effects) to validate the consomic rat panels as a tool to identify the genetic basis of drug efficacy and toxicity. As the era of genomics begins to impact medicine, we wonder how can progress be made without a reliable model system for pharmacogenetic testing? The consomic rat panels may represent the critical tool for the realization of personalized medicine.