The concept of a pre-clinical, drug screen for genetic effects was developed by PhysioGenix in Phase I of this project. The screen consists of inbred rats bred in a combinatorial fashion such that F1 offspring mimic the genetically diverse human population, while maintaining the phenotypic accuracy of an inbred strain. Phase I studies showed that the combinatorial rat panel (termed the PharmGenix Panel) can detect both the general and genetic components of adverse drug effects better than commonly used inbred or outbred strains. In Phase II studies, PhysioGenix will test eight more compounds to further validate that the PharmGenix Panel has enhanced sensitivity and specificity to predict toxic effects in kidney, liver, and heart. Unexpectedly, prospective clients our now requesting that we increase the amount of diversity captured, beyond the outbred. To accomplish this goal means that the number of animals required per toxicity screen will be proportionately increased. In response, supplemental studies proposed here will compare the results from two PharmGenix Panels (12 total Fls) to determine whether a subset of the rat strains can be used without significantly losing power. This is especially important when considering those compounds that have previously passed animal testing but failed in humans. ? ?
