Currently, the FDA asks for animal safety data to be included in all IND submissions. Most of these studies collect the standard endpoints, such as signs associated with dosing, clinical signs, body weight, food consumption, hematology, blood chemistry, organ weights, macro- and histopathology. These tests rarely require all of the tissue and therefore much of this valuable material goes unused.
This extra tissue can be used to develop a more complete data set. For example, subcellular fractions (e.g. S9 and microsomes or isolation) or total RNA can be isolated from most tissues. These can then be used to measure specific enzyme activities or to look at changes in gene expression caused by the test agent. Blood can be collected and used to prepare peripheral blood mononuclear cells (PBMCs) for use in stem cell technologies. The biochemical data obtained from subcellular fractions and the gene data from RNA extraction can provide greater insight into both the pharmacokinetic and pharmacodynamic effects of a test compound.
As little as one gram of tissue can provide enough material to prepare subcellular fractions, while less than half a gram of tissue can yield enough RNA to evaluate an array of target genes or gene panels, such as those controlled by Nrf2 or metabolism by cytochrome P450 enzymes.
IONTOX has designed our Ex-vivo data program to maximize the information that can be obtained from in vivo studies in the pharmaceutical and chemical industries.