Pre-clinical toxicity models
Determining how drugs are metabolised.
In our pre-clinical toxicity models, human embryonic stem cells (hESCs) are differentiated towards different cell types (neurons, hepatocytes, enterocytes, etc) and aslo in tissue-specific organoids. Such non-diseased cellular models have great advantage over current cell based toxicity tests in cell-type specific relevance. In addition, we are developing hESCs with deletion of genes that are responsible for the majority of drug metabolism, for example, CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2. These cellular pre-clinical models of drug metabolism are of great importance in determining how drugs are metabolised, if there are inhibitors or inducers of some enzymes of drug metabolism. This aspect is very relevant because according to the USA FDA 20% of patients who die in USA hospitals are the product of the adverse effects of drugs in which a drug potentiates or inhibits a drug metabolising enzyme, generating fatal effects.
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