Epistem's in vivo model of GI toxicity can be used to determine detrimental off-target effects of a novel therapeutic agent.
Following the identification of possible signs of intestinal toxicity, such as villus blunting and diarrhoea, Epistem's models can be applied to determine the target cell population, mechanism of action and kinetics of the response. This can be informative in establishing a dosing schedule with minimal off-target effects and progressing novel therapeutic agents through the drug discovery pipeline.
Novel therapeutic agent is administered and signs of intestinal toxicity are monitored. Using Epistem's expertise and in-house data on the crypt cell targets of existing therapeutic agents, suitable analysis can be performed to determine the target cell population, mechanism of action and pK/pD response.
- Weight loss
- Mucosal bleeding / occult blood
- Bowel weight : length ratio
- Crypt and villus length and number
- Muscle thickness
- Mucositis severity / ulcer size
- Apoptosis, differentiation and proliferation
- Protein expression
- Gene expression