GI Toxicity and Mucositis

GI Toxicity Models

Epistem's extensive knowledge of the gastrointestinal epithelium has been translated into models to assess the effects of novel therapeutic agents on the GI tract. Both in vitro and in vivo models can be applied to determine the type and level of toxicity and determine the cause of any observed pathologies.

An important consideration in the development of a novel therapeutic agent is the potential for off-target effects on the GI tract. The cells lining the crypts of the small intestine are the most rapidly proliferating in the body and therefore sensitive to the effects of many therapeutic agents. Damage to stem cells within the intestinal crypts leads to cell and villus loss, ulceration and inflammation of the epithelium, compromising the integrity of the GI tract.

Novel therapeutic agents which affect cell proliferation may induce hyperplasias, causing bowel obstruction and increasing the risk of developing cancer. Agents which affect cell differentiation can influence mucin production and absorptive function, impacting on the efficiency and integrity of the GI tract.

Epistem's models can be used to understand the potential to cause GI toxicity and define the mechanism of action. Once understood, it may be possible to determine a dosing regimen with an improved GI safety profile.

Epistem's Models of Gastrointestinal Toxicity:

H&E staining of normal crypts of the small intestine

H&E staining of normal crypts of the small intestine

PAS stained goblet cells on intestinal villi

PAS stained goblet cells on intestinal villi

© 2013-17 Epistem Ltd. : : last modified: 04 Nov 2013

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