GI Toxicity and Mucositis

 

Epistem's world renowned knowledge of gastrointestinal epithelial biology has been translated into a suite of pre-clinical models. The research of Epistem's co-founders, Prof. Chris Potten and Dr. Cath Booth, identified and characterised the location and behaviour of stem cells in the intestine, including the damaging effects of chemotherapy and radiotherapy on the various cell populations.

These models can be used to support the development of novel therapeutic agents to:

  • prevent or treat gastrointestinal or oral toxicity
  • evaluate the risk of novel therapeutics causing toxicity and devise dosing strategies to minimise off-target responses

Mucositis is a specific form of GI toxicity associated with oncology therapy. Epistem's gold standard in vivo mucositis models can be used to assess potential mucositis therapies and determine whether a novel therapeutic agent causes mucositis. Epistem's mucositis team have been working in this area for over 20 years and were involved in the pre-clinical development of the only licensed prophylactic treatment for oral mucositis; Kepivance® (palifermin marketed by Biovitrum AB). This expertise in radiation biology has been recognised by the NIH where Epistem's models of radiation induced intestinal toxicity have been employed to evaluate potential radiation countermeasures.

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The epithelium provides a barrier between the body and its environment. Due to its dynamic epithelial structure and rapid cell proliferative state, the lining of the small intestine provides a unique environment in which to understand epithelial changes, cell regulation and mechanism of action of novel therapeutic agents. The lining of the intestine consists of a single layer of cells that secrete and absorb substances during digestion. It undergoes continuous renewal: the epithelium covering the finger-like villi in the small intestine completely regenerates weekly.

Epistem's team have developed a powerful understanding of the fundamental control of cell turnover and differentiation in the intestine and have applied this knowledge to elucidate the cause of GI toxicity and how it may be controlled by therapeutics. The application of this understanding to commercial models remains unmatched in the field.

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

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