Organoids as novel tool for drug development

Organoids as novel tool for absorption, transport, metabolism and toxicology modeling in drug development

Hubrecht Organoid Technology (HUB) in partnership with Janssen Pharmaceutica established human and pre-clinical animal liver and gastrointestinal (GI) tract organoids and validated their use for pharmaceutical industry.  

The outcome of the project will improve all drug development processes resulting in reduced cost and timelines. Additionally, since organoids are recapitulating actual tissue responses to medicinal compounds safety assessment studies will be more predictive compare to traditional models which in the end will lead to improved therapeutics. Last but not least, use of pre-clinical animal model will reduce the use of animals in the drug development industry which is in accordance with the Three Rs (3Rs) principal in relation to the ethical use of animals in drug testing. 

Different differentiation media condition was tested to differentiate proliferating organoids to differentiated organoids containing physiologically representative epithelial cell types. Differentiated organoids were exposed to the most relevant liver or GI tract metabolizing enzyme substrates and shown that the organoids metabolism function is superior compared to current models. For permeability and transport studies, epithelium monolayers using organoids were established, differentiated and functionally validated. Differentiated monolayers were exposed to tool compounds to measure their barrier function, permeability and transport. Finally, human and pre-clinical animal species GI tract region organoids were exposed to multiple compounds and it was shown that organoids are capable to differentiate mode of action, interspecies, regional and organ specificity toxicity. 

In conclusion, pre-clinical toxicity assessment of compounds using organoids avoid costly traditional animal experiments and provide quick indication of drug safety allowing decision making at early stages of drug development. Therefore, organoid technology will have considerable impact on drug development costs and reduce the healthcare financial burden on the society.  

Summary
Drug development is often hampered due to the lack of reliable and relevant in vitro model systems to test newly developed medicinal compounds. Organoids are generated from adult stem cells and can faithfully recapitulate actual tissue responses to external stimuli. This project validated organoids application for drug development in the pharmaceutical industry.
Technology Readiness Level (TRL)
NULL
Time period
30 months
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