A range of animal models are currently used to examine emetic (nausea and vomiting) and taste aversive (palatability) side effects of novel chemical entities across the pharmaceutical, chemical, food and agribusiness industries. In the case of emesis, this effect is amongst the most common side effects of current drugs and can cause a dose-limiting toxicity, suggesting that the ability to predict these conditions in preclinical drug development is poor. This can have a substantial impact on drug development and patient compliance. The potential for drugs to cause nausea and vomiting is currently identified in a range of preclinical species including rodents, dog, ferret and non-human primates. These studies are time consuming and costly, and are associated with potentially considerable animal suffering.
Professor Robin Williams from Royal Holloway, University of London, has demonstrated that a simple biomedical model, the social amoeba Dictyostelium, could provide an effective, non-animal, medium-throughput screening model for assessing emetic and palatability liabilities in new chemical entities. They have shown a concentration-dependent response in Dictyostelium to a range of emetic, aversive and bitter compounds. These promising, initial results encouraged Professor Williams to work with the NC3Rs through the CRACK IT Solutions technology partnering hub to engage with the pharmaceutical industry to identify potential collaborators to further develop his model for assessing its utility in an industrial setting.
Through the partnering process, Professor Williams secured support from GlaxoSmithKline and the agrochemical company Syngenta to supply chemicals for which concentration-response data regarding nausea, vomiting or taste aversion is available from both animal models and human volunteers. CRACK IT Solutions funding supported the collaboration in generating proof-of-concept data to demonstrate that the Dictyostelium model is able to accurately and reproducibly identify the rank order of eight compounds supplied by GlaxoSmithKline with a range of bitter potencies.
Based on this, Professor Williams and GlaxoSmithKline are continuing to work together on developing the model further for industry application through a GlaxoSmithKline-funded PhD studentship. This will include further validating the model with a wider set of compounds and automating the assay to increase potential uptake across the industry. If successful, the Dictyostelium model could replace the rodent bitter taste test and reduce some of the animal use for assessing emetic liability.