We have funded two collaborations to integrate an insect model marketed by BioSystems Technology into the development pipeline of Demuris, an antibiotic drug discovery company, and to evaluate the potential to replace the use of rats in the acute oral toxicity testing of chemicals at Covance CRS, a global contract research organisation.
Solution provider: Dr Olivia Champion
Duration: 6 months + 6 months
Organisation: BioSystems Technology
Amount: £12k + £12k
Start date: 2016
Project partners: Demuris + Covance CRS
BioSystems Technology, a spin-out company founded by Dr Olivia Champion from the University of Exeter, was formed to provide research grade larvae of the wax moth Galleria mellonella (referred to as TruLarv). Wax moth larvae have been used extensively to study host/pathogen interactions, replacing the use of vertebrate models for some experiments. However, with pet-food grade larvae the main source, concerns about quality assurance and reproducibility have limited wider uptake of this model organism. TruLarv are weight and age defined, surface decontaminated and bred without the use of antibiotics or other drugs, making the model more amenable to industry users.
Working with Demuris, Olivia and her team demonstrated that TruLarv can be used to assess the toxicity and efficacy of naturally occurring antibiotics against Gram-negative and Gram-positive human pathogens. Based on this, Demuris is now purchasing the larvae from BioSystems Technology to evaluate their antibiotic compounds against a range of bacterial pathogens, saving around 200 animals a year.
Collaborating with Covance CRS, the team investigated whether TruLarv can minimise the use of rats in the acute oral toxicity testing of chemicals. They tested 19 chemicals provided by Covance CRS and compared the findings with historic data from rodent acute oral LD50 studies and two in vitro cytotoxicity assays. For chemicals classified as non-toxic, the level of concordance with the rodent data was 100% for TruLarv and 44% for the cytotoxicity assays. The findings were published in Chemosphere in 2018.
The high rate of false positives with the cytotoxicity assays suggests that fewer animal studies could be conducted by using TruLarv to generate data contributing to the evidence base for waiving testing for some chemicals. Covance CRS estimates they could replace the use of around 450 rats a year with TruLarv and Olivia continues to work with Covance CRS to realise this potential.
BioSystems Technology now export TruLarv to customers in 11 countries. In 2017, they received £100k from Innovate UK for the development of genetic tools to engineer the larvae.
Demuris provided crude actinomycete extracts for validation studies. Covance CRS supplied compounds for testing in TruLarv.
This case study was published in our 2019 CRACK IT Review.