Snakebite envenoming (SBE) annually kills ~100,000 people worldwide, with 4-fold more suffering life-altering morbidity. Antivenom, the only approved treatment, requires preclinical models to assess efficacy and safety as an essential part of the regulated manufacturing process. In accordance with the World Health Organization (WHO) ‘Guidelines for the production, control, and regulation of antivenom immunoglobulins’, the only validated assays to determine the potential clinical effectiveness of an antivenom are preclinical rodent models (typically mice). These procedures are rated ‘severe’ in the UK and EU, are labour-intensive and require high animal numbers. Following the inclusion of SBE on the WHO Neglected Tropical Disease list in 2017, supported by WHO’s SBE 2019 roadmap, there has been increased research into SBE therapies, focused on improved efficacy, safety and affordability. The increased activity in this area further emphasises the need for a validated, alternative model to the current severe models, to minimise the suffering of thousands of mice per year.
Galleria mellonella have gained momentum as a replacement for vertebrate models in the last decade. Developing a Galleria model for SBE would provide a lower-cost, lower-labour intensive, high-throughput non-vertebrate alternative model.
Following on from our promising pilot data, funded by an NC3Rs project grant we will aim to
- Validate the model to quantify snake venom induced coagulopathy, neurotoxicity and cytotoxicity to mirror pathology observed in rodent in vitro studies
- Complete LD50s (median lethal dose of venom) and ED50s (median effective dose of an antivenom) between Galleria and existing murine data, for a panel of 14 medically important venoms and 3 antivenoms.
- Advocate this model as an alternative to the severe-rated SBE mouse model through;
- incorporation of this model into routine practice at ICP and in academic settings,
- publications, conference presentations and delivering international workshops
- openly share our data on this website for others to access LD50 and ED50 results