Repositioning histone modifying enzyme (HME) inhibitors as next-generation flukicides

Fasciola hepatica is one of the aetiological trematodes of the global zoonotic disease, fascioliasis, which impacts agricultural, veterinary and medical systems on a global scale. Widespread use of the primary flukicide, triclabendazole (TCBZ) has led to developing anthelmintic resistance which threatens the security and sustainability of agricultural systems. Fascioliasis is now considered an emerging neglected disease and research efforts into novel therapies must urgently be prioritised. Histone modification enzymes (HMEs) have previously been targeted in anthelmintic development research, as studies in Schistosoma mansoni have demonstrated a targetable influence of these enzymes over parasite growth and development. This project aims to reposition HME inhibitors to determine their potential as novel flukicides. To achieve this, there are three main objectives:

1) Characterisation of the histone modification enzymes of Fasciola hepatica.
2) Validation of HMEs as potential targets for inhibitors.
3) Improvement of image analysis tools and AI models for motility and phenotype scoring in the juvenile stage.