Authors
D Cutress1; 1 Aberystwyth University - IBERS Discussion
The Liver flukes, Fasciola hepatica and F. gigantica are zoonotic parasitic flatworms of significant health and economic interest. Predictions on livestock production estimates losses at over $3 billion annually in reduction in meat, milk and other agriculturally significant yields. The WHO has also designated fascioliasis, liver fluke disease, as a neglected food borne human disease with up to 17 million infections and up to 200 million people living in areas at risk. In absence of vaccines, the current mainstay treatment is Triclabendazole (TCBZ); the only drug effective against both juvenile and adult flukes. However, evidence of TCBZ resistance is now confirmed worldwide and new chemical compounds are being discovered or designed and synthesised to novel protein targets in liver flukes to combat increasing TCBZ resistance. Sigma class glutathione transferases aka prostaglandin D synthases offers a key target, due to well characterised role in immune modulation and limited relationship to host orthologues and potential roles specific life cycle stages. Using structure - activity response studies and computer assisted modelling, drug structures are being designed and synthesised to screen for activity and specificity. Enzyme kinetic studies are being used to elucidate compound inhibitory profiles in comparison between native and recombinant enzymes, prior to lead compounds being measured for toxicity in cell lines and ultimately animal tolerance testing. 
