The Journey to Discovering a Flatworm Target of Praziquantel: A Long TRP

Infections caused by parasitic flatworms impose a considerable worldwide health burden. One of the most impactful is schistosomiasis, a disease caused by parasitic blood flukes. Treatment of schistosomiasis has relied on a single drug - praziquantel (PZQ) - for decades. The utility of PZQ as an essential medication is, however, intertwined with a stark gap in our knowledge asto how this drug works. No flatworm target has been identified that readily explains how PZQ paralyzes and damages schistosomes. Recently, a schistosome ion channel was discovered that is activated by PZQ and displays characteristics which mirror key features of PZQ action on schistosomes. Here, the journey to discovery of this target, properties of this ion channel,and remaining questions are reviewed.