Unit | Helminth Drug Development

Together with the Bio Engineering Laboratory at ETH we innovate on an “infected body-on-a-chip” microfluidic EIS platform for antischistosomal drug discovery. The device will allow us to measure continuous, online drug dose-response effects on the larval stage of schistosomes, rendering the screening process higher throughput, more objective, and richer in quality data. The chip will incorporate spherical myocardial and liver microtissues, which, upon exposure to the drug, will capture cardiotoxicity and hepatotoxicity. In summary, our work will transform antischistosomal drug discovery in multiple essential ways, which will ultimately result in novel treatment options.

Drug disposition of praziquantel in the target population has not been properly studied to date. In addition, the optimal dose of praziquantel in preschoolers is not known. We validated a dried blood spot method for praziquantel (Meister et al. 2016) to run pharmacokinetic studies in preschool-aged and school-aged children infected with Schistosoma mansoni and Schistosoma haematobium. Participating children received 20, 40 or 60 mg/kg praziquantel and underwent sampling at different time points. Data analysis is currently ongoing. We anticipate that our date will guide the selection of a safe and effective dose for preschoolers.

Drug combinations for the treatment of soil-transmitted helminthiasis are receiving increasing attention. We have conducted a series of pivotal trials over the past years, for example evaluated the efficacy and safety of oxantel pamoate-albendazole. In the next months we aim to conduct preliminary studies on the efficacy of albendazole and ivermectin in dose-response relationship studies in different population subgroups and study pharmacokinetic properties of ivermectin. In addition, studies have been launched to investigate the safety and efficacy of combinations with tribendimidin and moxidectin.