An estimated 1.5 billion people are infected with soil-transmitted helminths (STHs) causing a global burden of 1.9 million disability-adjusted life years (DALYs). Current treatment options are limited. Preliminary studies in my lab hint towards a gut microbiome mechanism responsible for treatment failures of the most efficacious treatment currently available, albendazole-ivermectin. I propose an innovative 5-year project (“DRUGSBUGS”) that holds promise for major breakthroughs in anthelminthic drug discovery and development. I will deepen the understanding of current and potentially upcoming anthelminthics, in particular the microbiome-driven modulation of anthelminthic treatment. I will investigate underlying gut microbial structures in human stool samples associated with efficacy of albendazole-ivermectin treatment. Findings will be experimentally validated in vitro and in vivo. In addition, I speculate that emodepside will emerge as a novel key player in the anthelminthic drug armamentarium, which will enhance efficacy and reduce the risk of selection of resistant helminth populations. DRUGSBUGS proposes two Phase 2a dose selection trials with emodepside against Trichuris trichiura and hookworm in adults. Subsequent Phase 2b studies will assess whether emodepside is superior to albendazole against hookworm and T. trichiura. Using a microsampling technique, I will characterize the pharmacokinetics of emodepside in patients infected with T. trichiura and hookworm. In parallel, investing in innovative new technologies in the field of drug discovery will facilitate the discovery and development of the next generation of anthelminthics. I propose to study drug effects on motility and viability of different STH larvae applying electrical impedance spectroscopy on a microfluidic chip platform. My proposed research is of considerable public health relevance since it will ultimately result in improved treatments for soil-transmitted helminthiases.
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