Unit | Helminth Drug Development

Testing Deworming Drugs with School Children, Pemba Island in Tansania, 2014

Our research team is interested in identifying and developing novel, broad spectrum and orally active drugs against helminthic diseases, including soil-transmitted helminthiasis, schistosomiasis and food-borne trematodiases.

Need for Novel Anthelminthic Drugs

Soil-transmitted helminthiasis, schistosomiasis and food-borne trematodiases affect hundreds of millions of people, particularly those living in poor rural communities of the developing world. So far, a vaccination is not available and is unlikely to be soon. Accordingly, therapeutic drugs, regularly administered, are the only way to control morbidity. Due to the fact, that only very few of those drugs are currently on hand the development of new, safe and efficacious anthelminthics is indispensable.

Our Research Activities

The research in our unit covers a broad spectrum of activities, from drug discovery to development, from bench work to clinical trials in the field. We are an interdisciplinary team of technicians, PhD students, Postdocs, or civil servants trained as biologists, pharmacists, epidemiologists or physicians. 

We maintain a unique and large range of helminth life cycles for our drug discovery work. In addition, we are developing assays to screen promising molecules for drug discovery . Another main research emphasis is preclinical work. We investigate the drug disposition and metabolic parameters of anthelminthic drugs and drug development candidates. Finally, we are running human clinical trials in endemic countries to assess the safety and efficacy of oral antihelminthics or drug combinations.

Infected Body-on-a-Chip

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.

Pharmacokinetics of Praziquantel

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.

Combination Chemotherapy for Soil-Transmitted Helminthiasis

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.

Gétaz M et al. A diagnostic tool for improved detection of Xanthomonas fragariae using a rapid and highly specific LAMP assay designed with comparative genomics. Plant Pathology. 2017(in press). DOI: 10.1111/ppa.12665

Moser W, Labhardt N.D, Cheleboi M, Muhairwe J, Keiser J. Unexpected low soil-transmitted helminth prevalence in the Butha-Buthe district in Lesotho, results from a cross-sectional survey. Parasit Vectors. 2017;10(1):72. DOI: 10.1186/s13071-017-1995-x

Cowan N, Vargas M, Keiser J. In vitro and in vivo drug interaction study of two lead combinations, oxantel pamoate plus albendazole and albendazole plus mebendazole, for the treatment of soil-transmitted helminthiasis. Antimicrob Agents Chemother. 2016;60(10):6127-6133. DOI: 10.1128/AAC.01217-16

Flores D, Panic G, Braissant O, Keiser J. A novel isothermal microcalorimetry tool to assess drug effects on Ancylostoma ceylanicum and Necator americanus. Appl Microbiol Biotechnol. 2016;100(2):837-846. DOI: 10.1007/s00253-015-7081-4

Cowan N, Raimondo A, Keiser J. Approved oncology drugs lack in vivo activity against Trichuris muris despite in vitro activity. Parasitol Res. 2016;115(11):4443-4446. DOI: 10.1007/s00436-016-5225-9