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Life cycle maintenance and drug-sensitivity assays for early drug discovery in Schistosoma mansoni

Lombardo, Flavio C. and Pasche, Valérian and Panic, Gordana and Endriss, Yvette and Keiser, Jennifer. (2019) Life cycle maintenance and drug-sensitivity assays for early drug discovery in Schistosoma mansoni. Nature Protocols, 14 (2). pp. 461-481.

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Official URL: https://edoc.unibas.ch/69737/

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Abstract

Drug discovery for schistosomiasis is still limited to a handful of academic laboratories worldwide, with only a few novel antischistosomal lead compounds being actively researched. Despite recent international mobilization against the disease to stimulate and promote antischistosomal drug discovery, setting up a drug-screening flow with schistosome parasites remains challenging. Whereas numerous different protocols to obtain and cultivate schistosomes have been published, those describing the drug-screening process are scarce, and none gather together parasite cultivation and early drug discovery procedures. To help overcome this hurdle, we provide here a set of integrated methods either adapted from already-published protocols or based on our long-term experience in schistosomiasis research. Specifically, we detail the establishment and maintenance of the complex and several-week-long Schistosoma mansoni life cycle in a laboratory setting, as well as the means of retrieving and culturing the parasites at their relevant life stages. The in vitro and in vivo assays that are performed along the drug-screening cascade are also described. In these assays, which can be performed within 5 d, the effect of a drug is determined by phenotypic assessment of the parasites' viability and morphology, for which stage-specific scoring scales are proposed. Finally, the modalities for testing and evaluating a compound in vivo, constituting a procedure lasting up to 10 weeks, are presented in order to go from in vitro hit identification to the selection of early lead candidates.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Lombardo, Flavio and Pasche, Valérian and Panic, Gordana and Endriss, Yvette and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:1754-2189
e-ISSN:1750-2799
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:12 Mar 2019 10:13
Deposited On:12 Mar 2019 10:13

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