Transient receptor potential channel activation targets multiple stages of the schistosome parasite.

Authors

Shashank Kulkarni, Sang-Kyu Park, Youssef Hamway, Lukas Friedrich, Jesko Kaiser, Evgeny G Chulkov, Claudia M Rohr, Cécile Häberli, Martin Horn, Tobias Hyun Ho Bäurle, Mario Pellegatti, Gary Grosser, Axel Becker, Rana Afshar, Andreas Becker, Nico Alexander Mell, Floriane Lignet, Philip Hewitt, Annika Hansen, Christian Brenneis, Jan Dvorak, Clarissa Prazeres da Costa, Jennifer Keiser, Jonathan S Marchant, Thomas Spangenberg

Published in

Science translational medicine. Volume 18. Issue 870. Pages eaed8353. Oct 07, 2026. Epub Oct 07, 2026.

Abstract

Schistosomiasis, a neglected tropical disease caused by infection with parasitic blood flukes of the genus Schistosoma, affects more than 250 million people worldwide. Currently, patients rely on a single medicine, praziquantel (PZQ), discovered half a century ago. To combat drug resistance and reach elimination of the schistosome parasite, alternative drugs to PZQ are required that treat and prevent disease. Here, we describe a drug candidate, M5493, with potent activity against multiple parasite life cycle stages. The target is a parasite transient receptor potential ion channel, distinct from the target of PZQ. To circumvent its limited bioavailability, the active agent was converted to prodrug M5493, which displayed robust activity against the schistosome parasite at doses as low as 5 milligrams per kilogram in mice infected with Schistosoma mansoni. Unlike the benzodiazepine meclonazepam, which displays clinical antihelminthic activity through the same target, M5493 showed no sedating side effects given that it did not engage GABA_A receptors. Overall, this compound has the potential to provide single-dose treatment, broad-spectrum efficacy against schistosome parasites at different life cycle stages, and transmission blocking activity.

PMID:
42842722
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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