Use of a cytochrome P450 humanized mouse model to refine schistosomiasis drug discovery
)-PZQ and 4OH-PZQ in 8HUM mice at 25 mg/kg bodyweight and >90% reductions in worm burdens at 100 mg/kg bodyweight (equivalent to that seen in WT mice administered PZQ at 400 mg/kg bodyweight). Our results revealed that 8HUM mice recapitulate key features of murine schistosomiasis while exhibiting human-relevant drug metabolism. These findings establish 8HUM as a refined translational platform for anti-schistosomal drug development, improving predictive accuracy and accelerating therapeutic discovery.
Authors
- O Polák
- Mary Evans (ORCID: https://orcid.org/0000-0003-1164-9932)
- Iain W. Chalmers (ORCID: https://orcid.org/0000-0001-8674-1181)
- Benjamin J. Hulme (ORCID: https://orcid.org/0000-0002-5638-6323)
- Gabriel Rinaldi (ORCID: https://orcid.org/0000-0002-7767-4922)
- Matthew Hegarty (ORCID: https://orcid.org/0000-0001-6547-3800)
- Ian H. Gilbert (ORCID: https://orcid.org/0000-0002-5238-1314)
- Sarah D. Davey (ORCID: https://orcid.org/0000-0001-8676-7330)
- Kevin D. Read (ORCID: https://orcid.org/0000-0002-8536-0130)
- V GUIMARAES
- Karl F. Hoffmann (ORCID: https://orcid.org/0000-0002-3932-5502)
- Frederick R. C. Simeons
- Andrew S. MacDonald (ORCID: https://orcid.org/0000-0002-5356-1149)
- Wayne Aubrey (ORCID: https://orcid.org/0000-0003-3351-1758)
- Amy Tavendale
- Nicola Caldwell (ORCID: https://orcid.org/0000-0002-1049-4185)
- Rémi Pichon (ORCID: https://orcid.org/0000-0002-5821-9529)
- Beatriz Baragaña (ORCID: https://orcid.org/0000-0002-0959-1113)
- Laste Stojanovski
- Alice H. Costain (ORCID: https://orcid.org/0000-0002-3920-7776)
- Josephine Forde-Thomas (ORCID: https://orcid.org/0000-0002-7202-3565)
- Kristin Lees
- Bismark Dankwa
- Brenda Kisia Odhiambo
- Yi-Hsuan Lee (ORCID: https://orcid.org/0009-0009-6530-6469)
- Martin T. Swain
- Laura Frame
- A. Kenneth MacLeod
Institutions
- Aberystwyth University (GB)
- Morpho (United States) (US)
- University of Dundee (GB)
- Universidade Federal de São Carlos (BR)
- Institute of Infection and Immunity (CA)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-04-10
- DOI
- https://doi.org/10.1073/pnas.2600197123
- Primary Topic
- Parasites and Host Interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome
- UK Research and Innovation