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U.S.A."],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:p>Prion diseases represent a unique biological paradigm with mechanistic parallels to other neurodegenerative conditions like Alzheimer\u2019s and Parkinson\u2019s diseases. However, the study of human prion pathobiology and the development of effective therapeutics has been severely constrained by the inability to propagate human prions in dividing cells\u2014forcing reliance on costly and slow animal bioassays. Here, we report the generation of EKV cells\u2014a humanized cell model which supports the robust, indefinite propagation of sporadic Creutzfeldt\u2013Jakob disease (sCJD) prions. We demonstrate that these cells replicate bona fide human prion infectivity in culture\u2014cell lysates induce lethal neurodegeneration in humanized mice that is clinically and neuropathologically indistinguishable from inoculation with sCJD-infected brain tissue. We use EKV cells to develop the Human Prion Assay (HPA), which quantifies sCJD infectivity with sensitivity comparable to gold-standard mouse bioassay, while reducing the experimental timeline from years to weeks. Furthermore, we demonstrate that established sCJD infection can be cured by an anti-prion protein antibody, validating the system as a high-throughput platform for drug discovery. This model bridges a critical translational gap, offering a renewable alternative to animal bioassays, a paradigm to dissect the biology of human sCJD prion disease and screen for therapeutic agents.<\/jats:p>","DOI":"10.1073\/pnas.2600341123","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T17:43:55Z","timestamp":1782841435000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt\u2013Jakob disease prions"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2892-1402","authenticated-orcid":false,"given":"Akin","family":"Nihat","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Prion Unit at University College London, University College London Institute of Prion Diseases","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Service Foundation Trust","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5198-8666","authenticated-orcid":false,"given":"Parineeta","family":"Arora","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Prion Unit at University College London, University College London Institute of Prion Diseases","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schmidt","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical Research Council Prion Unit at University College London, University College London Institute of Prion Diseases","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-505X","authenticated-orcid":false,"given":"Melissa L. 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