Author:
Groveman Bradley R.,Ferreira Natalia C.,Foliaki Simote T.,Walters Ryan O.,Winkler Clayton W.,Race Brent,Hughson Andrew G.,Zanusso Gianluigi,Haigh Cathryn L.
Abstract
AbstractCreutzfeldt–Jakob Disease (CJD) is a fatal, currently incurable, neurodegenerative disease. The search for candidate treatments would be greatly facilitated by the availability of human cell-based models of prion disease. Recently, an induced pluripotent stem cell derived human cerebral organoid model was shown to take up and propagate human CJD prions. This model offers new opportunities to screen drug candidates for the treatment of human prion diseases in an entirely human genetic background. Here we provide the first evidence that human cerebral organoids can be a viable model for CJD drug screening by using an established anti-prion compound, pentosan polysulfate (PPS). PPS delayed prion propagation in a prophylactic-like treatment paradigm and also alleviated propagation when applied following establishment of infection in a therapeutic-like treatment paradigm. This study demonstrates the utility of cerebral organoids as the first human 3D cell culture system for screening therapeutic drug candidates for human prion diseases.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
CJD Foundation
National Institutes of Health
Publisher
Springer Science and Business Media LLC
Cited by
37 articles.
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