Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease

Abstract Creutzfeldt–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 org...

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Autores principales:	Bradley R. Groveman, Natalia C. Ferreira, Simote T. Foliaki, Ryan O. Walters, Clayton W. Winkler, Brent Race, Andrew G. Hughson, Gianluigi Zanusso, Cathryn L. Haigh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/349388bbff72452db46c3047ea9cc10f
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spelling	oai:doaj.org-article:349388bbff72452db46c3047ea9cc10f2021-12-02T11:37:18ZHuman cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease10.1038/s41598-021-84689-62045-2322https://doaj.org/article/349388bbff72452db46c3047ea9cc10f2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84689-6https://doaj.org/toc/2045-2322Abstract Creutzfeldt–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.Bradley R. GrovemanNatalia C. FerreiraSimote T. FoliakiRyan O. WaltersClayton W. WinklerBrent RaceAndrew G. HughsonGianluigi ZanussoCathryn L. HaighNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bradley R. Groveman Natalia C. Ferreira Simote T. Foliaki Ryan O. Walters Clayton W. Winkler Brent Race Andrew G. Hughson Gianluigi Zanusso Cathryn L. Haigh Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
description	Abstract Creutzfeldt–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.
format	article
author	Bradley R. Groveman Natalia C. Ferreira Simote T. Foliaki Ryan O. Walters Clayton W. Winkler Brent Race Andrew G. Hughson Gianluigi Zanusso Cathryn L. Haigh
author_facet	Bradley R. Groveman Natalia C. Ferreira Simote T. Foliaki Ryan O. Walters Clayton W. Winkler Brent Race Andrew G. Hughson Gianluigi Zanusso Cathryn L. Haigh
author_sort	Bradley R. Groveman
title	Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
title_short	Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
title_full	Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
title_fullStr	Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
title_full_unstemmed	Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease
title_sort	human cerebral organoids as a therapeutic drug screening model for creutzfeldt–jakob disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/349388bbff72452db46c3047ea9cc10f
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Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt–Jakob disease

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