Therapeutic effect of curcumin derivative GT863 on prion-infected mice

Abstract In prion diseases, the cellular prion protein (PrPC) forms an abnormal, infectious, and disease-causing form known as PrPSc. Inhibition of prion propagation is a key approach for the treatment of these diseases. We report on a curcumin-based compound, GT863 (formerly known as PE859) that di...

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Main Authors: Kenta Teruya, Ayumi Oguma, Michiaki Okuda, Sara Iwabuchi, Hiroyuki Konno, Hiroyuki Arai, Yukitsuka Kudo, Hachiro Sugimoto, Katsumi Doh-ura
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-89317-1
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author Kenta Teruya
Ayumi Oguma
Michiaki Okuda
Sara Iwabuchi
Hiroyuki Konno
Hiroyuki Arai
Yukitsuka Kudo
Hachiro Sugimoto
Katsumi Doh-ura
author_facet Kenta Teruya
Ayumi Oguma
Michiaki Okuda
Sara Iwabuchi
Hiroyuki Konno
Hiroyuki Arai
Yukitsuka Kudo
Hachiro Sugimoto
Katsumi Doh-ura
author_sort Kenta Teruya
collection DOAJ
description Abstract In prion diseases, the cellular prion protein (PrPC) forms an abnormal, infectious, and disease-causing form known as PrPSc. Inhibition of prion propagation is a key approach for the treatment of these diseases. We report on a curcumin-based compound, GT863 (formerly known as PE859) that displays therapeutic efficacy when administered orally. GT863 inhibited abnormal prion protein formation in prion-infected neuroblastoma cells in a prion strain dependent manner: effectively for RML prion and marginally for 22 L prion. Treatment with ad libitum GT863-containing feed prolonged the incubation period of intracerebrally RML prion infected Tga20 mice by 217% increase in mean. Although the 263 K prion-infected Tg7 mice were less sensitive to GT863 than RML prion infected Tga20, treatment with ad libitum GT863-containing feed prolonged the incubation period by 39% increase in mean. The mechanism of the anti-prion effectiveness in vivo needs to be elucidated and managed. Nevertheless, GT863 could inspire the development of oral chemotherapy for prion diseases.
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spelling doaj-art-7e60f00b3a024ca2a2740285fa12925d2025-08-20T03:00:59ZengNature PortfolioScientific Reports2045-23222025-02-0115111010.1038/s41598-025-89317-1Therapeutic effect of curcumin derivative GT863 on prion-infected miceKenta Teruya0Ayumi Oguma1Michiaki Okuda2Sara Iwabuchi3Hiroyuki Konno4Hiroyuki Arai5Yukitsuka Kudo6Hachiro Sugimoto7Katsumi Doh-ura8Graduate School of Medicine, Tohoku UniversityGraduate School of Medicine, Tohoku UniversityGreen Tech Co., Ltd.Graduate School of Medicine, Tohoku UniversityGraduate School of Science and Engineering, Yamagata UniversityDepartment of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku UniversityDepartment of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer, Tohoku UniversityGreen Tech Co., Ltd.Graduate School of Medicine, Tohoku UniversityAbstract In prion diseases, the cellular prion protein (PrPC) forms an abnormal, infectious, and disease-causing form known as PrPSc. Inhibition of prion propagation is a key approach for the treatment of these diseases. We report on a curcumin-based compound, GT863 (formerly known as PE859) that displays therapeutic efficacy when administered orally. GT863 inhibited abnormal prion protein formation in prion-infected neuroblastoma cells in a prion strain dependent manner: effectively for RML prion and marginally for 22 L prion. Treatment with ad libitum GT863-containing feed prolonged the incubation period of intracerebrally RML prion infected Tga20 mice by 217% increase in mean. Although the 263 K prion-infected Tg7 mice were less sensitive to GT863 than RML prion infected Tga20, treatment with ad libitum GT863-containing feed prolonged the incubation period by 39% increase in mean. The mechanism of the anti-prion effectiveness in vivo needs to be elucidated and managed. Nevertheless, GT863 could inspire the development of oral chemotherapy for prion diseases.https://doi.org/10.1038/s41598-025-89317-1
spellingShingle Kenta Teruya
Ayumi Oguma
Michiaki Okuda
Sara Iwabuchi
Hiroyuki Konno
Hiroyuki Arai
Yukitsuka Kudo
Hachiro Sugimoto
Katsumi Doh-ura
Therapeutic effect of curcumin derivative GT863 on prion-infected mice
Scientific Reports
title Therapeutic effect of curcumin derivative GT863 on prion-infected mice
title_full Therapeutic effect of curcumin derivative GT863 on prion-infected mice
title_fullStr Therapeutic effect of curcumin derivative GT863 on prion-infected mice
title_full_unstemmed Therapeutic effect of curcumin derivative GT863 on prion-infected mice
title_short Therapeutic effect of curcumin derivative GT863 on prion-infected mice
title_sort therapeutic effect of curcumin derivative gt863 on prion infected mice
url https://doi.org/10.1038/s41598-025-89317-1
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