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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Summary: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.
ISSN:2045-2322