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<p>In prion diseases, the cellular prion protein (PrP<sup>C</sup>) forms an abnormal, infectious, and disease-causing form known as PrP<sup>Sc</sup>. 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&#xa0;L prion. Treatment with <i>ad libitum</i> GT863-containing feed prolonged the incubation period of intracerebrally RML prion infected Tga20 mice by 217% increase in mean. Although the 263&#xa0;K prion-infected Tg7 mice were less sensitive to GT863 than RML prion infected Tga20, treatment with <i>ad libitum</i> 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.</p>

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Therapeutic effect of curcumin derivative GT863 on prion-infected mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月14日

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  • Kenta Teruya,
  • Ayumi Oguma,
  • Michiaki Okuda,
  • Sara Iwabuchi,
  • Hiroyuki Konno,
  • Hiroyuki Arai,
  • Yukitsuka Kudo,
  • Hachiro Sugimoto,
  • Katsumi Doh-ura

摘要

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.