Amyloidophilic compounds for prion diseases

Kenta Teruya, Keiichi Kawagoe, Tomohiro Kimura, Chun Jen Chen, Yuji Sakasegawa, Katsumi Doh-ura

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Recent outbreaks of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease have aroused great concern in many countries and have necessitated the development of suitable therapies. We have demonstrated that sulfated glycans such as pentosan polysulfate and fucoidan, and amyloidophilic compounds such as amyloid dye derivatives, styrylbenzoazole derivatives, and phenylhydrazine derivatives have efficacies in prion-infected animals. Amyloidophilic compounds present potentialities not only as therapeutic candidates but also as prion amyloid imaging probes for use in nuclear medicine technology such as positron emission tomography. A representative of styrylbenzoazole compounds has been used recently for clinical trials of brain prion amyloid imaging in patients. On the other hand, a representative of phenylhydrazine compounds, compB, displays excellent effectiveness in prolonging the incubation times of infected animals when given orally. However, both its anti-prion effectiveness in vitro and its therapeutic efficacy in vivo are consistently dependent on the prion strain. This prion-strain-dependency is similarly observed in other amyloidophilic compounds. Therefore, aside from further improvement of the safety profiles and pharmacokinetic properties of such compounds, elucidation and management in the mechanism of the prion strain-dependent effectiveness is necessary. Nevertheless, because compB studies suggest that amyloidophilic compounds are also therapeutic candidates for Alzheimer's disease, amyloidophilic compounds might be attractive as drug candidates for various conformational diseases and hasten development of therapeutic drugs for prion diseases.

Original languageEnglish
Pages (from-to)15-22
Number of pages8
JournalInfectious Disorders - Drug Targets
Volume9
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

Keywords

  • Alzheimer's disease
  • Amyloid imaging
  • Amyloidophilic chemical
  • Prion disease
  • Sulfated glycan
  • Therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Microbiology (medical)

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