Amyloidophilic compounds for prion diseases.
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.
Teruya
Kenta
K
Department of Prion Research, Tohoku University Graduate School of Medicine, Sendai, Japan. doh-ura@mail.tains.tohoku.ac.jp
Kawagoe
Keiichi
K
Kimura
Tomohiro
T
Chen
Chun-jen
CJ
Sakasegawa
Yuji
Y
Doh-ura
Katsumi
K
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001393:Azoles / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D011134:Polysaccharides / Q000737:chemistry / Q000627:therapeutic use; D017096:Prion Diseases / Q000188:drug therapy* / Q000517:prevention & control; D011328:Prions / Q000032:analysis / Q000378:metabolism
D000682:Amyloid; D001393:Azoles; D006834:Hydrazines; D011134:Polysaccharides; D011328:Prions