NR AWEE
AU Doh-ura,K.; Rainov,N.; Ishikawa,K.; Kawasaki,Y.
TI Pentosan polysulfate and amyloidophilic chemicals for prion diseases
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-47
PT Konferenz-Vortrag
AB
Long-term cerebroventricular administration of pentosan polysulfate (PPS), a clinical approach based on our preclinical study in rodent models of prion diseases (Doh-ura et al. 2004), has been carried out in more than 20 patients with various types of diseases. Although its therapeutic efficacy remains to be confirmed, preliminary clinical experience indicates prolonged survival in some patients receiving long-term PPS. Further prospective investigation of PPS administration is necessary to obtain highquality evidence for its clinical benefits.
Administration of PPS requires surgical implantation of a continuous infusion pump and an intraventricular catheter. Although these devices and methods are licensed for routine clinical use in other neurological conditions, the requirements for a surgical procedure might present an obstacle for future clinical trials with intraventricular drugs compared to oral treatments with such agents as quinacrine or flupirtine. Furthermore, since Dr. Caughey and his colleagues discovered the anti-prion actions of Congo red, its derivatives and those of another amyloid dye, thioflavine, have been considered as anti-prion candidates.
We previously reported that some amyloid-imaging probes for Alzheimer's disease diagnosis are effective as anti-prion chemicals when administered intravenously (Ishikawa et al. 2004). We have developed and tested new amyloidophilic imaging chemicals that show better penetration of the blood-brain barrier. We have concluded that not only permeability, but also retention in the brain is important for anti-prion effectiveness (Ishikawa et al. 2006). This has been finally demonstrated using an orally administered amyloidophilic chemical, which has satisfactory permeability and relatively longer retention in the brain than the imaging chemicals and which is remarkably effective in prolonging the incubation times of intracerebrally infected mice.
Our findings with these amyloidophilic chemicals are encouraging, but further improvement of their safety and pharmacokinetic profiles is necessary before clinical application can be considered. Additional problems exist with prion strain-dependent effectiveness of these chemicals and with their reduced effectiveness if administered at later stages of the disease. Details of each research area introduced here will be presented in respective posters.
AD K. Doh-ura, K. Ishikawa, Y. Kawasaki: Department of Prion Research, Tohoku University Graduate School of Medicine, Sendai, Japan; N. Rainov: Department of Neurosurgery, Zentralklinikum Augsburg, Augsburg, Germany; Department of Neurosurgery, Martin-Luther-University Halle-Wittenberg, Halle, Germany. E-mail: doh-ura@mail.tains.tohoku.ac.jp
SP englisch
PO Italien