NR AOSH
AU Farquhar,C.F.; McConnell,I.; Cumming,S.; Boyle,A.; Prescott,R.J.; Turner,M.L.; Bruce,M.E.
TI Pentosan polysulphate has prophylactic potential for transmissible spongiform encephalopathies
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-09
PT Konferenz-Poster
AB vCJD differs from sporadic CJD in that infectivity and disease associated PrP deposition are not confined to the central nervous system but are also disseminated throughout the lymphoid system. Blood transfusion, treatment with blood products, re-use of surgical instruments and cell and tissue transplantation therefore present potential vCJD transmission risks. We and others have shown that high dose injectable polyanions, such as pentosan polysulphate (PPS), significantly increase survival time when given to rodents within weeks of peripheral exposure to normally lethal TSE doses. We now show that repeated intraperitoneal PPS administration completely protects mice from high dose ME7 scrapie given intraperitoneally. However, as this treatment regime results in coagulopathy, we also explored the effects of oral PPS administration. Surprisingly, given its low bioavailability, a high dose oral bolus of PPS can protect mice from normally lethal oral scrapie exposure. Even much lower, more clinically relevant, multiple oral PPS doses increase survival time in mice orally or parenterally exposed to high dose scrapie. Repeated oral delivery of PPS is also effective in extending survival in mice parenterally infected with bovine BSE or a mouse-passaged BSE strain, 301V. Oral PPS administration is licensed in the US for the treatment of interstitial cystitis in humans and is well tolerated in the long term. We have seen no deleterious consequences of long term oral treatment of mice with PPS. PPS prophylaxis has potential application after probable vCJD exposure through needlestick injury, transfusion or surgery. Furthermore, mixing PPS with highly infectious brain homogenate ex vivo prior to oral or parenteral delivery to mice can increase survival time dramatically, and may have application in disinfection protocols.
AD Christine F. Farquhar, Irene McConnell, Simon Cumming, Aileen Boyle, Moira E. Bruce, Neuropathogenesis Unit, Institute for Animal Health, Edinburgh,Scotland; Robin J. Prescott, Medical Statistics Unit, University of Edinburgh, Scotland; Marc L. Turner, Scottish National Blood Transfusion Service and University of Edinburgh, Scotland
SP englisch
PO Deutschland