NR AXLY
AU Farquhar,C.; Cumming,S.; McConnell,I.; Laing,F.; Boyle,A.; Turner,M.L.; Bruce,M.E.
TI Scrapie Affected Mice Survive Longer with Parenteral Pentosan Polysulphate
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.10
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB There is no treatment for TSEs. Pentosan polysulphate (PPS) is a heparin analogue with anti-coagulant, -thrombotic, -inflammatory and -viral activity. We have shown that PPS increases survival time, and reduces susceptibility, if given parenterally early in rodent scrapie pathogenesis. Serial delivery further increases survival time, and prolongs life in mice inoculated with BSE. Mice surviving PPS ingress into the CNS soon after TSE inoculation live significantly longer than controls. This suggests that PPS may be effective even after neuroinvasion, although the general finding from a range of animal models is that the later PPS therapy is initiated the smaller the increase in survival time obtained. PPS chemistry is thought to preclude CNS uptake from the periphery therefore some TSE affected patients received intra-ventricular PPS. Some vCJD affected individuals have survived considerably longer than those untreated, although atrophy progresses. We aimed to determine:- 1. how long after mice are intravenously exposed to low dose scrapie parenteral PPS has efficacy. 2. whether subcutaneous or intravenous injection of PPS is more effective We will present proof of principle data showing that injecting PPS parenterally after symptoms appear can increase survival time. This demonstrates indirectly that PPS can enter the CNS from the periphery. While drug access may at this stage reflect loss of blood brain barrier integrity, the further development and testing of parenteral dose ranging and delivery strategies is required. These studies in rodents require translation into sheep models. Such data may obviate the need for surgical procedures for intra-ventricular catheter and pump placement in human patients which can carry significant potential for complications. Funding Department of Health UK No 121/6978 and EU NeuroPrion "STOPPrions"
AD C. Farquhar, S. Cumming, I. McConnell, F. Laing, A. Boyle, M.E. Bruce, Neuropathogenesis Unit, RI, UK; M.L. Turner, Scottish National Blood Transfusion Service, RIE, UK
SP englisch
PO Schottland