NR AXMJ
AU Forloni,G.; Colombo,L.; De Luigi,A.; Naggi,A.; Torri,G.; Casu,B.; Piovesan,P.; Ghirardi,O.; Penco,S.; Salmona,M.
TI Use of Heparin Derivatives for Therapeutic Intervention of Transmissible Spongiform Encephalopathies
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.124
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Several studies have indicated a role of glycosamiglicans (GAGs) in the pathogenesis of transmissible spongiform encephalopathy (TSE). On the other hand, GAGs derivatives have been proposed for therapeutic approaches to TSE. We investigated the anti-prion activity of two heparins derivatives (ST 2808 and ST1830) in vitro and in vivo models. The two drugs were tested in comparison with low molecular weight heparin, enoxaparin in prion-infected murine neuroblastoma cells, (N2A) and in Syrian hamsters experimental scrapie. We found that ST2808 and ST1830 as well as enoxaparin, in a micromolar range, strongly reduced the accumulation of pathological prion protein (PrPsc) in N2A. Syrian hamsters were inoculated intraperitoneally with 50 µl of 263K-infected brain homogenate at 10-2 and at 10-4 dilution and chronically treated with the drugs. The treatment started 1 hour or 24 hours after the inoculation and continued three times a week until the onset of symptoms in the control inoculated group. The treatment with ST2808 and ST1830 (2.5 mg/Kg, i.p) significantly prolonged the survival of the animals inoculated with homogenate at the higher dilution (10-4, median survival: control = 259 days, ST 1830 = 475 days p< 0.001, ST2808 = 545 days, p<0.001) and in some cases the treatments completely abolished the cerebral accumulation PrPsc and the development of the disease. In contrast the treatment with the derivatives produced only a slight and not significant increase of the survival time (median survival: control = 203 days, ST 1830 = 236 days, ST2808 = 226 days) when the animals were inoculated with the homogenate at lower dilution (10-2). Although further conditions need to be tested before to draw a final conclusion, the results indicate that the heparin derivatives tested can be considered for therapeutic or prophylactic approach to TSE.
AD G. Forloni, Istituto di Ricerche Farmacologiche, Neuroscience, Italy; L. Colombo, A. De Luigi, M. Salmona, Istituto di Ricerche Farmacologiche, Biochemistry, Italy; A. Naggi, G. Torri, B. Casu, G. Ronzoni Institute for Chemical and Biochemical Research, Italy; P. Piovesan, O. Ghirardi, S. Penco, Sigma-Tau laboratories, Italy
SP englisch
PO Schottland