NR ATNI
AU Engelstein,R.; Ovadia,H.; Gabizon,R.
TI Treatment of scrapie infected hamsters with immunomodulators
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-06
PT Konferenz-Poster
AB The immune system is believed to be involved in prion disease pathogenesis, in particular in the peripherally transmitted disease. We therefore tested the effect of several immunomodulating agents on prion disease incubation time in IP infected hamsters. In parallel, we also tested their effect on the accumulation of PrPsc in ScN2a cells, a well establish method to asses the anti prion activity of candidate compunds. Tilorone has been shown to display antiviral and antitumoral activity, as well as to enhance NK cell activity. Linomide is an immunomodulatory drug shown to be effective in various models of autoimmunity without causing non-specific immunosuppression. Copaxone, a drug used for the treatment of multiple sclerosis, caused the preferential production of IgG1 over IgG2 antibodies. Both Linomide and Tilorone are also known to induce the lysosomal storage of sulphated glycosaminoglycans, which connections with prion disease are widely documented. While Linomide treatment did not change significantly prion disease incubation time in the scrapie infected hamsters, Tilorone administration starting 7 days before infection considerably shortened disease incubation time in scrapie infeted hamsters. Interestingly, Copaxone treatment postponed disease symptoms and death very significantly, but only when it was administared from the day of prion inoculation or even as a single dose mixed with the prion inoculum, but not when administration of the drug commenced 14 days post inoculation. As opposed to the diverse effects of the agents on prion disease incubation time, all drugs significantly reduced the accumulation of PrPsc in ScN2a cells. We conclude that immunomodulating agents can have disparate effects on the pathogenesis of prion infection, depending on their mechanism of action. In addition, we show once again that reduced accumulation of PrPsc in cells is not a reliable model to assess the activity of candidate anti-prion compou
AD Roni Engelstein, Haim Ovadia, Ruth Gabizon, Department of Neurology; The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem Israel
SP englisch
PO Deutschland