NR ATGE
AU Tagliavini,F.
TI Therapeutics for human prion diseases: current status and perspectives
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-35
PT Konferenz-Vortrag
AB
The prion diseases are fatal neurodegenerative disorders of humans and animals that are sporadic or inherited in origin and can be transmitted. The pathogenic mechanism underlying these conditions is a conformational conversion of the cellular prion protein (PrPc) into disease-specific, ß-sheet-rich forms (PrPsc) that possess abnormal physicochemical properties such as insolubility and protease resistance. The accumulation of PrPsc in the central nervous system is accompanied by glial activation and nerve cell degeneration. Evidence indicates that PrPsc plays a central role in the pathogenesis of brain changes as well as in propagation and transmissibility of the disease process, by converting PrPc into a likeness of itself. Accordingly, PrPc and PrPsc represent the primary targets for therapeutic strategies.
The urgency to develop anti-prion agents has remarkably increased following the emergence of variant of Creutzfeldt-Jakob disease (vCJD), as the result of human exposure to BSE-infected material. Since 1995, more than 160 vCJD patients have been identified and there is concern about a future outbreak of this condition as well as a secondary vCJD epidemic resulting from donation of blood, tissues or organs, and use of contaminated surgical instruments. A large number of molecules have been tested in an attempt to find therapeutic agents for prion diseases, but only a few classes of compounds have had any beneficial effect in in vivo and/or in vitro models. Some of these compounds such as quinacrine, pentosan polysulphate and flupirtine maleate, already used in humans to treat other pathological conditions, have been recently tried in patients with CJD, even though no treatment is known to have significant effects in experimentally infected animals once the clinical symptoms have developed. The results of these studies will be reviewed and alternative therapeutic approaches will be discussed.
AD F.Tagliavini, National Neurological Institute "Carlo Besta", Milano, Italy
SP englisch
PO Deutschland