NR AWND
AU Salmona,M.; De Luigi,A.; Diomede,L.; Colombo,L.; Manzoni,C.; Capobianco,R.; Mangeri,M.; Miccolo,C.; Forloni,G.; Tagliavini,F.
TI Use of tetracyclines for therapeutic intervention of transmissible spongiform encephalopathies
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-51
PT Konferenz-Vortrag
AB In the last 15 years we have been working for the identification of molecules with anti-prion activity. We found that tetracyclines are potentially very useful drugs since they (i) are already used in human therapy, (ii) interact with and revert the protease resistance of PrPsc extracted from scrapie-infected animals and patients with all forms of Creutzfeldt-Jakob disease (CJD), (iii) decrease the prion titre, and (iv) prolong survival of peripherally infected animals. In the last five years, a small series of CJD patients received compassionate treatment of doxycycline, and a retrospective analysis showed a significantly longer survival than untreated patients. On this ground a double-blind pilot clinical trial in CJD patients has been recently commenced in Italy. To extend the therapeutic potential of tetracylines, the efficacy of direct infusion of the compound in advanced stages of infection is being investigated. Since intraventricular infusion of doxycycline solutions caused overt acute toxicity to animals, we decided to entrap the drug into multilamellar vesicles (MLV). Syrian hamsters were inoculated intracerebrally with 25 µl of a 10-4 dilution of 263K-infected brain homogenate. Then a single intraventricular infusion of 25 µg/animal of doxycycline entrapped into MLV was administered after 30 days. At the time of writing, after one month from drug treatment, no deaths caused by doxycycline toxicity was observed.
AD M. Salmona, A. De Luigi, L. Diomede, L. Colombo, C. Manzoni, G. Forloni: Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy; R. Capobianco, M. Mangeri, C. Miccolo, F. Tagliavini: Istituto Neurologico Nazionale "Carlo Besta", Milan, Italy
SP englisch
PO Italien