Effectiveness of anthracycline against experimental prion disease in Syrian hamsters.
Prion diseases are transmissible neurodegenerative conditions characterized by the accumulation of protease-resistant forms of the prion protein (PrP), termed PrPres, in the brain. Insoluble PrPres tends to aggregate into amyloid fibrils. The anthracycline 4'-iodo-4'-deoxy-doxorubicin (IDX) binds to amyloid fibrils and induces amyloid resorption in patients with systemic amyloidosis. To test IDX in an experimental model of prion disease, Syrian hamsters were inoculated intracerebrally either with scrapie-infected brain homogenate or with infected homogenate coincubated with IDX. In IDX-treated hamsters, clinical signs of disease were delayed and survival time was prolonged. Neuropathological examination showed a parallel delay in the appearance of brain changes and in the accumulation of PrPres and PrP amyloid.
Tagliavini
F
F
Istituto Nazionale Neurologico Carlo Besta, via Celoria 11, 20133 Milano, Italy.
McArthur
R A
RA
Canciani
B
B
Giaccone
G
G
Porro
M
M
Bugiani
M
M
Lievens
P M
PM
Bugiani
O
O
Peri
E
E
Dall'Ara
P
P
Rocchi
M
M
Poli
G
G
Forloni
G
G
Bandiera
T
T
Varasi
M
M
Suarato
A
A
Cassutti
P
P
Cervini
M A
MA
Lansen
J
J
Salmona
M
M
Post
C
C
D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism; D006224:Cricetinae; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008647:Mesocricetus; D011328:Prions / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012608:Scrapie / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014404:Tubulin / Q000032:analysis
D000682:Amyloid; D011328:Prions; D012333:RNA, Messenger; D014404:Tubulin; C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin