Drug treatment for CJD?
prion-associated disorders such as Creutzfeldt-Jakob disease,
according to new research presented at ICAAC.
The 50-year-old malaria drug quinacrine could provide the first treatment for prion-associated neurodegenerative disorders such as Creutzfeldt-Jakob disease, according to new research presented at the Intersciences Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago, USA.
Prion-associated neurodegenerative disorders are uniformly fatal with no proven therapy to date. Importantly, early evidence suggests that quinacrine may be active against new variant CJD, thought to be linked to the consumption of meat tainted with bovine spongiform encephalopathy.
Earlier studies using neuroblastoma cells infected with scrapie - a prion disease of sheep - have shown that giving exposing prions to quinacrine in vitro inhibits their replication.
In the latest study, conducted by researchers at the University of California San Francisco in the USA, it was shown for the first time that quinacrine can achieve concentrations in central nervous system tissue that are high enough to inhibit replication.
"In brain tissue, the primary site of prion infection, tissue concentrations were five to seven times that of plasma," said the researchers, led by UCSF's Bernard Guglielmo. The brain tissue levels achieved (1500-1900ng/gm) were approximately 10-fold that required for maximal inhibition of prion replication in the in vitro model.
In the study, two strains of mice were administered 37.5 mg/kg/day or 75 mg/kg/day of oral quinacrine for four weeks. A set of three mice at each dosage was sacrificed weekly for eight weeks and plasma and brain, liver, spleen tissue were sampled.
Quinacrine was found to be highly tissue bound, particularly in liver (800 times plasma level) and spleen (200 times plasma), and brain tissue (10 times plasma).
