Phenothiazines: potential management of Creutzfeldt-Jacob disease and its variants.
Creutzfeldt-Jakob disease acquired from bovines (nvCJD) has been responsible for nearly 100 deaths in the UK and thousands more may die in the years to come. New variant CJD (nvCJD) is incurable and although clinical diagnosis is becoming more precise, the diagnosis is only certain at autopsy. Phenothiazine derivatives inhibit production of prions, the disease causing agent, in cultured neuroblastoma cells, and an advanced case of nvCJD was recently brought to remission by the use of these agents in combination with an antimalarial. In this review we present direct and circumstantial evidence in support of a model describing the manner by which the intracellular antimicrobial activity of phenothiazines might cause the destruction of intracellular prions.
Amaral
L
L
Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349-008, Lisbon, Portugal. lamaral@ihmt.unl.pt
Kristiansen
J E
JE
D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000188:drug therapy*; D006801:Humans; D010640:Phenothiazines / Q000494:pharmacology / Q000627:therapeutic use*; D011328:Prions / Q000187:drug effects; D014407:Tumor Cells, Cultured
D010640:Phenothiazines; D011328:Prions