Phenothiazines: potential management of Creutzfeldt-Jacob disease and its variants

Creutzfeldt-Jakob disease acquired from bovines (nvCJD) has been responsibl e for nearly 100 deaths in the UK and thousands more may die in the years t o come. New variant CJD (nvCJD) is incurable and although clinical diagnosi s is becoming more precise, the diagnosis is only certain at autopsy. Pheno thiazine derivatives inhibit production of prions, the disease causing agen t, in cultured neuroblastoma cells, and an advanced case of nvCJD was recen tly 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 anti microbial activity of phenothiazines might cause the destruction of intrace llular prions. (C) 2001 Elsevier Science B.V. and International Society of Chemotherapy, All rights reserved.