Two drugs that doctors have long used to treat malaria and certain psychotic illnesses may one day find a new use. According to findings reported today in the Proceedings of the National Academy of Sciences, the drugs effectively combat infectious prion proteins¿which can cause Creutzfeldt-Jakob disease and other fatal, neurodegenerative orders¿in infected mouse cells.
A prion is a deformed, infectious version of the so-called cellular prion protein, which exists in healthy humans and many animals. The body is thought to regularly rid the brain's nerve cells of misfolded prion proteins. When that doesn't occur, however, the prion sets off a wave of destruction, converting normal proteins into the disease-causing form. In the new study, however, prion research pioneer Stanley B. Prusiner of the University of California at San Francisco and his colleagues found that the malaria drug quinacrine and chlorpromazine, which is approved to treat conditions like schizophrenia, actually inhibited the conversion of normal prion protein into the infectious kind. Indeed, more than three weeks after discontinuing treatment, the infected mouse cells remained free of prion infection.
Though quinacrine proved considerably more potent than chlorpromazine in the cell-based study, chlorpromazine's superior ability to cross the blood-brain barrier may ultimately make it more useful in treating people. Indications of that may come in an upcoming clinical trial, in which the researchers plan to test the two drugs separately and in combination. "It's a big leap from findings in cell culture to those in humans, and we do not know if we will see a favorable response in humans," team member Carsten Korth notes. "But the results we saw, in a cell model we consider valid, make this lead worth pursuing immediately."