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Drugs for malaria and psychosis may offer hope to people with CJD

BMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7310.416b (Published 25 August 2001) Cite this as: BMJ 2001;323:416
  1. Deborah Josefson
  1. San Francisco

    Doctors at the University of California in San Francisco are starting clinical trials for Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD) with quinacrine and chlorpromazine, after finding that the drugs inhibited the propagation of prions in a mouse neuroblastoma cell culture line (Proceedings of the National Academy of Sciences 2001;98:9836-41.).

    News media have disclosed that two patients have already begun treatment and that one of them, Rachel Forber, a 20 year from the United Kingdom with probable vCJD, has shown substantial clinical improvement. Ms Forber reportedly started treatment in July and has regained the ability to speak and to feed herself. The other patient has not improved, according to news reports. Officials at the University declined to comment on these reports.

    CJD and vCJD, the human equivalent of bovine spongiform encephalopathy (BSE), are rare neurological disorders caused by the abnormal accumulation of prion proteins in the brain, ultimately destroying neuronal function.

    The researchers in California, led by Dr Carsten Korth, a psychiatrist and postdoctoral fellow in Dr Stanley Prusiner's laboratory, screened drugs for their ability to inhibit prion propagation in a mouse neuroblastoma cell line infected with scrapie prions. Only drugs known to cross the blood-brain barrier were selected.

    The antipsychotic chlorpromazine, and the related drugs promazine and acepromazine (a drug used in animals), caused disappearance of the abnormal prions after six day treatments at concentrations of 2μM to 10μM.

    Quinacrine, an antimalarial, was 10 times as potent and was effective at doses as low as 200nM. None the less, because chlorpromazine crosses the blood-brain barrier more efficiently than quinacrine, it may ultimately be more effective than quinacrine.

    The Californian researchers speculate that phenothiazine derivatives may also be effective in diseases like Alzheimer's.

    Dr Bruce Miller, chief of neurology at the University of California in San Francisco, will lead a clinical trial in the United States, while a concurrent trial will be held in Europe, where most patients with vCJD are. Patients with advanced disease will be excluded from the trial.

    For more information on the trials, see www.som.ucsf.edu/orus/ind/

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