Published online 16 August 2001 | Nature | doi:10.1038/news010823-1

News

Prion and on

Promise abounds for prion-disease treatments - or does it?

Malignant prions (gold) crowd round a cell.Malignant prions (gold) crowd round a cell.© SPL

Antibodies may help to fight prion diseases, such as mad cow disease and human Creuzfeldt-Jacob disease (CJD), a new study hints, rounding out the recent spate of announcements of potential treatments for the fatal illnesses1,2,3.

Diseases such as CJD, bovine spongiform encephalopathy in cows and scrapie in sheep are thought to occur when malformed prion proteins bind to normal brain proteins, bending them out of shape. Misshapen protein clumps are thought to form spongy plaques in the brain, eventually leading to dementia and death.

Several antibodies cleared prion clumps out of cultured mouse brain cells. They seem to interrupt the conversion of normal prions by malignant ones, researchers say.

"One of the antibodies we studied binds to a region on normal prions where we think they interact with pathogenic prions," says David Peretz of the University of California, San Francisco (UCSF). "The other antibodies bind to regions where the prions would change shape, and seem to stabilize them."

The hope is that antibodies could eventually be developed into a vaccine, or even a treatment, if they can be shown to cross from the blood to the brain, Peretz says.

Clinical trials

Peretz led the experiment in prion pioneer Stanley Prusiner's laboratory, which earlier this week announced new results adding to growing evidence that a malaria and a schizophrenia drug are promising candidates for treating prion diseases2.

Human clinical trials of the medicines have been approved by the US Food and Drug Administration. Scheduled to begin within a few weeks, these will be the first human tests of prion-disease treatments.

The drugs, quinacrine and chlorpromazine, block the formation of malignant prion clumps in infected mouse cell cultures. Unlike other compounds that have been shown to clear prion aggregates, these two can cross from the bloodstream into the brain.

However, it is not clear whether quinacrine and chlorpromazine will work in humans, researchers warn. "The paper deals with the action of chemicals in tissue-culture cells," says Charles Weissmann of the Medical Research Council Prion Unit at Imperial College, London.

"There's quite a step from there to knowing what happens in a patient," says Weissmann, whose group last month showed that an antibody similar to one studied by the UCSF researchers clears prion clumps in cultures3.

One patient

The UCSF team has treated two patients with suspected CJD under a "compassionate use" provision of the food and drug administration, allowing researchers to test drugs that are already approved for other illnesses on dying patients. One patient has not responded to treatment, says UCSF spokeperson Jennifer O'Brien. In the other patient, it is too early to say.

Media attention has focused on the latter patient, Rachel Forber, a 20-year-old British woman. Her parents told reporters that she has shown a marked improvement after being treated by UCSF researchers, who have refused to comment, citing patient confidentiality.

Even if Forber's reported improvement stands the test of time and scrutiny, scientists urge caution. "This is one single patient; we don't know whether psychological effects like the placebo effect could be playing a role," warns Bruno Oesch, a prion researcher at the University of Zurich. 

  • References

    1. Peretz, D. et al. Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412, 739 - 743 (2001). | Article | PubMed | ISI | ChemPort |
    2. Korth, C. et al. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proceedings of the National Academy of Sciences 98, 9836 - 9841 (2001). | Article | ISI | ChemPort |
    3. Enari, M. et al. Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proceedings of the National Academy of Sciences 98, 9295 - 9299 (2001). | Article | ISI | ChemPort |