London

Britain's Medical Research Council is set to embark on a rigorous clinical trial of a treatment for Creutzfeldt–Jakob disease (CJD). The trial will initially assess the effects of only one drug — a compound that few experts expect to be effective. But the trial has been designed to allow newly discovered drugs to be rapidly tested, a move that doctors hope will sort out the chaos that has been caused in the past by dying patients' demands for access to untested treatments.

The study, which is expected to receive final ethical approval within the next few months, will look at treatments for all forms of CJD. This includes variant CJD — thought to be contracted through eating meat infected with bovine spongiform encephalopathy (BSE) — and sporadic CJD, a rare condition with no known cause. About 900 people in Britain have died from these diseases since 1990.

Patients have been eager to get their hands on any possible treatment for these conditions. That includes quinacrine — the drug that will be tested first in the trial. Quinacrine, which was initially developed as a malaria treatment, was shown in lab tests with cell cultures to inhibit the formation of prions — the proteins thought to cause CJD (C. Korth, B. C. H. May, F. E. Cohen and S. B. Prusiner Proc. Natl Acad. Sci. USA 98, 9836–9841; 2001). Stanley Prusiner, who led that study and also won a 1997 Nobel Prize for his work on prions, backed the use of quinacrine to treat CJD patients and, at around the same time, reported that the symptoms of a British CJD sufferer had improved after taking the drug.

Media coverage, as well as Prusiner's endorsement, led to a scramble to use the drug before any proper trial had been done, regardless of the fact that useful effects in cell cultures are often not replicated in animal tests. “It was premature to state that it was good for patients,” says Adriano Aguzzi, a neuropathologist at University Hospital Zurich in Switzerland.

Since then, hopes for quinacrine have dimmed. Evidence from human CJD sufferers suggests that it has little effect, says Richard Knight, a neurologist at the National CJD Surveillance Unit in Edinburgh. Animal experiments carried out since then have also failed to show unambiguously that the drug works (P. Brown Neurology 58, 1720–1725; 2002).

Nevertheless, Knight says that the British trial will be welcomed by patients, as it should reveal whether quinacrine has any effect, however minor. More importantly, he adds, the trial will allow rigorous assessment of other drugs as soon as any potential benefit is revealed.

The trial will not put an end to the use of untested drugs, however. At present, one drug in demand from CJD patients is pentosan polysulphate. Unpublished work carried out by Katsumi Doh-ura, a prion researcher at Tohoku University in Sendai, Japan, suggests that this compound can delay the onset of symptoms in mice infected with disease prions.

Patients have taken the battle to court and won the right to be given the drug. But because it has to be injected into the brain, and is linked to side-effects such as impaired blood clotting, it has been considered too dangerous to include in the British trial.