Antibodies cripple prions
Therapy looks best yet to tackle brain disease.
6 March 2003

HELEN PEARSON

Prion diseases are caused by the twisting and clumping of normal brain proteins.
© SPL

The possibility of using antibodies to treat variant Creutzfeldt-Jakob disease (vCJD) receives a boost this week, with the first promising results from an animal trial.

The lethal brain condition - which is a human version of mad cow disease - occurs when healthy proteins called prions become twisted and clump together. Probably caught from eating infected beef, there is currently no known cure for the condition.

A team of London researchers injected mice with antibodies that latch onto prions. The animals, who had another form of prion disease called scrapie, stayed healthy for at least two years, rather than dying by the time they reached seven months1.

This is the first therapy to show such promise against animal symptoms. "It's a quantum leap in the efficacy of any treatment against prion disease," claims study leader Simon Hawke of Imperial College.

Winning battle

The new results come days after another encouraging report about prion diseases: that the predicted vCJD epidemic may be smaller than was feared. New figures2 show that the number of new British cases fell from a peak of 28 in 2000, to 17 in 2002.

Even so, the future death toll may lie anywhere between 10 and 7,000 in Britain alone, according to recent predictions3. "It's an untreatable, universally fatal disease," says prion researcher Neil Cashman of the University of Toronto in Canada.

Besides therapy with antibodies, anti-prion drugs are also being developed. In 2001, one British vCJD patient was reported to have made an astonishing recovery during a trial of quinacrine, an anti-malarial, and chlorpromazine, an anti-psychotic.

But the woman has since died - and the final trial results are expected to be disappointing. "There's no slam-dunk in chemotherapy," says Cashman. He agrees that antibodies now look to be the most hopeful therapy.

Hawke's team injected their antibody into mice that were 30 days into the disease - before symptoms occur, but at a time when prions are multiplying ferociously. The antibodies probably prevent normal prions folding into the misshapen, disease-causing form.

Before the antibodies can be tested in people, the mouse version will need to be altered - or 'humanized' - so that it can be tolerated by the body. It might also have to be shot straight into the brain, because it cannot diffuse there from the blood.

Hawke hopes that his result will also spur the development of antibodies against other diseases caused by abnormally folded proteins. Strings of protein clog the brains of Alzheimer's patients, for example.

Doctors are wary of using antibodies against Alzheimer's after a human trial of a vaccine that aimed to raise antibodies against the brain plaques backfired in 2001. Several patients in the study developed brain inflammation. "This should give [renewed] impetus," says Hawke of the new findings.