Brain infected with prions

Infected with prions, the brain of a vCJD victim reveals spongy areas (yellow).

Simon Fraser/Science Source

Mad cow disease remains a threat. New blood tests could detect it

The “mad cow disease” epidemic that killed more than 200 people in Europe peaked more than a decade ago, but the threat it poses is still real. Eating meat contaminated with bovine spongiform encephalopathy and its hallmark misshapen proteins, called prions, can cause a fatal and untreatable brain disorder, variant Creutzfeldt-Jakob disease (vCJD). Thousands of Europeans are thought to be asymptomatic carriers, and they can spread prions through blood donations. So for years, researchers have sought a test to safeguard blood supplies.

This week, two teams bring that goal closer. They describe methods for detecting prions in blood that proved highly accurate in small numbers of samples from infected people and controls. “There is new technology to go forward, and it looks promising,” says Jonathan Wadsworth, a biochemist who studies prion disease at University College London. “These are definitely very welcome papers.”

Analyses of discarded appendix and tonsil samples suggest that as many as one in 2000 people in the United Kingdom carries abnormal prions—misfolded variations of a naturally abundant protein, which prompt surrounding healthy proteins to fold and clump abnormally. No one knows how many of these carriers will ever develop vCJD; incubation periods as long as 50 years have been reported. Once symptoms occur—first depression and hallucinations, and eventually dementia and loss of motor control—patients survive about a year. Four people are known to have contracted vCJD through a blood transfusion from an infected donor.

But screening for prions is difficult, because they are scarce in blood. Both new tests, described online in Science Translational Medicine, rely on a method that amplifies prions by culturing them with normal proteins and then agitating them with sound waves. That process breaks off fresh clumps of malformed proteins, which can more efficiently convert their neighbors. “Each can act as a seed to make this reaction go exponentially faster,” explains Claudio Soto, a neurobiologist at the McGovern Medical School at the University of Texas Health Science Center in Houston, whose lab developed the technique.

In their new paper, Soto and his team tested their approach on blood from 14 vCJD patients and 137 controls. The test was positive in all vCJD patients and none of the controls. The second study, led by microbiologist Daisy Bougard at the University of Montpellier in France, used the same amplification technique, but first concentrated prions from the sample by capturing them with magnetic nanobeads. The technique flagged 18 vCJD patients out of 256 samples. It also detected prions in blood donated by two vCJD patients before they showed symptoms—a first. “That’s very encouraging,” Wadsworth says.

But neither study analyzed enough samples to predict false positive rates across millions of samples in a blood bank, Wadsworth notes. “We have this ethical dilemma—how do you tell people they may have a fatal disease when we don’t know whether the test is specific?” And because the United Kingdom accepts more than 2 million blood donations a year, he says, even a low false positive rate could needlessly deplete the donor pool. Both teams are now working to validate their tests on larger sets of samples.