Academy Press

A simple test for mad cow disease and its human equivalent, variant Creutzfeldt-Jakob disease (vCJD), may be one step closer to reality. Until now, tests for these diseases have required biopsies of brain or tonsil tissue. But in the 1 March issue of Nature Medicine, researchers describe a new test that reliably detects the signature of similar diseases in the blood of mice and sheep. If the same technique also works on human and bovine blood, it could help diagnose CJD in people and provide a cheap and easy way to make sure cattle raised for meat are disease-free.

Mad cow disease, CJD, and a sheep disease called scrapie are all transmissible spongiform encephalopathies (TSEs), which turn brain tissue into something resembling a sponge. Most researchers believe the culprits are prions, normal cellular proteins that turn deadly when they undergo a shape change. Because prions have no DNA or RNA, they can't be detected with sensitive genetic assays like those used to detect HIV. Designing antibodies that differentiate between the two versions of the protein is difficult, too.

To sidestep the obstacles, prion researcher Gino Miele and colleagues at the Roslin Institute in Midlothian, Scotland, took an indirect approach. Taking a cue from recent research suggesting that prions multiply in the spleen before invading the brain, the team members focused their attention on that organ. Reasoning that prions might cause changes in gene expression, they analyzed levels of some 10,000 RNA transcripts in the spleens of normal and TSE-infected mice.

Levels of one of them--the transcript for a protein called erythroid differentiation-related factor (EDRF)--were reduced in affected animals' spleens. They also turned out to be reduced in their blood and bone marrow. EDRF levels were also lower than normal in the blood of scrapie-infected sheep and in the bone marrow of infected cattle--the two tissue types to which the team had access. The researchers have no idea why EDRF production goes down after an infection, but they hope that the protein--which they also found in blood and bone marrow of healthy humans--will also be a marker for vCJD.

"It's a nice piece of work and a very clear result," says Robert Gallo, director of the Institute of Human Virology at the University of Maryland, Baltimore. However, he notes, it remains to be seen if the test works in humans. EDRF levels could be a useful diagnostic, Gallo says, as long as they don't vary too much across the healthy population. Paul Brown, a prion researcher at the National Institute of Neurological Disorders and Stroke, adds that it's also uncertain whether the test would detect infection before symptoms set in. Once patients get sick, they have only a few months to live, and there's no need for a test to establish a prion disease after they die, he says.