Antibody Found for Pathogenic Prions

Scientists have found an antibody to the aberrant protein found in the dreaded "mad cow disease" and Creutzfeldt-Jakob disease (CJD) in humans. The serendipitous discovery, reported in tomorrow's issue of Nature, might lead to an easy and cheap diagnostic test for the so-called "prion" diseases--which at present can be diagnosed definitively only by examining a brain after death.

Prion diseases, according to the leading theory, occur when "infectious proteins" called prions misfold and then recruit normal proteins to do likewise. The misshapen proteins clump together, eventually killing brain cells. Scientists had been able to detect both forms of the prion protein (PrP) by creating antibodies, specialized immune cells that recognize specific proteins. But no one had found an antibody that could target only the aberrant form.

Bruno Oesch of the University of Zurich and his colleagues didn't have any false hopes when they set out to find a better antibody against normal PrP in cows. His team immunized mice bred to have no PrP with the protein. A few weeks later, the scientists culled antibody-producing cells from the animals' spleens. To their surprise, they found an antibody that ignores normal PrP and latches onto the misfolded PrP from brains of cows with bovine spongiform encephalopathy, from mice with a prion disease called scrapie, and from CJD victims. "We don't really know why we have been the lucky ones" to find the new antibody, says Oesch. Co-author Kurt Wüthrich, also of the University of Zurich, says the new antibody may zero in on the dangerous PrP because it attaches to three different regions of the protein--regions which are distant from one another in the normal conformation, but are close together in the misfolded aggregate.

The antibody still must jump through several hoops before it could be used to diagnose living people or check for tainted beef. First, the researchers must find out if the antibody can latch onto extremely low concentrations of misshapen PrP in spinal fluid or blood. They also need to make sure it reacts only with prions, says Clarence Gibbs, a virologist at the U.S. National Institute of Neurological Disorders and Stroke. If those questions are answered, however, Gibbs says the antibody could have "great possibilities."

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