Antibodies isolated for pathogenic prions
Scientists have now succeeded in isolating an antibody against the disease-causing form of the prion protein. They hope that this will enable faster diagnosis of Creutzfeldt-Jakob disease and mad cow disease be certain of death. According to most scientists, the diseases occur when infectious proteins - called prions - fold in the wrong way and then cause normal proteins to respond in the same way. The misshapen proteins clump together and eventually kill brain cells.
Researchers have also been able to detect both forms of the prion protein (PrP) at the same time by generating antibodies - large molecules that can recognize foreign substances and possible pathogens in the body. So far, however, no one has been able to find an antibody that only responds to the pathogenic variant of the prion protein.
Bruno Oesch from the University of Zurich and his colleagues therefore did not have false hopes when they searched for a better antibody against the normal PrP from cows. His team injected the bovine protein into mice that had been bred out of their own PrP. A few weeks later, the scientists removed antibody-producing cells from the animals' spleens. To their surprise, they found an antibody that ignores normal PrP and only attaches itself to the misfolded PrP. The antibody recognizes the protein in brain samples from cows with bovine spongiform encephalopathy (BSE), mice with a prion disease called scrapie, and victims of Creutzfeldt-Jakob disease (Nature 6 November 1997).
"We really don't know why we were lucky enough to find the new antibody," says Oesch. His co-author Kurt Wüthrich, also from the University of Zurich, believes that the new antibody selects for the dangerous PrP because it binds to three different regions of the protein, which in the normal form are far apart in the misfolded variant but lie close together.
The antibody still has to pass several tests before it can be used to diagnose live humans or check contaminated beef. The researchers first need to determine whether the antibody detects extremely low concentrations of malformed PrP in the spinal fluid or in the blood.
