Mad cow disease (BSE), which has caused the death of more than 200,000 cattle and 165 people in the U.K., has now abated. But other prion disorders are on the rise, and there is concern that new strains will infect humans. Prions are not readily transmittable from species to species, but once they have broken through the species barrier they can rapidly adapt and become contagious within the species. Intensive work is now underway to find new, more sensitive methods for detecting these potentially deadly protein structures and distinguish between various strains.
The method now being presented in the journal Nature Methods is based on a fluorescent molecule, a so-called conjugated polymer, which was developed at Linköping University.
The research team infected genetically identical laboratory mice with BSE, scrapie (which afflicts sheep), and CWD (chronic wasting disease or “mad elk disease,” which is epidemic in the central U.S.) for several generations in a row. Gradually new strains of prions emerge, making the diseases more fatal to the mice. Tissue samples from mice were examined using the fluorescent molecule, which seeks out and binds with prions. This is signaled by a shift in color. By tweaking the molecule, the team has been able to get it to show different colors depending on the structure of the prioneach prion strain emits its own optical fingerprint.
This is an important difference compared with other techniques used to find prions, such as antibodies and the well-known stain Congo red.
The technique has also proven to work well on tissue sections from dead animals, such as cows infected with BSE. Now the scientists want to move on and look for alternative sample-taking methods for diagnosing and tracking prion diseases in humans in early stages.
The method would then be useful for screening blood products, since there is a risk that people can be carriers of prions without having any symptoms of disease. In the U.K. it was discovered that 66 people had received blood from blood donors who were infected with the human form of BSE (a variant of Creutzfeldt-Jakob’s disease, vCJD), and among them, four individuals have been shown to be infected (source: Health Protection Agency, Jan. 2007).
“Using our methods, we can directly see the structure of the prions and thereby deduce the disease,” says Peter Nilsson, one of the lead authors of the article. Nilsson developed the technique as a doctoral student at Linköping University and now, as a post-doctoral fellow with Professor Adrian Aguzzi’s research team in Zürich, has been applying the technology to prion diseases. After New Year’s he will assume a post-doc position at Linköping.
“For us researchers it is truly exciting to use this technique to understand more about both prions and other defectively folded proteins that give rise to similar disorders, such as Alzheimer’s,” says Peter Hammarström, co-author and research director of the prion laboratory at Linköping.
Another co-author is Kurt Wüthrich, the 2002 Nobel laureate in chemistry.
The article “Prion strain discrimination using luminescent conjugated polymers” by Christina J Sigurdson, K Peter R Nilsson, Simone Hornemann, Guiseppe Manco, Magdalini Polymenidou, Petra Schwartz, Mario Leclerc, Per Hammarström, Kurt Wüthrich, and Adriano Aguzzi was published in Nature Methods online on November 18 and will appear in the December issue of the printed journal.