Public Release:  Scientists at the Scripps Research Institute find a way to block prions that cause mad cow disease

Scripps Research Institute

La Jolla, CA, August 16, 2001 -- Scientists working at The Scripps Research Institute (TSRI) and at the University of California, San Francisco, have published a paper in the current issue of the scientific journal Nature that describes an antibody that clears prion infection in cell culture. This finding may point the way to a treatment for mad cow disease and its human equivalent.

"[The antibody] stops the whole process," says Professor Dennis R. Burton, Ph.D.

Prion infections are known to cause bovine spongiform encephalopathy, or mad cow disease, and one form of the same disease in humans, called variant Creutzfeldt-Jakob Disease. BSE itself is believed to have originated from a sheep form of the disease called scrapie.

Diseases like mad cow are unusual because unlike most infectious diseases, the infectious material is not a virus or bacteria but malformed prion protein--chemically the same as normal human proteins. These proteins are expressed throughout the body and sit anchored onto the surfaces of cells in a wide variety of tissue, particularly on cells in neuronal tissue.

"The prion protein starts out with one shape that is innocuous, and ends up with another shape that is deadly," says Burton.

Infectious prions from an animal with mad cow disease, for instance, will initially cause normal prion proteins in the brain of a healthy cow to misform into the infectious form. Then these prions will act on more normal prion protein to produce more and more misfolded protein that accumulates and eventually leads to brain damage with a sponge-like appearance.

"Prions," says investigator Anthony Williamson, Ph.D., "have a Jekyll and Hyde personality."

Burton and Williamson, who are both in the Department of Immunology at TSRI, originally developed several antibodies in order to probe the structure and biochemistry of prion proteins and investigate the way in which the binding of infectious prions to the normal prion protein occurs.

But one antibody they designed seems to halt the infection all together. This antibody, called Fab D18, binds to the normal form of the prion protein and prevents the infectious form from binding in cell culture.

Significantly, the normal cellular machinery degraded whatever infectious prions remained, suggesting that the antibody has the potential to cure established infection.

The finding is also significant because it provides a potential therapeutic target--a highly effective human drug might be designed to bind to the same place as Fab D18.

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The research article, "Antibodies inhibit prion propagation and clear cell cultures of prion infectivity," appears in the August 16, 2001 issue of the British journal Nature and is authored by David Peretz, R. Anthony Williamson, Klotoshi Kaneko, Julie Vergara, Estelle Leclerc, Gerold Schmitt-Ulms, Ingrid R. Mehlhorn, Gluseppe Legname, Mark R. Wormald, Pauline M. Rudd, Raymond A. Dwek, Dennis R. Burton, and Stanley B. Prusiner.

The research was funded in part by the National Institutes of Health and is a collaboration between TSRI and the Prusiner laboratory at the University of California, San Francisco.

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