Prion Brain Disorder Lying Dormant?

LONDON--Although the outbreak in the United Kingdom of a rare, fatal degenerative condition called variant Creutzfeldt-Jakob disease (vCJD)--the human equivalent of "mad cow disease"--appears to have subsided, it may not be over. New findings from research on mice, published in next month's Nature Genetics, reveal why a similar disease linked to prions develops at different speeds in different animals and suggests that more cases of human vCJD--so far 22 have been confirmed--may be on the way.

Mad cow disease, CJD, and related illnesses are thought to be caused by infectious proteins called prions that react with normal counterparts in the brain, killing cells and resulting ultimately in death. Studies in mice and sheep have suggested that genetic differences can greatly influence the time it takes for individuals to show symptoms after infection. But a British team at the Institute of Animal Health (IAH) at sites in Newbury and Edinburgh and at the University of Edinburgh have shown that, when infecting mice with the sheep version of the disease, known as scrapie, the amino acid sequence of the host's normal prion protein determines the disease's incubation period. "The results prove beyond any doubt that variations in the host protein sequence determine the incubation period," says IAH director Chris Bostock.

Earlier work on mice had shown that the normal prion protein in the brain occurs in two forms, a and b; the British team found that mice with form b consistently develop scrapie more quickly than those with form a. The only differences between the two forms are two amino acids. Although researchers previously could not rule out that other genetic differences between mice may contribute to scrapie's progression, the new findings do rule them out, says Bostock: "The protein sequence differences are responsible and not any other genetic component."

The results suggest that different forms of human prions may affect CJD's incubation time. "So far, all the cases of new variant CJD, linked to the outbreak [of the related disease in cows], have had a particular form of the brain protein," says George Carlson at the McLaughlin Research Institute in Great Falls, Montana. This form is similar to mouse type b, associated with shorter incubation periods. However, says Bostock, "we don't yet know whether humans with other forms are resistant or have longer incubation periods."

Posted in Biology