Antibodies raise hopes of prion disease cure

 作者:疏弗     |      日期:2019-03-06 01:15:16
By Andy Coghlan Antibodies which “cured” mouse cells of scrapie have raised hopes that the human form of mad-cow disease will one day be treatable. So far, 100 people have succumbed to variant Creutzfeldt Jakob Disease (vCJD). Thousands more could fall sick, warn epidemiologists, so a treatment is needed urgently. But pioneers of the latest breakthrough warn against false hope. “These are tissue culture cells, so we still have to find whether the same thing happens in animals, let alone in people,” says Charles Weissmann, who led the research at the Medical Research Council’s Prion Unit at St Mary’s Hospital, London. Weissmann grew mice cells in the lab and infected them with a strain of mouse scrapie to mimic infection with vCJD. As expected, the cells began producing prions, malformed versions of a normal protein found on the cell surface, especially in brain cells. It is these prions, given the symbol PrPSc, which clog up the brains of people with vCJD, sheep with scrapie and cows with BSE. But when Weissmann exposed the infected cells to an antibody codenamed 6H4, it halted the production of the prion proteins. The cells remained “healthy” for at least six weeks after the antibody treatment had been given. As an unexpected bonus, prion protein that had accumulated beforehand disappeared as well. This was a surprise, as prion proteins are widely thought to be virtually indestructible. “It means that, contrary to what people thought, PrPSc is not that stable,” says Weissmann. “As it turns out, it is destructible … and it’s probably enzymes that degrade it.” The antibody works by blocking the normal version of the prion protein, called PrPC and produced on the surface of cells. He thinks this lends weight to the theory that it is through physical contact with this normal version of the protein that the abnormal prion protein infects a cell and replicates itself inside. To add further credence to this, Weissmann treated some of the infected cells with a bacterial enzyme that strips a cell of all its surface proteins, including PrPC. As with the antibody, production of the prions dried up once PrPC was no longer available. Encouraging as the results are, Weissmann warns that the treatment might not work in people. “The next step is to try it in mice,” he says. Even if it worked in animals, researchers would need to develop different antibodies that mask the human PrPC protein. Secondly, researchers would need to find a way of getting the antibodies into the brain, again, not a trivial task. But he says that similar approaches to treat Alzheimer’s disease have begun to yield interesting results. Elan Pharmaceuticals in Dublin, Ireland, announced on Monday progress with AN-1792, a “vaccine” against Alzheimer’s disease. The vaccine compound resembles amyloid protein, the substance in the plaques that affect the brains of people with Alzheimer’s. The hope is that AN-1792 tricks the body’s immune system into attacking and disposing of the plaque. Elan claims that tests on 100 patients with mild to moderate Alzheimer’s showed that some developed an “immunological response” to AN-1792. Elan is now planning tests in 375 patients in the US and Europe. Journal reference: Proceedings of the National Academy of Sciences (vol 98,