CJD Secret Discovered -
New Research Directions Open Up
BBC News Sci/Tech
The critical moment when Creutzfeldt-Jakob disease and BSE strikes the brain has been captured in a test tube for the first time.
The breakthrough is a major step forward for the future development of new diagnostic tests and possibly even effective treatments of the fatal diseases.
"It opens up new research directions to understand CJD and BSE," said the research leader, Professor John Collinge, Director of the UK's Medical Research Council's Prion Unit.
"While it leads to the possibility of developing much better diagnostic tests, our eventual goal of an effective treatment for these devastating brain diseases still remains an enormous challenge," he added.
Deadly transformation
The breakthrough has unmasked the mysterious mechanism by which normal proteins in the brain are transformed into a different, deadly form.
This happens when a rogue protein, called a prion, corrupts a perfectly normal protein, PrP, which usually sits on the surface of brain cells. It is believed that the prion alters the shape of the normal protein.
The result is that the altered proteins cannot dissolve as normal and build up in hard clumps or "plaques", killing the cells they form in.
These clumps are the "holes" which characterise the prion brain diseases and cause the brain damage which is ultimately fatal.
But just how the prion persuades the normal protein to change was until now completely unknown. Catching the conversion in the act allowed the British scientists to discover that just one, subtle change is responsible.
Single bond
"We now know that the conversion involves breaking a single bond in the molecule using conditions which exist normally within cells," explains Professor Collinge.
"This remarkable property of prion protein is unprecedented: no other protein has yet been shown to be able to exist in two such entirely unrelated shapes."
The team was convinced they had exposed the disease's secret when their altered protein formed clumps which were indistinguishable from the rogue form which accumulates in the brain in BSE and CJD.
New drugs
The scientists believe the new information should make it possible to create antibodies which detect the rogue protein specifically. This would mean new diagnostic tests for prion disease in humans and animals.
Also, knowing how the switch from normal to rogue protein occurs could help researchers develop new drugs to treat and prevent prion disease.
The research is published in Science magazine and was funded by the Medical Research Council and the Wellcome Trust.