- 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