Understanding BSE and CJD Advances Vaccines and Diagnostic Tests

Embargo until 00.01hrs - 19 March 1999

Understanding BSE and CJD Advances Vaccines and Diagnostic Tests

A team of UK researchers have made a major advance in understanding how the brain protein involved in BSE in cattle and Creutzfeldt Jakob Disease (CJD) in humans causes so much damage, according to new research published in the current issue of Science magazine.

Prion diseases, such as BSE and scrapie in animals, and CJD in humans all involve conversion of a normal cell protein, known as the prion protein or PrP, into an abnormal or rogue form. This rogue PrP is thought to be the infectious "prion" which causes these diseases. It replicates by converting normal PrP into more rogue PrP, setting off a chain reaction which leads to its progressive accumulation and brain damage. The difference between the normal and rogue forms of PrP is known to relate to their shape but until now just how the conversion from normal to abnormal PrP takes place has remained a mystery.

Now researchers have managed to capture this remarkable and unprecedented change in a test tube, as Professor John Collinge at the Imperial College School of Medicine and Director of the Medical Research Council Prion Unit, who led the research team explains: "There are two major building blocks from which proteins are constructed, known as alpha helices and beta sheets. Normal PrP is nearly all alpha structure, while the rogue form is largely beta. Using a genetically engineered form of normal soluble prion protein, we have managed to capture, for the first time, the moment when the change occurs.

"We now know that the conversion involves breaking a single bond in the molecule using conditions which exist normally within cells. 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," continued Professor Collinge.

Furthermore, this protein, when placed in concentrations of salt seen normally in the brain, forms clumped, aggregated material indistinguishable from the rogue form which accumulates in the brain in BSE and CJD. For the first time this provides an explanation of how these prions actually replicate.

This research, funded jointly by the Wellcome Trust, the world's largest medical research charity, and the Medical Research Council (MRC) represents a major advance in understanding the key events in prion disease. Armed with this new information, it should be possible to make antibodies which detect beta-PrP specifically, offering the opportunity of new diagnostic tests for prion disease in humans and animals. Knowing how the switch from normal to rogue occurs could help researchers develop new drugs. It may in the future be possible to use beta-PrP to develop new strategies for therapies and prevention of prion disease.

Professor Collinge said: "Understanding how to inter-convert the prion protein between its alpha and beta forms opens up new research directions to understand CJD and BSE. While this 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".

Professor John Collinge was working in collaboration with Dr Tony Clarke of the University of Bristol and the MRC Prion Unit, Dr John Waltho at Sheffield University and Professor Helen Saibil at Birkbeck College.

For further information: Ifeanyi Uwechue ([email protected]) / Noorece Ahmed / Catherine Nestor Wellcome Trust Press Office Tel: 0171 611 8612/8540 / 8846 Fax: 0171 611 8416 Pager: 01893 366023

Notes to Editors: 1. Professor Collinge is a Principal Research Fellow of the Wellcome Trust, and is Director of the Medical Research Council Prion Unit. He is also a consultant neurologist at St. Mary's Hospital and the National Hospital for Neurology and Neurosurgery in London.

2. The Wellcome Trust is the world's largest medical research charity with an annual spend of £300 million. The Wellcome Trust supports more than 3,000 researchers, at 300 locations, in 30 different countries - laying the foundations for the healthcare advances of the next century and helping to maintain the UK's reputation as one of the world's leading scientific nations. As well as funding major initiatives in the public understanding of science, the Wellcome Trust is the country's leading supporter of research into the history of medicine.

3. The Medical Research Council (MRC) established since 1913, aims to improve health by promoting research into all areas of medical and related science. It is funded mainly by the government, but is independent in its choice of which research to support. About half of the MRC's expenditure of £323.8 million is invested in over 40 of its Institutes and Units, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.