NR AODX
AU Bradbury,J.
TI Molecular marker for Creutzfeldt-Jakob-disease may facilitate diagnosis
QU Lancet 1996; 348(9036): 1230
PT Article
VT
Since last week, when Prof John Collinge (London, UK) announced the most direct evidence to date for a link between bovine spongiform encephalopathy (BSE) and new variant Creutzfeldt-Jakob disease (nvCJD), his results have been discussed widely in the scientific community and the media. But the reaction has been more measured than in March when the first nvCJD cases were reported. As Prof Tony Minson (Cambridge, UK) says, "Although many scientists were wishfully hoping that a direct link between the diseases would not be shown, I doubt if many of us were really that surprised". In common with other commentators, he stresses that the new results are not absolute proof that nvCJD and BSE are linked. "The identification of nvCJD in the UK earlier this year was circumstantial evidence of BSE infection in man", he says, "but the new data make us more confident of a link between the two diseases".
The molecular test devised by Collinge et al (Nature 1996; 383: 685-90) looks at different glycoforms of abnormal, protease-resistant prion protein on western blots. The pattern of the different forms depends on the origin of the prion (figure). The important result highlighted by Collinge is that human brain extracts from patients with nvCJD behave like extracts from BSE-infected cows. Collinge has also demonstrated that when brain extracts from patients with CJD or from cows with BSE are injected into mice, the pattern of glycoforms in mouse brain extract is the same as in the source material.
Collinge's group has injected brain material from CJD and nvCJD patients into transgenic mice carrying the human prion protein. Mice injected with CJD material develop clinical disease within 200 days but, as yet, the mice injected with nvCJD have not, even though they were injected up to 500 days ago. James Ironside (Edinburgh, UK) says that the reason for this difference is not clear but may be because the human gene put into the transgenic mice is homozygous for valine at codon 129 whereas, so far, all confirmed cases of nvCJD have been homozygous for methionine here. "The codon 129 polymorphism may affect disease incubation time", says Ironside.
Collinge's team is now investigating the possibility of detecting abnormal prion proteins in tissues other than brain. In scrapie-infected sheep, prion protein can be detected in lymph nodes and tonsils. The combination of clinical screening, pathology, and biochemistry may allow clinicians to diagnose nvCJD more easily in the future, suggests Ironside.
14 cases of nvCJD have now been confirmed and Ironside says that the CJD Surveillance Unit in Edinburgh is currently investigating a few more potential cases. In common with Collinge and Minson, Ironside says the timing of the BSE epidemic in cattle and the probable long incubation period of nvCJD, mean that any potential nvCJD epidemic is unlikely to happen for 2-3 years, but he concludes that "We must make looking at therapeutic options a priority now".
ZR 0 Zitate
SP englisch
OR Prion-Krankheiten 2