Human transmissible spongiform encephalopathies (TSEs) are rare diseases of hereditary, infectious or "sporadic" origin. Infectious TSEs are caused by yet unidentified agents, possibly an abnormal isoform (prion) of a normal host protein. These enigmatic properties require special efforts for diagnosis and research. A new variant of Creutzfeldt-Jakob disease (nv-CJD) in the UK and France is probably linked to bovine spongiform encephalopathy (BSE), causing world-wide concern about safety of beef and bovine products. Nv-CJD can be diagnosed only by pathological examination; however, it has a signature pattern on Western blots which is similar to that of BSE. Moreover, strains of animal TSEs when transmitted into mice, may be typed by a signature pattern of histopathology. Thus the origin of some TSEs might be tracked by these techniques. However, only a limited number of human TSEs has been investigated by modern techniques. To gain much needed insight into distribution and origin of European TSE cases, study of as many cases as possible is important for epidemiology, clinical medicine, public health and consumer protection in Europe. The European Centraliæd Facility of Human Transmissible Spongiform Encephalopathies (TSECFAC) aims at a systematic study of human TSEs, in particular to
- provide improved clinical diagnostics of human TSEs including EEG and neuro-imaging audit, and CSF testing for neural proteins;
- standardise, perform quality control of, and harmonise diagnostic methods and criteria of human TSEs in Europe, and establish the role of clinical tests such as EEG, CSF testing for neural proteins and neuroimaging in terms of sensitivity and specificity;
- provide neuropathological diagnosis and analysis of tissue pathology including histology, Immunocytochemistry and morphometry;
- examine the presence of PrPres in tonsils, spleen and leukocytes of TSEpatients, in order to investigate the diagnostic and pathogenetic potential of these materials;
- perform molecular studies including PRNP DNA analysis and PrPres analysis by Westem blotting, in order to monitor the PRNP haplotype of TSE patients, to develop a routine PCR assay, to explore the physicochemical "signature"pattern of PrPres in various human TSEs and to assess agent strain variation in human TSEs in Europe and compare with data from animal TSEs; - perform transmission into wild type and transgenic mice for identification of strain types; in-vitro transfection assays to establish an in-vitro test for infectivity; and pathogenetic modelling to study neuro invasiveness and spread from peripheral sites to the central nervous system.
As multi-disciplinary approach, TSECFAC will effectively complement existing clinical-epidemiological and neuropathological networks in Europe which will provide material for investigation. TSECFAC will integrate 9 European laboratories with established reputation in the field, acting together as "European Centralised Facility without walls". Given the variety and laboriousness of tasks, the large amount of samples to be analysed, the continuous need for quality control and assessment of optimal methodology, and the obvious need to keep the trafficking of patient samples to a minimum, the close collaboration of strategically situated dedicated laboratories appears optimal for the study of human TSEs in Europe.