Transmissible spongiform encephalopathies (or prion diseases) are neurodegenerative diseases that affect a broad spectrum of mammalian species.  These diseases manifest themselves after an incubation period that is generally lengthy (several decades in man), and they are always fatal.  At the heart of the pathological process is a protein called a prion.  The normal prion protein, PrPc, is expressed in its natural state by a very large number of cell types.  In affected individuals, this protein accumulates in the tissues in an abnormal form called PrPSc.  The PrPSc protein is currently considered to be the infective agent causing prion diseases. 

In man, the commonest form of transmissible spongiform encephalopathy (approximately 1 case per million individuals per year) is the sporadic form of Creutzfeldt-Jakob disease.  If no source can be identified, cases are deemed to be of sporadic origin.  The inter-human transmission of Creutzfeldt-Jakob disease (iatrogenic) (e.g. following the administration of extracted growth hormone or a transplant of tissues from patients incubating the disease) has been reported in numerous countries.

Several clinical forms of sporadic Creutzfeldt-Jakob disease have been described.  Until now, study of the abnormal prion protein (PrPsc) found in these patients made it possible to identify two variants, Type 1 and Type 2, but their detection did not seem to be correlated consistently with the clinical diversity of this disease.

In order to better characterise the relationships that may exist between different clinical types in sporadic cases and the diversity of the forms of PrPSc, the scientists studied a cohort of 41 sporadic cases of Creutzfeldt-Jakob disease.

Thanks to new investigative techniques, previously developed on animal prion strains by INRA and CEA researchers, analysis of the samples collected from these patients enabled identification of the Type 1 and Type 2 previously described, and also revealed the existence of two other subgroups which appeared to correspond to different clinical forms of the disease.

These four biochemical signatures were also identified in a cohort of 12 patients with iatrogenic forms of the disease.  Different types of PrPSc could be identified in French patients following the administration of extracted growth hormone.  This observation may suggest the contamination of extracted growth hormone from different sources, i.e. from the pituitary glands of several individuals suffering from sporadic Creutzfeldt-Jakob disease.

These results open the way to a clearer understanding of the diversity of the infective agents causing this disease.

The research teams are currently performing further studies on mouse models in order to confirm that each of the biochemical signatures identified corresponds to biologically distinct agents.