Study indicates human susceptibility for variant Creutzfeldt-Jakob disease transmission

According to an article published online today (Monday March 27, 2006) by The Lancet Neurology, all individuals could be susceptible to transmission of variant Creutzfeldt-Jakob disease (vCJD) through routes such as blood transfusion, and, because of long incubation times before onset of symptoms, a significant level of infection might already be present in the population.

Estimates of the extent of the UK epidemic of vCJD have varied greatly with the predicted number of future cases ranging from the low hundreds to hundreds of thousands. Variations and mutations in the prion protein (PrP) gene affect disease susceptibility, although the underlying mechanisms are unknown. Variations at a particular point on the PrP gene--codon 129--can affect the transformation of the PrP into the disease-associated form (PrPSc).

A team of researchers from Edinburgh, UK, led by Professor Jean Manson, have analysed the transmission of BSE and vCJD in four lines of genetically altered (transgenic) mice after they were injected with brain material from cases of vCJD and BSE. Transgenic mice were produced that express the variations found in human PrP gene at codon 129--methionine (MM), methionine/valine (MV), and valine (VV). The team found that vCJD was transmitted to mice with all three genetic variations with different pathological characteristics. Disease transmission occurred most readily with VV mice, followed by MV, and then MM. Furthermore, the long incubation periods during which PrPSc was deposited in the transgenic mice predict that infection could be present in human beings, with all genotypes, for a substantial time before clinical onset of symptoms. The authors conclude: "A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public-health issue."

In an accompanying Reflection and Reaction article, Corinne Lasmézas comments that although a small number of VV individuals could become asymptomatic carriers, since only 10% of the population carries two V alles the impact of this partly reassuring finding is reduced.

Jean Manson, Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, King's Buildings, West Mains Road, Edinburgh EH9 3JF, UK. T) 0131 667 5204

Notes to editors
The Reflection and Reaction article states that 40% of the Caucasian human population has the MM genetic variation, 10% VV, and 50% MV.

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