PrPTSE detection

CSF PMCA

Development and evaluation of a diagnostic test for Creutzfeldt-Jakob disease based on the detection of PrPSc in cerebrospinal fluid using in vitro amplification techniques including protein misfolding cyclic amplification

2007: 1 years / Grant: 85 000 euros

CSF Real Time QuIC

Development and evaluation of a diagnostic test for sporadic and variant Creutzfeldt-Jakob disease (CJD) based on the detection of PrPSc in the cerebrospinal fluid (CSF) using real-time QuIC analysis

2010: 1 years / Grant: 68 000 euros

Project: The initial objective of the project “CSF PMCA” was to assess whether PMCA could be used for the detection of PrPTSE in biological fluid such as cerebro-spinal fluid (CSF) or blood. A. Green subsequently proposed, in the project “CSF Real Time QuIC”, to use a new technique based on QuIC method, named Real-time quaking-induced conversion (RT-QuIC). RT-QuIC is an assay in which disease-associated prion protein promotes a rapid conformationalconversion of recombinant PrP into misfolded PrP and aggregates of PrP that can be monitored in real time according to the incorporation of the amyloidophylic thioflavin T.

Main results and related published data: The consortium showed that the RT-QuIC method makes it possible to distinguish between CSF samples from both CJD and vCJD patients from CSF samplesfrom patients with other protein-misfolding diseasessuch as Alzheimer’s disease. In a pilot study using 108 CSF samples, they also showed for sCJD that the sensitivity and specificity of the RT-QuIC method could reach 91% and 98% respectively. This wasconfirmed in another group of 118 CSFsamples with a sensitivity of 87% and a specificity of 100%. These results were thusconvincing and encourage the use of RT-QuIC for the biochemical diagnosis of sCJD. Recently, in the context of a ring trial involving 11 differentcenters, an almostcomplete concordance between the centers was obtained on 25 CSF with the RT-QuIC method. These results attest thus to the reliability and reproducibility of the method that are prerequisite criteria before the introduction of the method into clinical practice.