Optimisation, harmonisation and standardisation of real-time QuIC analysis of CSF in the diagnosis of sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurological disease which causes a very rapid form of dementia. Most people with the disease die within 6 months of having their first symptoms. The brains of people with sCJD are full of an abnormally twisted form of a protein called prion protein. This abnormal prion protein forms large clumps which are found throughout the brain and stop it functioning normally. The diagnosis of sCJD is made in life by doctors examining the patient for the presence of neurological features of sCJD and the results of investigations such as EEG, MRI and the presence of a protein called 14-3-3 in the fluid surrounding the brain (cerebrospinal fluid-CSF). However each of these investigations may be positive in other diseases and a definite diagnosis of sCJD can only be made by examining the brain tissue either after death or by a brain biopsy. Recently a new test, called real-time quaking-induced-conversion (RT-QuIC), has been developed which can detect the presence the abnormal prion protein in CSF. Scientific studies have shown RT-QuIC can identify patients with sCJD more accurately than CSF 14-3-3. There is a lot of interest in establishing this test in many laboratories throughout Europe and the aim of this project is to make sure that all laboratories performing RT-QuIC do it in a similar way and get comparable results. This is important as it ensures that the diagnosis of sCJD throughout Europe is as consistent as possible.

This proposal focuses on the optimisation of a recently developed analytical procedure called real-time quaking-induced conversion (RT-QuIC) which detects disease-associated prion protein in cerebrospinal fluid (CSF) of patients with sporadic Creutzfeldt-Jakob disease (sCJD). Two independent studies have shown recently that analysing CSF samples from patients with suspected sCJD using this technique has enabled those patients with disease to be identified with a high degree of sensitivity and specificity. This is a major advance in the development of a disease-specific pre-mortem diagnostic test for sCJD and there is considerable interest in establishing this test as a routine diagnostic test in Europe. It is important that RT-QuIC is optimised in terms of analytical performance and that there is a common approach to the clinical application of this technique, prior to its widespread use. It is crucial that this happens in a co-ordinated manner to ensure consistency between laboratories and that the factors affecting the test performance are thoroughly investigated. This is a focussed and well-defined project with clear objectives and is achievable within the time-frame allocated. The consortium consists of well respected scientists and clinicians who have a wealth of experience in harmonising and standardising diagnostic tests for sCJD. They are well known to each other and have collaborated closely in the past. In addition we have as advisory experts the scientists who have developed this technique to ensure that the consortium has the best possible scientific support. Once this test is harmonised and standardised across Europe it has the potential to lead to more accurate pre-mortem diagnosis of sCJD.

The impact of this project will be to introduce a new diagnostic test for sporadic CJD in a standardised manner to ensure that the diagnosis and surveillance of CJD is harmonised throughout Europe.