Lacroux C, Comoy E, Moudjou M, Perret-Liaudet A, Lugan S, Litaise C, Simmons H, Jas-Duval C, Lantier I, Béringue V, Groschup M, Fichet G, Costes P, Streichenberger N, Lantier F, Deslys JP, Vilette D, Andréoletti O. Preclinical detection of variant CJD and BSE prions in blood. PLoS Pathog. 2014 Jun;10(6):e1004202. Epub 2014 Jun 12 PubMed.
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Risk of blood-born transmission of variant CJD has been a matter of concern for many years. Strong measures such as blood filtration and donor exclusion criteria have been adapted in order to minimize the risk for humans. Only few blood transfusion-related cases have been identified so far, however, a recent study in the U.K. reported the presence of PK-resistant PrP in asymptomatic carriers in appendices and estimated the prevalence of vCJD in the general population as high as 1:2000 in the age cohort born between 1941 and 1985.
These high numbers are in contrast to few clinically affected patients on one hand, and only few cases which could be linked to blood transfusions on the other. However, in the absence of a definite screening test, the potential for disease transmission between humans via blood remains.
The work reported here relates to the further development of the protein amplification technique, which was reported for the first time by Claudio Soto (Soto et al., 2002) and is called PMCA-protein misfolding cyclic amplification. The basic principle is the amplification of misfolded prion aggregates via repeated sonication and seeding with various substrates, which lead to detectable levels of the abnormal protein.
PMCA has been demonstrated to work in various fluids and now, for the first time, using blood of affected patients. In addition, the pathological aggregates were detected at early clinical and preclinical disease stages in animal models. In humans, the assay identified three out of four vCJD samples, which demonstrates the possibility for blood test development. Further methodological development on test stability and robustness as well as applicability will follow.
PMCA and other newly developed techniques, such as RT-QuIC and eQuIC, open a completely new field for detection of misfolded proteins, which might be relevant not only for prion diseases of humans and animals, but also other degenerative disorders, Alzheimer’s disease, or synucleinopathies.
References:
Soto C, Saborio GP, Anderes L. Cyclic amplification of protein misfolding: application to prion-related disorders and beyond. Trends Neurosci. 2002 Aug;25(8):390-4. PubMed.
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