Detecting Prions in Blood
Prion diseases are a group of rare, fatal brain diseases that affect animals and humans. They are caused by normally harmless proteins that become abnormal and form clumps in the brain. One form, called variant CJD (vCJD), is associated with eating meat from cattle infected with bovine spongiform encephalopathy, commonly known as “mad cow” disease.
People may have vCJD for years before symptoms—such as depression, hallucinations, moving difficulties, and dementia—appear. These “silent” carriers have small amounts of prions in their bloodstreams and can transmit the disease to others via blood transfusions. The only current method to diagnose vCJD is to perform a biopsy or a postmortem analysis of brain tissue. Thus, a noninvasive test to detect prions in blood is a medical priority.
Two research groups recently developed blood tests to detect prions. One of the groups, led by Dr. Claudio Soto of the University of Texas Health Science Center at Houston, was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), and National Center for Advancing Translational Sciences (NCATS).
Prions are scarce in the bloodstream and difficult to measure. Both teams developed methods to amplify the prions in blood samples using a technique called protein misfolding cyclic amplification (PMCA). PMCA relies on the characteristic nature of prions to cause certain healthy proteins to clump abnormally and convert into prions.
Soto’s group first combined healthy proteins with known concentrations of infectious vCJD prions. They intermittently agitated these mixtures with sound waves. The agitation helped break the prions into smaller chunks. This increased the number of prions that could then convert healthy proteins into prions. Using this method, the scientists were able to detect more than a billion-fold dilution of prions using an anti-prion antibody.
The scientists next tested whether the technique could be used to detect prions in blood samples from 14 people with vCJD and 153 controls. The controls included healthy people as well as people with different neurological or neurodegenerative disorders, including sporadic CJD, the most common form of CJD. The assay flagged all the vCJD samples correctly.
In the second paper, a French research group described a similar approach testing a blinded panel of blood samples. That team identified 18 vCJD patients in a group of 256 samples.
“Our findings, which need to be confirmed in further studies, suggest that our method of detection could be useful for the noninvasive diagnosis of this disease in pre-symptomatic individuals,” Soto says. Early diagnosis would allow potential therapies to be tested before substantial brain damage occurred. This technique would also allow blood contaminated with prions to be detected and removed from the blood supply.
Both teams are now working to validate their methods using larger samples sizes.
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Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease. Concha-Marambio L, Pritzkow S, Moda F, Tagliavini F, Ironside JW, Schulz PE, Soto C. Sci Transl Med. 2016 Dec 21;8(370):370ra183. doi: 10.1126/scitranslmed.aaf6188
Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease. Bougard D, Brandel JP, Bélondrade M, Béringue V, Segarra C, Fleury H, Laplanche JL, Mayran C, Nicot S, Green A, Welaratne A, Narbey D, Fournier-Wirth C, Knight R, Will R, Tiberghien P, Haïk S, Coste J. Sci Transl Med. 2016 Dec 21;8(370):370ra182. doi: 10.1126/scitranslmed.aag1257
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