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A noninvasive method for diagnosing prion diseases before symptoms appear has important implications for transfusional medicine. Articles in Science Translational Medicine describe the results of two separate teams of investigators that used similar techniques to identify variant Creutzfeldt-Jakob (vCJD) disease through a blood test.
Autopsy was once the definitive option for diagnosing patients with human prion diseases. These are highly infectious—and fatal—neurodegenerative conditions. Complications arise when asymptomatic carriers of these diseases either donate blood or undergo surgeries. This could possibly lead to an iatrogenic transmission of the disease, said Daisy Bougard, PhD, in an interview with Science Translational Medicine.
Bougard, of the Etablissement Français du Sang, INSERM, Université de Montpellier, led one of the studies with a team of researchers from France and the United Kingdom.
The team employed a blood diagnostic test to conduct a blinded identification study of 18 people from France and Britain with vCJD and 238 without the disease. In describing how the test works, Bougard said researchers first used magnetic beads coated with a ligand to capture infectious prion proteins from plasma samples.
This step “enables the concentration of prion proteins present in plasma and their separation from blood-associated inhibitors of protein misfolding cyclic amplification, or PMCA,” she said during the interview.
The next step was to use PMCA to amplify abnormal prions on beads, thus reproducing in vitro the conversion of prion proteins from normal to infectious form during the incubation phase of the disease. “The method requires the presence of a minimum quantity of abnormal prion protein and excess amounts of the normal prion protein and allows us to amplify abnormal prion protein up to a level that is detectable by standard immunoassay, such as western blot,” Bougard explained.
The assay was able to diagnose vCJD with 100% diagnostic specificity and 100% sensitivity, something that other blood tests in development have failed to do. In another important finding, the test was able to detect silent carriage of the disease in two blood donors several years before they developed symptoms of vCJD.
In another study, researchers from the University of Texas Health Science Center at Houston (UTHealth), and other investigators from Chile, Italy, and the U.K. used PMCA technology to develop a similar blood test that detected abnormal prion proteins in blood from 14 vCJD-infected individuals and 153 controls. The control group included individuals with sporadic Creutzfeldt-Jakob disease (sCJD), those with other neurodegenerative or neurological disorders, and healthy individuals.
The noninvasive method used in the UTHealth study was able to achieve what Bougard’s research team did: detect prions with 100% sensitivity and specificity in blood samples taken from vCJD subjects.
Researchers from both studies acknowledged that further research needs to take place on their respective methods, but overall, expressed optimism that these tests show promise as an efficient, non-invasive method for detecting prion contamination in the blood supply and, subsequently, vCJD in silent carriers.
UTHealth’s study results suggest that the test “could be useful for the noninvasive diagnosis of this disease in pre-symptomatic individuals,” said senior author Claudio Soto, MD, director of the George and Cynthia Mitchell Center for Alzheimer's disease and Related Brain Disorders at UTHealth, in a statement. “Early diagnosis would allow any potential therapy to be given before substantial brain damage has occurred,” said Soto, who developed the assay for the study in her laboratory.
Bougard said the assay used in her research has the potential to differentiate vCJD from other forms of CJD, as well as “evaluate the efficacy of processes for prion removal; and study the distribution of the infectious agent in different blood fractions.”