Eating beef from an animal infected with mad cow disease can lead to an untreatable condition that attacks the brain and is universally fatal, but symptoms can take decades to emerge. Thankfully, a new blood-screening technology can spot the condition, known as variant Creutzfeldt-Jakob disease, with 100 percent accuracy, perhaps years before it attacks.  

Misfolded proteins called prions cause both mad cow and variant Creutzfeldt-Jakob disease. Once they invade the brain, they begin recruiting normal proteins and forcing them to adopt the same abnormal shape. The prions and the blighted proteins clump together forming increasingly large aggregate deposits that wreak havoc on the brain and invariably lead to death. The disease, however, has a long incubation period. “In the case of humans, the estimation goes from several years to a few decades,” says Claudio Soto, a neurologist at McGovern Medical School at UTHealth in Houston. “So it could be that you're exposed one day and then, 40 years after, you develop the disease.”

In the interim, the prions hang out in non-brain tissues such as the appendix and tonsils, and because they do not cause symptoms, the infected person becomes a silent carrier. Perhaps the worst outbreak of variant Creutzfeldt-Jakob disease occurred in the United Kingdom during the 1980s and 1990s, when large swaths of the population were exposed to beef contaminated with mad cow disease. Since then, there have been 277 cases in the U.K. and an epidemiological study published in 2013 estimates that another 1 in 2,000 people there, about 30,000 in total, are silent carriers. While it is not clear how many of these people will go on to develop the disease, blood donations from silent carriers could jeopardize the country’s blood supply, according to Soto. The new screening test stands to alleviate the uncertainty, however.

Soto led the team behind one of two studies published today in Science Translational Medicine that assessed a diagnostic test for variant Creutzfeldt-Jakob disease, which can detect very low levels of prion proteins in the blood.

Soto’s team and a team led by Daisy Bougard of the French Blood Establishment in Montpellier, France ran the test on blood samples from variant Creutzfeldt-Jakob disease patients in the U.K. and France. The two teams used slightly different methods, but the basic idea was the same: the test essentially mimics the progression of the disease in an accelerated, artificial environment. First the prion proteins are separated from the blood and combined with normal proteins, which take on an abnormal shape, forming aggregate clumps. Then, the aggregates are pulled apart and recombined with more normal proteins. The process is repeated over and over again, in effect replicating the prion proteins until very small quantities are amplified enough to be easily detected. If there are no prions present in the blood, nothing happens.

Between the two studies, the test was able to identify a total of 32 cases of variant Creutzfeldt-Jakob disease with 100% percent accuracy, and there were no false positives among the 391 controls, which included regular blood donors, patients with a different form of Creutzfeldt-Jakob disease, and patients with other neurological diseases. In addition, Bougard’s group was able to diagnose variant Creutzfeldt-Jakob disease in the blood of two patients 1.3 and 2.6 years before they developed clinical symptoms. The results not only confirm that the test can accurately diagnose the disease, but also suggest that it may be able make the diagnosis before patients develop symptoms, which could be particularly important in places like the U.K. with a large number of silent carriers. The test
will “improve the safety of our blood supply [by eliminating] any blood samples that may be potentially contaminated with prions,” says Soto, “which will in turn diminish the possibility of people getting infected, and eventually developing this fatal disease.”

Soto founded a startup called Amprion to develop the technology. The company is currently working on optimizing the test and obtaining approval in the United States and Europe to use it for blood screening. Soto expects it to be commercially available within one to two years.

Paul Brown, formerly a senior investigator in the Laboratory of Central Nervous System Studies at the National Institutes of Health, who was not involved in the studies praised the accuracy of the test, saying that the two papers “reflect the immense progress that testing has undergone during the past decade.” However, he pointed out that variant Creutzfeldt-Jakob disease is no longer a major global problem, with only two cases in 2016, and said the test would have been more useful during the peak of the epidemic.

Christina Orrú, a neurologist at the National Institutes of Health, who was not involved in the studies, thinks the test is still needed to screen and monitor prion contamination in the blood supply. “We currently don’t really understand the implications of silent carriers and if they could harbor another wave of variant Creutzfeldt-Jakob disease, particularly in the U.K.,” she says.

Sylvain Lehmann, a neurologist at France’s National Center for Scientific Research, who was not involved in the studies was also impressed by the sensitivity and specificity of the test, saying that the findings confirm that silent carriers can transmit the disease. Because the current versions of the test are complicated, labor-intensive and time consuming, they are not necessarily suitable for screening large volumes of blood, he says, but they could be useful for confirming a diagnosis, especially in silent carriers, or detecting variant Creutzfeldt-Jakob disease in at-risk patients who received a contaminated blood transfusion.

The test may also have other applications. Soto and Bougard point out that while variant Creutzfeldt-Jakob disease is rare, more common neurodegenerative disorders like Alzheimer’s and Parkinson’s are caused by a similar process of misfolded proteins aggregating in the brain and causing damage. Both are hopeful that the new test can be adapted to screen for these diseases at an early stage, before symptoms occur.

“This is a big problem with all these brain diseases, that when the disease manifests clinically, it's always very late, and at the time that the brain is largely destroyed,” says Soto. “We are trying to develop a blood test to detect Alzheimer's disease and Parkinson's disease before the clinical symptoms of the disease appear so we have better possibilities for therapies to work.”