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A US-led research team has developed a technique to filter potentially deadly prion proteins from blood. They suggest that the method should be used routinely in attempts to remove prions, which can cause variant Creutzfeldt-Jakob disease (vCJD), from blood products used for transfusions.
The method could offer better protection than the current practice of removing white blood cells from donated blood, say the researchers, led by Robert Rohwer of the University of Maryland, Baltimore. Previous studies have shown that around a half of the abnormal, infective prion proteins are in white blood cells, so removing these can help reduce the risk of infection. But infective prions are also found in the blood plasma.
Of the 200 vCJD cases recorded worldwide, only a few have involved contaminated blood transfusions, but health officials are still worried about this possible transmission route. Several countries have banned blood donations from people who have lived in Britain, where many people have potentially eaten meat containing infective prions.
Despite the relatively few cases of this devastating, untreatable disease, researchers worry that many other people might be carriers. According to a survey of samples from tonsil and appendix removals, as many as 4,000 British people may be harbouring the disease, which can remain dormant for decades, without showing symptoms. There is currently no test to detect abnormal prions in humans, meaning that it is impossible to identify these people.
In a bind
Routine filtering of blood to remove any prions would sidestep the danger, Rohwer argues.
He and his colleagues searched databases of millions of molecules to find ones that bind to the prion protein. They eventually identified a resin, called L13, that binds to both the normal and disease-causing forms.
They tested the resin using hamster blood spiked with the prions that cause scrapie, a disease related to vCJD. They then used this blood to transfuse hamsters. Around half of the animals injected with untreated blood developed disease, but the nearly 200 hamsters injected with blood filtered with L13 remained disease-free. The researchers report their findings in The Lancet1, and are commercialising the technology.
The problem is that effectiveness of the filtration will be very difficult to verify in people, because although there is a test for infective prions in hamster blood, no such test yet exists for humans. The only people known to contain infective prions are those suffering from the disease, and they have always been too unwell to have large volumes of blood removed for research.
"It's going to be very difficult to check that the new method works for human blood," says Marc Turner, an expert on prion disease at the Edinburgh Blood Transfusion Centre, UK. He says that his group will carry out an independent evaluation of the filtration method to see whether it is worth using routinely in blood banks. But without a human test, it is difficult to prove that the filter is effective.
Through the net
And a small fraction of the prions may slip through the net. Rohwer's team previously tested the compounds' abilities to mop up prions from a sample of infected hamster brain tissue. "One part in 10,000 simply wasn't adsorbed," he says. "It seems to be in a form that would just keep going through the resins." Without a blood test it is impossible to tell whether this would also occur in blood.
Rohwer points out, however, that even blood from heavily infected people contains only 5,000 infective doses' worth of prions, so filtering of donated blood should bring the amount well below the amount required to cause disease.
Health officials may nevertheless question the economic wisdom of adopting the new method without being able to find out exactly how many people are symptomless carriers. Even in Britain, it is not known whether the 4,000 people inferred from the tonsil survey are capable of spreading the disease, and whether a second wave of clinical cases will materialize.
Rohwer, a co-founder of the company that developed the technology, says that the method should be no more costly than removing white blood cells, and that it is better to be safe than sorry. "Retrospectively, some people might say it was a waste [if the epidemic does not materialize]," he says. "But what if the cases did turn up?"
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References
- Gregori L., et al. Lancet, 368. 2226 - 2230 (2006).
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