Blood test detects deadly prions
Process could one day halt unwitting spread of brain disease in humans.
For years, experts have feared that thousands of people are unknowingly carrying and transmitting the human form of mad cow disease: new-variant Creutzfeldt-Jakob disease (vCJD). Now a blood test could help to ease their worries, or confirm their worst nightmare.
Researchers have succeeded in reliably detecting the malformed proteins that cause vCJD in blood samples taken from hamsters. Their test takes only a few days to complete.
If the procedure works as well in humans, it could be used to check stocks in blood banks. At the moment there is no such screening process; two of the people who have died of vCJD in Britain are thought to have picked up the disease from transfusions.
If improved, the test might also be used to screen animals for the disease before they enter the food chain.
The rare disease is thought to be caused by the formation of abnormal proteins in the brain known as prions. These misshapen proteins apparently multiply by changing the conformation of normal proteins that they come into contact with, eventually leading to a fatal neurodegenerative illness.
Prions concentrate in the brain, making it hugely challenging to detect the few that circulate in the blood. To find out whether an animal is infected with the disease, experts must kill it to obtain brain tissue for tests.
Some scientists have tried extracting blood from live subjects and injecting this into another animal's brain. They then wait, typically for months, to see whether the animal receiving the shot develops the clinical traits of the disease.
But this method only succeeds in picking up on an infection 31% of the time it is present, says neuroscientist Claudio Soto from the University of Texas in Galveston. Moreover, it is not clear whether blood taken from humans can cross the species barrier to reproduce the illness in test animals such as hamsters.
Soto decided to develop another option: amplifying the negligible levels of the misshapen proteins in blood to a detectable level.
His team overcame the first barrier to this goal four years ago, when it managed to replicate deadly prions from hamster brains.
The technique involves mixing normal proteins with tiny amounts of the infectious version in a test tube, causing the abnormal molecules to multiply and clump together over a period of about half an hour. A pulse of sound then breaks up the clumps, freeing the misshapen proteins to repeat the process.
Soto and his team have now improved and automated this process, making it a viable test. A microwave-sized machine can run 140 of these cycles in about 70 hours.
Tests on 18 diseased and 12 healthy hamsters revealed that this method could detect prions 50% of the time they were present after two 140-cycle runs. After six runs this was boosted to 89%. The test did not give any false positives, they report in Nature Medicine1.
Soto says that adapting the technique to run tests on human blood should not take longer than six months. But he says it will need much more testing, and adds that there are ethical issues about screening for a disease that has no known cure. "That's an important question that someone has to resolve," says Soto.
"As with most breakthroughs, you have to wait for it to be confirmed in other laboratories before you claim victory," says Pierluigi Gambetti, who directs the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, Ohio. He notes that the initial injection of infectious prions into the hamsters' brains created a stab wound that may have helped prions spread into the bloodstream. This unusual circumstance may have artificially boosted the test's sensitivity, he says.
In any case, the test may help to answer the question of how many silent carriers there are living in Britain. Solving this would help to predict future incidence of disease, and might give pharmaceutical companies reason to invest in a treatment.
- Castilla J., Saa P. & Soto C. et al. Nature Med., advanced online publication doi:10.1038/nm1286 (2005).
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