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Rare and deadly, Creutzfeldt-Jakob disease remains a bit of a medical mystery

Creutzfeld-Jacob disease occurs in about one to two in every million people each year, most often in late middle-age. Andrew Mason/Flickr, CC BY-SA

Rare and deadly, Creutzfeldt-Jakob disease remains a bit of a medical mystery

Creutzfeld-Jacob disease occurs in about one to two in every million people each year, most often in late middle-age. Andrew Mason/Flickr, CC BY-SA

Creutzfeld-Jacob disease (CJD) is a rare degenerative disease of the brain that causes rapidly progressive loss of memory and muscle control followed by death, usually within 12 months of onset. In developed countries such as Australia, it occurs in about one to two in every million people each year, most often in late middle-age.

The recent report that Frank Burton – a former financial officer of the Sydney Swans – has contracted CJD and only has a short time to live, is a real tragedy for the man and his family.

But the reporting of such a celebrity case only serves to highlight that we still don’t know how to prevent a disease that most often goes unreported in the media, and unremarked on, except by family and friends.

Two Nobel prizes later

Inevitably, media about CJD has been intermittent, reflecting changes in attention and our understanding over the years.

By the 1960s, scientists had recognised that the microscopic changes in the brain of CJD patients were spongiform, that is, they resembled the porous structure of a sponge. And they knew this was similar to what happened in the brain of people dying from kuru, a disease that had become an epidemic among the isolated Fore people in Papua New Guinea.

Kuru was known to almost certainly result from the cannibalism of diseased individuals. It was shown to be transmissible to chimpanzees following injection of kuru brain, and CJD was also subsequently shown to be transmissible.

Carleton Gajdusek, the American physician and medical researcher who won the 1976 Nobel Prize for leading that work, initially thought that CJD and kuru were caused by related viruses. But no such virus could be identified in the brains of CJD or kuru patients. And it eventually became clear that the capacity to transmit disease to animals depended on a changed structural protein in diseased tissue.

A Papua New Guinean tribe - though not this one - suffered a ‘kuru’ epidemic, which was linked to cannibalism. John William Lindt/Wikimedia Commons, CC BY

This transmissible protein was named a “prion” by the American neurologist and biochemist Stan Prusiner. He also developed the concept that, over time, a small amount of an abnormal (injected) prion could create more of itself by changing the shape of the normal prion in brain, leading to the onset of “prion diseases” such as CJD or kuru.

The prion concept was well supported by animal experiments, leading to a Nobel Prize for Prusiner in 1997.

By the 1980s, there had been alarming reports of CJD being inadvertently transmitted to human patients by grafts of dura mater, the tough outer membrane enveloping the brain and spinal cord. And by hormones prepared from deceased people who were presumably incubating CJD, whose tissues must have been contaminated by abnormal prions.

Medical authorities moved to eliminate the risk by banning such grafts, and by sourcing hormones prepared using recombinant DNA rather than hormones prepared from human tissues.

But the 1980s delivered another shock when mad-cow disease (BSE or bovine spongiform encephalopathy) erupted in the cattle population of the United Kingdom and other countries. The outbreak was traced to the practice of using meat and bone meal, prepared from slaughtered cattle, as a feeding supplement for calves.

It was soon realised that this practice (effectively bovine cannibalism) was amplifying the proportion of altered prion in successive generations of cattle, and driving the BSE outbreak.

Soon after action was taken to control the outbreak, there were concerns about whether the inadvertent consumption of BSE-affected tissues by the British public would result in transmission of prion disease to humans. Sure enough, in 1995, the first cases of variant CJD – a version of the illness that results from BSE exposure – were diagnosed, affecting people at a much younger age than the more usual (sporadic) form of CJD.

By 2013, when the outbreak of variant CJD seemed over, there had been 177 cases recognised in United Kingdom, with smaller numbers in other, less affected countries. Over the same time period, there had been some 2,000 cases of sporadic CJD in the United Kingdom.

Reducing risk

Medical authorities have acted to reduce the possibility of human-to-human transmission of CJD by introducing more stringent procedures for cleaning and sterilising surgical instruments that might inadvertently transmit traces of prion from person to person.

People who ate meat contaminated with mad-cow disease developed ‘variant CJD’. Global Panorama/Flickr, CC BY

Restrictions on blood transfusion were also introduced to reduce the possibility that blood donors might have been exposed to BSE-affected material. But that was not before three people in the United Kingdom had developed variant CJD after exposure to a blood transfusion from a person who later developed the disease.

Although the epidemic of variant CJD now seems to be over, there are unanswered questions about the number of people in the United Kingdom who were exposed to BSE, and who might still be at risk of disease, or of transmitting it to others.

Australia is fortunate in that we didn’t have outbreaks of BSE or variant CJD. And if the world attends to feeding practices in cattle and other species, it’s unlikely there will be any future outbreaks of transmissible versions of prion disease in animals or people.

Still, the origin of sporadic CJD, the most usual transmissible form of the disease in humans, remains something of a puzzle. Early Australian work indicated that sporadic CJD risk was slightly greater in people with a history of surgery. This is consistent with the idea that a seeding dose of altered prion might have been transmitted by surgery or transfusion many years previously.

Subsequent work suggests sporadic CJD risk may be most increased in people exposed to surgery as children. There’s continuing uncertainty about this, but we should be reassured on two grounds: first that sporadic CJD is still very rare, so that the absolute risk is still only one to two for every million people. And second that the necessary steps have already been taken to reduce the possibility of any further transmission by way of surgery or blood transfusion.

We can trust these preventive measures will serve us well into the future. Meanwhile as research proceeds, we should come to better understand why abnormal prions are more likely to cause disease when exposure happens at younger ages.

One possibility is that older people are often protected from abnormal prions by an immune response, which is less effective in younger people. Such understanding could open up new ways of preventing prion diseases.

Correction: This article previously said “Blood donations are now routinely tested to exclude any contaminated with altered prions.” This is incorrect and the sentence has been removed.