Prion disease describes a group of progressive conditions that affect the brain and nervous system of humans and animals. In people these disorders impair brain function, causing memory changes, personality changes and problems with movement that worsen over time. The signs and symptoms of prion disease typically begin in adulthood, and the course of these disorders ranges from a few months to several years.
It is important to note however that these disorders are very rare. They affect about one person per million worldwide each year.
Familial prion diseases of humans include classic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal insomnia. These conditions form a spectrum of diseases with overlapping signs and symptoms.
One type of prion disease that has received widespread media coverage over the years occurring in humans, is variant Creutzfeldt-Jakob disease (vCJD), acquired by eating beef products obtained from affected cattle. (In cows, this form of prion disease is known as bovine spongiform encephalopathy, BSE, or more commonly “mad cow” disease). CJD typically affects people over 40-years-old. It occurs worldwide although incidence is higher among Northern African Jews.
vCJD is most common in the United Kingdom. In the early 1980s, because of relaxed regulations for processing animal by-products, tissue from sheep infected with Scrapie, a prion disease, was introduced into cattle feed. Thousands of cattle developed bovine spongiform encephalopathy (BSE) or mad cow disease. Some people who ate meat from affected cattle developed vCJD.
Because the incubation period in BSE is long, a connection between BSE and contaminated feed was not recognized in the UK until BSE had become an epidemic, which was controlled by massive slaughter of cattle. In the UK, the annual number of cases of vCJD between 2000 and 2002 ranged from 17 to 28. Although vCJD has been restricted to the UK and Europe thus far, BSE has been reported in North American cattle.
About 70% of patients present with memory loss and confusion, which eventually occur in all patients. 15 to 20% present with in coordination and ataxia, which often develop early in the disease. Myoclonus provoked by noise or other sensory stimuli (startle myoclonus) often develops in the middle to late stages of disease. Although dementia, ataxia, and myoclonus are most characteristic, other neurologic abnormalities (e.g., hallucinations, seizures, neuropathy and movement disorders) can occur. Ocular disturbances (e.g. visual field defects, diplopia, dim or blurred vision) are common. Death typically occurs after six to 12 months, commonly due to pneumonia.
Another example of an acquired prion disease is Kuru, which was identified in the South Fore tribe in Papua New Guinea. The disease is now almost nonexistent and is believed to have existed for only a short time before it was first described in 1957. The Fore were isolated both from Western civilization and from other natives by very mountainous terrain, and Kuru has not been described in any other location.
Kuru was spread by the endocannibalistic funeral practices of the Fore. Family members were ritualistically cooked and eaten following their death, with the closest female relatives and children usually consuming the brain, which was the most infectious organ. The women scooped the brain tissue out with their bare hands and did not subsequently wash them for weeks. During this time they were handling, caring for, and possibly infecting their young children. The effects on the Fore were devastating, wiping out whole villages at the height of the disease.
Generally it is thought that mutations in the PRNP gene cause prion disease. Familial forms of prion disease are caused by inherited mutations in the PRNP gene; however only a small percentage of cases run in families. Most cases are sporadic, which means they occur in people without any known risk factors or gene mutations. Rarely, prion diseases can be transmitted by exposure to prion-contaminated tissues or other biological materials from affected individuals.
The PRNP gene provides instructions for making a protein called a prion protein (PrP). Normally, this protein seems to be involved in transporting copper into cells. It may also play a role in protecting brain cells and helping them communicate. In the alpha-helical configuration, PrP usually is sensitive to protease degradation and is termed PrP-sen. Disease results when the PrP is reconfigured into the beta-sheet configuration, which is resistant to protease degradation. This configuration is termed PrP-res.
The PrP-res proteins are resistant not only to protease degradation but also to radiation, heat, and most other processes that destroy proteins. Neither the transmissible agent nor the disease-producing agent contains any DNA or RNA. Because they are naturally occurring proteins, immunologic response to the infection is absent. This abnormal protein accumulates in the brain forming clumps that damage or destroys nerve cells. The loss of these cells creates microscopic sponge-like holes in the brain, which leads to the signs and symptoms of prion disease.
Familial forms of prion disease are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent. In some people, familial forms of prion disease are caused by a new mutation in the PRNP gene. Although such people most likely do not have an affected parent, they can pass the genetic change to their children. The sporadic, iatrogenic, and acquired forms of prion disease, including Kuru and variant Creutzfeldt-Jakob disease, are not inherited.
Recent research suggests experiments on mice may help scientists understand the workings of the prion protein. Last week, Swiss researchers stated there is evidence that prions play a vital role in the maintenance of the sheath surrounding our nerves.
They say it is possible that an absence of prions causes diseases of the peripheral nervous system. One expert said there was growing evidence that the prion had a number of important roles in the body.
The study from scientists at the University Hospital in Zurich, looked at mice bred with fewer prion proteins. While these mice are known to be resistant to prion diseases equivalent to vCJD in humans, they showed a number of abnormalities, including a degeneration, later in life, of the peripheral nerve cells, and the protective myelin sheath which surrounds them.
Peripheral nerves are those which link the limbs and organs to the central nervous system – the spinal cord and brain.
Looking more closely, researchers examined the effects of removing the prion protein in both the nerve cells themselves, and the Schwann cells surrounding them, which are responsible for making the myelin sheath. While removing protein from the Schwann cells had no effect, taking it from the neurons led to a breakdown of the myelin and degeneration of the nerve cells.
They said that the knowledge that prion protein played some role in the healthy upkeep of nerve cells could offer a new avenue of research into diseases affecting humans. However, scientists caution that it is too early to pick out a particular peripheral nerve condition which might correspond to the mouse experiments.
As well as the latest research in the journal Nature Neuroscience, other studies have indicated prions may protect us from Alzheimer’s disease or even play a role in our sense of smell.
Ultimately Prion diseases provide a hugely fascinating threat to human health yet there is increasing evidence of a contrary possibly positive function in certain instances, although much more research is required.
