The prion diseases are a group of rare and invariably fatal brain disorders that occur in both animals and humans. They are unusual in that the infective agent is neither a virus nor a bacterium, but an abnormal form of the prion protein (PrP) that is normally found in the brain. Prion disease leads to the development of tiny holes within brain tissue, giving it a characteristic “spongiform” appearance at post-mortem. Hence, prion diseases are also known as the transmissible spongiform encephalopathies (TSEs).
The best known of the human prion diseases is Creutzfeldt-Jakob disease (CJD), which affects about one person in one million. This rare disease came to public attention in 1996, with the announcement of a new form of CJD in the United Kingdom. Research has suggested that variant CJD is transmitted through exposure to beef contaminated by bovine spongiform encephalopathy (BSE), a prion disease of cattle.
There are four forms of CJD, the major form of prion disease. Sporadic CJD accounts for around 85% of cases and familial CJD accounts for most of the rest. There have been about 200 cases of variant CJD around the world, and a few people have contracted so-called iatrogenic (caused by a treatment) CJD from prion contamination occurring through medical treatment. The other human prion diseases are Gerstmann-Straussler-Scheinker (GSS) syndrome and familial fatal insomnia (FFI), which resemble familial CJD, and kuru, an almost extinct disease confined to the Fore people of New Guinea.
Prion diseases are marked by progressive deterioration of brain function that is always fatal. Sporadic CJD affects mainly people over 50 years old and is marked by ataxia—a shakiness and unsteadiness caused by damage to the cerebellum at the base of the brain which controls movement. Dementia (a deterioration of memory and other mental functions), swallowing difficulties, jerky movements, and blindness rapidly set in and the patient usually dies within six months.
In familial CJD, GGS, and FFI, the onset of the disease may be at a younger age and the disease's course measured in years rather than months. In FFI, as the name suggests, a major feature in a progressive and untreatable form of insomnia is caused by damage to the thalamus, the part of the brain regulating sleep-wake cycles.
WORDS TO KNOW
IATROGENIC: Any infection, injury, or other disease condition caused by medical treatment is iatrogenic (pronounced eye-at-roh-GEN-ik).
PRIONS: Any infection, injury, or disease condition caused by medical treatment is iatrogenic (pronounced eye-at-roh-GEN-ik).
SPONGIFORM: Spongiform is the clinical name for the appearance of brain tissue affected by prion diseases, such as Creutzfeld-Jakob disease or bovine spongiform encephalopathy. The disease process leads to the formation of tiny holes in brain tissue, giving it a spongy appearance.
Human Prion Diseases:
- Creutzfeldt-Jakob Disease (CJD)
- Variant Creutzfeldt-Jakob Disease (vCJD)
- Gerstmann-Straussler-Scheinker Syndrome
- Fatal Familial Insomnia
Animal Prion Diseases:
- Bovine Spongiform Encephalopathy (BSE)
- Chronic Wasting Disease (CWD)
- Transmissible mink encephalopathy
- Feline spongiform encephalopathy
Variant CJD has a younger age of onset than sporadic CJD and is marked by psychiatric problems and pain and odd sensations in the limbs. The time course of the disease is longer than in sporadic CJD with ataxia setting in at a later stage. In iatrogenic CJD and kuru, ataxia is the main feature and dementia is unusual.
All prion diseases are transmissible under laboratory conditions, yet only variant CJD, iatrogenic CJD, and kuru are infectious in the way this term is usually understood. The source of abnormal PrP in these disorders is either beef contaminated with BSE or exposure to brain tissue from someone with CJD.
In sporadic CJD and familial CJD, as well as in GGS and FFI, a spontaneous or inherited mutation in the PrP gene leads to the generation of abnormal PrP within the patient's brain—without any outside infection. This goes on to interact with normal PrP causing the characteristic spongiform damage within the brain.
All prion diseases are very rare, occurring with a frequency of about one per one million of the population—or fewer— around the world. There have been about 200 cases of variant CJD in eleven countries, to date, most of which have occurred in the United Kingdom. Kuru has all but disappeared since the Fore people ceased the funeral practices that exposed them to the risk of the disease.
There are no proven cures for any of the prion diseases, although there are a number of drugs being developed for CJD. Drugs can be given to ease the symptoms, such as valproate or clonazepam for jerky movements.
The American researcher Stanley Prusiner (1942–) was awarded the 1997 Nobel Prize for Medicine or Physiology for his work on prions. But there is still much more to be learned about how prions work. For instance, routes of transmission are not well understood. Prion diseases may be present without symptoms for many years, putting people at risk of infection. Therefore a better understanding of prions is an important challenge for neurology research.
The emergence of variant CJD in the 1980s in the United Kingdom among mostly young people sparked an epidemiological investigation that garnered worldwide attention. After the disease was linked with contaminated feed consumed by cattle in the U.K. that resulted in the cattle contracting bovine spongiform encephalopathy (BSE), the British beef industry suffered severe losses as over 150,000 cattle were slaughtered, many countries banned beef imports, and consumption of beef at home in the U.K. dropped dramatically. As other cases of variant CJD were linked to contaminated surgical instruments, stricter controls were put into place for decontamination and disposal of surgical instruments and tissues that could be infected with prions. In 2000, a British report titled “The BSE Inquiry” concluded that individual cattle were probably infected with BSE in the 1970s, that disease became epidemic as a consequence of an intensive farming practice (the recycling of animal protein, including prions, in ruminant feed), and that BSE had been transmitted to humans, enabling the new human prion disease (vCJD) to emerge.
Ridley, R.M., and H.F. Baker. Fatal Protein: The Story of CJD, BSE and Other Prion Disease. Oxford: Oxford University Press, 1998.
The BSE Inquiry Report. “Home Page.” <http://www.bseinquiry.gov.uk/index.htm> (accessed May 15, 2007).
Centers for Disease Control and Prevention. “CJD (Creutzfeldt-Jakob Disease, Classic).” April 13, 2007 <http://www.cdc.gov/ncidod/dvrd/cjd/> (accessed February 21, 2007).
Centers for Disease Control and Prevention. “vCJD (Variant Creutzfeldt-Jakob Disease).” January 4, 2007 <http://www.cdc.gov/ncidod/dvrd/vcjd/index.htm> (accessed February 21, 2007).
U.K. Creutzfeldt-Jakob Disease Surveillance Unit. “National Creutzfeldt-Jakob Disease Surveillance Unit.” February 5, 2007 <http://www.cjd.ed.ac.uk> (accessed February 21, 2007)