Prion diseases are fatal degenerative * brain diseases that can be transmitted between species, as when meat from cattle with mad cow disease is eaten by humans; or inherited, as when a genetic mutation is passed from parent to child as in Creutzfeldt-Jakob disease (CJD). These diseases cause sponge-like holes in the brain.
Prusiner spent two decades studying self-reproducing prions when other scientists did not believe they existed. Shunned by the scientific community at the time, Prusiner proved that prions are infectious proteins that cause brain disease in people and animals. The Nobel Prize was awarded to him for discovering this new type of disease-causing agent that contains no DNA.
Prion diseases are brain diseases that were incurable as of 2016. They can be caused by infection, be inherited due to genetic mutation, or occur without either of these causes. Infectious prion diseases include scrapie in sheep and goats; kuru * in cannibalistic humans in Papua New Guinea; and mad cow disease (BSE), which is transmitted to humans who consume infected beef products. It is possible to transmit prion diseases through injections of infected material or contaminated blood transfusions * , through organ transplants, and by incompletely sterilized surgical instruments.
Hereditary prion diseases include CJD, fatal familial insomnia (FFI), and Gerstmann-Stráussler-Scheinker disease (GSS). Hereditary prion diseases are caused when a certain protein found on the surface of neurons is mutated so that a prion protein forms. In addition, sometimes prion diseases occur without an infectious or genetic explanation—these are called sporadic cases.
GSS is rarer than CJD, striking 1 person in every 10 million people. These disorders are likely to be underreported because prion diseases may be misdiagnosed as other neurological disorders. Kuru appears in approximately 1 percent of the New Guinea population. Kuru is found mostly in children older than 5 and adult females below 40 years of age.
An epidemic * of mad cow disease, or Bovine spongiform encephalopathy (BSE), began in the United Kingdom in 1985, when cattle feed was contaminated with brain tissue from scrapieinfected sheep. More than 180,000 cattle were infected before the disease was brought under control. Cattle feed containing animal remains was banned in 1988. In 1989 slaughter techniques that allow nerve tissue to be included in beef intended for human consumption were banned. More than 1 million cattle may have been infected with BSE in the United Kingdom.
To prevent the spread of BSE to the United States, severe restrictions were placed on the importation of ruminants (cud-chewing grazing animals such as cattle) and ruminant products from Europe. Nonetheless, BSE appeared in American cattle in December 2003, when the U.S. Department of Agriculture (USDA) announced a possible diagnosis in a cow from Washington State. The infected cow was believed to have been imported from Canada in 2001, and had been slaughtered for human consumption. The USDA recalled all beef slaughtered in the same slaughter plant on the same date as the infected cow. Many people turned to vegetarian diets, and many restaurants stopped serving beef. The number of new BSE cases declined sharply after 2005.
When prions are eaten, they are absorbed through Peyer's patches in the small intestine, which are lumps of lymphoid tissue that allow the passage of gut antigens * straight through them. Peyer's patches transfer microorganisms to the immune system * and normally support a protective immune response. But prions do not activate an immune response. Prions taken up by Peyer's patches travel to various sites in the lymphatic system, such as lymph nodes * and the spleen * . Because lymph sites often have many nerves, prions gain access to the nervous system, making their way to the spinal cord and eventually the brain.
Prions are harder to kill than bacteria and viruses. They cause plaque buildup in the brain similar to that seen in Alzheimer's disease * . Most brain cells contain enzymes that break down these deposits, but prions are resistant to these enzymes. The plaques continue to grow and cause damage to the brain. Brain damage shows up as loss of coordination, paralysis, dementia * , and wasting, followed by death. Pneumonia can occur in patients with prion diseases. All prion diseases were incurable as of 2016.
Prion diseases can be inherited in an autosomal dominant * manner, which means that if one parent carries the mutation, each offspring has a 50 percent chance of inheriting the mutation. Patients with a familial prion disease have inherited at least one copy of a mutated gene. There are a variety of possible mutations, and each type of mutation results in a different type of prion disease.
Each of the diseases described here occurs due to an inherited genetic mutation. What distinguishes these diseases is the specific gene or gene sequence that has been affected. In addition, some cases of prion diseases occur without any medical explanation. These cases are called sporadic, meaning “occasionally” or “in scattered instances.”
GSS typically occurs in individuals between 35 and 55 years of age. It is characterized by progressive dementia, unsteady gait, and difficulty speaking, and it takes between 2 to 10 years before the patient dies. GSS is almost always inherited but has been known to occur sporadically as well.
CJD was first described in the 1920s as a one-year-long progressive dementia followed by death. One symptom of CJD is marked intellectual impairment, behavioral changes, and a variety of abnormal movements, including twitching. CJD typically occurs in individuals between 50 and 75 years of age. While CJD is an inherited disease, most cases of CJD are sporadic. Other CJD cases are due to accidental exposure to infected material.
FFI typically occurs in individuals between 18 and 60 years of age. This disease is characterized by progressive sleep disturbance classified as untreatable insomnia * , ataxia * * , a brain region controlling sleep and wakefulness. Sporadic FFI has been reported without the characteristic gene mutation.
Scrapie was first described in sheep and goats more than 200 years ago. It is transmitted through feed contaminated with nerve tissue. It can also be transmitted through pasture infected with the placental * tissue of infected sheep. The term scrapie comes from the behavior of infected sheep, who rub up against the fences of their pens to remain upright despite severe difficulty in walking and balancing, and losing muscular coordination due to brain damage.
Kuru was described in 1950 as a progressive loss of muscular coordination and gait control associated with a shivering tremor. Infected individuals were sick for three to nine months before they died. The word kuru comes from the Fore language and means “tremor.” This disease occurs mostly among the Fore highland people of southern New Guinea, whose cultural practices involved a ritual in which they ate the brain tissue of recently deceased family members. The brain tissue was ground into a pale grey soup, heated, and consumed. Statistically, women of the Fore tribe were more likely than men to develop kuru, probably because women handled the brain tissue and prepared the soup. These women were infected through small skin abrasions and through eating the soup. The symptoms of kuru resemble those of CJD. After this ritual practice stopped, the disease disappeared; the last known sufferer died in 2005.
Humans consuming infected beef are at risk of BSE. BSE is very hard to control because it can be transmitted between many types of species. Whereas food items containing blood or nerve tissue are potential vectors (agents that carry the disease) of human infection, milk and milk products from cows are not believed to pose any risk of transmitting the BSE prion to humans.
While CJD is an inherited disease, it can be acquired through accidental exposure to CJD prioncontaminated material through a medical procedure using tainted human matter or incompletely sterilized surgical instruments. Recipients of corneal transplants and of grafts * Variant Creutzfeldt-Jakob disease
The disease referred to as vCJD appeared in 1996 during the mad cow disease epidemic in the United Kingdom. These patients were infected with prions from contaminated beef, the BSE prion. Mad cow disease, as it is called in cattle, is responsible for this form of prion disease in humans. Victims of vCJD are usually young, and on average they die in their late 20s. The incubation period before the onset of symptoms may be as long as 40 years. Variant CJD affects people from 15 to 65 years of age. Symptoms include psychiatric problems, visual disturbances, intellectual impairment, loss of muscular coordination, and gait disturbances that follow a pattern similar to that of CJD. The illness lasts at least six months before death occurs. There had been only four cases of vCJD reported in the United States as of 2016. Two of the four patients are thought to have acquired the disease while living in the United Kingdom. The last of the four patients died in Texas in 2014.
Cats and mink are susceptible to species-specific forms of TSE. In many Midwestern states, some elk and mule deer carry a form of TSE called chronic wasting disease (CWD). CWD prions may possibly be transmissible to humans who eat venison the same way as mad cow disease can be transmitted to humans who eat contaminated beef. All mammals may have the potential to carry prion diseases.
There is no single diagnostic test for any prion disease. Physicians initially rule out other treatable forms of dementia. Standard diagnostic tests include a spinal tap * to exclude other diseases and an electroencephalogram (EEG) * to record the patient's brain wave pattern. CT scans * and MRIs * can rule out the possibility of stroke and reveal characteristic patterns of brain degeneration associated with various types of prion diseases.
Many cases of prion diseases may have been misdiagnosed as other neurodegenerative disorders. But modern diagnosis also depends on detection of prion proteins and identification of genetic mutations. A genetic sequence analysis can be performed for a number of different mutations associated with familial CJD. The types of mutations present determine which symptoms will be most prominent. Confirmation requires tests of brain tissue obtained through brain biopsy * or autopsy * . Brain biopsies are usually performed only when required to exclude another treatable condition.
There was no known effective treatment to stop or cure prion diseases as of 2016. Treatment focuses on alleviating the patients’ symptoms and increasing their comfort. Treatment may include pain relievers, catheters to collect urine, intravenous fluids to maintain hydration, and repositioning the patient frequently to avoid bedsores * . There is no recovery or rehabilitation for prion diseases. Prions bring about slow degeneration of the central nervous system, inevitably leading to death. A very long time period may pass between a patient becoming infected and the first appearance of symptoms; the incubation process may take up to 40 years in humans. Once the symptoms appear, the patient generally dies within a few months to a few years, with rapidly progressive symptoms.
See also Creutzfeldt Jakob Disease
Ingram, Jay. Fatal Flaws: How a Misfolded Protein Baffled Scientists and Changed the Way We Look at the Brain. New Haven, CT: Yale University Press, 2013.
Legname, Giuseppe, and Gabriele Giachin. The Prion Phenomena in Neurodegenerative Diseases: New Frontiers in Neuroscience. Hauppauge, NY: Nova Science, 2015.
Prusiner, Stanley B. Madness and Memory: The Discovery of Prions—A New Biological Principle of Disease. New Haven, CT: Yale University Press, 2014.
Centers for Disease Control and Prevention. “Prion Diseases.” http://www.cdc.gov/prions/index.html (accessed March 4, 2016).
Medical Research Council Prion Unit. “Prions and Prion Disease.” UCL Institute of Neurology. http://www.prion.ucl.ac.uk/clinic-services/information/prion-disease/ (accessed March 4, 2016).
Merck Manual, Consumer Version. “Prion Diseases.” http://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/prion-diseases/ (accessed March 4, 2016).
Centers for Disease Control and Prevention. 1600 Clifton Rd., Atlanta, GA 30329-4027. Toll-free: 800-232-4636. Website: http://www.cdc.gov (accessed March 4, 2016).
Creutzfeldt-Jakob Disease Foundation. 341 W. 38th St., Suite 501, New York, NY 10018. Telephone: 212-719-5900. Website: http://www.cjdfoundation.org (accessed March 4, 2016).
National Institute of Neurological Disorders and Stroke. PO Box 5801, Bethesda, MD 20824. Toll-free: 800-352-9424. Website: http://www.ninds.nih.gov/index.htm (accessed March 4, 2016).
National Prion Disease Pathology Surveillance Center. Case Western Reserve University, 2103 Cornell Rd., 5129 WRB, Cleveland, OH 44106-7288. Telephone: 216-368-3611. Website: http://case.edu/med/pathology/centers/npdpsc/ (accessed March 4, 2016).
U.S. Food and Drug Administration. 10903 New Hampshire Ave., Silver Spring, MD 20993. Toll-free: 888-463-6332. Website: http://www.fda.gov (accessed March 4, 2016).
* degenerative (dee-JEN-er-uh-tiv) means progressively worsening or becoming more impaired.
* neurologist (new-RHAL-eh-jist) is a physician who specializes in diagnosing and treating diseases of the nervous system.
* kuru (KUR-ew) is a progressive fatal brain disease characterized by tremors and loss of muscle coordination caused by eating contaminated brain tissue from other humans who had the disease.
* blood transfusion (trans-FYOOzhunz) is the process of giving blood (or certain cells or chemicals found in the blood) to a person who needs it due to illness or blood loss.
* epidemic (eh-pih-DEH-mik) is an outbreak of disease, especially infectious disease, in which the number of cases suddenly becomes far greater than usual. Usually epidemics are outbreaks of diseases in specific regions, whereas widespread epidemics are called pandemics.
* antigens (AN-tih-jens) are substances recognized as a threat by the body's immune system, which triggers the formation of specific antibodies against the antigen.
* immune system (im-YOON SIStem) is the body system composed of specialized cells and the substances they produce that helps protect the body against disease organisms.
* lymph nodes (LIMF) are small bean-shaped masses of tissue containing immune system cells that fight harmful microorganisms. Lymph nodes may swell during infections.
* spleen is an organ in the upper left part of the abdomen that stores and filters blood. As part of the immune system, the spleen also plays a role in fighting infection.
* cerebrospinal fluid (seh-ree-broSPY-nuhl) is the fluid that surrounds the brain and spinal cord.
* Alzheimer's disease (ALTS-hymerz) is a condition that leads to gradually worsening loss of mental abilities, including memory, judgment, and abstract thinking, as well as changes in personality.
* dementia (dih-MEN-sha) is a loss of mental abilities, including memory, understanding, and judgment.
* autosomal dominant refers to a mode of inheritance in which only one copy of an abnormal gene is necessary to cause disease.
* insomnia is an abnormal inability to get adequate sleep.
* ataxia is a disorder involving an unsteady gait.
* thalamus (THAL-uh-mus) is a pair of large egg-shaped areas located in the middle of the brain just under the cerebral cortex. The plural form is thalami.
* placenta (pluh-SEN-ta) is an organ that provides nutrients and oxygen to a developing baby; it is located within the womb during pregnancy.
* grafts are tissue or organ transplants.
* spinal tap, also called a lumbar puncture, is a medical procedure in which a needle is used to withdraw a sample of the fluid surrounding the spinal cord and brain. The fluid is then tested to detect signs of infection.
* electroencephalogram is an instrument that records the electrical activity of the brain.
* CT scans, or computed tomography (to-MOG-ra-fee) scans, use computers to view structures inside the body. Formerly called computerized axial tomography (ΟAT).
* MRI, which is short for magnetic resonance imaging, produces computerized images of internal body tissues based on the magnetic properties of atoms within the body.
* biopsy (BI-op-see) is a test in which a small sample of skin or other body tissue is removed and examined for signs of disease.
* autopsy (AW-top-see) is an examination of a body after death to look for the cause of death or the effects of a disease.
* bedsores, also called pressure sores, are skin sores caused by prolonged pressure on the skin and typically are seen in people who are confined by illness or paralysis to beds or wheelchairs.