Prion diseases: Kuru and Creutzfeldt-Jakob syndrome

SIGNIFICANCE: Kuru and Creutzfeldt-Jakob syndrome are rare, fatal diseases of the brain and spinal cord. Nerve cell death is caused by the accumulation of a protein called a prion, which appears to be a new infectious agent that interferes with gene expression in nerve cells. Understanding these diseases has far-reaching implications for the study of other degenerative mental disorders.

Causes, Symptoms, and Treatment

Kuru and Creutzfeldt-Jakob syndrome, degenerative diseases of the human central nervous system, are among a group of diseases that also affect cattle (mad cow disease) and sheep (scrapie). They have been classified in several ways, including “slow-virus” infections (because of the extremely long incubation period between contact and illness) and “spongiform encephalopathies” (because of the large holes seen in the brain after death). However, a virus that may cause such a disease has never been found, and the body does not respond to the disease as an infection. The only clue to the cause is the accumulation of a transmissible, toxic protein known as a prion; therefore, these disorders are now known simply as “prion diseases.”

According to the book Creutzfeldt Jakob Disease, released in 2024, about 350 cases of the condition were diagnosed in the United States annually. It usually begins in middle age with symptoms that include rapidly progressing dementia, jerking spastic movements, and visual problems. Within one year after the symptoms begin, the patient is comatose and paralyzed, and powerful seizures affect the entire body. Death occurs shortly thereafter. The initial symptom of the illness (rapid mental deterioration) is similar to other disorders; therefore, diagnosis is difficult. No typical infectious agent (bacteria or viruses) can be found in the blood or in the fluid that surrounds the brain and spinal cord. X-rays and other scans are normal. There is no inflammation, fever, or production. Brain wave studies are, however, abnormal, and at autopsy, the brain is found to have large holes and massive protein deposits in it.

Kuru is found among the Fore tribe of Papua New Guinea. Until the early 1960s, more than one thousand Fore died of kuru each year. Anthropologists recording their customs described their practice of eating the brains of their dead relatives in order to gain the knowledge they contained. Clearly, some infectious agent was being transmitted during this ritual. Such cannibalism has since stopped, and kuru has declined markedly. Kuru, like Creutzfeldt-Jakob syndrome, exhibits the same spongiform changes and protein deposits in the brain after death. Similarly, early symptoms include intellectual deterioration, spastic movements, and visual problems. Within a year, the patient becomes unresponsive and dies.

The outbreak of “mad cow” disease in the mid-1990s in Great Britain led to widespread fear. Thousands of cattle were killed to prevent human consumption of contaminated beef. The cows were infected by supplemental feedings tainted by infected sheep meat. Animal-to-human transmission of these diseases appears to occur, and research has shown that human-to-animal infection is possible as well.

Both kuru and Creutzfeldt-Jakob syndrome, as well as the animal forms, have no known treatment or cure. Because of the long incubation period, decades may pass before symptoms appear, but once they do, the central nervous system is rapidly destroyed, and death comes quickly. It is likely that many more people die of these disorders than is known because they are so rarely diagnosed.

Properties of Prions

Most of the research on diseases has focused on scrapie in sheep. It became clear that the infectious particle had novel properties: It was not a virus as had been suspected, nor did the body react to it as an invader. It was discovered that this transmissible agent was an abnormal version of a common protein, which defied medical understanding. This protein is normally secreted by nerve cells and is found on their outer membranes. Its gene is on chromosome 20 in humans. The transmissible, infectious fragment of the prion somehow disrupts the nerve cell, causing it to produce the abnormal fragment instead of the normal protein. This product accumulates to toxic levels in the tissue and fluid of the brain and spinal cord over many years, finally destroying the central nervous system.

Prion infection appears to occur from exposure to infected tissues or fluids. Transmission has occurred accidentally through nerve tissue transplants and neurosurgical instruments. Prions are not affected by standard sterilization techniques; prevention requires careful handling of infected materials and extended autoclaving of surgical instruments (for at least one hour) or thorough rinsing in chlorine bleach. The agent is not spread by casual contact or air, and isolating the patient is not necessary.

Other human degenerative nervous system diseases whose causes remain unclear also show accumulations of proteins to toxic levels. Alzheimer’s disease is the best-studied example, and it is possible that a process similar to that in prion diseases is at work. The discovery of prions has far-reaching implications for genetic and cellular research. Scientists have already learned a startling fact: Substances as inert as proteins and far smaller than viruses can act as agents of infection.

Key terms

• dementiamental deterioration ranging from forgetfulness and disorientation to complete unresponsiveness
• prionshort for “proteinaceous infectious particle,” an element consisting mainly of protein and generally lacking nucleic acid (DNA and RNA), which is often the causative agent behind various spongiform encephalopathies

Bibliography

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