Understanding Prion Diseases

by National Institute of Health

Prion diseases are a related group of rare, fatal brain diseases that affect animals, including humans. Also known as transmissible spongiform encephalopathies (TSE), they include bovine spongiform encephalopathy (BSE, or "mad cow" disease) in cattle; Creutzfeldt-Jakob disease (CJD) in humans; scrapie in sheep; and chronic wasting disease in deer and elk.

Much about TSE diseases remains to be discovered. The diseases are characterized by certain misshapen protein molecules that appear in brain tissue. Normal forms of these prion protein molecules reside on the surface of many types of cells, including brain cells, but scientists do not understand what normal prion protein does. On the other hand, scientists believe that abnormal prion protein, which clumps together and accumulates in brain tissue, is the likely cause of the brain damage that occurs in TSE diseases. Scientists do not have a good understanding of what causes the normal prion protein to take on the misshapen abnormal form.

Variant Creutzfeldt-Jakob Disease

In some cases, TSE diseases appear to be infectious. For example, there is good evidence that a newly discovered TSE disease-variant CJD (vCJD)-was first spread to humans from cattle infected with BSE, although that type of transmission is believed to be very inefficient. Identifying the transmissible agent is still an ongoing area of research. A leading hypothesis about the origin of vCJD is that abnormal forms of prion protein ingested through diseased meat sicken people by causing normal human prion protein to form incorrectly. This change from normal to abnormal prion protein spreads to the brain, where the misshapen protein aggregates in the spaces between brain cells and produces disease. An alternative hypothesis is that the disease is transmitted by a virus, which subsequently triggers the process of forming abnormal prion protein.

Health officials in the United Kingdom have responded to evidence that beef infected with BSE may have spread vCJD to humans. Since the 1980s, when the mad cow epidemic began in the United Kingdom, millions of cattle in Europe have been destroyed. Worldwide, there have been 153 reported cases of vCJD, according to the Centers for Disease Control and Prevention (CDC). All of these cases were among people who ate beef in a country with a BSE outbreak, and nearly all (143 cases) were in the United Kingdom.

The first North American case of mad cow disease was found in Canada in May 2003. Discovery of the first U.S. case of mad cow disease followed in December 2003 in a Washington state cow. No cases of endemic vCJD have been reported in the United States.

An older human TSE, Creutzfeldt-Jakob disease, is similar to vCJD but progresses much more quickly and affects older people. It can be both inherited and transmitted through infection, although some cases occur sporadically without a known cause.

Chronic Wasting Disease

A different TSE disease called chronic wasting disease has been detected in U.S. deer and elk populations. So far, scientists have uncovered no evidence that deer or elk with chronic wasting disease might transmit some form of TSE disease to people who eat deer or elk or have close contact with them. More research must be done to determine whether chronic wasting disease poses any risk to humans, particularly because it is spreading over a wider geographical area in the United States.

Basic Research

NIAID scientists at RML are examining how abnormal prion protein molecules cause TSE diseases. RML is one of the world's premiere laboratories for studying TSE diseases: scientists there co-discovered and were among the first to clone the prion protein gene. RML has had an active TSE research program since the 1960s. NIAID scientists also discovered that abnormal prion protein can convert normal prion protein to the abnormal form. This also may account for the disease process in the brain.

In 2005, RML scientists published findings from two significant TSE studies.

One study showed that when prion protein was modified to remove a membrane "anchor" in laboratory animals, scrapie infection caused formation of abnormal prion protein, but remarkably did not result in disease. It is believed that without the membrane anchor, the abnormal prion protein is unable to damage the brain cells. These results suggest that drugs aimed at blocking interactions between normal and abnormal prion protein might be able to halt the progress of disease.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.