Mad Cow Disease Agent Causes Heart Damage in Mice

LA JOLLA, California, July 10, 2006 (ENS) - Prions - the same disease agents that cause the fatal brain illness known as mad cow disease and its human variant - also cause a form of heart disease in mice, scientists at Scripps Research Institute have found.

The finding raises the possibility that heart infection could be a type of prion disease, and that these prion diseases could travel through the blood.

"Until now, prion disease has been thought of as a chronic neurological condition," says Scripps Research Professor Michael Oldstone, MD, who led the research. "Our study has shown, however, that it can have other manifestations, therefore expanding the types of conditions it could cause."


Dr. Michael Oldstone studies infectious diseases at The Scripps Research Institute in La Jolla, California. (Photo courtesy TSRI)
Prion diseases - known as transmissible spongiform encephalopathies because of the sponge-like holes created in the brain - include scrapie in sheep, mad cow disease in cattle, chronic wasting disease in deer and elk, and newvariant Creutzfeldt-Jacob disease in humans.

These diseases are infectious, but they are not caused by viruses or bacteria. Instead, prion diseases appear to be transmitted by a protein, a misfolded form of a normal cellular protein, the prion.

In prion diseases, the normal form of the prion protein is converted into an abnormal, misfolded form. The hallmark of prion diseases is the accumulation of these abnormal prions in the central nervous system.

Disease occurs because the abnormal proteins have the ability to convert normal prion proteins into the abnormal form. Like bad apples spoiling the lot, the infectious prions will multiply and form plaques, known as amyloid proteins, which can interfere with normal function in the brain.

In the newly reported study, investigators at Scripps Research found infectious misfolded prion protein in amyloid deposits in the heart muscle of mice.

Amyloids are waxy protein deposits that stiffen the heart, limit its pumping ability, and typically lead to fatal heart stoppage.

Although several types of protein are known to form heart amyloid, this is the first time prion protein amyloid in heart tissue has been identified. prions

A normal prion is on the left, compared to an abnormal misfolded, disease-causing prion on the right. (Photo courtesy UBC)
The new research will provide scientists with an animal model in which to study heart amyloidosis, a family of heart diseases that affect humans.

The paper published on Friday in an advanced, online edition of the journal "Science" describes the research, which is supported by a grant for the study of prion disease from the National Institute on Aging, a part of the National Institutes of Health.

After their initial discovery, Scripps Research investigators secured the help of Kirk Knowlton, MD, chief of the division of cardiology at the University of California, San Diego.

Dr. Knowlton investigated the effect of prion protein amyloid on mouse heart function, and discovered that it decreased the heart's ability to pump blood.

In addition, unusually high levels of scrapie infectivity were identified in the blood of the same mice used in the heart study.

Dr. Oldstone, a professor of neuropharmacology, says this is the first system in which prion disease agents were found "reproducibly and reliably" at high concentrations in the blood.

"Undoubtedly, this work will enable scientists to pursue new theories about the effects of these deadly brain wasting diseases," said Elias Zerhouni, MD, director of the National Institutes of Health. "The implications of this research could be vital to our efforts to slow or stop these diseases."


Prions are abnormal misfolded proteins. (Photo courtesy BLTC Research)
Of the prion diseases, bovine spongiform encephalopathy (BSE), or mad cow disease, has caused widespread public concern since it appeared in cattle in England in 1986 and since then in other countries in Europe, Japan, Canada, and the United States.

The first major outbreak of mad cow disease in Britain is believed to have originated with the now outlawed practice of feeding cattle meat and bone meal derived from other slaughtered animals. Chronic wasting disease in U.S. deer and elk is also of concern, as the abnormal protein has been found in both wild and farmed animals.

Scientists now know that humans who eat meat from BSE-infected cattle may be susceptible to the incurable prion disease new variant Creutzfeldt-Jakob. There are now more than 140 such cases, most in the United Kingdom.

Currently, in the United States individuals who lived in the UK for three months or more during the outbreak of mad cow disease from 1980 to 1996 are asked not to donate blood. In the UK, only people born after the outbreak may donate.

Today, a precise diagnosis of a prion disease can only be made upon autopsy.

In the future, the Scripps finding could help scientists answer basic questions such as how prions travel in the bloodstream, as well as develop a blood-based diagnostic test to identify brain wasting diseases and possibly a way to filter or chemically treat blood to remove any infectious prion disease agents.

American Stanley Prusiner, MD, first proposed the term prion in the early 1980s after he found evidence of neurological diseases caused by agents that appeared resistant to the processes that normally destroy nucleic acids. Once highly controversial, the idea won Prusiner the Nobel Prize for Medicine in 1997.