Prions Cause Heart Damage in Mouse Study

Damage from prion protein gives the brains of affected cows a sponge-like appearanceDr. Al Jenny, courtesy of the U.S. Dept. of Agriculture Animal and Plant Health Inspection Service.

Brain-wasting diseases that kill by causing sponge-like holes in the brain are believed to be caused by abnormal forms proteins called prions. Scrapie in sheep, Creutzfeldt-Jacob disease in humans, mad cow disease in cattle and chronic wasting disease in deer and elk are all examples of this family of diseases. A new study shows that laboratory mice infected with the agent that causes scrapie have high levels of scrapie in their hearts several hundred days after being infected in their brains. Heart infection could be a new, previously unknown aspect of this disease.

Last year, researchers at the Rocky Mountain Laboratories (RML), part of NIH's National Institute of Allergy and Infectious Diseases (NIAID), collaborated with researchers at The Scripps Research Institute and learned that scrapie-infected mice engineered without an "anchor" for the prion protein on the membrane of cells regularly lived for more than 600 days, ultimately dying of old age. Wild mice infected with scrapie typically die after about 150 days. In this earlier research, signs of a prion protein buildup were most prominent near blood vessels in the mouse brains.

In the new study, published online on July 6, 2006, by the journal Science, the researchers, with the help of Dr. Kirk Knowlton of the University of California, San Diego, report a similar prion protein accumulation in heart muscle. They discovered that this protein buildup decreased the heart's ability to pump blood.

The new research provides cardiologists an animal model in which to study heart amyloidosis, a family of heart diseases that affect humans, according to Dr. Bruce Chesebro, an RML virologist and a senior author of the new paper. Amyloidoses involve 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 has been found in heart muscle and also found to cause heart malfunction," says Dr. Chesebro.

Unusually high levels of the abnormal prion protein were also found in blood of the mice used in the study. In the future, this finding could help scientists develop a blood-based diagnostic test to identify brain-wasting diseases and possibly lead to a way to filter or chemically treat blood to remove infectious prion diseases, says Dr. Chesebro.