|Prion Disease Infectivity Causes Heart Damage in Mouse Study
Laboratory mice infected with the agent of scrapie — a brain-wasting disease
of sheep — show high levels of the scrapie agent in their heart several
hundred days after being infected in the brain, indicating that heart infection
might be a new aspect of this disease, according to a research paper released
online today by the journal Science.
Collaborators in the work include scientists at the Rocky Mountain Laboratories
(RML), part of the National Institute of Allergy and Infectious Diseases (NIAID)
of the National Institutes of Health.
"Undoubtedly, this work will enable scientists to pursue new theories about
the effects of these deadly brain wasting diseases," says NIH Director Elias
A. Zerhouni, M.D. "The implications of this research could be vital to our efforts
to slow or stop these diseases."
“Although much work remains to be done, the diseased hearts seen in this mouse
study have similarities to human amyloid heart disease, which is potentially
significant,” says NIAID Director Anthony S. Fauci, M.D.
Scrapie belongs to a group of diseases called prion diseases, also known as
transmissible spongiform encephalopathies or TSEs because of the sponge-like
holes created in the brain. In addition to scrapie in sheep, prion diseases include
Creutzfeldt-Jacob disease in humans, mad cow disease in cattle and chronic wasting
disease in deer and elk. The cause of prion diseases, still under debate, may
be abnormal aggregated forms of prion protein.
The new research has provided cardiologists an animal model in which to study
heart amyloidosis, a family of heart diseases that affect humans, says Bruce
Chesebro, M.D., 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. “That’s exciting for cardiologists,
because this study connects the two fields of research.”
Last year, Dr. Chesebro’s research group from Hamilton, MT, collaborated with
Michael Oldstone, M.D., and other researchers at The Scripps Research Institute
in La Jolla, CA, and learned that scrapie-infected mice engineered without an “anchor” between
the membrane of cells and the prion protein regularly lived for more than 600
days, ultimately dying of old age, according to Dr. Chesebro. Wild mice infected
with scrapie typically die after about 150 days.
In this earlier research, signs of prion protein amyloid were most prominent
near blood vessels in the mouse brain. In the newly reported study, researchers
at Scripps found similar amyloid in heart muscle. They then secured the help
of Kirk Knowlton, M.D., chief of the division of cardiology at the University
of California, San Diego, who investigated the effect of prion protein amyloid
on mouse heart function, discovering that it decreased the heart’s ability to
Unusually high levels of scrapie infectivity were also found in the blood of
the same mice used in the heart 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 any
infectious prion disease agents, says Dr. Chesebro.
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NIAID is a component of the National Institutes of Health. NIAID supports
basic and applied research to prevent, diagnose and treat infectious diseases
such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis,
malaria and illness from potential agents of bioterrorism. NIAID also supports
research on basic immunology, transplantation and immune-related disorders,
including autoimmune diseases, asthma and allergies.
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Agency — includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational medical
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