Study Shows How Mad Cow Prions Hitch a Ride Into Intestine



Tue Dec 14 14:00:00 2004 Pacific Time

Study Shows How Mad Cow Prions Hitch a Ride Into Intestine: They
Piggyback on Iron-Storing Proteins After Surviving Digestive Juices

CLEVELAND, Dec. 14 (AScribe Newswire) -- A new study from the
Department of Pathology at Case Western Reserve University School of
Medicine shows that the infectious version of prion proteins, the main
culprits behind the human form of mad cow disease or variant
Creutzfeldt-Jakob Disease (vCJD), are not destroyed by digestive enzymes
found in the stomach. Furthermore, the study finds that the infectious
prion proteins, also known as prions, cross the normally stringent
intestinal barrier by riding piggyback on ferritin, a protein normally
absorbed by the intestine and abundantly present in a typical meat dish.

The study appears in the Dec. 15 issue of the Journal of

Prions are a modified form of normal proteins, the prion
proteins, which become infectious and accumulate in the nervous system
causing fatal neurodegenerative disease. Variant CJD results from eating
contaminated beef products from cattle infected with mad cow disease. To
date, 155 cases of confirmed and probable vCJD in the world have been
reported, and it is unclear how many others are carrying the infection.

According to the study's senior author Neena Singh, M.D., Ph.D.,
associate professor of pathology, little is known about the mechanism by
which prions cross the human intestinal barrier, which can be a
particularly difficult obstacle to cross.

"The mad cow epidemic is far from over, and the continuous spread
of a similar prion disease in the deer and elk population in the U.S.
raises serious public health concerns," said Singh. "It is therefore
essential to understand how this disease is transmitted from one species
to another, especially in the case of humans where the infectious prions
survive through stages of cooking and digestion."

Using brain tissues infected with the spontaneously occurring
version of CJD which is also caused by prions, the researchers simulated
the human digestive process by subjecting the tissue to sequential
treatment with digestive fluids as found in the human intestinal tract.
They then studied how the surviving prions are absorbed by the intestine
using a cell model. The prions were linked with ferritin, a cellular
protein that normally binds excess cellular iron to store it in a
soluble, non-toxic form within the cell.

"Since ferritin shares considerable similarity between species,
it may facilitate the uptake of prions from distant species by the human
intestine,"said Singh."This important finding provides insight into the
cellular mechanisms by which infectious prions ingested with
contaminated food cross the species barrier, and provides the
possibility of devising practical methods for blocking its uptake," she
said. "If we can develop a method of blocking the binding of prions to
ferritin, we may be able to prevent animals from getting this disease
through feed, and stop the transmission to humans."

Currently, Singh's group is checking whether prions from distant
species such as deer and elk can cross the human intestinal barrier.

The study was supported by National Institutes of Health grants.

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CONTACT: George Stamatis, CWRU School of Medicine Media
Relations, 216-368-3635


Founded in 1843, the Case Western Reserve University School of
Medicine is the largest medical research institution in Ohio and among
the top 20 medical schools for research funding from the National
Institutes of Health. Eleven Nobel laureates have been affiliated with
the school. The School of Medicine also is recognized for outstanding
achievements in education. In 2002, it became only the third medical
school in history to receive a flawless report from the national body
responsible for accrediting the nation's medical schools. Annually, the
School of Medicine educates more than 600 M.D. and M.D./Ph.D. students.
The School of Medicine is affiliated with University Hospitals of
Cleveland, MetroHealth Medical Center, the Louis Stokes Cleveland
Department of Veterans Affairs Medical Center, and Cleveland Clinic
Foundation, with which it opened the Cleveland Clinic Lerner College of
Medicine of Case Western Reserve University this year.

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