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Researchers Induce A New Transmissible Prion Disease

02.03.2010
Researchers at the Baltimore Veterans Affairs (VA) Medical Center and the University of Maryland School of Medicine have conducted a study on prion disease and found that transmissible spongiform encephalopathy (TSE) can be induced without an outside catalyst like a virus.

TSE (also known as prion diseases) are a group of progressive conditions affecting the brain and nervous systems of many animals and humans. The conditions include Creutzfeldt-Jakob disease (the human form of mad cow disease), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia and kuru, all forming a spectrum of overlapping signs and symptoms caused by a myriad of tiny holes in the cortex that give it the appearance of a sponge. The disease impairs brain functions leading to both mental and physical deterioration over time.

Using a synthetic prion protein made in E. coli, the researchers induced a new form of TSE. Their study findings—published in January 2010 issue of Acta Neuropathol (with open access at Springerlink.com)— indicate a slow progression of the disease after the observance of first clinical signs, which is typical of how the disease unfolds in both humans and large animals, than in smaller animals such as rodents.

One of the study’s lead researchers, Robert Rohwer, PhD, director of Molecular Neurovirology Laboratory at the VA Maryland Health Care System and an associate professor at the University of Maryland School of Medicine, says the result is an “important milestone in establishing that the native wild-type prion protein is sufficient to induce prion disease in normal wild-type hosts. The interpretation of previous transmissions with synthetic prion proteins has been confounded by the use of mutant proteins and mutant host recipients subject to spontaneous disease.”

This result, Rohwer said, does not explain the many discrepancies “that have supported skeptics of the prion hypothesis like myself, and there is enormous work yet to be done to reconcile these apparent inconsistencies. However, the new insights, tools and focus provided by these discoveries promise to greatly accelerate the pace of those efforts.” Rohwer noted that the disease being induced “was itself unique and fascinating” and may prove valuable as a window on its progression in humans, cattle and sheep.

Rohwer, together with Ilia Backakov, PhD, an associate professor at the School of Medicine and director of the Prion Insitute at the University of Maryland’s Biotechnolgical Institute, inoculated Golden Syrian hamsters with synthetic E.coli recombinant prion proteins, while at the same time inoculating other hamsters with comprehensive slightly altered controls. During this first passage, all but two of the hamsters survived to old age (18 months) without any sign of disease. The researchers investigated the brains of each hamster at 18 months old for evidence of the TSE infection, finding that one animal showed definite signs of infection and one suspicious. They homogenized the brains of both the possibly infected and apparently uninfected animals that had been inoculated with prion protein and some control group hamsters, and then inoculated the homogenates in new animals. Again the animals appeared normal for more than a year after the inoculation, but then the animals began developing symptoms of TSE disease.

“There had been infection in the first passage, but the disease progression was so slow it didn’t have time to advance to a symptomatic form within the hamster’s lifespan,” said Rohwer.

In the hamsters from the second passage, a higher concentration of infectivity meant the infection process started at a higher level, causing the animals to reach a symptomatic stage of disease before their life’s end.

The research resulted in two findings, one being the ability of synthetic wild-type prion protein to induce prion disease in normal wild-type hosts and the other being the development of a new strain of hamster prion disease with a unique presentation for rodents that may prove valuable for investigating the longer duration TSE illnesses of larger animals like humans and cattle.

The VA Maryland Health Care System (VAMHCS) provides a broad spectrum of medical, surgical, rehabilitative, mental health and outpatient care to veterans at two medical centers, one community living & rehabilitation center and five outpatient clinics located throughout the state. More than 52,000 veterans from various generations receive care from the VAHMCS annually. Nationally recognized for its state-of-the-art technology and quality patient care, the VAHMCS is proud of its reputation as a leader in veterans’ health care, research and education. It costs nothing for Veterans to enroll for health care with the VA Maryland Health Care System and it could be one of the more important things a Veteran can do. For information about VA health care eligibility and enrollment or how to apply for a VA medical care hardship to avoid future copayments for VA health care, interested Veterans are urged to call the Enrollment Center for the VA Maryland Health Care System, Monday through Friday, from 8 a.m. to 4:30 p.m. at 1-800-463-6295, ext. 7324 or visit www.maryland.va.gov

Rosalia Scalia | Newswise Science News
Further information:
http://www.maryland.va.gov

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