News & Events
Medical researchers in Canada and the US discover hidden side of prion diseases - November 30, 2011
Fatal prion diseases, which include BSE or "mad cow disease," have a hidden signature
Medical researchers in Canada and the United States recently published their joint findings that fatal prion diseases, which include BSE or "mad cow disease," have a hidden signature. Findings published this month in the peer-reviewed journal, Public Library of Science (PLoS) Pathogens, demonstrate that up to seven months before an animal shows physical signs of having a prion infection, a particular prion protein in the brain was being eradicated. This member of the prion family is known as shadoo protein.
"What we discovered is that as the early prion disease process unfolds in an infected brain, that the shadoo protein is simultaneously disappearing," said lead author and co-principal investigator, David Westaway, a researcher in the Faculty of Medicine & Dentistry at the University of Alberta. "This is telling us there is a process within the disease that we were previously unaware of, a process that is happening before the infected animals are getting sick. It's telling us that the brain cells are more active in defending themselves than what we thought they were. The brain cells are in fact trying to get rid of the prion protein and as a consequence, this bystander shadoo protein is being destroyed unintentionally. "This finding suggests that prion diseases are dynamic and not necessarily unstoppable, that there could be a cellular process trying to destroy the infectious prions as they appear. And if we could help that process a little bit more, that might be an avenue to attenuate the disease."
"Westaway, who works in both the Division of Neurology of the Faculty of Medicine & Dentistry, and the Centre for Prions and Protein Folding Diseases at the U of A, collaborated with a team of researchers from Ontario, the University of California, the Institute for Systems Biology in Washington, the McLaughlin Research Institute in Montana and a researcher in Germany, on this discovery. The same day this paper was published, very similar findings were published by a team of researchers from the University of California, which demonstrates "these new chemical changes are a concrete and reproducible hallmark of prion disease," says Westaway. Co-principal investigator George Carlson, from the McLaughlin Research Institute, added: "Given that shadoo may be destroyed by a process that actually targets infectious prions, it was surprising that when we increased the amount of shadoo in laboratory models that the course of disease was not changed. We need to understand why." The next step for Westaway's research team is to determine why this shadoo protein is disappearing. The finding opens up a new window of research opportunities. "We need to better understand this. We want to solve this mystery," he says.
The research was funded by the Canadian Institutes of Health Research, Alberta Innovates – Health Solutions, the Alberta Prion Research Institute, the National Institutes of Health and the United States Public Health Service.
SIGNIFICANT NEW FUNDING BUILDING PRION RESEARCH IN ALBERTA (Edmonton, June 17, 2009)
$15 million allocated to new projects, infrastructure and attracting world-class recruits
Prion diseases affect animals and humans. They can be infectious and cause fatal neurological disease. Right click & play the video.
Recent investments by the Alberta Prion Research Institute (APRI), and the Alberta Ingenuity Fund (AIF), which total nearly $15 million, have been committed to support new research infrastructure, university and industry-led research projects, and the recruitment of new prion researchers to Alberta. Support from APRI and AIF has attracted additional funding from industry and other provincial and federal agencies, amounting to $26 million, for basic pre-commercial research and development across the province.
Honourable Doug Horner, Minister of Advanced Education and Technology (AET), was on hand at the University of Alberta to make the announcement.
“We’ve begun to realize the range of social, economic and health benefits for Albertans that are waiting to be discovered through prion research,” said Doug Horner, Minister of Alberta Advanced Education and Technology. “For instance, researchers have found that there may be common factors between prion diseases and other human diseases such as autism and Alzheimer’s. Not only can this research help us find solutions to global social and health issues, but it will also enhance the growth of Alberta’s Next Generation Economy.”
Building provincial capacity in prion research has led to the recruitment of experts Drs. Valerie Sim, Debbie McKenzie and Judd Aiken, to the Centre for Prions and Protein Folding Diseases at the University of Alberta. Industry projects aimed at basic and pre-commercial research involving partnerships with industrial collaborators – Sanimax and ChemRoutes Corporation, have received funding from various partnersincluding : AIF’s nanoWorks Program, the National Institute for Nanotechnology, APRI, PrioNet Canada and the University of Alberta. These effective partnerships between industry and provincial and federal agencies allows for optimal investments in the area of prion research. Another key aspect of this announcement is the funding towards the new bio-safety level 2 laboratory, at the University of Calgary, which will allow APRI funded researchers to study different forms of prions.
“APRI’s immediate goal is to unravel the mysteries associated with prions. But the end result is more than just answers. In working to achieve our goals, we are building research capacity and expertise here in Alberta,” said Dr. Kevin Keough, interim Executive Director of APRI.
EMBARGOED UNTIL NOON, EASTERN U.S. TIME, AUGUST 16, 2007
New prion protein discovered by Canadian scientists may offer insight into mad cow disease
Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. “Our team has defined a second prion protein called ‘Shadoo’, that exists in addition to the well-known prion protein called ‘PrP’ ” said Professor David Westaway, director of the Centre for Prions and Protein Folding Diseases at the University of Alberta in Edmonton, Canada.
“For decades we believed PrP was a unique nerve protein that folded into an abnormal shape and caused prion disease: end of story. This view is no longer accurate,” Westaway adds. The study was conducted jointly by the University of Toronto, University of Alberta, Case Western Reserve University (Ohio) and the McLaughlin Research Institute (Montana). The research is published in the EMBO Journal and represents a culmination of work initiated at the University of Toronto in 1999, and then continued more recently at the University of Alberta.
This is the first discovery since 1985 of a new brain prion protein. “A second prion protein had been inferred by other research, based on indirect studies and the examination of DNA sequences,” said lead author Joel Watts, a graduate student at the University of Toronto’s Centre for Research in Neurodegenerative Diseases. “But we not only demonstrate that this theoretical protein really exists and shares several properties with healthy PrP; we have also defined an unexpected alteration in prion infections.
“As the PrP molecule alters shape and accumulates in a prion-affected brain, the Shadoo protein seems to disappear,” Watts added. Since proteins in a living cell are the molecules “that do the work, this is likely to be significant,” he said. “Many facets of a prion disease like BSE are puzzling,” Westaway said. “The puzzles include the cause of death of brain cells, the function of normal prion proteins, and the rules governing emergence and spread of prions from animal to animal. We believe the Shadoo protein can give us a fresh purchase on these important questions.” Westaway is one of two new inaugural scholars at the U of A’s Centre for Prion and Protein Folding Diseases. The scholar program was established recently by the Alberta Prion Research Institute.