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Professors' work with infectious proteins will continue with NIH grant

Not a virus, not bacteria, prion proteins still manage to infect animals and humans, spreading such deadly diseases as mad cow and chronic wasting disease, both of which have been the subject of public health concerns in recent years.

And unlike viruses or bacteria, the prion is usually content to bide its time — laying in wait, deep in tissues — for years, sometimes decades, before manifesting itself. To this point, research has largely focused on prion infection’s endgame — the latter stages of a disease like mad cow, but a trio of researchers, including two from Creighton University, have earned a five-year, $2.44 million grant to look more closely at initial infection, to determine how prions enter the body and begin their work.

“We found some really important things happen immediately after infection that most people have overlooked,” said Anthony Kincaid, PhD, a professor of pharmacy sciences in the School of Pharmacy and Health Professions, and a co-primary investigator on the grant. “Yes, an animal can be exposed and shows no outward signs, but the agent initially establishes a foothold in specific tissues and is detectable in those tissues, sometimes within 15 minutes.”

Kincaid, along with fellow primary investigators Jason Bartz, PhD, in the Department of Medical Microbiology and Immunology in the Creighton School of Medicine, and Candace Mathiason, Ph.D., in the Department of Microbiology, Immunology and Pathology at Colorado State University, will be studying those tissues where prions initially dig in, and observing the proteins’ behavior shortly after infection.

Though a therapeutic is not part of the study, earlier detection could help forestall outbreaks of disease, especially in animal populations, and could also prevent humans from spreading the disease, say, through blood donations.

In prion infection, prions enter a body and begin a process known as misfolding among healthy protein strands in the central nervous system. The process is not unlike what happens in such degenerative diseases as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis or Lou Gehrig’s disease, so some insight into the pathology of those diseases may be an ancillary benefit of the study.

“Biochemically, there are a lot of shared features with these other diseases,” Bartz said.

Within the scientific community, it’s only within the last 10 years that prions have been widely accepted as infectious agents. Kincaid and Bartz pointed to a 1998 book by the Pulitzer Prize-winning author Richard Rhodes titled Deadly Feasts, that explores the origins of prion-spread diseases, starting with the mortuary feasts of the Fore people of Papua New Guinea and the spread of a neurodegenerative disease known as kuru.

“I keep waiting for someone to make a movie about this,” Kincaid said. “How this all came about really is that incredible. It’s a whole new paradigm and it took a significant amount of time for people to get on board with this. Everyone was still trying to prove it was a virus but in the highlands of New Guinea, there was an epidemic and without question, it stemmed from prions.”

Most of the research on the proteins is still in the early stages, but Kincaid and Bartz were both early relatively entrants into the field of study and are hoping to further build on their work with the new grant.

The interdisciplinary, inter-institutional nature of the study — with investigators from pharmacy, medicine and veterinary sciences, along with collaboration from a Creighton physicist and an environmental engineer from the University of Nebraska-Lincoln working with Bartz’s lab — means a complex problem will get several different perspectives.

“These are diseases that affect humans and other animals, so to be able to collaborate across an interdisciplinary spectrum will give us a fuller understanding of what’s happening early on,” Bartz said. “We’ll be using different techniques from the different disciplines, hoping that three approaches can give us a more comprehensive look.”


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