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From: TSS ()
Subject: Developing a live animal test for CWD Shortcut to diagnosis: prions in blood samples
Date: July 12, 2006 at 2:31 pm PST

07/11/2006
Shortcut to diagnosis: prions in blood samples
Developing a live animal test for Chronic Wasting Disease is one of the first projects underway at South Dakota State University’s Center for Infectious Disease Research and Vaccinology (CIDRV).

CIDRV, a multiuniversity unit headquartered within SDSU’s Department of Veterinary Science, was established in spring 2005 with partial funding from S.D. Gov. Mike Rounds’ 2010 Research Initiative. One of the center’s mandates is to promote economic development in South Dakota by providing research-based assistance to local biotechnology industries.

Alan Young, associate professor of veterinary science and a CIDRV faculty member, is lead investigator for SDSU in a partnership between CIDRV and Rural Technologies, Inc. (RTI), a Brookings-based contract research company.

RTI obtained a $750,000 grant from the U.S. Department of Defense’s Small Business Technology Transfer Program for the project. The company contracted with CIDRV and USDA National Animal Disease Center (NADC) in Ames, Iowa, to conduct parts of the research.

“Basically, it’s a cooperative contract that arises from work that we originally started in our lab at SDSU and that has since become translated into a potential new bioassay to look for Chronic Wasting Disease in live animals,” Young explained.

Chronic Wasting Disease (CWD) is a deadly neurological disease that affects cervids (elk, deer, and moose). It belongs to a category of diseases known as transmissible spongiform encephalopathies (TSE), caused by abnormal prion proteins. Other TSE diseases include scrapie, mad cow disease and Creutzfeldt-Jacob disease in humans.

Existing tests for CWD are only available for deceased animals because they are performed on brain tissue. However, Young’s research suggests that it is possible to construct a test on a blood sample from a living animal.

“Most people think of CWD and other prion diseases as being neurological diseases that affect the brain and neurological tissues. Neuronal cells are hard to get at for diagnosis, which is why virtually all of our existing licensed tests for CWD, scrapie, mad cow disease or Creutzfeldt-Jacob disease are post-mortem tests. Basically, we look at a section of brain tissue to see if it’s positive,” Young said.

However, infectious prions are found in other places as well.

“In fact, the earliest place that we see the infectious prion show up is in lymphoid tissue such as lymph nodes or tonsils,” he said. “They are also found in immune cells, which have the advantage that we find them in the blood.”

Infectious prions appear in the blood and lymph nodes in such small quantities that they are very difficult to detect. But Young’s research gets around this problem by focusing on a specific type of immune cells that appear to proliferate the prions.

“We chose to look at the involvement of a particular type of immune cells called follicular dendritic cells (FDC). They interact with migratory cells in the immune system called B-cells, which make antibodies, and they seem to concentrate the prions in this process,” he said.

The scientists developed a method to cultivate FDCs in a tissue culture dish, and they found that the cells were able to “grow” infectious prions.

“The FDCs were actually capable of capturing the infectious prions and replicating them so they would be detectable,” said Young.

“What we hope to do is to develop a blood test for CWD where we can actually use blood taken from a live animal, place it under our cultures, and then detect the presence of the infectious prion,” he said.

A live animal test would be particularly useful for commercial deer farmers, Young said.

“Some deer farmers have been hit very hard by CWD,” he said. “It’s difficult for them to determine if they have a CWD infection in their herd because there’s no test to use on live animals.”

While Young’s research is still in its early stages, he said the method is very promising.

“We’ve done some preliminary tests, and it’s very clear that we are able to detect low levels of the infectious prion molecules using our cultured follicular dendritic cells,” Young said. “We have data suggesting that we can in fact do this from the blood of sheep. We’re now using the same mechanism with blood from cervids. So we’re fairly confident that the system will work.

“The bottom line is that we think we have the capability of developing a live animal test for CWD and other prion diseases as well,” he said.

The goal is to have a commercial test available within the next few years, said Christopher Mateo, RTI manager of operations. He added that while the current research is focused on CWD, potentially the method could be used to develop similar tests for other prion-based diseases.

“RTI’s partnership with SDSU helps us develop technology based on research conducted at the CIDRV. The scientists focus on the basic mechanisms for how the disease works, and RTI translates that research into a marketable product,” Mateo said.

David Francis, CIDRV director and professor of veterinary science at SDSU, said that this is one of the first CIDRV projects that has reached a stage where technology is being developed into a product, and it is a prime example of CIDRV’s goals.

“The center has an economic development mission. One of the reasons that we exist is to help support entrepreneurial activity,” Francis said.

“So of course we’re excited about the opportunity to assist RTI with their grant, and we are encouraging other SDSU scientists to do the same. This is helping to fulfill the obligation that we incurred when we got the funding to establish the center,” he said.

For more information, Dr. Alan Young can be reached at (605) 688-5982 or by e-mail at alan.young@sdstate.edu; and Dr. David Francis can be reached at (605) 688-5680 or by e-mail at David.Francis@sdstate.edu.

http://www3.sdstate.edu/SDSU/NewsDetail45702.cfm?ID=46,5244


TSS



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