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