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New Center Aims to Reduce Radiation Injury After Terrorist Attack

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Duke Health News 919-660-1306

DURHAM, N.C. -- The real threat of nuclear and
radiation-based "dirty-bomb" terrorist attacks has prompted the
National Institute of Allergy and Infectious Diseases (NIAID)
to fund a $22.25 million radiologic anti-terrorism center at
Duke University Medical Center. The center's immediate tasks
are creating a rapid and inexpensive screening test to gauge a
person's exposure level and developing new drugs that treat
radiation's most toxic effects.

"Significant nuclear material is missing around the world,
and these materials could possibly enter the black market where
they would be acquired by terrorists," said Nelson Chao, M.D.,
director of the Duke Adult Bone Marrow Transplant Program. Chao
will direct the multi-institution Center for Medical
Countermeasures Against Radiation, together with Mark Dewhirst,
M.D., and John Chute, M.D. It is one of eight such centers
being established nationwide.

"Unfortunately, very few medical products exist to counter
the variety of acute and long-term toxicities that can result
from nuclear or radiologic attacks, so we must develop a range
of different products and medical approaches to protect and
treat such a population."

Already underway are experiments to bolster the natural
abilities using human growth factor and hematopoietic (blood)
stem cells to rescue bone marrow after radiation damage. Bone
marrow is the first organ most severely affected by radiation
exposure –- it is the factory for blood and immune cells -- so
mitigating radiation's effects is essential to preventing bone
marrow failure and other life-threatening complications, said
Chao.

The Duke team will collaborate with more than a dozen
academic medical centers, pharmaceutical companies and federal
research laboratories to develop drugs and therapies that
reduce radiation injury and to study ways to enhance bone
marrow and blood cell proliferation. The discoveries they yield
will ultimately play a role in the treatment of patients
undergoing stem cell transplants, therapeutic radiation for
cancer, and immune recovery among patients with faulty immune
systems, he said.

Equally pressing is the need for a quick and simple method
to distinguish severely injured patients from the worried
individuals following a radiologic attack, said Chao. In the
event of a radiation exposure, the immediate surge of patients
seeking medical evaluation could easily overwhelm local medical
facilities and thereby delay treatment of the sickest
patients.

Chao cited the Cesium 137 exposure in Goiania, Brazil, as an
example of how quickly a situation can escalate into panic.
Approximately 200 people were exposed to the radioactive
material, but over 100,000 people turned out to be screened for
possible injuries. The ability to properly triage patients with
medical needs while simultaneously allaying fears among the
population at large is of critical importance for those in the
vicinity of an event, he said.

Yet screening patients for radiation exposure currently
requires repeated blood collections over a period of several
days. By then, severe damage to the blood-and immune systems,
as well as the lungs and gastrointestinal tract -– the most
sensitive organs -- may have already occurred.

The latest technology being pursued as a rapid test is a
laser that measures changes in the luminescence of tooth enamel
which follows exposure to gamma radiation. Secondarily, the
team is developing a blood test that will pinpoint specific
gene changes that accompany varying levels of radiation
exposure.

Developing tests that indicate the radiation dose a
particular individual received is essential for properly
treating exposed patients, said Chao. Injuries could range from
obvious burns and external tissue damage to less apparent bone
marrow failure accompanied by bleeding, infections and a
heightened lifetime risk of cancer.

Bone marrow and stem cell transplants can reconstitute
damaged blood and immune systems, yet they require months of
treatment and highly specialized medical expertise that isn't
widely available, said Chao. Developing quicker and less
invasive methods of treating radiation damage will equip
community hospitals with the tools necessary to manage large
scale radiation exposure within their local population, said
Chao.

To make such treatments more widely available, the
scientists will analyze and test drugs which are already FDA
approved for human use related to other diseases. Novel
compounds will later be developed and tested if currently
existing drugs fail to demonstrate effectiveness in treating
radiation damage.

On the screening front, geneticists will develop genetic
"signatures" that depict how specific genes are altered by
varying doses of radiation. Scientists will administer high,
intermediate and low doses of radiation to mice and to people
undergoing cancer treatments. The scientists will analyze blood
samples from radiation-exposed individuals to determine the
impact of each dose on specific genes.

In other studies, the team will develop and test therapies
that: prevent lung damage caused by reactive oxygen species –-
damaging byproducts of radiation exposure -- using synthetic
compounds already in use for other diseases and to assess the
role of innate immune responses in inflammation and
radiation-induced lung injury;

• test the capacity of human growth hormone (HGH), already
in human use, to accelerate recovery of blood- and immune cells
following radiation injury;

• cultivate and expand the population of hematopoietic stem
cells by culturing them together with primary endothelial
cells, which secrete growth factors essential to stem cell
growth;

• stimulate proliferation of human hematopoietic stem cells
and enhance the repair of endogenous (native) stem cells by
stimulating a key regulatory pathway for blood stem cell
formation called the Wnt pathway;

• Assess the efficacy of somatostatin and its analogues in
the prevention of gastrointestinal toxicity and contribution of
gastrointestinal microbes in radiation induced injury.

For a complete list of centers participating in the project,
go to: http://radccore.mc.duke.edu

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