University of Nebraska Medical Center researchers have received a four-year,
$1.7 million grant from the U.S. Department of Defense to develop an efficient
way to protect humans against the toxic effects of nerve agents used in
chemical warfare. Nerve agents are chemicals related to the organophosphorus
group of pesticides, which interfere with the functioning of the nervous
system.
The goal of the study is to find a way to treat people who have been
exposed to chemical warfare nerve agents, which can be fatal or cause extensive
health damage, said Oksana Lockridge, Ph.D., principal investigator of
the grant. The Army is very interested in getting a protection against
chemical warfare agents, because the agents are so easy to make, said
Dr. Lockridge, associate professor in the UNMC Eppley Institute for Research
in Cancer and Allied Diseases and department of biochemistry and molecular
biology.
The study will use gene and protein therapy, the treatment of disease
by replacing, altering or supplementing a gene or protein responsible for
the disease, to better protect against effects of nerve agents. A technique
being tested through Dr. Lockridges research is administration of a protein
applied through a skin patch.
We know the identity of a human enzyme, butyrylcholinesterase, that
will neutralize any pesticide or chemical warfare agent very effectively
without being toxic to a person or an animal, Dr. Lockridge said.
With this protection, you wont even know you got hit with something.
Butyrylcholinesterase is found in blood, the liver, and other tissues;
however, its function is not specifically known.
Breathing 10 milligrams the weight of a grain of rice – of the deadliest
nerve agent, called VX, can kill in 15 minutes. Symptoms of nerve agent
exposure include reduced vision, diarrhea, vomiting, paralysis and respiratory
failure. Ultimately, individuals experience convulsions and go into a coma.
An antidote kit called the Mark I, distributed to U.S. troops during the
Gulf War, is currently available for protection against death by nerve
agent exposure. Dr. Lockridges study is looking for a better alternative.
Chemical warfare was used in the 1995 Toyko subway terrorist attacks,
when members of a cult placed sarin gas on the trains, killing 12 and injuring
more than 5,500. Agents such as sarin, VX and tabun are inexpensive
and easy to manufacture and have been used as weapons of terrorism and
defense mechanisms for third world countries.
A method must be developed that shields humans from the effects of
chemical warfare agents and provides medical treatment for those who become
exposed, she said.
Dr. Lockridges study also is relevant to Nebraska farmers because of
the similarity in makeup of chemical warfare agents and pesticides. About
80,000 cases of pesticide poisoning are reported annually in the United
States. Common pesticides such as roach and ant killers are in the same
class of chemicals as the chemical nerve agents.
With the system of gene and protein therapy currently developed in Dr.
Lockridges lab, the cost of protecting one person is at least $1 million.
The researchers are looking for ways to lower the cost so it would be a
realistic option to protect the general public.
Co-investigators of the study are Steven Hinrichs, M.D., associate professor
of pathology and microbiology and director of the Nebraska Public Health
Laboratory; and Angie Rizzino, Ph.D., professor in the Eppley Institute
and department of biochemistry and molecular biology.