Illinois Neuroscience Project Takes Aim at GWI Treatment

The following news story is about a treatment development project funded by the Gulf War Illness (GWI) Congressionally Directed Medical Research Program (CDMRP).  The project was approved using Fiscal Year 2008 funds.

The full public abstract, courtesy of the CDMRP website, is posted below the news article.

-AH

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By ANDY KRAVETZ

of the Journal Star

Posted Aug 16, 2012 @ 09:49 PM

Last update Aug 17, 2012 @ 12:23 AM

PEORIA, Ill. -- A local researcher is beginning studies that could possibly lead to new treatments for veterans suffering from Gulf War syndrome.

While any new medication is years off, Dr. Stephen Lasley, professor of pharmacology at the University of Illinois College of Medicine at Peoria, hopes his work could lead to the reversal of the disorder or at least provide some relief to the thousands of veterans of the 1991 Gulf War who have experienced symptoms.

He also hopes to find a way to prevent the same thing from happening to a new group of veterans.

"We want to make sure that we don't do this again," he said.

Lasley is working with a researcher in West Virginia to try to re-create what it was like for veterans 20 years ago as part of a Pentagon effort to better understand Gulf War Illness, which wasn't officially recognized as a disease or syndrome until years after soldiers came home.

Lasley plans to inject mice with the anti-nerve gas drug pyridostigmine bromide as well as pesticides used in the Gulf, and then expose the rodents to a compound that is similar to but less lethal than the nerve gas sarin.

The basic theory is that several factors, such as battlefield stress, pesticides and anti-nerve gas drugs combined to cause neurological reaction in veterans who were there. The exact combination isn't known and likely wouldn't be, given the length of time and the large number of people exposed as well as the different situations the troops were in.

Lasley believes the stress component is critical to the equation.

"It's an important component, and I don't think most people give much thought to the kind of stress that they are undergoing while they are there," he said. "Most of the other people working in this area have not hit upon the importance of the stress factor at this junction."

One thing is clear: Veterans who were in the Gulf suffer from chronic fatigue, loss of muscle control, diarrhea, migraines, dizziness, memory problems and loss of balance far more than those who weren't in the Middle East.

Lasley calls it a "sickness behavior" in that there isn't a single microbe or pathogen causing the illness, yet people still feel bad.

"It's like when you have a head cold and you take over-the-counter medicine. Your symptoms might get better, but you still feel bad," he said.

This is the second Defense Department grant Lasley has received. Earlier, he studied the effects of depleted uranium, a heavy metal used in ammunition and tank armor, on brain functions.

While he found that it is "nasty stuff" and does have some effect on cognitive functioning, he was unable to create a definitive link between Gulf War illness and depleted uranium. Instead, it appears that it, along with the other environmental factors, played some role.

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Andy Kravetz can be reached at 686-3283 or akravetz@pjstar.com. Read more at his military blog, inFormation, on pjstar.com and follow him on Twitter @andykravetz.

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PUBLIC ABSTRACT

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model 

Principal Investigator: LASLEY, STEPHEN M 
Institution Receiving Award: ILLINOIS, UNIVERSITY OF, CHICAGO 
Program: GWIRP 
Proposal Number: GW080150 
Funding Mechanism: Investigator-Initiated Research Award 
Partnering Awards: 
Award Amount: $718,326.00

Many veterans still suffer from Gulf War Illness (GWI) even though it has been many years since they were in the war theater. Our goal is to find out what happened to the troops in the 1991 Gulf War that caused GWI; once we understand the causes, it will help us to find treatments that will work in treating veterans suffering from GWI. We all know how miserable we are when we have a cold or the flu -- we don't want to eat or socialize, we have trouble thinking, our muscles ache, our stomachs might be upset, and we have no energy. Unpleasant as these feeling are, these "sickness" behaviors have a real purpose; they help our body to recover from infection. Our body knows when it is attacked by bacteria and other foreign invaders and responds in a very programmed way; our body detects the invader and releases substances that communicate with the brain and result in behaviors that conserve energy. These inflammatory substances also are released when we get a cut or other type of injury and are an important part of the healing process. 

As helpful as these chemicals are, they become a problem if the level of them is too high or they stay around too long. You might ask why we are talking about "sickness" behavior when our project concerns GWI. We noticed when veterans with GWI list their symptoms many of them sound like "sickness" behavior. We have an idea (hypothesis) that some of the chemicals that our troops used in the first Gulf War to control insects and keep these pests away from their bodies and the places they lived, as well as the pills they took to guard against possible nerve gas exposure, may be responsible. There is another characteristic of war that may play a role in GWI. Being in a war zone also can be very stressful and the body responds by releasing hormones like cortisol. Short duration exposures to cortisol are not harmful but can be bad if the levels stay high for a long time as they might in a war zone, especially one where troops needed to be extra vigilant about nerve gas attacks. It is possible these chemicals, either alone or along with the stress of the war theater, resulted in "sickness" behavior. Furthermore, we think the brain may have been changed so much by these exposures that a low level of "sickness" behavior continues to this day, and/or the brain "overreacts" to bacterial or other insults so the magnitude or duration of the symptoms of "sickness" behavior are much greater.

Because it is unethical to test our idea by exposing another group of people to chemicals like DEET or the pyridostigmine-containing anti-nerve gas pills, we will test it by exposing mice to these same chemicals. Mice are very useful for this because they show the biochemical aspects of "sickness" behavior much in the say way as humans, so we are confident our research will provide important information about GWI and its treatment. 

First, we want to know if chemicals the troops were exposed to cause the same brain changes seen with infections. Using mice exposed to a nerve gas-like agent, we already have some data showing that this is the case. By treating mice with a "stress" hormone, we also know that this can make the effects of a nerve agent on the brain worse.

 Because we can collect brain tissue from the treated mice, we can also say with certainty where in the brain these inflammatory substances do their work. Also, mice have a much shorter lifespan than humans so we can test them for what would be equal to many years in a human's life. In this way we will be able to tell if the brain is changed or supersensitive for a long period after exposure to the Gulf War chemicals. Finally, in previous experiments on other drugs and chemicals toxic to the brain, we have tested the antinflammatory effects of a drug already approved for use in humans. We found that this drug, minocycline, markedly suppresses brain inflammation. 

We will therefore use this same drug to attempt to suppress brain inflammation caused by exposure to chemicals and the stressful environment of the 1991 Gulf War. Because this drug already is approved for use by the Food and Drug Administration, we hope it can be used very soon for treating GWI if our results in mice show that it works.