DOD CDMRP Posts 4 New Research Projects Gulf War Illness

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The list for at least a portion of the Gulf War Studies to be funded  by 2010 funds are listed below, there are 4 listed reflecting a total of 3,053,903.

Keeping an eye for more announcements of the funding from 2010 Awards!

The studies so far look like Grade A studies including California, Wisconsin, Colorado, and Alberta,Canada.  They are diverse looking at Fight or Flight Imbalance(neuro, immune, hormonal)(computer stimulation), oxidative stress(Calif)(biomarkers 20 ill gulf war veterans times 2 for total of 40 veteran test subjects), Wisconsin will have:  Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gulf War Syndrome(biomarkers, sleep study, and  high density electroencephalography and CO will have: Exhaled Gas Frequency Comb Spectroscopy Distinguishing Biomarkers in Gulf War Illness Syndrome (John Hall, Ph.D., shared the 2005 Nobel Prize in Physics for his discovery of this innovative technique that is called Frequency Comb Spectroscopy) Biomarkers!

The complete details appear below but these studies are going in the right direction to find biomarkers but we need much more on treatment modalities.    More updates soon!

Theory-Driven Models for Correcting “Fight or Flight” Imbalance in Gulf War Illness

Principal Investigator: BRODERICK, GORDON
Institution Receiving Award: ALBERTA, UNIVERSITY OF
Program: GWIRP
Proposal Number: GW093042
Funding Mechanism: Investigator-Initiated Research Award
Partnering Awards:
Award Amount: $678,953.00

View Technical Abstract

PUBLIC ABSTRACT
Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and Post-Traumatic Stress Disorder (PTSD) are poorly understood illnesses that have a broad impact on the body’s communication and control systems (nervous and hormone systems) as well as its repair and defend functions (immune system). Traditional medical research looks for broken parts in these systems without paying much attention to how the parts fit together and whether or not the complete assembly is well tuned and operating at peak efficiency.

In this proposal we intend to examine how poorly tuned the fight-or-flight survival response may have become in patients with Gulf War Illness. In much the same way as pilots use simulators to understand the capabilities of their aircraft during flight training, we will use a computer mock-up of the human body’s fight-or-flight response to improve our understanding of GWI. Using simulations we hope to map the new characteristics of this altered survival response in sick veterans and find safe ways of bringing it back into its normal performance envelope.

This map will help us in two ways. First, it will tell us what to look for in new recruits who might be especially at risk (screening) for developing GWI under the specific conditions. Second, it will also tell us where in the body, and how, this survival response should be adjusted in servicemen that are already ill. Because we will be working with a mock-up of the whole system, we expect to identify not only those treatment options that could help but, almost as importantly, those that could have dangerous side effects.

Computer simulations have accelerated the design of aircraft, cars, and other sophisticated machinery. In a similar way we expect that this computer-aided design approach will shorten the time to clinical trials and help improve the focus and quality of these trials. At the end of this 3-year project it is our objective to have in hand a set of blueprints for the most promising of these clinical trials.

Finally, these simulations can be adjusted to mimic the response of a specific individual. As a result, this work could help lead to treatments that are customized on a person-to-person basis. This is important because we suspect that not all patients suffer from the same variant of GWI and we know from experience that not all patients react in the same way to the same therapy.
 

Oxidative Stress

Principal Investigator: GOLOMB, BEATRICE
Institution Receiving Award: CALIFORNIA, UNIVERSITY OF, SAN DIEGO
Program: GWIRP
Proposal Number: GW093063
Funding Mechanism: Investigator-Initiated Research Award
Partnering Awards:
Award Amount: $927,000.00

View Technical Abstract

PUBLIC ABSTRACT
Background: Gulf War veterans (GWV) experienced an unprecedented array of environmental exposures to chemicals, vaccines, oil fires, heat, and other factors that each contribute to a specific type of toxic effects to cells called “oxidative stress” (OS). It is this against which antioxidants seek to protect.

There is evidence that some of these exposures are linked to Gulf War illness (GWI); and in fact mediate their toxicity via OS. Additionally, there is reason to suspect that GWI may be driven by cumulative exposure to OS. Large short-term exposures to external (environmental) OS can lead to long-term increases in internally produced OS.

This is because OS can damage cell elements in a fashion that leads them to produce, on an ongoing basis, more oxygen free radicals (i.e. OS). (They may arise further if there are any depots of toxic substances in the tissue; but this is not necessary for long-term increases in OS.) This ongoing OS can produce further damage and may lead to symptoms that fit the pattern that ill GWV report.

If this is shown to be true, it would be a breakthrough because it would lead to means to protect against similar problems in future personnel in military and also civilian settings. In addition, it may lead to approaches to treat ill GWV; and approaches to track the benefits of treatments being tested. Thus, it is important to determine if markers of OS can be identified that individually or in their pattern are linked to illness in GWV.

There are a range of markers that are related to OS, and each has been found useful in a different complement of settings. Some protect against OS, or are driven up or down with OS, or both.

Goal: This study seeks to examine a spectrum of such markers related to OS, to see which markers, individually or as part of a pattern, discriminate GWI from controls; and relate to severity of illness within affected GWV.
Approach: To accomplish this we will recruit 40 affected GWV, and 40 healthy controls. In a first phase, we will look at half — assessing a spectrum of OS markers in 20 with GWI and 20 controls to see which OS markers or patterns discriminate GWI, and are most strongly linked to illness severity within GWI.

The most promising markers will be reappraised in the remaining 20 affected GWV and 20 controls to see whether patterns of markers retain their discriminating power. We capitalize on two innovative approaches that learn discrimination patterns by being told the answer (“supervised” learning via backpropagation neural networks); or by picking up on natural groupings in the data (“unsupervised” approach using a technique called Independent Component Analysis or ICA). A pioneer in both techniques will serve as a co-investigator and direct this portion of the study.

Benefits: This study will do several important things. It will determine the relation of GWI to OS — a pivotally important factor that may be absolutely fundamental to advancing knowledge regarding GWV. It will enhance understanding of mechanism of GWI, which in turn will suggest approaches for promising treatments. It will yield objective markers tied to illness that can be tracked during testing of candidate treatments.

By assessing which are the very best OS markers in relation to GWI, it will enhance quality and cost effectiveness of future studies that seek to include assessments of OS, enabling them to focus on only the best markers of OS and avoid unproductive markers. It will advance understanding the cause of GWI. Finally, it will directly suggest approaches to protect future servicepersons and also civilians from vulnerability to problems in similar settings.

It may afford patterns of OS that enable objective diagnosis of GWI, overcoming the longstanding concerns and complications to GWV associated with GWI being defined purely by symptoms. Use of sophisticated unsupervised and supervised approaches that uncover higher order statistics in the data, undertaken by a premier authority in their use, will maximize prospects for that objective.
 
Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gulf War Syndrome

Principal Investigator: JUERGENS, TIMOTHY M
Institution Receiving Award: WISCONSIN, UNIVERSITY OF, MADISON
Program: GWIRP
Proposal Number: GW093035
Funding Mechanism: Investigator-Initiated Research Award
Partnering Awards:
Award Amount: $705,654.00

View Technical Abstract

PUBLIC ABSTRACT
Gulf War Illness is a serious condition affecting many veterans who served in the 1991-1992 Gulf War. Fatigue is one common symptom that causes problems in the lives of these veterans. Many studies to date have identified a number of body systems that act abnormally in Gulf War Illness, such as the fight-or-flight system, the immune system which responds to an infection, or the inflammatory system, which responds to an injury.

A common pathway for many of these abnormalities may be that they affect the systems that help a person stay awake in the day and fall asleep at night. One piece of feeling sleepy or awake is related to the amount of time you stay up and what you are doing in that time, so you are more tired after being awake a long time, such as staying up late. Other symptoms also often come with that, including not feeling as mentally sharp, and even increased sensitivity to pain. Another piece of the sleep/alert system is one that runs on about a 24-hour clock over and over.

This may be what helps you sometimes feel like you have a second wind, after feeling tired at some point in the day. It is also what sometimes makes people feel crummy after they fly somewhere over many time zones, or work a job at night, even if they get what seems to be enough hours of sleep. Some things that can be measured run predictable patterns with this approximately 24-hour rhythm, including the chemical melatonin, and your body temperature.

I plan to assess these two parts of the system that help a person sleep in the night and stay awake in the day, for differences in veterans of the Gulf War who have persistent fatigue compared to those who do not have fatigue. I think abnormalities in these systems account for the fatigue Gulf War veterans feel.

This assessment will include seeing how a person responds to having one hand in warm water, with a normal response being to heat up the other hand to balance out the heat. Since temperature is closely tied to sleep, it has been shown that people who do not have their other hand heat up are the ones who have trouble sleeping.

Other parts of the assessment will look at temperature changes all day and night in a person to monitor their 24-hour rhythm, as well as melatonin changes over part of that time, to see if they are not going up like they should as a person falls asleep. We will also look at brain waves with electrodes stuck on the head overnight in a sleep lab, to see changes that may reflect how restorative a person’s sleep has been. This study will include cutting edge technology that lets us look at how brain areas respond to activation in other areas, more helpful information than just viewing one isolated part of the brain’s activity alone.

The results of this study will help guide more clear treatments for Gulf War Illness by being able to address problems that are found in this sleep and alerting system. It will bring some tools used to study other conditions with some similar symptoms to the Gulf War Illness field, including a highly technical and new tool for looking at brain wave activity in sleep called high density electroencephalography.

Depending on the findings, there are a number of logical next treatment steps which could be implemented in the next 5 years. These may include temperature manipulations, medications that influence temperature and sleep, light, and maybe even a cooling cap at night to cool the head. It will also help guide more specific research into causes of body systems that have gone wrong and are contributing to symptoms.
 
Exhaled Gas Frequency Comb Spectroscopy Distinguishing Biomarkers in Gulf War Illness Syndrome

Principal Investigator: REPINE, JOHN E
Institution Receiving Award: COLORADO, UNIVERSITY OF, DENVER
Program: GWIRP
Proposal Number: GW093021
Funding Mechanism: Investigator-Initiated Research Award
Partnering Awards:
Award Amount: $742,296.00

View Technical Abstract

PUBLIC ABSTRACT
The Problem: Gulf War Illness is an important but poorly defined clinical disorder. For unknown reasons, veterans who have the disorder often have many symptoms including fatigue, joint pain, memory loss, and/or severe headaches. There is no clear consensus or understanding of the cause and no specific objective diagnostic tests for the syndrome and, accordingly, Gulf War Illness remains difficult to definitively diagnose, monitor, treat and prevent. Thus, there is great need for gaining new knowledge regarding the cause and consequences of the disorder. One of the best ways to accomplish this objective will be to develop tests that can objectively generate biomarkers that can be used to characterize the disorder and to select and evaluate potential therapies for Gulf War Illness afflicted individuals.

Our Approach: We propose to use a powerful new technology to study Gulf War Illness to gain new understanding and develop distinguishing biomarkers for Gulf War Illness. One of our collaborators, John Hall, Ph.D., shared the 2005 Nobel Prize in Physics for his discovery of this innovative technique that is called Frequency Comb Spectroscopy. The advantages of the approach are that multiple molecules can be measured non-invasively, simultaneously, sequentially, repeatedly, accurately and with great sensitivity (in parts per billion) on small samples of exhaled breath gas.
Our Objectives: We will use this new technique to measure exhaled gas breath samples from rats that have inhaled pesticides, combustion generated small airborne particles, and/or been treated with pyridostigmine: These three insults have all been implicated as contributors to Gulf War Illness.

In addition, we will use this novel biomarker technique to determine and compare biomarker molecules in the breath of Gulf War Illness afflicted individuals with healthy veterans, cigarette smokers, smoke-exposed individuals, and healthy human subjects.

Potential Results, Clinical Application, Rationale and Impact: We anticipate that exhaled gas breath measurements made using this new non-invasive biomarker technology will (1) distinguish individuals with Gulf War Illness from normal healthy subjects thereby providing a needed objective biomarker for classifying and determining any progression in the syndrome, (2) provide new understanding regarding any potential underlying abnormality which might be reflected by exhaled biomarkers and contribute to the symptoms of Gulf War Illness veterans, (3) show the effects of three implicated insults on molecules in the exhaled breath of well-controlled experimental rat models and in the process provide a way to directly compare the exhaled gas biomarker findings in humans with Gulf War Illness to the exhaled gas biomarker patterns from rats that have been exposed in controlled experiments to Gulf War insults, (4) produce new insights that might be useful in developing new treatment and/or prevention strategies for Gulf War Illness and (5) provide biomarker analysis as a way to sequentially measure the effectiveness of various therapies in Gulf War Illness.

It is anticipated that we will generate convincing results regarding the potential of this new Nobel-Prize winning technology during the three year period of study. For this and other reasons, commercial companies are interested in developing a simplified model which can make these measurements relatively inexpensively and be located in many convenient locations nationally.

The ability to produce objective criteria for diagnosing and monitoring individuals with Gulf War Illness holds great promise for improving the lives of these important veterans and perhaps preventing this type of condition in the future.

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