Thursday, March 30, 2017

BOSTON UNIVERSITY: Identifying Biomarkers of Gulf War Illness

SOURCE:  Boston University School of Public Health, by Lisa Chedekel, March 29, 2017


Identifying Biomarkers of Gulf War Illness

POSTED ON: March 29, 2017 TOPICS: gulf war illness, veteran health, veterans
serviceman-flagTwenty-five years after the first Gulf War, scientists still do not know the exact biological mechanisms that are making about one-third of the 697,000 veterans who served in the war sick.
But a new multi-institution study in the journal Neurotoxicology & Teretology, co-authored by a School of Public Health researcher, provides evidence that Gulf War Illness (GWI) stems from neuronal and glial injury affecting both the gray and white matter cells of the brain, and identifies serum autoantibodies that may prove useful as biomarkers of the illness.
The research team found “significantly elevated levels” of eight autoantibodies linked to certain central-nervous system cytoskeletal proteins (including tau, tubulin, myelin basic protein and glial fibrillary acidic protein) in a sample group of 20 Gulf War veterans, compared to a control group—a finding that suggests a “possible new avenue” for identifying an objective biomarker of Gulf War Illness. Glial fibrillary acidic protein—a marker of glial astrocyte injury—completely distinguished between the GWI cases and the controls in the study.
“These results confirm the presence of neuronal injury/glial activation in these veterans, and are in agreement with the recent reports indicating that 25 years after the war, the health of veterans with GWI is not improving and may be getting worse,” the authors said.
The serum autoantibodies “may prove useful as biomarkers of GWI, upon validation of the findings using larger cohorts in our ongoing multi-site study.”
Study co-principal investigator Kimberly Sullivan, a research assistant professor of environmental health and principal investigator on the Gulf War Illness Consortium project, which includes nine study sites, said the new study provides “objective, blood-based evidence of damage to the brains of sick Gulf War veterans. It indicates that, at least at some point, these veterans had a leaky blood-brain barrier that allowed these CNS proteins to enter their bloodstream and activate the immune system.”
Sullivan said she was hopeful that the work would lead to a simple blood test for GWI, and perhaps other toxicant-induced disorders, “if our larger, ongoing study shows the same promising results as this initial study.”
The complex of symptoms known as Gulf War Illness includes memory and attention problems, fatigue, chronic muscle and joint pain, headaches, persistent diarrhea, respiratory difficulties and skin rashes.  
Past research has shown that exposure to pesticides, the nerve gas agent sarin, and ingestion of pyridostigmine bromide (PB)—prophylactic pills intended to protect troops against the effects of possible nerve gas—are associated with GWI and neurological dysfunction. These so-called “toxic wounds” resulted in damage to veterans’ nervous systems and immune systems, including reduced white and gray matter in veterans’ brains, past studies have shown.
Combined with prior findings, the new study indicates that alterations in the brain’s cytoskeletal proteins, as evidenced by circulating autoantibodies, appear to be associated with chronic neuro-inflammation and oxidative stress, which cause the chronic health problems reported by sick veterans.
There is no treatment for GWI, and veterans’ advocates have complained that the Department of Veterans Affairs has been reluctant to recognize the illness as a toxicant-induced disorder.
The new study found significant increases in the levels of some of the eight autoantibodies among GWI veterans, including a 9.27-fold increase for calcium—calmodulin kinase II (CaMKIII); a six-fold increase for glial fibrillary acidic protein (GFAP); and a 4.83-fold increase in tau protein. Those elevated levels are consistent with the veterans’ exposure during their deployments to compounds such as pesticides and sarin gas, the research team said. Similar effects have been found in GWI animal models.
The study was led by Mohamed Abou-Donia of Duke University Medical Center, with co-authors from: Beth Israel Deaconess Medical Center, Harvard Medical School, Zagazig University in Egypt, and Menoufia University in Egypt.
The Gulf War Illness Consortium, which has developed blood and stem cell repositories, recently received nearly $3 million in funding from the Department of Defense for four additional “New Investigator” studies aimed at identifying biomarkers and genetic risk factors involved in the illness. Sullivan said that utilizing the GWIC biorepositories will allow for faster results in the new research. The new studies include:
  • Research to be conducted in collaboration with the Naval Research Laboratory that will examine epigenetic DNA changes in affected veterans to identify “altered gene expression markers”—meaning that protective genes may have been turned off by environmental exposures, causing the chronic health symptoms.
  • Exploring the association between development of GWI and exposure to cholinergic compounds (pesticides and nerve agents) in subgroups of veterans with specific combinations of genotypes that are less able to detoxify these chemicals. The study will be led by Patricia Janulewicz, SPH assistant professor of environmental health.
  • Developing a computerized diagnostic system for GWI using “machine learning” that incorporates multiple biomarker data, in order to generate probability scores at the individual veteran level and gauge potential risks for symptoms of GWI. The study will be led by researcher Bang-bon Koo, a postdoctoral associate in the BU School of Medicine.
  • Using a stem cell biorepository bank to determine whether GW-relevant chemical exposures cause the cytoskeletal protein, tau, in neurons to go awry, and if so, whether the resulting symptoms can be reversed with several FDA-approved medicines. The study will be led by Drexel University investigators.

Friday, March 24, 2017

New research links Gulf War Illness to gastrointestinal disturbances

SOURCE:  Press Release, University of South Carolina (EurekaAlerts)



New research links Gulf War Illness to gastrointestinal disturbances

Findings may point to new treatments for elusive disorder
A new study from the University of South Carolina has found a gastrointestinal link that could help explain many of the health issues facing those with Gulf War Illness (GWI) as well as opening new pathways to treatment options that may improve both gastrointestinal and neurological symptoms associated with the disorder. 
The research is the first study to link the gastrointestinal disturbances of GWI with changes in the intestinal microbiota. This connection potentially explains both the gastrointestinal inflammation and the neurological abnormalities (e.g., impairments to cognition, memory, learning) that define GWI. 
GWI exposures alter the microbiome (i.e., bacterial content in the gut), and the affected microbiota then produce endotoxins, which pass through a thinned lining of the gut (i.e., leaky gut) and into the blood where they circulate throughout the body. These compounds trigger an inflammatory response that, in turn, initiates several neurological abnormalities commonly observed in GWI. 
The findings were published by PLOS ONE and led by Saurabh Chatterjee, associate professor of environmental health sciences at USC's Arnold School of Public Health. The study looked at how the various exposures experienced by Gulf War veterans might have changed the microbiome. "Humans and animals have specific types of bacteria that help aid various physiological processes, including digestion, absorption, immunity and gut integrity, and when external factors change the bacterial composition in our digestive systems, we have problems," says Chatterjee. "Obesity, metabolic syndrome, inflammatory bowel syndrome, and liver disease have already been linked with changes in bacterial composition of the gut."
Characterized by symptoms such as chronic headache, cognitive difficulties, debilitating fatigue, widespread pain, respiratory problems, sleep problems, gastrointestinal problems, and other unexplained medical abnormalities, GWI continues to affect 25-32 percent of the 700,000 U.S. veterans who served in the 1990-1991 Persian Gulf War. Twenty years of scientific research has traced these symptoms to Gulf War chemical exposures and the drugs taken during deployment that were meant to prevent or counteract these exposures. However, the vast majority of these studies have focused on neurological effects (rather than gastrointestinal), and none of them have successfully revealed the pathways through which GWI affects the brain. 
The study showed that not only did exposures to the suspected GWI agents lead to inflammation in the intestines, but to neuroinflammation as well. "Usually, the gut is very selective about letting only certain elements from what we eat and drink into our blood--thanks to good bacteria," explains Chatterjee. "But when the composition changes due to an increase in certain bad bacteria, this causes disruption to the mucosal lining of the intestinal walls--leading more intestinal contents to leak into the blood."
Once in the blood, the toxins travel throughout the body to affect the different organ systems. It is through this path that the toxins reach the brain, causing the neuroinflammation and corresponding neurological symptoms that previous studies have extensively linked to GWI. Now that scientists can explain the neurological symptoms that characterize GWI, a new paradigm of research has been unlocked--one related to treatment options.
"We know that many diseases like obesity, liver disease, and inflammatory bowel syndrome can be cured or at least decreased by consuming good bacteria, like probiotics," says Chatterjee. "Now that this connection has been established, it opens the door to new studies where GWI patients take probiotics for a longer period of time and, hopefully, see improvement in symptoms connected with metabolic syndrome, gastrointestinal disturbances, and maybe even neuroinflammation."
SOURCE:  PLOSone, March 22, 2017



Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease in tight junction protein Occludin with a concomitant increase in Claudin-2, a signature of a leaky gut. Resultant leaching of gut caused portal endotoxemia that led to upregulation of toll like receptor 4 (TLR4) activation in the small intestine and the brain. TLR4 knock out mice and mice that had gut decontamination showed significant decrease in tyrosine nitration and inflammatory mediators IL1β and MCP-1 in both the small intestine and frontal cortex. These events signified that gut dysbiosis with simultaneous leaky gut and systemic endotoxemia-induced TLR4 activation contributes to GW chemical-induced neuroinflammation and gastrointestinal disturbances.

Tuesday, March 21, 2017

**URGENT ACTION ALERT** -- 5 Minutes to Help -- Gulf War Illness treatment research

ACTION NEEDED:   Very specific -- Ask your Congressperson in the U.S. House of Representatives to sign onto the "Bergman-Sablan""Dear Colleague Letter for Gulf War Illness treatment research funding" (FY18)  READ BELOW for more details before calling.

DEADLINE for sign on's:  Friday, March 31, 2017 (U.S. House of Representatives only, no U.S. Senate yet)

HAS YOUR REP. COSIGNED?  Click here for the CURRENT list of cosigners (check to see if yours is signed on yet before calling their DC office to request they sign on) AND IF THEY HAVE NOT PLEASE CALL THEM TO ASK THAT THEY DO!

(The Senate has not yet begun its appropriations work for this year, but that will be coming soon.)


( - Key members of Congress have launched a renewed bipartisan initiative to continue the Gulf War Illness Research Program (GWIRP) to develop treatments for Gulf War Illness.  

The GWIRP is part of the Congressionally Directed Medical Research Program (CDMRP) administered by the U.S. Department of Defense under Congressional direction.  

VA and scientific estimates show that Gulf War Illness affects between one-fourth and one-third of the veterans of the 1991 Gulf War.   The consensus among Gulf War Illness medical researchers is increasingly clear:  With the a concerted national effort, effective treatments can likely be found.

This year’s effort is being led in the House by Rep. Jack Bergman, LtGen, USMC (Ret.) (R-MI) and Rep. Gregorio Sablan (I-NMI), and supported by Rep.’s Phil Roe, M.D. and Tim Walz, CSM, ARNG (Ret.).   

As a retired three-star Marine Corps general, Gen. Bergman, a veteran of the Vietnam War, is the highest ranking former military person ever to serve in Congress.  Sablan represents the U.S. territory of the Northern Mariana Islands (NMI) and has been a strong supporter of the program for years, with deep concerns about the effects of Agent Orange in the NMI.  

And, as a retired Command Sergeant Major, Walz, a veteran of Operation Enduring Freedom, is the highest ranking enlisted person ever to serve in Congress.  Dr. Roe is the Chairman of the full House Veterans' Affairs Committee, and Walz is the Ranking Member of the minority party on the Committee.

Last year, 74 Members of the U.S. House of Representatives signed onto the Dear Colleague letter in support of FY17 Gulf War Illness treatment research funding.  Thirteen (13) members of the House Veterans’ Affairs Committee were among those cosigners, led by Rep. Phil Roe, M.D. (R-TN) and Rep. Tim Walz, CSM, ARNG (Ret.) (D-MN), including  then-Chairman of the House Committee on Veterans’ Affairs (HVAC) Jeff Miller (R-FL), then-Ranking Member Corrine Brown (D-FL) , Vice-Chairman Gus Bilirakis (D-FL), and five Subcommittee Chairs or Ranking Members.

While the U.S. Senate has not yet launched this year's appropriations efforts, watch in the coming weeks for a parallel effort led by a longstanding champion of this program, U.S. Senate by Senator Tammy Baldwin (D-Wisconsin), who will again lead this year's push in the Senate continued funding for the unique, treatment-focused medical research program aimed at improving Gulf War veterans' health and lives.  

Information below shows what you can do in just five minutes to support this critically important national effort to help our nation's Gulf War veterans.



1.  Find your Congressperson in the U.S. House of Representatives:
    • (U.S. HOUSE) Find your Congressman/Congresswoman here (near the top right corner, enter your zip code).  

2.  Call his or her Washington, DC office [not their office(s) back in their district or home state] , and ask for the legislative staff person who handles Defense Appropriations.  
    • If you get their voicemail, leave a detailed voicemail with your specific request (below).

3.  State your name and that you are a constituent, and very briefly (in 1 or 2 sentences at most) state your connection to Gulf War Illness
    • [For example:  "I'm among the one-in-three veterans of the 1991 Gulf War suffering from Gulf War Illness".  
    • Or, "I'm the wife/husband/son/daughter/parent of a Gulf War veteran suffering from Gulf War Illness."
    • Or, "I'm one of many other veterans besides those who served in the Gulf War and I'm also suffering from a chronic multi-system illness like Gulf War Illness."
    • Etc.

4.  State that there is a "Dear Colleague" letter that you are specifically requesting the Congressman/Congresswoman sign onto.  

5.  Provide the name of the "Dear Colleague" letter (there is no bill number -- this is a "Dear Colleague" request to get funding into a bill -- specifically the FY18 Defense Appropriations Act):  
  • (U.S. HOUSE)  The "Bergman-Sablan Dear Colleague Letter for FY18 Gulf War Illness treatment research funding."  

6.  State that this is to continue funding for a successful, treatment-focused program and there were 74 cosigners last year.

7.  State the sign-on deadline (this is a hard deadline)March 31, 2017 (U.S. House). The Congressman/Congresswoman will likely want to support the one-fourth to one-third of Gulf War veterans and others suffering from Gulf War Illness.  

[Staff contacts, in case they ask are:  U.S. House of Representatives:  Rep. Jack Bergman (Chris Mataranga); Rep. Gregorio Sablan (Frances Diaz).  U.S. Senate:  Sen. Tammy Baldwin (Jeremy Steslicki).]

8.  Ask if you can email the staffer with a short one-pager about the program.  This is very important.  Then right away, email them the link to this document:  

About the Gulf War Illness Research Program (GWIRP), March 2017:
9.  Ask that the staff person follow-up with you to let you know the Senator's or Congressman's/Congresswoman's decision.

10.  Thank the staff person for their time.


If they say they will sign on, post a comment below this post with the name of the Senator or Congressperson and the name of the staffer and that they will or will not sign on.  

Follow-up in 2-3 days to find out the status, if you haven't heard back.

  • Be polite
  • Be pleasant
  • Be urgent
  • Be respectful
  • Be convincing
  • Be brief
  • Be SPECIFIC with the REQUEST:  Sign onto the "Baldwin" (U.S. SENATE) or "Bergman-Sablan" (U.S. HOUSE) "Dear Colleague Letter for Gulf War Illness treatment research funding"  
  • Do not argue with, get angry with, or threaten the staffer in any way.  






The overall goal of the program is to find effective treatments for the officially estimated quarter-of-a million veterans of the 1991 Gulf War and others who are still suffering from the debilitating effects of Gulf War Illness.

These veterans were directly impacted by a veritable toxic soup of hazardous exposures during the short but intense war, and the best efforts our nation can provide to assist them.  


You can email, call, or electronically message your two U.S. Senators who represent you and your state in the U.S. Senate and your Congressman or Congresswoman who represents you in the U.S. House of Representatives.  

See above for "10 quick and easy steps" to make your request.  

Many Members of Congress have an option to submit your comments from a quick form right on their webpage.


In the U.S. House of Representatives, Rep. Jack Bergman, LTG, USMC (Ret.) (R-Michigan) and Rep. Gregorio Sablan (D-U.S. Territory of Northern Mariana Islands) are co-leading this effort.  Both serve on the House Committee on Veterans' Affairs. 

House Veterans Affairs Committee Chairman Rep. Phil Roe, M.D. (R-Tennessee) and Ranking Member Rep. Tim Walz (D-Minnesota) are backing this.   

In the United States Senate, U.S. Senator Tammy Baldwin (D-Wisconsin) is leading the bipartisan effort for the Senate.  

This is a fully bipartisan effort.


The effort is to support the treatment-focused Gulf War Illness CDMRP.  Their effort is calling for House Members to support this important program by signing onto a "Dear Colleague" letter requesting adequate continuation funding for this successful, unique, and important program.  


Reports by the National Academy of Sciences’ Institute of Medicine (IOM)2 (pp. 10, 260-64) and the Congressionally-mandated VA Research Advisory Committee (RAC) on Gulf War Veterans’ Illnesses3 emphasize that “effective treatments, cures, and, it is hoped, preventions” for GWI can “likely be found,” “…through a concerted national effort and rigorous scientific input.” In addition, important discoveries made by the GWIRP may also help protect current and future U.S. military service members at risk of similar toxic exposures. (RAC 2014, pp. 1, 4, 5, 13, 78, 83; IOM 2010, pp. 10, 260-64.)


The RAC, more than 50 FY15 Independent Budget Veterans’ Service Organizations (IBVSO’s), scientist GWIRP panelists,1,5 and numerous consumer reviewers serving with the GWIRP have expressed strong support for the GWIRP to improve the health and lives of veterans suffering from GWI.   

The FY15 IBVSO’s said the GWI CDMRP, “has made great strides in the
short time it has been operating,” and the IBVSO’s (DAV, PVA, VFW, and 27 others) for the 115th Congress (2017-18) are asking Congress to “…provide sufficient funding to resume robust research to identify effective treatments...”

The program is supported by the nation's leading Veterans Service Organizations.  FY17 funding supporters included:  the American LegionAMVETS; Association of the U.S. Navy (AUSN); Burnpits360; Disabled American Veterans (DAV); Lung Cancer Alliance; National Gulf War Resource Center (NGWRC); National Vietnam & Gulf War Veterans Coalition (NVGWVC); Paralyzed Veterans of America (PVA); Sergeant Sullivan CircleToxic Wounds Task Force; Veterans for Common Sense (VCS); Veterans of Foreign Wars (VFW); Vietnam Veterans of America (VVA). 
The FY15 Independent Budget Veterans Service Organizations (IBVSO’s, composed of AMVETS, DAV, PVA, VFW, and 53 other organizations that serve veterans) stated that the GWI CDMRP, “has made great strides in the short time it has been operating.” (pp. 126-27)


Right away.  The deadline is fast approaching. 


The sign-on deadline for Congresspersons in the U.S. House of Representatives to sign-on is March 31, 2017, and for Senators in the U.S. Senate it has not yet been announced.  Typically, their offices need one or more days to secure approval to sign-on.  




The Gulf War Illness Research Program (GWIRP), part of the Congressionally Directed Medical Research Program (CDMRP), a Congressionally directed activity funded under the U.S. Department of Defense, has a comprehensive website on the GWI program at: .  The GWIRP also publishes an overview of the program in its GWIRP program booklet.  

The GWIRP also publishes an overview of what is known scientifically about Gulf War Illness:  The Gulf War Illness Landscape .

Veterans for Common Sense (VCS), a leading national veterans' education and advocacy organization, has published the following two documents about the Gulf War Illness Research Program:


The Congressionally Directed Medical Research Program, which is administered by the U.S. Department of Defense (U.S. Army Medical Research and Materiel Command) provides information for prospective researchers, including how to apply.

Funding announcements are typically made in the late Spring of each year, but timing may vary quite a bit from year to year, depending upon Congressional appropriations.  


Recent research shows that chemical exposures are causally associated with Gulf War Illness.  Psychiatric causes have been ruled out.  

This paper reviews the recent medical literature on the health of 1991 Gulf War veterans, focusing particularly on the central nervous system and on effects of Gulf War toxicant exposures:

Another important advance for finding treatments for Gulf War Illness, funded by the GWIRP, was published in March 2017:


A copy of the actual letter that Members of the House are actually signing onto is here:


--Anthony Hardie, Author and Gulf War veteran advocate.