Closing in on a Medical Mystery
SPH leads team searching for Gulf War illness answers
It is a medical mystery that has confounded doctors and patients alike for more than two decades: why tens of thousands of veterans of the first Gulf War continue to be dogged by a complex and debilitating web of symptoms 22 years after they were exposed to potential toxins, such as pesticides and sarin gas.
Now, researchers from a consortium of institutions headed by the School of Public Health are launching a massive four-year, $5 million study to test the theory that a chronic inflammation in the brain is activating brain and immune pathways to cause ailments such as joint and muscle pain, memory problems, fatigue, headaches, and gastrointestinal distress.
Funded by the Department of Defense, the study will bring together neuropsychologists, neuroscientists, immunologists, geneticists, and others from nine institutions to try to pinpoint a physical cause for symptoms—affecting an estimated 175,000 to 250,000 veterans of the 1991 Gulf War—that have so far defied explanation.
“I’m excited about this because I think we’re really at a point of figuring out what’s causing Gulf War illness,” says study lead investigator Kimberly Sullivan, an SPH research assistant professor of environmental health. “I think we’re close. Hopefully in four years, we’ll be a lot closer.”
The study will probe whether exposure to chemicals may have kicked off a process in which damaged neurons are continually activating the immune cells in the brain, called microglia, which can cause inflammation, muscle pain, headaches, and concentration problems, among others. Past studies, including several by Roberta White, SPH associate dean for research and a professor and chair of environmental health and a School of Medicine professor of neurology, found that the brains of veterans exposed to toxic chemicals had lower volumes of white matter, a component of the brain that helps nerve cells communicate, a deterioration that could be activating the microglia.
“There’s been a convergence of studies showing an impact on the brain and immune system,” says Sullivan (right). “If you get caught in these chronic activation loops, one of the results is that you could suffer chronic symptoms. When in pain pathways, this could result in chronic pain; in memory pathways, it could cause cognitive problems.
“The good news is, if we can identify the mechanism, there are treatments being developed for this kind of inflammation in the brain. Treatment options could be targeted directly to the problem.”
As many as one-third of the 700,000 U.S. military personnel who participated in the short-lived 1991 Gulf War suffer from a chronic multisymptom illness believed to have been triggered by chemical and biological agents. A congressionally mandated panel of experts that includes White and Sullivan has affirmed that the condition is linked to exposure to toxic chemicals, among them pesticides and pyridostigmine bromide (PB), a drug given to troops to protect against nerve gas.
But the mechanism of the illness has remained a mystery. Just last month, theInstitute of Medicine (IOM) issued the latest in a series of studies, conducted on behalf of the Department of Veterans Affairs, which cautioned against a one-size-fits-all approach to treating Gulf War illness, recommending instead individualized treatment by teams of clinicians.
For years Gulf War veterans have been frustrated with the government’s slow response to their health problems and the lack of effective treatments. Some veterans’ advocates have complained that the VA has not taken their health ailments seriously, portraying them as psychological rather than physical.
The consortium’s work has taken on added importance because some of the symptoms reported by the more recent Iraq and Afghanistan veterans—including headaches, chronic pain, disrupted sleep, fatigue, and memory problems—overlap with the Gulf War veterans’ symptoms, although they may be triggered by a different mechanism.
Sullivan, who is associate scientific director of the congressionally directedResearch Advisory Committee on Gulf War Veterans’ Illnesses, says the first step in determining treatments is pinpointing the cause.
The consortium members, Baylor University, Miami VA Medical Center/Nova Southeastern University, Australia’s University of Adelaide, Drexel University, the University of Colorado, Temple University, the BU School of Public Health, theCenters for Disease Control and Prevention, and the National Institutes of Health, will perform studies examining markers in the blood and brain fluid, in addition to brain imaging (MRI and PET scans) and memory testing, to try to identify the source of the inflammation and biomarkers of the condition. Studies also are planned on animals, to test initial treatments.
Much of the imaging work on Gulf War veterans will be conducted at the BU Medical Campus, while animal and other testing will be done at other institutions.
“We need all these experts in different fields because we want to approach this problem from different angles,” Sullivan says, noting that previous studies have focused on “a piece of the puzzle—neuropsychologists look at their piece, immunologists and gastroenterologists look at theirs. We’re trying to bring all the pieces together.”
If the brain-immune pathway is confirmed as the root of the problem, she says, researchers hope to be able to “treat the mechanism, as opposed to the individual symptoms.”
In a separate trial, Sullivan and her colleagues are developing a possible treatment, involving intranasal insulin, to target such neuroinflammation. Researchers from the Boston VA Medical Center, the James J. Peters VA Medical Center in the Bronx, and the Icahn School of Medicine at Mount Sinai are involved in that trial, funded by a $1.7 million award from the Department of Defense. Intranasal insulin has been found to improve memory and attention, reduce neuroinflammation, and modulate cortisol levels.
Sullivan, whose research grew out of work she had done with White, has been chasing the cause of Gulf War illness for almost two decades. She says it is impossible to give up the hunt when so many veterans are still suffering and leads for developing treatments are now within reach.
“These vets are still having symptoms 22 years later,” Sullivan says. “It’s clear something happened to them that isn’t resolving over time. This is different than the primary kinds of trauma and blast exposures that many Iraq and Afghanistan veterans are experiencing” during a prolonged ground war.
Lisa Chedekel can be reached at firstname.lastname@example.org.
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