Closing in on an Answer: BUSPH Leads Consortium Probing Cause of Gulf War Illness.

Like a tape recording on a loop, the health symptoms dogging tens of thousands of veterans of the first Gulf War have not abated in 22 years, long after the troops were exposed to potential toxins, such as pesticides and sarin gas.

Now, a consortium of researchers headed by the BU School of Public Health is launching a massive, $5 million study to test the theory that a chronic inflammation in the brain is continuously activating brain and immune pathways to cause ailments such as joint and muscle pain, memory problems, fatigue, headaches and gastrointestinal distress.

Kimberly SullivanFunded by the Department of Defense, the study will bring together neuro-psychologists, neuroscientists, immunologists, geneticists and other researchers from nine institutions to try to pinpoint a physical cause for a cluster of symptoms — affecting an estimated 175,000 to 250,000 veterans of the 1991 Gulf War– that has 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,” said Kimberly Sullivan, research assistant professor of environmental health at BUSPH and lead investigator of the four-year study. “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 and other sickness behaviors, such as muscle pain, headaches and concentration problems. Past studies, including several by BUSPH’s Roberta White, associate dean for research and chair of environmental health, found that veterans exposed to toxic chemicals had lower volumes of white matter in their brains – a deterioration that could be activating the microglia.

“There’s been a convergence of studies showing an impact on the brain and immune system,” Sullivan said. “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,” she continued. “Treatment options could be targeted directly to the problem.”

As many as one-third of the 700,000 military troops who participated in the short-lived 1991 Gulf War suffer from a chronic multi-symptom illness that is 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, including 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, the Institute of Medicine (IOM) issued the latest in a series of studies, conducted on behalf of the Department of Veterans Affairs, that cautioned against a one-size-fits-all approach to treating Gulf War illness, instead recommending individualized treatment by teams of clinicians.

Gulf War veterans for years have expressed frustration with the government’s slow response to their health complaints and the lack of effective treatments. Some veterans’ advocates have complained that the VA has not taken their health ailments seriously and has portrayed their problems as psychological, rather than physical.

The consortium’s work has taken on added importance because some of the symptoms reported by more recent Iraq and Afghanistan veterans — including headaches, chronic pain, disrupted sleep, fatigue and memory problems — overlap with the symptoms experienced by the Gulf War veterans, although they may be triggered by a different mechanism.

Sullivan, who serves as associate scientific director of the congressionally-directed Research Advisory Committee (RAC) on Gulf War Veterans’ Illnesses, said the first step in determining treatments is pinpointing the cause.

The consortium will perform a host of 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 said. She said 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, Sullivan said, researchers hope to be able to “treat the mechanism, as opposed to the individual symptoms.”

Among the possible treatments to target such neuro-inflammation is one being developed by Sullivan and colleagues that involves intranasal insulin. Researchers from the Boston and Bronx VA medical centers and the Mount Sinai School of Medicine in New York 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 neuro-inflammation, 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 said it is impossible to give up the hunt when so many veterans are still suffering, and when leads for developing treatments are now within reach.

“Twenty-two years later, these vets are still having symptoms,” she said. “It’s clear something happened to them that isn’t resolving over time.” She added: “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.

Besides BU, the members of the new consortium include: Baylor University; Miami VA Medical Center/ Nova Southeastern University; the University of Adelaide, Australia; Drexel University; the University of Colorado; Temple University; the Centers for Disease Control and Prevention; and the National Institutes of Health.

Submitted by: Lisa Chedekel

chedekel@bu.edu