How did Ali Keshavarzian, MD, a gastroenterologist at Rush University Medical Center, get involved in Parkinson's disease research? He became inspired to learn more when his sister was diagnosed with the condition in the late 1990s.
Keshavarzian already knew of the research showing that Parkinson's patients often have gastrointestinal (GI) problems and emotional stress along with the disease. It was his sister, however, who insisted these issues had actually caused her Parkinson's disease, rather than just being part of it. Although Keshavarzian assured his sister this was not the case, he kept the idea in mind.
The aha! moment
Keshavarzian went with his sister to the Rush Parkinson's Disease and Movement Disorders Center for her treatment. There, they met with Kathleen Shannon, MD, a movement disorders specialist, who, along with treating patients, conducts Parkinson's research. Keshavarzian and Shannon began a series of conversations about their respective research.
In late 2006, Keshavarzian attended a seemingly unrelated GI seminar. There, he heard how laboratory research showed that alcohol, which can cause gastrointestinal permeability (or gut leakiness), can also cause brain damage similar to Parkinson's disease. If lipopolysaccharide (LPS), a toxin produced by bacteria that is usually contained in the intestines, was introduced into other parts of the body, damage to the brain lasted longer.
"It suddenly dawned on me that maybe my sister was right," Keshavarzian says. He began to theorize: "We know that stress, like alcohol, can cause the gut to leak. What if stress causes leaks that let LPS into the body? A person would have to have a genetic susceptibility for the disease, but the LPS leakage might be the trigger for Parkinson's." He turned immediately to Shannon.
"I got an email from Dr. Keshavarzian while he was still at the seminar, saying that his sister might be right, that Parkinson's disease actually starts in the gut with toxin leaks," Shannon says. "This email inspired a series of meetings to brainstorm how we might look into the idea."
Shannon recruited Jeffrey Kordower, PhD, a neurology researcher at Rush, to help with the project. Building on previous findings in the fields of neurology and gastroenterology, Keshavarzian created a hypothesis, and the team began testing it through a clinical trial. In the end, the trial (results published in May 2012) showed promising results that link LPS that leaks out of the intestine with a chain of nerve-cell changes that move to the brain and become Parkinson's disease. If further research confirms this connection, it may transform the way investigators approach the disease (see "From the lab to the clinic").
It doesn’t surprise Shannon that such a discovery grew from a spark lit by Keshavarzian’s sister. "Almost all of our ideas are inspired by listening to patients," she says.
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