The Department of Defense has awarded a multi-institutional team of scientists a series of grants totaling $4.37 million to investigate the potential role of airborne pollutants as triggers of Parkinson's disease via the nose.
"It increasingly appears that a complicated mix of biological and environmental factors contribute to Parkinson's," said study lead Patrik Brundin, M.D., Ph.D., director of VARI's Center for Neurodegenerative Science. "Unraveling this tangled web will go a long way in helping us develop ways to evaluate an individual's risk for the disease as well as developing therapies to prevent, slow or stop its onset and progress."
To undertake the four-year study, Brundin has teamed up with collaborators Caleb Finch, Ph.D., the ARCO/F. Kieschnick Professor in the Neurobiology of Aging and University Professor at University of Southern California's Leonard Davis School of Gerontology; Honglei Chen, M.D., Ph.D., professor of epidemiology and biostatistics at Michigan State University College of Human Medicine; and Todd Morgan, Ph.D., Research Professor of Gerontology also at the USC Leonard Davis School.
The project will be supported by three Department of Defense grants--$1.4 million to Brundin, $1.45 million to Finch and $1.5 million to Chen.
Finch and Morgan have previously shown that airborne particulates cause inflammation that spreads from the nose into the brain in disease models while Chen studies Parkinson's disease incidence on a population-wide scale.
Together, they will investigate how long-term exposure to airborne particulates relates to Parkinson's onset later in life. Increasing evidence suggests that inflammation in the nose, which is directly connected to the brain's olfactory region, could be among the first triggers of the disease.
An estimated 90 percent of people with Parkinson's disease have problems with their sense of smell or entirely lose it in the years preceding their diagnosis.
"The nose is a direct gateway into the body and, in fact, it is one of first places we see evidence of Parkinson's pathology in the form of abnormal alpha-synuclein proteins," Brundin said. "From there, it appears that these proteins move from the olfactory bulb deeper into the brain, leaving a path a destruction that manifests as symptoms such as loss of sense of smell and, eventually, motor deficits."
Environmental factors, such as pollution, are likely low-level contributors that are superimposed upon genetic influences and age, the greatest single risk factor for Parkinson's. The team believes that younger people, particularly those born with low genetic risk, may be able to cope with nasal inflammation and live a long life without developing the disease. Other elements also play a role.
"At the same time, gender differences may also be a factor in the greater vulnerability of men to Parkinson's," Finch said.
After their initial studies, the team will explore whether anti-inflammatory medications may be able to slow the progression of Parkinson's. They include the over-the-counter anti-inflammatory drug ibuprofen, and an experimental anti-diabetic drug called MSDC-0160.
In 2005, Chen and his associates published evidence that ibuprofen may significantly reduce the risk of Parkinson's disease. MSDC-0160, meanwhile, has shown promise for slowing Parkinson's progress in lab models of the disease, according to a 2016 study from Brundin's lab.
They also plan to use the rigorous population-scale methods to compare groups of people who have lost their sense of smell in late adulthood versus those who have not. The clues found in their genetic profiles and health histories, including use of anti-inflammatory medications, may yield important correlations that the team can follow up in the lab, Chen said.
"This is an exciting opportunity for joined forces of basic and population scientists to search for the origins of Parkinson's disease," Chen said.
Between seven to 10 million people have Parkinson's disease worldwide. Currently, there is no way to definitively diagnose the disease and no therapies that slow or stop its progression.
All medical decisions should be made in close consultation with a physician, including prolonged use of ibuprofen.