Barrow researchers investigate whether environmental manganese exposure can lead to Parkinson’s disease
$2.9 million NIH grant-funded study will expand on previous research of environment impact in South Africa
Backed by a $2.9 million R01 grant from the National Institutes of Health, Barrow Neurological Institute researchers are expanding their efforts to test a hypothesis that exposure to environmental manganese, two orders of magnitude below the typical occupational exposure, is associated with the progression of Parkinson’s symptoms.
The five-year grant will also allow researchers to test a theory that manganese induces parkinsonism by promoting inflammation in the brain. Parkinsonism is the umbrella term used to describe brain conditions that cause slowed movement, stiffness, gait imbalance, and tremors.
Society has long relied on manganese to produce steel and other alloys, making the inexpensive and abundant mineral a staple of the construction industry. More recently, manganese has become important in the burgeoning electric vehicle battery market.
“We hope this work will ultimately inform environmental regulations for manganese worldwide,” said Brad Racette, MD, Chair of Neurology at Barrow Neurological Institute, part of Dignity Health St. Joseph’s Hospital and Medical Center. “Our study also addresses an environmental justice concern raised by individuals who often are not represented in health research.”
Dr. Racette is collaborating with epidemiologist Gill Nelson, PhD, of the University of the Witwatersrand in Johannesburg, South Africa; epidemiologist Susan Nielson, PhD, environmental engineer Jay Turner, DSc, of Washington University in St. Louis; and biostatistician Lianne Sheppard of the University of Washington in Seattle.
The research follows a study five years ago, also funded by NIH, that was undertaken after residents in Meyerton, South Africa, contacted that country’s environmental enforcement officials with concerns about the smelter in their community. At the time, the smelter was the world’s largest manganese producer and had been operating for more than 50 years.
Dr. Racette, who has been conducting manganese research for more than 20 years, launched a pilot study with Dr. Nelson in 2013 to address the concerns of Meyerton citizens. This led to an NIH-funded study of more than 800 Black South African residents—about 700 of whom had exposure to emissions from the Meyerton smelter. The study recruited the remaining participants from a non- exposed community about 50 miles away for comparison.
The researchers performed clinical exams on the participants, measuring their motor and cognitive functions as well as their mood. They observed a pattern: the Meyerton residents performed poorly in all three areas compared to the non-exposed population.
The study also measured the amount of manganese polluting Meyerton’s air, which was similar to other manganese point sources throughout the world.
With this R01 grant, Dr. Racette and his team will revisit the same cohort in South Africa to determine whether the participants’ motor and cognitive symptoms have worsened over time. The researchers will also expand their assessments to include loss of smell, a possible early indicator of Parkinson’s disease, and non-motor symptoms of the disease, such as bladder and bowel dysfunction.
To better understand how manganese exposure may be wreaking havoc on the brain, the researchers will also scan the brains of about a quarter of the participants using magnetic resonance imaging (MRI). The scans will include sequences designed to specifically assess neuroinflammation, which emerged as a likely disease mechanism in the preliminary data.
The smelter shut down in 2020, but Dr. Racette’s team found that air concentrations of manganese remained very high in the community.
The new study will culminate in developing and disseminating information to Meyerton residents. “It really brings it full circle to the community,” Dr. Racette said. “They brought the question to us, and we’ll report back to them.”
The issue is urgent in South Africa, which produces more than a third of the world’s manganese.
Dr. Racette said the story of the Meyerton smelter represents a common theme in occupational and environmental research: the communities harmed by a particular industry often benefit very little, if at all, from that industry.
“Very few people in the Meyerton settlements we studied actually worked at the smelter,” Dr. Racette explained. “The people who have been poisoned with decades of pollution probably have received very little economic benefit from this facility. It’s a serious health equity and environmental justice issue.”
And Dr. Racette fears history will repeat itself with the manganese battery industry, which is growing to meet the worldwide demand for electric vehicles. “The virtue of the electric vehicle goes away completely if we’ve poisoned a developing country in the process of trying to manufacture a clean-energy vehicle,” he said.