What's Driving the 'World's Fastest-Growing' Brain Disease'?

Batya Swift Yasgur, MA, LSW

March 16, 2023

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson's disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson's disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, New York, called PD "the world's fastest-growing brain disease," and told Medscape Medical News that it "may be largely preventable."

"Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson's may be the latest," he said. "Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson's is increasingly rare, not common."

The paper was published online March 14 in the Journal of Parkinson's Disease.

Invisible, Ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers note.

"Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications," including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it's been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors note, in anaerobic conditions, perchloroethylene often transforms into TCE "and their toxicity may be similar."

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn't confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It's present in a substantial amount of groundwater in the US and it "evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected," the researchers note.

"Exposure can come via occupation or the environment and is often largely unknown at the time it occurs," Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. "Certain pesticides…are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the US." Rather, "other factors" are involved, and "TCE is likely one such factor."

Yet, "despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited."

To fill this knowledge gap, Dorsey and his co-authors of the book Ending Parkinson's Disease: A Prescription for Action, took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

"Like many genetic mutations (e.g., Parkin) and other environmental toxicants…TCE damages the energy-producing parts of cells, i.e., the mitochondria," said Dorsey.

TCE and PCE "likely mediate their toxicity through a common metabolite." Because both are lipophilic, they "readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses," the researchers hypothesize.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might "partially explain the link to PD."

Animal studies have shown that TCE "caused selective loss of dopaminergic neurons." Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as "ubiquitous" in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but "millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution."

They note that TCE contaminates up to one third of US drinking water, has polluted the groundwater in more than 20 different countries on five continents and is found in half of the 1300 most toxic "Superfund" sites that are "part of a federal clean-up program, including 15 in California's Silicon Valley, where TCE was used to clean electronics."

Although the US military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlight seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, "unaware of its toxicity." His father also died of esophageal cancer, "which is linked to TCE," the authors of the study write. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledge that the role of TCE in PD, as illustrated by the cases, is "far from definitive." For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlight the need for more research and call for cleaning and containing contaminated sites, monitoring TCE levels and publicly communicating risk and a ban on TCE.

Recall Bias?

Commenting for Medscape Medical N ews, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), notes that the authors "are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure."

Another limitation is that TCE exposure is very common, "as argued in the paper." But "most people with exposure do not develop PD," Gilbert pointed out. "By probing the TCE exposure of those who already have PD, there is a danger of recall bias."

Gilbert, an associate professor of neurology at NYU Langone Medical Center who was not involved with the study, acknowledges that the authors "present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD."

In the meantime, however, there are "well-established health risks of TCE exposure, including development of various cancers," she said. Therefore, the authors' goals appear to be educating the public about known health risks; working to clean up known sites of contamination; and advocating to ban future use of TCE.

These goals "do not need to wait for [proof of] firm causation between TCE and PD," she stated.

Dorsey reports he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications and owns stock in several companies. The other authors' disclosures can be found in the original paper. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.

J Parkinsons Dis. Published online March 14, 2023. Full text

Batya Swift Yasgur, MA, LSW is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).

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