As 2023 drew to a close, the Parkinson’s community worked together to bring important legislation to the attention of policymakers for consideration. Thanks to the voices of people with Parkinson’s, as well as caregivers, advocates, clinicians, researchers, and industry stakeholders, the National Plan to End Parkinson’s Act was successfully passed in the US House of Representatives.

CND Life Sciences’ CEO, Richard Morello, and Chief Medical Officer, Dr. Todd Levine, were on The Hill during this effort. Dr. Levine commented: “We are deeply appreciative of the time provided by legislators in discussing the allocation of federal resources for the Parkinson’s disease community. We look forward to CND’s continued engagement with lawmakers in the development of policies that will support the work of all stakeholders focused on advances in the diagnosis, prevention, and treatment of Parkinson’s disease and related conditions.”

A key component of this bill and ongoing advocacy work involves research on risk factors for Parkinson’s disease (PD) and potential for prevention of PD. This article focusing on environmental toxins is a continuation of our Insights series on risk factors for Parkinson’s disease.

Environmental toxins are increasingly recognized as a major risk factor for the development of Parkinson’s disease. The increasing incidence of PD is thought to parallel increasing industrialization and associated exposures to environmental toxins. Environmental toxins have been shown to trigger inflammation, mitochondrial damage, and oxidative stress. Due to specific vulnerability of dopaminergic cells to these factors, environmental toxins are implicated in dopaminergic neuronal cell death associated with the development of Parkinson’s disease.

Pesticide exposure has long been linked to Parkinson’s, and pesticides are associated with neurotoxicity in several ways. Paraquat, rotenone, and glyphosate are just a few among many culprits that have been identified through epidemiologic studies as toxins that increase Parkinson’s risk, particularly among those with occupational exposures, such as agricultural workers.

Pesticides have been shown to impair intestinal barrier integrity, leading to gut and systemic inflammation, with microbial metabolites mediating multiple inflammatory and metabolic cascades. This results in accumulation of misfolded alpha-synuclein and neurodegeneration. An additional mechanism of neurotoxicity separate from inflammation includes free radical production. Free radicals cause direct cellular damage and affect neuronal clearance of damaged or degraded proteins, further increasing cellular injury.

One study found that 23% of cases of Parkinson’s in both men and women were associated with exposure to pesticides, herbicides, or military-related chemical exposures. Agent Orange and trichloroethylene (TCE) are toxins known to affect Veterans, with an increased incidence of PD in this population. Agent Orange was a powerful herbicide used by US military forces during the Vietnam War to eliminate forest cover and crops. The deadly chemical dioxin, a component of Agent Orange, has been associated with Parkinson’s disease.

TCE is an industrial solvent that has been found in food, air, and water, and is increasingly recognized as one potential cause for the exponential increase in cases of Parkinson’s disease observed over the past few decades. TCE was demonstrated to be present in contaminated drinking water at Camp Lejeune, and one study found that Veterans exposed to unsafe levels of TCE had a 70% higher risk for developing PD decades after exposure.

Another major environmental etiology for a multitude of health problems is fine particulate matter associated with air pollution. Fine particulate matter has been shown to cross the blood-brain barrier and can generate an immune response, observable by assessing blood and cerebrospinal fluid levels of cytokines. These cytokines are inflammatory signaling mediators, promoting the swelling of tissue, leading to cell death and vascular damage.

Researchers at Barrow Neurological Institute were able to confirm a strong nationwide association between incident PD and fine particulate matter using geospatial analytical techniques. The study noted that regional differences in Parkinson’s disease incidence might reflect regional differences in the composition of particulate matter, with some areas containing more toxic components than others.

Environmental exposures are increasingly recognized as risk factors in the pathogenesis of Parkinson’s disease, and many studies have shown how these exposures are contributing to the increasing incidence of Parkinson’s. The voices of the Parkinson’s community will continue to be instrumental in efforts aimed at prevention of PD. Reducing toxic environmental exposures that contribute to Parkinson’s, and potentially so many other conditions, will depend on evidence-based regulations developed in the interest of public health. At CND, we will continue to support these efforts, and eagerly await the day when “The National Plan to End Parkinson’s Act” becomes law.

References: