Amyotrophic lateral sclerosis (ALS) patients with higher levels of organic pollutants in their blood have reduced survival rates, according to a study conducted in Michigan.
A combination of genetic susceptibility and environmental risk factors may contribute to ALS. The team at the University of Michigan (U-M) ALS Center of Excellence had already shown that ALS patients have higher blood concentrations of persistent organic pollutants (POPs) — chemicals that remain for a long time in the environment and can spread via food or air — compared with healthy controls.
According to the Centers for Disease Control and Prevention, Michigan has one of the highest rates of ALS in the United States.
“We believe the answer may lie in the fact that Michigan is both an industrial and agricultural state,” Eva Feldman, MD, PhD, the study’s senior author and founder of U-M’s ALS Center of Excellence, said in a press release.
The widespread use of pesticides throughout the state’s farming history has resulted in their absorption in the ground and potential accumulation in rivers and the Great Lakes, both in sediments and fish. Michigan is also one of the greatest generators of toxic waste in the country. Man-made polychlorinated biphenyls (PCBs) were in use for electrical and hydraulic equipment until 1979. Similar to pesticides, these chemicals degrade slowly and may affect the environment for a long time.
“Once you’re exposed they may accumulate in your body. They get into the fat and can be released into the blood. We’re particularly concerned about ALS patients who have been exposed to higher amounts of these chemicals,” said Stephen Goutman, MD, the study’s lead author and the director of U-M’s ALS clinic.
However, understanding this risk has been challenging because of the difficulty in assessing the effects of distinct toxins, or their combination, on ALS onset or progression.
Therefore, the investigators used an environmental risk score (ERS) to evaluate the combined health effects of multiple pollutants on ALS survival as a way to provide insight on disease development and find modifiable risk factors.
A total of 167 adult patients (99, or 59.3%, were men) were included in the study, 119 of whom died during the study period. The median age at diagnosis was 60.9 years, and the median time from symptom onset to diagnosis was approximately one year. Among the participants, 28.7% had bulbar-onset — affecting the muscles of the head and neck — 33.5% had cervical-onset, and 37.7% had lumbar-onset ALS.
Also, 58.7% of the participants used non-invasive ventilation, and 10.8% had a family history of ALS. Riluzole (marketed as Rilutek by Sanofi, and as Tiglutik by ITF Pharma) was used by 116 of the 125 patients with a history of riluzole use.
The participants were divided into groups based on the concentration of pollutants in their blood. The group with the highest exposure to pollutants had a more than two-fold greater risk of mortality compared with those in the group with the lowest exposure. Among 23 compounds, the largest contributors to this risk score were PBDE 154 and PCB 118.
The median survival since ALS diagnosis was one year and 11 months in participants exposed to higher amounts of pollutants, and two years and six months in patients with the lowest exposure. The data also showed that a longer time between symptom onset and diagnosis significantly correlated with a lower rate of death.
“This study helps characterize and quantify the combined effects of POPs on ALS and supports the concept that environmental exposures play a role in disease pathogenesis,” the scientists wrote.
“Our research shows that environmental pollution is a public health risk that we believe must be addressed,” Feldman said.
Added Goutman: “Our concern is that not only are these factors influencing a person’s likelihood to get ALS, but also speeding up disease once they have it.”
According to Feldman, having clearer understanding of ALS development will help in the pursuit of a cure. The team will next test if the results are validated in a separate group of patients, which would establish the framework for a national study.
The investigators will also try to understand the metabolism and interactions of pesticides and pollutants in patients with ALS, and how specific chemicals correlate with disease onset, progression, and survival.
“If we can determine what these chemicals are doing to our organs, brains and motor neurons, then we can develop drugs to counteract those effects,” Goutman said.
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