ALS Risk and Survival: Does High Pesticide Exposure Have an Impact?

Exposure to persistent organic pollutants (POP) increases the risk of developing amyotrophic lateral sclerosis (ALS), and exposure to an increased number of POPs is associated with shorter ALS survival. These are the findings of a study published in the Journal of Neurology, Neurosurgery, and Psychiatry.

Exposure to pesticides, metals, and other environmental factors have been implicated in the development of ALS. Researchers must identify these causative environmental exposures, so that targeted therapies can be developed to treat ALS or prevent its onset.

In a case control cohort study, a team of researchers at the University of Michigan analyzed plasma samples collected from 164 patients with ALS and 105 control individuals. They sought to replicate results from their previously published study that indicated that POPs were associated with ALS risk and survival.

The researchers used isotope dilution with triple quadrupole mass spectrometry using an updated method combined with gas chromatography to detect 3 classes of POPs — polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) — at the organic chemistry laboratory at the University of Michigan. They then calculated the environmental risk score based on a summation of total exposures detected.

Per plasma sample analysis, compared with control participants, patients with ALS demonstrated statistically significant exposure to 8 of 22 PCBs and 7 of 10 OCPs, whereas exposure to 4 PBDEs did not significantly differ between the groups.

ALS risk was strongly associated with an exposure mixture consisting of the OCPs alpha-hexachlorocyclohexane (odds ratio [OR], 1.167), hexachlorobenzene (OR, 1.14), trans-nonachlor (OR, 1.03) and cis-nonachlor (OR, 1.34). The combined effects of these 4 OCPs increased ALS risk from the 25^th to the 75^th percentile according to the environmental risk scores compared to the control population (OR, 2.58; P <.001).

Exposure to 24 out of the 36 studied POPs negatively impacted ALS survival, particularly exposures to PBDE-47 and trans-nonachlor (both P <.05). The cumulative effect of all 36 POPs corresponded to shorter ALS survival rate (hazard ratio [HR], 1.65; 95% CI, 1.23-2.23; P =.001) based on quartiles of exposure according to the Environmental Risk Score.

Compared with individuals with ALS in quartile 1 with the least amount of POPs exposure, those with ALS in quartile 4, who therefore were exposed to more POPs, demonstrated shorter survival rates (HR, 2.31; 95% CI, 1.30-4.13; P =.005).

“These data continue to support POPs as important factors for ALS risk and progression and replicate findings in a new cohort,” the researchers concluded. “Assessments of POPs in non-Michigan ALS cohorts are encouraged to better understand the global effect and the need for targeted disease risk reduction strategies.”

Study limitations included the small sample size, the single-center and cross-sectional nature of the study design, potential bias due to compensation for control participation, and a use of an updated method of detecting POPs, which did not exactly replicate methods used in the previous study and potentially may alter results.

Disclosures: Several study authors declared patents for ALS therapeutics. Please see original source for full list of disclosures.