# Metabolomic Signatures Linking ALS to Persistent Organic Pollutant Exposures

> **NIH ALLCDC R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $530,000

## Abstract

ABSTRACT
ALS is a progressive and fatal neurodegenerative disease with complex unknown pathogenesis. Recent
evidence supports a gene-time-environment hypothesis whereby environmental exposures trigger
neurodegeneration when superimposed on a genetic risk profile. Supporting this premise, long-term adverse
environmental exposures are linked to ALS risk, environmental pollutant exposures strongly correlate with ALS
prevalence, and we have shown that persistent organic pollutants (POPs), in particular measured
organochlorine pesticide and reported pesticides, exposures strongly increase ALS risk in a subset of ALS
patients from Michigan. Therefore, there is a critical need to understand how the “ALS exposome,” defined as
the lifetime of environmental exposures, contributes to ALS risk and drives disease pathogenesis. In this
proposal, we will harness the power of advanced metabolomics analyses to gain insight into the effect that
environmental exposures, such as residential and occupational exposures, have on the metabolome. As
metabolites reflect the impact of exogenous exposures on cellular processes, metabolomics has emerged as
the new frontier in exposome research. Our objective is to identify the metabolomics signatures that associate
with POP exposures and historical exposure risk factors, and associate with ALS progression. Our central
hypothesis is that POP exposures will lead to conserved metabolomic signatures in both plasma and central
nervous system (CNS) tissues. In Aim 1, we will use longitudinal plasma from ALS participants from our unique
University of Michigan ALS Patient Repository (UMAPR) with high versus low concentrations of POPs, as well
as plasma from geographically dispersed healthy control subjects, to better characterize how POP exposures
impact the metabolome. In Aim 2, we will evaluate whether metabolomic signatures are shared in ALS subjects
with similar occupational and residential exposure risks and whether these signatures diverge in subjects with
disparate risks in order to yield insights into causal mechanisms from prior epidemiologic studies. Finally, in
Aim 3, we will determine whether metabolomic signatures in ALS subject plasma are present in post-mortem
brain and spinal cord tissue and correlate with exposures. Overall, completion of these aims will establish a
comprehensive and rigorous dataset of metabolomic signatures associated with exposures to POPs, as well as
residential and occupational exposure risk histories across the disease course, to provide insight into the
influence of exposures on the onset and progression of ALS. These outcomes will have an important positive
translational impact by identifying modifiable factors that can mitigate the risk of developing ALS, uncovering
associated metabolic changes that represent biomarkers, and guiding future studies on new pathophysiologic
disease mechanisms.

## Key facts

- **NIH application ID:** 9973034
- **Project number:** 5R01TS000289-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Eva Lucille Feldman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2020
- **Award amount:** $530,000
- **Award type:** 5
- **Project period:** 2018-09-30 → 2021-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973034

## Citation

> US National Institutes of Health, RePORTER application 9973034, Metabolomic Signatures Linking ALS to Persistent Organic Pollutant Exposures (5R01TS000289-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9973034. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*