# Metabolic Alteration in Presymptomatic and Symptomatic ALS Study (MAPS ALS Study)

> **NIH NIH K23** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $229,635

## Abstract

Project Summary/Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating disease with upper and lower motor neuron dysfunction
and degeneration leading to progressive weakness and death due to dysphagia and respiratory failure. There
is an urgent need to develop effective treatment to stop or reverse the progression. However, this has proven
to be challenging due to an incomplete understanding of the pathogenesis and delay in the diagnosis of ALS.
There are data supporting biomarkers of mitochondrial dysfunction, energy expenditure (EE) and body
weight/composition as early indices of incident clinical disease. Identification of these markers could facilitate
earlier intervention to prevent or delay disease progression as well as provide information on therapeutic
targets in individuals at genetic risk for ALS. I hypothesize that 1) the plasma lipid mediators (lipidome) can
accurately differentiate ALS, and primary lateral sclerosis (PLS) subjects from controls 2) body
weight/composition and EE differ between C9orf72+ ALS, presymptomatic C9orf72 mutation carriers
(C9orf72+ Pre-ALS) participants and controls 3) certain metabolic profiles will predict symptom onset in
C9orf72+ Pre-ALS participants. In this proposed study, I will 1) investigate the plasma lipidome profile of ALS
and PLS subjects to identify lipid mediators as diagnostic biomarkers in motor neuron disease, 2) evaluate
body weight/composition and EE in C9orf72+ ALS and Pre-ALS to measure changes in energy metabolism
in advance of and through the course of disease, and 3) follow a cohort of C9orf72+ Pre-ALS participants
annually to track the emergence of ALS symptoms and signs to determine if certain metabolic profiles predict
symptom onset in this genetically predisposed population. Successful completion of this project would provide
key data to 1) establish the lipidome profile as a diagnostic biomarker for ALS and PLS, and 2) provide the
foundation for a prospective cohort study of C9orf72+ Pre-ALS individuals to determine if the lipidome profile
and metabolic markers (body composition, EE) could serve as a premonitory marker for the phenotypic
conversion from asymptomatic to symptomatic ALS. This K23 award will provide the support needed to
complete the proposed research and to further develop my expertise in three major scientific areas, 1)
expertise in lipidome data production and analysis, 2) expertise in metabolism and EE, and 3) mastery of
advanced statistical techniques for clinical applications. I will leverage the research training I receive in the
K23 to lead a longitudinal cohort study of pre-ALS participants to determine the relationship between
metabolic changes and clinical manifestations of ALS. My overarching goal is to identify early diagnostic
biomarkers and therapeutic targets for the development of an effective treatment to prevent or delay the
progression of ALS.

## Key facts

- **NIH application ID:** 10829479
- **Project number:** 5K23NS131586-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ikjae Lee
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,635
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829479

## Citation

> US National Institutes of Health, RePORTER application 10829479, Metabolic Alteration in Presymptomatic and Symptomatic ALS Study (MAPS ALS Study) (5K23NS131586-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10829479. Licensed CC0.

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