# Oxidized microRNAs identification in ALS patient samples

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $54,744

## Abstract

PROJECT SUMMARY
 A growing body of evidence implicates oxidative stress in Amyotrophic Lateral Sclerosis (ALS).
Nevertheless, it is currently unknow if it is a cause, a by-product or a consequence of disease. The effects of
oxidative stress on cellular damage caused by reactive oxygen species is usually attributed to modifying proteins
and DNA. However, RNA oxidation occurs ten times more often than DNA oxidation. Importantly, high levels of
oxidized RNA are detected in relevant neuronal tissues of patients with ALS while, mouse models of ALS show
increased RNA oxidation in motor neurons of the spinal cord at an early pre-symptomatic stage. What remains
lacking, however, is an understanding of the functional relationship between RNA oxidation and ALS onset and
progression. Thus, there is a critical need to identify which motor neuron transcripts are oxidized in early, pre-
symptomatic stages of ALS and how this dysregulation contributes to neuronal death and other molecular
hallmarks of ALS. I believe that there are many, yet to be discovered, RNA Binding Proteins (RBPs) that are
crucial for controlling the fate of oxidized RNAs. We hypothesize that RNA oxidation drives motor neuron
degeneration in ALS by dysregulating proper RNA processing by RBPs. We will test this hypothesis by (1)
elucidating, in iPSC-derived motor neurons, the RNA targets and the consequences of depletion of known RBPs
that interact with oxidized RNAs and identify novel ones; (2) identifying and comparing oxidized RNAs in iPSC-
derived motor neuron models; and investigating, at a single cell resolution, the effects of RNA oxidation on
transcription, translation and RBP-RNA interactions in iPSC-derived spinal organoid ALS models. This project
will generate the foundational methods and insights to enable early, pre-symptomatic-stage diagnostic
approaches and interventions to reduce RNA oxidation levels in high-risk individuals.

## Key facts

- **NIH application ID:** 11090259
- **Project number:** 3R00NS121511-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Isaac Alexander Chaim
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $54,744
- **Award type:** 3
- **Project period:** 2024-07-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11090259

## Citation

> US National Institutes of Health, RePORTER application 11090259, Oxidized microRNAs identification in ALS patient samples (3R00NS121511-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11090259. Licensed CC0.

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