# Using motor neuron specific miRNA to understand and develop novel therapeutics for motor neuron disease

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $448,083

## Abstract

Project Summary
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder characterized by loss of
motor neurons in the brain and spinal cord, and death from failure of respiratory muscles 3-5 years after
diagnosis. The only FDA approved drug for ALS, Riluzole, is only marginally effective. A key to
developing effective therapies is to understand why the disease affects only motor neurons. We
hypothesize that understanding distinct expression profiles of motor neurons will inform their selective
vulnerability to ALS, enabling the development of novel biomarkers and therapeutics for both sporadic
and genetically inherited ALS, frontotemporal dementia (FTD)-associated ALS, and other motor neuron
diseases. During the prior award period, we developed a powerful approach to studying microRNAs
(miRNAs), which are key regulators of physiological and pathological processes, and generated the first
ever profile of miRNAs enriched in motor neurons in ALS rodent and human spinal cord. Consistent
with our hypothesis that a motor neuron-enriched miRNA profile would inform motor neuron disease
mechanisms, we defined a pharmacoresponsive miRNA biomarker in ALS that reports on motor neuron
loss and dysfunction in animal models. We propose to further develop this biomarker by elucidating the
impact of miRNA release on ALS disease progression through non-cell autonomous mechanisms,
assessing miRNA release from motor neurons and presence in CSF during disease in ALS models and
human patients, and determining whether miRNAs define susceptibility of specific motor neuron pools,
as not all motor neurons are equally susceptible to degeneration in ALS and ALS-FTD. With our lab's
prior experience with motor neuron degeneration models and miRNAs, strong local collaborations for
bioinformatics, outstanding neurodegenerative disease colleagues, and PI's record of successful
translation of therapeutics into humans, our team is uniquely positioned to carry out these studies. Our
motor neuron specific miRNA approach has a high likelihood of providing insight into the mechanisms
underlying motor neuron degeneration and may also be the foundation for a novel therapy for ALS,
FTD, and other motor neuron diseases.

## Key facts

- **NIH application ID:** 9872216
- **Project number:** 5R01NS078398-09
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** TIMOTHY M. MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,083
- **Award type:** 5
- **Project period:** 2012-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872216

## Citation

> US National Institutes of Health, RePORTER application 9872216, Using motor neuron specific miRNA to understand and develop novel therapeutics for motor neuron disease (5R01NS078398-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872216. Licensed CC0.

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