# Presynaptic degeneration in ALS mouse neuromuscular junctions and a targeted therapeutic approach

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $154,870

## Abstract

Project Summary/Abstract:
Amyotrophic Lateral Sclerosis (ALS) in a neurodegenerative disease that results in the
progressive deterioration and loss of function of the motor neurons leading to paralysis. Studies
indicated that synaptic transmission at neuromuscular junctions (NMJs) is reduced in early
stages of the disease NMJ denervation occurs while neuronal cell bodies in the spinal cord
remain intact. This observation in which NMJ dysfunction precedes motor neuron death
suggests ALS is a “dying-back” neuropathy. The etiology of ALS is currently unknown, and no
effective treatment exists for ALS to improve neuromuscular transmission, which would improve
quality of life for ALS patients by increasing neuromuscular strength and may prolong lifespan.
Therefore, my long-term goal is to identify a new intervention method to improve neuromuscular
function by reducing dying-back neuropathy in ALS. Our strategy is to test a novel Cav2-specific
voltage-gated calcium channel gating modifier that we have developed (GV-58), a
pharmacological intervention that enhances the activation of the neuromuscular system. GV-58
is innovative because it is based on a target that has not been tested previously for ALS, namely,
strengthening synaptic transmission to maintain NMJ innervation. Here, we propose to
characterize neuromuscular weakness at different stages of disease progression in SOD1G93A
ALS model mice and test the effects of GV-58 both acutely and after daily chronic administration.
This is to determine if GV-58 can play a role in delaying disease onset or in recovery of NMJ
strength and whether that can lead to improved SOD1G93A mouse survival.

## Key facts

- **NIH application ID:** 10575500
- **Project number:** 1R03NS130425-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Yomna Badawi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $154,870
- **Award type:** 1
- **Project period:** 2022-09-19 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10575500

## Citation

> US National Institutes of Health, RePORTER application 10575500, Presynaptic degeneration in ALS mouse neuromuscular junctions and a targeted therapeutic approach (1R03NS130425-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10575500. Licensed CC0.

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