# Targeting the EphA4 in motor neuron disease: a structure-based approach

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2023 · $408,514

## Abstract

Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease that affects motor neurons.
Mutations in the gene SOD1 (superoxide dismutase 1) and in chromosome 9 seem the most prevalent
in those affected by the disease. Despite tremendous efforts aimed at identifying contributing factors
for ALS, the mechanisms underlying motor neuron death have not yet been fully elucidated and
consequently no effective treatment is currently available for ALS. Several clinical trials have been
initiated based on drugs selected from animal studies, however, these ultimately failed. Obviously
among the possible reasons for such failures is the lack of a proper drug target responsible for the
onset and progression of ALS and associated pharmacological tools. In this regard, numerous recent
studies clearly suggest that the EphA4 receptor tyrosine kinase is a potential drug target for ALS and
that targeting its ligand–binding domain may provide a possible avenue to novel and effective
therapeutics. Based on these premises, we have previously recently obtained the first bona fide EphA4
agonistic agents targeting its ligand binding domain, that are brain penetrant and show protection in
cellular and animal models of the disease. Our studies aimed at further optimizing and characterizing
this series will provide critical pharmacological tools and mechanistic insights on the role of the EphA4
modulation in the progression of ALS, and the data gathered in this study will be critical in supporting
the development of these agents into innovative targeted therapeutics for ALS.

## Key facts

- **NIH application ID:** 10736509
- **Project number:** 2R01NS107479-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Maurizio Pellecchia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $408,514
- **Award type:** 2
- **Project period:** 2018-07-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10736509

## Citation

> US National Institutes of Health, RePORTER application 10736509, Targeting the EphA4 in motor neuron disease: a structure-based approach (2R01NS107479-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10736509. Licensed CC0.

---

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