# Spinal Subpial Gene Delivery for Treatment of Amyotrophic Lateral Sclerosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $617,646

## Abstract

Project Summary
Current clinical data show that there is no effective treatment of sporadic or any form of hereditary amyotrophic
lateral sclerosis. Our previous work and preliminary data show that two-level spinal subpial delivery of AAV9-
shRNA-SOD1 vector is highly effective in blocking the disease development or progression if treatment is
initiated in adult pre-symptomatic or early-symptomatic ALS mouse (SOD1G37R) or ALS rat (SOD1G93A). This
functionally-defined protection correlated with a high degree of spinal α-motoneuron, interneuron and white
matter preservation, and silencing of ALS-causing mutated SOD1 gene expression seen in the entire length of
the spinal cord in both mouse and rat ALS models. At present no long post-treatment survival periods have been
systemically studied as yet. In our proposed studies, using the SOD1G93A rat model, we will define: i) The
maximum duration of clinically defined treatment effect after subpial delivery of AAV9-shRNA-SOD1 in adult pre-
symptomatic or early symptomatic SOD1G93A rats. ii) In a separate cohort of wild-type SD rats and pigs, a SOD1
silencing vector will be used to study the toxicity threshold after endogenous SOD1 gene silencing. The aims,
research design, and methods have been developed to focus on mutated SOD1 gene-induced ALS, and to
generate comprehensive efficacy and initial safety data to support future pre-clinical development of this
treatment approach, as a novel therapeutic strategy for augmenting mutated SOD1 gene-caused ALS.

## Key facts

- **NIH application ID:** 10880697
- **Project number:** 5R01NS130104-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** MARTIN MARSALA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $617,646
- **Award type:** 5
- **Project period:** 2022-09-28 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880697

## Citation

> US National Institutes of Health, RePORTER application 10880697, Spinal Subpial Gene Delivery for Treatment of Amyotrophic Lateral Sclerosis (5R01NS130104-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10880697. Licensed CC0.

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