# Alternative delivery of adeno-associated virus therapeutic vector for the treatment of neuromuscular disorders

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $487,911

## Abstract

Project Summary/Abstract
Gene therapy using Adeno-associated viral vectors (AAVs) is a very promising tool for treatment of many mus-
culoskeletal disorders. Multiple strategies are currently in clinical trials using either intramuscular (IM) or intra-
vascular (IV) delivery of the vector. Despite promising initial results, the effect is only local for IM treatment or
requires a large amount of virus for IV delivery since the dose is calculated per kilogram body weight. While
suitable for small children, AAV therapies become more problematic for the treatment of teenagers or adults
due to high vector production costs as well as potential safety concerns at very high doses. In addition, many
muscular disorders also display pathology of the nervous system (NS). Therefore, efficient simultaneous tar-
geting of both the muscle and NS would likely enhance therapeutic outcomes. In this project, our objective is to
test the efficiency of delivering the gene therapy vectors through cerebral spinal fluid (CSF) instead of IV injec-
tions in order to target both muscle and nervous system. This delivery technique is innovative and based on
our preliminary data, which supports our hypothesis that CSF delivery of the vector could substantially reduce
the required amount of viral vector in order to target both muscle and NS as higher viral vector amount is re-
quired for transducting both NS and muscles using IV. In Aim 1, we will determine optimal CSF dosing in wild
type mice. We will also test CSF dosing in a mouse model of Duchenne Muscular Dystrophy (the Dup2 mouse
model) to ensure that muscle damage does not alter vector spreading. In Aim 2, we will use the Dup2 mouse
model to assess the extent to which CSF delivery of a therapeutic vector (AAV9.ACCA) can achieve therapeu-
tic effects. The experiments proposed in Aim 3 will compare the ability of IV and CSF delivery routes to target
muscles and NS in non-human primates when using a tenfold lower dose compared to previous studies using
IV delivery. This collaborative project will be achieved thanks to the combined expertise of the several laborato-
ries: Dr. Wein who has generated both the AAV9.ACCA vector and the Dup2 mouse model used in this study;
Dr. Flanigan, an expert in gene therapy and neuromuscular disorders, and Drs. Burghes, Arnold and Meyer,
world-renown and highly successful leaders in gene therapy and CSF delivery techniques. The impact of this
study cannot be overstated, as the results would be of high interest globally for a very large patient community,
as well as researchers working on other neuromuscular disorders. The results from this study could be applied
to many neuromuscular disorders.

## Key facts

- **NIH application ID:** 9993344
- **Project number:** 5R01AR073908-02
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Kathrin Meyer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $487,911
- **Award type:** 5
- **Project period:** 2019-08-09 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993344

## Citation

> US National Institutes of Health, RePORTER application 9993344, Alternative delivery of adeno-associated virus therapeutic vector for the treatment of neuromuscular disorders (5R01AR073908-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9993344. Licensed CC0.

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