# Ablation of Non-Myogenic Progenitor Cells as a New Therapeutic Approach to Duchenne Muscular Dystrophy

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $149,234

## Abstract

Abstract
Duchenne muscular dystrophy (DMD) is a deadly genetic disease characterized by a lack of dystrophin
expression, resulting in progressive weakening and wasting of skeletal and cardiac muscles. Currently, there is
no cure for DMD. The approved hormonal treatments have side effects and delay the disease progression only
transiently. The emerging gene correction strategies, although effective in mouse models, are likely to be of limited
immediate value to patients due to issues associated with virus-mediated gene therapy. Therefore, new approaches
to suppress the disease progression are needed. Myogenic muscle progenitor cells (MPCs), also known as
satellite cells, become dysfunctional (reduced proliferation and differentiation capacities) as disease progresses,
coincidentally with reduced muscle regeneration, aggravating fatty infiltration, and fibrotic tissue accumulation in
skeletal muscle. Mesenchymal stromal cells (MSCs) are non-myogenic progenitors of fibroblasts and adipocytes.
We and others have reported that MSCs get activated during the disease progression in DMD and turn into
fibroadipogenic progenitors (FAPs) that proliferate, induce MPC dysfunction and contribute to muscle pathology.
Our preliminary data indicates that FAPs express markers of adipocyte progenitors, also known as adipose
stromal cells (ASCs), the MSCs derived from fat tissue, suggesting ASCs as a source of FAPs. The goal of this
application is to test whether DMD pathogenesis can be delayed via depletion of MSC-derived FAPs in the
mouse model. In Aim 1, an inducible genetic ablation of proliferating MSC will be performed using a suicide
transgene. In Aim 2, pharmacological ablation will be performed with a hunter-killer peptide targeting ASCs. We
will test if DMD progression, measured as MPC dysfunction, fatty infiltration, fibrotic tissue accumulation, and
the resulting loss of skeletal muscle function, can be suppressed by these experimental treatments. We predict
that ablation of FAPs derived from MSCs/ASCs from the dystrophic milieu will delay MPC depletion and DMD
progression. Information obtained from these studies will help develop new therapeutic approaches for treating
muscular dystrophy.

## Key facts

- **NIH application ID:** 10013124
- **Project number:** 5R21AR074132-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Johnny Huard
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $149,234
- **Award type:** 5
- **Project period:** 2019-09-09 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013124

## Citation

> US National Institutes of Health, RePORTER application 10013124, Ablation of Non-Myogenic Progenitor Cells as a New Therapeutic Approach to Duchenne Muscular Dystrophy (5R21AR074132-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10013124. Licensed CC0.

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