# Potential therapies for the muscular dystrophies

> **NIH NIH P50** · UNIVERSITY OF FLORIDA · 2021 · $358,894

## Abstract

Abstract
The multifaceted pathologies associated with muscular dystrophies, particularly Duchenne muscular dystrophy
(DMD), represent major challenges to the development and clinical implementation of effective therapeutics for
these diseases. AAV gene therapy, delivering a µdystrophin construct to all striated muscles, is now poised to
bring about transformative alterations in DMD disease course. However, a number of significant hurdles
remain before it can be successfully applied to all DMD patients. There is a need to prevent and resolve
fibrosis in order to improve the efficiency of delivery and enable the use of lower viral doses. Additional
therapeutics may be needed to slow the skeletal muscle disease progression that remains after µdystrophin
therapy. Perhaps the most critical issue facing AAV gene therapy for DMD is that current µdystrophin designs
and vector doses are optimized for skeletal muscle without sufficient evaluation of the potential impact on
cardiac muscle function. The aims of this project are motivated by our observations in the D2.mdx model of
DMD: (1) µdystrophin overexpression is highly beneficial for skeletal muscle, but it does not completely prevent
progressive fibrosis, especially in the diaphragm; (2) AAV delivery is markedly less efficient in highly fibrotic
muscle; (3) µdystrophin fails to rescue the heart; and (4) countermeasures can compensate for deficiencies of
the µdystrophins, and may form the basis of combination therapies for DMD.

## Key facts

- **NIH application ID:** 10288583
- **Project number:** 2P50AR052646-16A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** H Lee Sweeney
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $358,894
- **Award type:** 2
- **Project period:** 2005-09-25 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288583

## Citation

> US National Institutes of Health, RePORTER application 10288583, Potential therapies for the muscular dystrophies (2P50AR052646-16A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10288583. Licensed CC0.

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