# Understanding and Improving Therapies for the Muscular Dystrophies through Noninvasive Biomarkers

> **NIH NIH P50** · UNIVERSITY OF FLORIDA · 2021 · $325,031

## Abstract

Project Summary/Abstract
Project 3 serves as the translational project for this Center application, complementing preclinical
therapeutic development in Projects 1 & 2. Building on our expertise in noninvasive magnetic
resonance (MR) biomarker development, we will examine metabolic remodeling in patients with
Duchenne muscular dystrophy (DMD) treated with emerging therapies and the most common
form of limb girdle muscular dystrophy, LGMDR1 (also referred to as LGMD2A). Effective clinical
management in both forms of muscular dystrophy will likely require multiple concomitant
treatment strategies, which can have positive or negative metabolic consequences.
Our central hypothesis is that disease progression in dystrophic muscle is associated with
metabolic remodeling, which can be modulated by different pharmacologic strategies and
exploited to provide novel biomarkers for therapeutic development. Obesity and an increase in
metabolic risk factors have been recognized as hallmark features of DMD, exacerbated by
chronic use of glucocorticoid steroids (GC). Micro-dystrophin (µDys) gene therapy has emerged
as a promising treatment strategy, with significant restoration of dystrophin protein and
favorable clinical data in early stage clinical trials. However, due to the truncated nature of the
µDys protein, impaired nNOS localization and/or aberrant calcium handling are expected to
persist post gene therapy (Focus of Project 1). In addition, immune response management
requires concomitant chronic use of GC. To gain further insight into the effects of µDys gene
therapy in individuals with DMD, Aim 1 will examine MR biomarkers of muscle metabolism,
inflammation, and composition in DMD patients treated with AAV-µDys. The disease course will
be characterized in multiple muscles and compared with the disease trajectory in untreated, age
matched DMD (historical data) and Becker muscular dystrophy patients; the latter patients are
expected to mirror the phenotypic profile post-gene therapy. In Aim 2, we will leverage
extensive natural history data/biosamples and access to ongoing clinical studies to examine the
effect of different GC dosing regimens (Synergy with Project 2) and chronic GC exposure on
both muscle and whole-body metabolism in DMD. Finally, in Aim 3, we will extend our
biomarker work to LGMDR1, an underserved patient population in therapeutic development. We
will use a combination of MR biomarkers and metabolomics to characterize the natural history of
disease progression and help identify therapeutic targets and novel biomarkers for future clinical
trials.

## Key facts

- **NIH application ID:** 10288585
- **Project number:** 2P50AR052646-16A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** GLENN WALTER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $325,031
- **Award type:** 2
- **Project period:** 2005-09-25 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288585

## Citation

> US National Institutes of Health, RePORTER application 10288585, Understanding and Improving Therapies for the Muscular Dystrophies through Noninvasive Biomarkers (2P50AR052646-16A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10288585. Licensed CC0.

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