# MR Assessment of Bioenergetics and Microvascular Function in Dystrophic Muscle

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $335,912

## Abstract

Project Summary
The overall objective of this project is to evaluate the potential of novel magnetic resonance imaging (MRI) and
localized 31phosphorus-magnetic resonance spectroscopy (31P-MRS) measures of bioenergetics and
microvascular function to monitor disease progression and treatment in dystrophic muscle. Duchenne
muscular dystrophy (DMD) is characterized by progressive muscle weakness, deteriorating functional
capabilities, loss of independence, and early death. Muscles in children with DMD are deficient in dystrophin,
which is accompanied by a lack of sarcolemma-localized neuronal nitric oxide synthase (nNOS). Although
there is no cure for DMD, a number of promising therapies are being developed and evaluated, and young
boys are predominantly being targeted as subjects. However, reliable markers of disease progression are
lacking, particularly in young boys. Recent studies have shown considerable promise in muscle energetic
status measured with 31P-MRS as an early marker of pathology in dystrophic muscle. The cause of these
energetic disturbances (e.g., reduced phosphocreatine) is poorly understood, as well as the response to
disease progression and treatment. The lack of neuronal nitric oxide synthase (nNOS) in dystrophic muscle
has been attributed to cause reduced blood flow during and following skeletal muscle contractions in DMD, and
may also contribute to the reported energetic perturbations and increased susceptibility to damage in
dystrophic muscle. In aim 1 we will use a murine model (mdx) to provide insight into the relationship between
energetic status and microvascular function in dystrophy using high resolution MR. In aim 2, we will establish
the effects of treatment with an established AAV-microdystrophin vector with and without the nNOS binding
domain. Finally, in aim 3, we will apply these methods to the lower extremity of boys with DMD and unaffected
controls in a range of ages using a cross sectional design. MR measures will evaluate 1) heterogeneity of
energetic status among muscles using 31P 2D chemical shift imaging and 2) microvascular function using MRI
blood oxygenation-level dependent (BOLD) contrast and arterial spin labeling (ASL). Furthermore, we will test
the day-to-day variability of these measures in DMD and controls. The overall hypothesis of this project is that
localized MR measures of bioenergetics and microvascular function will enable early detection of disease
pathology at a young age, will be responsive to disease progression, and will be effective in monitoring
improvements with treatment in dystrophic muscle. We anticipate that the results will lead to reproducible
methods that can be implemented to evaluate potential treatments targeted at DMD and other neuromuscular
diseases.

## Key facts

- **NIH application ID:** 9989793
- **Project number:** 5R01AR070101-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Sean C Forbes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,912
- **Award type:** 5
- **Project period:** 2016-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989793

## Citation

> US National Institutes of Health, RePORTER application 9989793, MR Assessment of Bioenergetics and Microvascular Function in Dystrophic Muscle (5R01AR070101-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989793. Licensed CC0.

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