# Mechanisms of corticosteroids in dystrophic cardiomyopathy

> **NIH NIH R01** · CHILDREN'S RESEARCH INSTITUTE · 2023 · $76,046

## Abstract

Corticosteroids provide an important drug class for treatment of numerous forms of heart failure and chronic
inflammation, together affecting over 432 million people. In Duchenne muscular dystrophy (DMD), drugs that
target corticosteroid receptors are used to treat heart and skeletal muscle. Our lab developed a first-in-class
dissociative steroid that shows efficacy as both a heart-protective and anti-inflammatory drug. Our work in the
mdx mouse model of DMD was critical for moving this drug, vamorolone, into DMD clinical trials (now in Phase
2b). In early cell and animal studies, vamorolone showed anti-inflammatory efficacy while avoiding key side
effects. Subsequently, we discovered new readouts of drug activity and important impacts of corticosteroids on
dystrophic hearts. Cardiomyopathy is a feature of both the severe muscle disease DMD (caused by loss of
dystrophin) and the milder muscle disease Becker muscular dystrophy (dystrophin in-frame deletions). As
promising new therapies are being developed that seek to convert severe DMD genotypes into milder Becker-
like phenotypes, importance of treating dystrophic hearts should grow because cardiomyopathy is the leading
cause of Becker mortality. Moving forward, it will be important to address knowledge gaps regarding the
mechanisms of selective steroids, roles of specific steroid receptors in the heart, and impacts of steroids on
Becker-like hearts. This knowledge is important because cardiomyopathy is a leading cause of DMD mortality
and current corticosteroids have problematic safety profiles.
Our long-term goal is to dissect mechanisms of steroid signaling that can be selectively targeted to improve
treatment of chronic pediatric diseases. This can greatly improve outcomes for DMD in a way that also impacts
much larger groups of heart, muscle and inflammatory diseases. The objective of this grant is to dissect
mechanisms of corticosteroid receptors that impact dystrophic cardiomyopathy. The advanced expertise and
tools developed by our lab place us in a unique position to accomplish this using a combination of cell culture,
receptor mutation, tissue-specific knockout, micro-dystrophin gene therapy, and animal model systems. We
propose the central hypothesis that 11β-hydroxysteroid agonists activate receptor transactivation to drive
progression of dystrophic heart pathology. Our rationale is that identifying corticosteroid mechanisms which
can be selectively targeted will provide a basis for the improved treatment of DMD and other diseases with
heart failure or chronic inflammation.

## Key facts

- **NIH application ID:** 10669137
- **Project number:** 5R01HL153054-04
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Christopher Ryan Heier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $76,046
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-11-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10669137

## Citation

> US National Institutes of Health, RePORTER application 10669137, Mechanisms of corticosteroids in dystrophic cardiomyopathy (5R01HL153054-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10669137. Licensed CC0.

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