# Developing nicorandil and companion biomarkers for DMD cardiomyopathy therapy

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $443,780

## Abstract

The dystrophin gene mutations found in Duchenne muscular dystrophy (DMD) contribute to progressive
weakness and failure of skeletal and cardiac muscles. Steroid treatment and advances in respiratory therapy
have increased the life expectancy for DMD by 10 years; however, these patients now succumb to complications
associated with cardiomyopathy in their late twenties and early thirties. Currently, there is no cure or selective
treatment for the ultimately fatal dystrophin-deficient cardiomyopathy. The mechanisms underlying dystrophin-
deficient cardiomyopathy are not fully established, but significant amounts of data indicate that oxidative stress,
altered calcium signaling, and mitochondrial damage contribute to dystrophin-deficient cardiomyocyte
malfunction and death. Using human DMD induced pluripotent stem cell derived cardiomyocytes, and the
muscular dystrophy (mdx) mouse model, we have shown that the pharmaceutical nicorandil protects against
dystrophin-deficiency in the heart and cardiomyocyte. Nicorandil also modulates the levels of microRNAs
secreted from the DMD-cardiomyocytes encapsulated in extracellular vesicles. Here we are further developing
nicorandil as a therapeutic to treat DMD cardiomyopathy and to develop miR-related biomarkers to monitor
therapeutic efficacy. We will test whether nicorandil protects against the development of cardiomyopathy in the
muscular dystrophy mouse, modulates miR levels in secreted extracellular vesicles, and whether nicorandil-
responsive miRs modulate reactive oxygen species formation, calcium cycling, and mitochondrial function in
dystrophin-deficient cardiomyocytes. Results from these studies will be clinically relevant and may impact the
development of new treatments for this devastating disease.

## Key facts

- **NIH application ID:** 9869027
- **Project number:** 5R01HL134932-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Michael William Lawlor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $443,780
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869027

## Citation

> US National Institutes of Health, RePORTER application 9869027, Developing nicorandil and companion biomarkers for DMD cardiomyopathy therapy (5R01HL134932-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9869027. Licensed CC0.

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