# Treatment of Duchenne Muscular Dystrophy with the Muscle Calcium Pump

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $616,487

## Abstract

Project Abstract
Cytosolic calcium overload is a pivotal pathogenic mechanism in Duchenne muscular dystrophy (DMD), a
lethal debilitating muscle disease. Elevated cytosolic calcium triggers proteolysis and muscle cell death.
Sarco/endoplasmic reticulum calcium ATPase 2a (SERCA2a) is the calcium pump that removes cytosolic
calcium in both skeletal and cardiac muscle. Unfortunately, the SERCA2a level is reduced in DMD muscle.
Enhancing SERCA2a expression may restore cytosolic calcium homeostasis and reduce muscle disease in
DMD. To explore this novel therapy, we generated an adeno-associated viral vector (AAV) to express
SERCA2a. We injected the AAV SERCA2a vector via the tail vein to mdx mice, the most commonly used
DMD model. Treatment significantly improved skeletal muscle force and heart function. To translate our
findings to large mammals, we propose to test AAV SERCA2a therapy in symptomatic DMD dogs, the best
large animal model for DMD. We hypothesize that AAV SERCA2a therapy can significantly enhance cytosolic
calcium removal and ameliorate skeletal muscle and heart disease in dystrophic dogs. To test this hypothesis,
we will pursue two specific aims. In our first aim, we will test whether regional AAV SERCA2a therapy can
ameliorate limb muscle disease and improve function. Regional therapy holds potential to improve the life
quality of patients, especially these at late-stage. In our second aim, we will test whether systemic AAV
SERCA2a therapy can lead to bodywide improvement in affected dogs. DMD affects all muscles in the body.
Whole body muscle therapy will result in maximal protection. In summary, our proposed studies will generate
the critical large animal data for a future human trial.

## Key facts

- **NIH application ID:** 10000043
- **Project number:** 5R01AR070517-05
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Dongsheng Duan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $616,487
- **Award type:** 5
- **Project period:** 2016-07-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000043

## Citation

> US National Institutes of Health, RePORTER application 10000043, Treatment of Duchenne Muscular Dystrophy with the Muscle Calcium Pump (5R01AR070517-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10000043. Licensed CC0.

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