# Sarcolipin in Duchenne Muscular Dystrophy

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $349,800

## Abstract

PROJECT SUMMARY
 Duchenne muscular dystrophy (DMD) is the most common lethal muscle wasting disease caused by
dystrophin deficiency. There is no effective treatment exists for this disease. The current therapeutic strategies
aimed to either replace or compensate for the lack of dystrophin also face major challenges such as targeting
cardiac and respiratory tissues and fibrosis. Therefore, recent studies are focused to prevent directly the
consequences of dystrophic process. Identification of such alternative therapies could complement the existing
strategies and enhance the effectiveness of treatment for this lethal disease. Abnormal intracellular Ca2+
overload is an important, early pathogenic event that initiates and perpetuates disease progression in DMD.
We recently found that sarcolipin (SLN), a potent inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase
(SERCA), is significantly increased in the skeletal and cardiac muscles of mouse models of DMD. Similar to
rodents, SLN levels are high in myoblasts and muscles of a canine model of DMD and in muscle biopsies of
DMD patients. In muscle cells, SERCA accounts for ≥ 70% of Ca2+ removal from the cytosol during excitation-
contraction coupling. Therefore in dystrophic muscles, chronic inhibition of SERCA by high-levels of SLN could
majorly contribute to the abnormal elevation of cytosolic Ca2+. Accordingly, reducing SLN expression is
anticipated to improve SERCA function, restore intracellular Ca2+ homeostasis and reduce dystrophic
pathology. Towards this goal, we genetically ablated SLN expression in mouse models of DMD. Preliminary
studies suggest that reduction in SLN expression is sufficient to improve SERCA function and mitigate DMD.
Here, we propose to evaluate the potential mechanisms by which SLN reduction mitigates skeletal muscle
pathology and cardiomyopathy in mouse models of DMD. In addition, we propose to determine whether
targeting SLN expression mitigate DMD in preclinical settings. We will specifically test the following
hypotheses: 1) SLN overexpression limits skeletal muscle regeneration in DMD, 2) Reduction in SLN
expression can improve cardiac SERCA function and prevent cardiomyopathy, and 3) Postnatal AAV mediated
SLN gene silencing therapy can ameliorate DMD. The outcomes of these studies will identify SLN as a
potential therapeutic target for the treatment of DMD and associated cardiomyopathy.

## Key facts

- **NIH application ID:** 10008963
- **Project number:** 5R01AR069107-05
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** GOPAL Jegadeesh BABU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $349,800
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10008963

## Citation

> US National Institutes of Health, RePORTER application 10008963, Sarcolipin in Duchenne Muscular Dystrophy (5R01AR069107-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10008963. Licensed CC0.

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