PPMD Grants University of Missouri School of Medicine $105,000 to Develop Enhanced Micro-Dystrophin Targeting Cardiac Function in Duchenne Muscular Dystrophy

VCBeat (WeChat Official Account: vcbeat) has learned that the Parent Project Muscular Dystrophy (PPMD), the largest and most comprehensive non-profit organization in the United States, has been dedicated to finding therapies for Duchenne Muscular Dystrophy (DMD). Recently, the organization awarded a grant of $105,000 to a project at the University of Missouri School of Medicine, encouraging the medical school to develop a mini-dystrophin, aiming toImproving Cardiac Function in Patients with Duchenne Muscular Dystrophy. This project is led by Dr. Dongsheng Duan, Professor of Medical Research at the University of Missouri School of Medicine.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder caused by mutations in the DMD gene. These mutations block the synthesis of its encoded product, dystrophin. The disease primarily affects boys. Statistics show that approximately 1 in every 5,000 live male births worldwide is affected by this condition. Patients typically experience muscle weakness or atrophy due to progressive skeletal muscle degeneration during the preschool years. They usually lose the ability to walk entirely between the ages of 7 and 12, and most succumb to death in their twenties due to cardiac and respiratory muscle failure.

“Although the molecular genetic etiology of Duchenne muscular dystrophy (DMD) is well understood, and gene therapy research based on this foundation is emerging in abundance, the challenge of etiologic treatment remains unresolved, and there is still no effective cure for DMD. The study led by Dr. Dongsheng Duan is therefore of paramount importance at this critical juncture,” explained Abby Bronson, Senior Vice President of Research Strategy at PPMD.

Duchenne muscular dystrophy is caused by mutations in the patient's dystrophin gene. Currently, clinical trials of gene therapy for Duchenne muscular dystrophy have made progress. This therapy uses a gene transfer vector (adeno-associated virus, AAV) to inject an exogenous dystrophin gene into the muscle tissue of patients with Duchenne muscular dystrophy. Since the dystrophin gene is the largest gene on human chromosomes and cannot be fully packaged into adeno-associated viruses used for gene delivery, a mini-dystrophin gene has been clinically developed, showing promising results.

However, Abby Bronson explained, “While these therapies have made significant strides in improving patients’ skeletal muscle, their impact on cardiac function may be less pronounced. Research has found that refining the DMD gene sequence within the micro-dystrophin gene may help improve cardiac function.”

The project led by Dr. Dongsheng Duan aims to improve cardiac function in patients by studying two distinct domains of the DMD gene.

In some patients with dystrophin expression, the absence of specific domains in the DMD gene is associated with a higher incidence of cardiomyopathy. This domain, which is crucial for cardiac function and is known as the “heart domain,” will be incorporated into a modified mini-dystrophin gene.

Another specific domain of the DMD gene that affects cardiac function in patients is known as the “CT domain.” In current clinical trials, the CT domain has not been included in the mini-dystrophin gene construct because it does not contribute to skeletal muscle function. However, studies have shown that combining the CT domain with the mini-dystrophin gene demonstrates the ability to protect cardiac function in preclinical models.

Exploring these two domains of the DMD gene will provide deeper insights into how to construct mini-dystrophin genes to improve cardiac function in patients. Dr. Dongsheng Duan and his team express their gratitude to Parent Project Muscular Dystrophy for its continued support of the project. Although this study focuses on improving cardiac function in patients through an optimized mini-dystrophin (micro-dystrophin) gene, Dr. Dongsheng Duan aims to further develop mini-dystrophin genes capable of simultaneously enhancing both skeletal muscle and cardiac function in individuals with Duchenne muscular dystrophy (DMD).