First cardiovascular gene therapy trial in U.S. for people with Duchenne muscular dystrophy begins at KU Medical Center

The first clinical trial for cardiovascular gene therapy for people with Duchenne muscular dystrophy in the United States has begun at the University of Kansas Medical Center. KU Medical Center is one of three study sites for the MUSIC-DMD clinical trial, which is investigating a gene therapy treatment for cardiomyopathy in adults with Duchenne muscular dystrophy (DMD). Heart failure resulting from cardiomyopathy is the leading cause of death in people with DMD, a genetic disorder that primarily affects males.

“This is a very big deal, for the DMD community and for rare diseases,” said Pradeep P.A. Mammen, M.D., professor of cardiovascular medicine and division chief for Advanced Heart Failure Therapeutics and Cardiac Transplantation at KU Medical Center and the principal investigator for the MUSIC-DMD study. “The initiation of this trial marks an important step forward in addressing the cardiac complications that ultimately affect nearly all patients with Duchenne muscular dystrophy.”

A rare disease but one of the most common forms of muscular dystrophy, DMD affects more than 300,000 people around the world. DMD is caused by a mutation in a gene known as dystrophin, which produces the largest protein in the human body. That protein, whose function Mammen likens to a shock absorber in a car, protects muscle cells. This protein is not produced in patients with DMD, which, in addition to weakening skeletal muscle, leads to cardiomyopathy and heart failure.

Before the 2000s and prior to advancements in respiratory, pulmonary and orthopedic care, few boys with DMD lived until adulthood. Cardiac complications have become increasingly prevalent as these patients live longer, but very few therapies have been developed for adults with DMD. Current treatments for DMD-associated cardiomyopathy rely on standard heart failure medications, which have shown limited effectiveness in these patients.

The gene therapy in the MUSIC-DMD trial (Modulation of SERCA2A In the Cardiomyopathy of Duchenne Muscular Dystrophy) targets the production of a protein known as SERCA2a, which is deficient in patients with DMD-induced cardiomyopathy. The SERCA2a protein is critical for the heart to be able to contract and relax and pump blood throughout the body.

Using a catheter-based system that infuses an experimental gene therapy directly into the main coronary arteries, the MUSIC-DMD trial will deliver extra copies of the gene that produces the SERCA2a protein to the heart muscle cells. The goal of this gene therapy is to increase the production of the SERCA2a protein and regulate the movement of calcium, which helps the heart pump blood properly.

Up to 12 adult participants will be enrolled across low-dose, high-dose, and control groups in the MUSIC-DMD­ study, a Phase 1b trial that will primarily evaluate the safety of the gene therapy. The trial is sponsored by Sardocor, the clinical development division of Medera Inc., a clinical-stage biopharmaceutical company focused on targeting cardiovascular diseases by developing next-generation therapeutics.

“This milestone represents a pivotal advancement in the treatment of DMD-associated cardiomyopathy,” said Ronald Li, Ph.D., CEO and co-founder of Medera. “As survival rates improve due to respiratory interventions, cardiac complications have emerged as the leading cause of mortality in DMD patients. Our Sardocor division’s innovative, first-in-human gene therapy offers a promising solution to address this critical unmet medical need.”

The researchers will compare the treated participants with non-treated participants. All participants will continue to take their current heart medications and be followed closely for two years, during which they will undergo cardiac magnetic resonance imaging at baseline and at the end of each year. At the end of two years, they will move into biannual, long-term follow-up.

After this phase 1b study is completed, future studies will evaluate the efficacy of the treatment.

“We are hoping that we can improve heart function,” said Mammen. “We hope this adjuvant therapy helps keep these patients stable and prolongs their lives. That’s why we’re enrolling participants into this critical clinical trial.”