Duchenne Muscular Dystrophy: Advancements Research in the Pipeline

What is Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy (DMD) is a disease that affects mostly boys, causes progressive muscle weakness, gradually steals boys’ ability to walk, and leads to early death. 

Who Is Affected?

Duchenne muscular dystrophy (DMD) is an X-linked disease. That means that it’s a genetic disease carried on X-chromosome and typically inherited through the mom. Because it is inherited this way, Duchenne muscular dystrophy usually affects boys. Approximately one in 3,500-5,000 boys have Duchenne muscular dystrophy. 

What Are the Symptoms?

Duchenne muscular dystrophy is a disease of the muscles. Symptoms are present in early childhood and include:  

• Low muscle tone
• Enlarged calf muscles
• Delay in meeting developmental milestones
• Progressive muscle weakness
• A waddling gait
• Presence of a Gower’s maneuver 

How Is Duchenne Diagnosed?

The gold standard way to diagnose DMD is genetic testing. Providers can easily order genetic testing to look for errors in the gene that causes DMD. Thanks to the improved ability to identify genetic mutations that cause DMD, and improved therapeutic options, states are beginning to add DMD to newborn screening. Ohio is the first state to include DMD in all newborn screenings, starting in early 2024. 

Blood tests screening for an enzyme called creatine kinase and muscle biopsies are part of the diagnostic process before genetic testing, and for newborns.

What’s It like for Families Living with a Loved One Affected by Duchenne?

Living with DMD, or living with a loved one who has Duchenne, poses different challenges depending on the person’s age. When boys with DMD are young, they can benefit from physical therapy (or alternatively, wearing night splints), stretching, and may need an individualized education plan at school. As boys grow older, their needs change. They require lifts, power wheelchairs, and modified beds. Aides at home or in the classroom can help them complete activities of daily living. Later in life, men may require devices to assist with breathing or eating. 

What Treatment Is Available?

For a long time, the only treatments available for people with DMD were targeted at managing symptoms. These included:  

• Corticosteroids, such as prednisone, which is proven to prolong the ability to walk by approximately 2 years.
• Medications to manage stress on the heart by preventing the development of scar tissue in the heart muscle.  
• Machines that help the person with DMD breathe when their breathing support muscles become weak. 
• Nutritional supplements and medicines to help people with DMD maintain healthy bone density. 

Now, gene therapy options can offer significant improvements in the quality of life for people with DMD. These therapies work by addressing the source of the problems – the gene that codes for the protein dystrophin.  

The dystrophin protein is critical for healthy muscle function. People with DMD have a mutation in the gene that codes for dystrophin. This causes their body to produce too little protein or protein that doesn’t work the way it should. 

Exon skipping is an approach that uses small, synthetic pieces of genetic material to cause the protein-building machinery of the cell to skip the mutated portions of the gene. Exon skipping can help cells produce functional but shortened dystrophin proteins. To date, the Food and Drug Administration (FDA) has approved four exon-skipping therapies for DMD.  

Gene replacement therapy is an approach that uses a virus that does not harm humans to deliver a small yet functional copy of the dystrophin gene to cells. On June 22, 2023, the FDA approved the first gene replacement therapy for patients with DMD. ELEVIDYS, a one-time, intravenous gene therapy, delivers a smaller but functional version of the dystrophin gene. This enables the muscle cells to make a smaller but functional version of the dystrophin gene.  

ELEVIDYS was approved using an accelerated approval process. It is currently approved for patients aged 4 to 5 years old. The FDA will review data from ongoing studies in the future to determine if the therapy should be made available to other age groups.  

What’s in the Pipeline?

Researchers in the Center for Gene Therapy at Nationwide Children’s are leading the way in developing new treatments for DMD. Areas of research include exon skipping, nonsense suppression, anti-inflammatory drugs, gene editing, and gene therapy. Researchers and doctors work with others by participating in studies happening around the world. They also lead studies at Nationwide Children’s that are not happening anywhere else.