Duchenne: A Rare Genetic Neuromuscular Disease

DMD

Duchenne muscular dystrophy, sometimes shortened to DMD or just Duchenne, is a rare genetic disease. It predominantly affects males, but, in rare cases, can also affect females. Duchenne causes the muscles in the body to become weak and damaged over time and is eventually fatal. The genetic change that causes Duchenne—a mutation in the DMD gene—happens before birth and can be inherited, or new mutations in the gene can occur spontaneously. Muscle weakness becomes increasingly noticeable between the ages of 3 and 5, and most patients use a wheelchair by the time they are 12. During adolescence, heart and breathing muscles weaken, leading to serious, life-threatening complications.

Duchenne affects approximately 1 in 3,500 to 5,000 males born worldwide.

Duchenne is caused by a change or mutation in the gene that encodes instructions for creating dystrophin, an essential protein for muscle strength. Dystrophin is a protein that plays a key structural role in muscle fiber function. In healthy muscle, dystrophin interacts with other proteins at the cell membrane to stabilize and protect the cell during regular activity involving muscle contraction and relaxation. Genetic testing can confirm the diagnosis and identify the disease-causing mutation in the dystrophin gene.

Individuals with Duchenne produce little or no dystrophin in their muscle.

Without dystrophin, normal activity causes excessive damage to muscle cells, and over time is replaced with fat and fibrotic tissue.

Duchenne tissue

To learn more about Duchenne visit Duchenne.com.

Genetic Testing

Genetic testing is a critical step in diagnosing any genetic disease. Knowing the specific mutation can affect decisions on which therapeutic approaches might be appropriate for disease management.

Decode Duchenne provides free genetic testing, interpretation, and counseling to people with Duchenne or Becker muscular dystrophy who meet certain eligibility criteria and who have been unable to access genetic testing in the past due to financial barriers, such as cost or lack of insurance coverage. Sarepta is a proud sponsor of Decode Duchenne, a program of Parent Project Muscular Dystrophy that is administered by Duchenne Connect.

RNA Exon Skipping for Duchenne

Duchenne is caused by a genetic mutation in the dystrophin gene. Most commonly, one or more exons (parts of the gene) are missing, causing errors in the instructions for making dystrophin. This results in the body not being able to produce enough—or any—working dystrophin protein. The goal of exon skipping is to allow the body to make a shorter form of the dystrophin protein.

Micro-dystrophin Gene Therapy for Duchenne

An important development approach aimed at slowing or stopping the progression of Duchenne is gene therapy. The science behind gene therapy is significantly different from RNA exon skipping. Rather than correcting for missing or damaged exons in the dystrophin gene, it aims to deliver a separate, potentially functional version of the gene to take over the job of producing the essential dystrophin protein. 

Because dystrophin is the largest gene in the body, it is unable to fit into the vector responsible for delivering the gene to the muscle. To solve for this problem, our researchers took a portion of the dystrophin gene and created a smaller, but potentially functional micro-dystrophin gene.

Clinical Trials

Sarepta currently has multiple clinical trials for Duchenne underway in both gene therapy and RNA exon-skipping.

Duchenne Resources

The groups below—many founded by parents within the Duchenne community—help connect patients and families to education, research, support services, and the broader Duchenne community. Here are just a few of the organizations that work to raise both awareness of Duchenne and funds directed toward research while providing programs and information to help those with Duchenne.

 

Duchenne Resources

Additional Resources