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Duchenne Muscular Dystrophy Advancements: Research in the Pipeline

Jun 16, 2016

Duchenne muscular dystrophy is a genetically inherited, terminal disease of the muscles that steals boys’ lives typically by their third decade of life. Currently, there is no cure for Duchenne and only supportive treatments to increase both quality and quantity of life can be employed. However, there is a vast network of doctors and scientists around the world working furiously to find a cure. Below are just a few of the arenas of research that the team at Nationwide Children’s are developing.

Standard Therapy: Steroids
Only one class of medication is scientifically proven to change the course of Duchenne muscular dystrophy (DMD) – corticosteroids. Steroids can prolong a boy’s ability to walk by approximately two years, while supporting other body systems.

Two drugs in this class are used. Prednisone, available commercially in the US, is well studied and inexpensive. Alternatively, some families choose Deflazacort. This medication is not FDA approved, and many families pay high costs to get this medication from Europe or Canada, as they believe it has fewer side effects. An expanded access trial is currently underway in the US that provides Deflazacort free of charge to families. This trial aims to gather additional data to see if Deflazacort is successful, with a goal of obtaining FDA approval to market the medication commercially in the US.

Exon Skipping
This technology aims to change the way the body reads the gene responsible for DMD. The DMD gene is made up of 79 exons, or pieces, that must be arranged in a specific order to function and create dystrophin, a protein necessary for muscle membrane stability.

When exons are missing or out of place, the body cannot read the code properly and DMD occurs. Depending on which pieces are missing, a change in the code can be in frame (readable by the body), or out of frame (unreadable). Unreadable changes in the DNA are more frequently associated with a more severe outcome, like Duchenne.

In frame changes are more frequently associated with a diagnosis of Becker muscular dystrophy, a milder form of the disease. For boys with eligible mutations, we can help the body read the gene by expanding the missing information just enough to put a deletion back in frame, and make a partially functional protein. There has been a significant amount of publicity surrounding exon skipping recently, as the FDA will soon make a decision about Eteplirsen, a drug that could be the first approved medication for the management of Duchenne.

Nonsense Suppression
Nearly two thirds of boys with Duchenne have deletions or duplications in the DMD gene. However, the other third of boys with Duchenne have different kinds of changes in their DNA that are much smaller, but equally as harmful to the muscles. A portion of these boys have a type of genetic change called a “nonsense mutation.” These are changes in the DNA that make the code unreadable. Ataluren, which is still under investigation, is a medication that attempts to help the body read through these types of changes, potentially leading to improved function with boys for Duchenne.

Myostatin Inhibition
Myostatin is a protein that regulates muscle growth. When myostatin is blocked, muscles grow unregulated, and become enlarged. Many teams and companies are working to create myostatin blockers for boys with Duchenne. This will permit boys’ muscles to continue to grow and gain strength, instead of atrophy and weaken.

Gene Therapy
The team at Nationwide Children’s Hospital’s Center for Gene Therapy is a leader in the development of this technology. While gene therapy isn’t one specific treatment, it’s a method of delivery. Gene therapy uses a viral “envelope” to transfer missing or augmented genetic information into the body. A variety of trials are underway using this method and much promise has been shown.

Gene Editing
Likely still far from human trials, gene editing via CRISPR-Cas9 is one of the most exciting fields of research. The technology allows scientists to edit genes much in the way we edit a Word document. Using the CRISPR gene and Cas9 protein, scientists can cut a gene, insert or remove genetic material, and reattach the pieces together. With research underway and much to be learned, this technology could be used to treat DMD, as well as a multitude of other genetic conditions.

Featured Expert

Nationwide Children's Hospital Medical Professional
Rachel Schrader, CPNP-PC

Rachel Schrader, MS, RN, CPNP-PC serves as the nurse practitioner for Nationwide Children’s Hospital’s neuromuscular, MDA, and SMA clinics. She graduated with her master’s degree from Ohio State University.

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700 Children’s® features the most current pediatric health care information and research from our pediatric experts – physicians and specialists who have seen it all. Many of them are parents and bring a special understanding to what our patients and families experience. If you have a child – or care for a child – 700 Children’s was created especially for you.