Duchenne Muscular Dystrophy: A Progress Update (Podcast)

Recent advances in gene therapy and collaborative care are transforming treatment approaches to Duchenne muscular dystrophy (DMD), a severe, progressive neuromuscular disorder presenting in early childhood.

“Duchenne muscular dystrophy is caused by mutations in the gene that encodes the dystrophin protein, preventing this protein from forming,” explains Alexandra Bonner, MD, a Cleveland Clinic pediatric neurologist specializing in neuromuscular disorders. “A key question in gene therapy for DMD is whether we can deliver the full-length dystrophin gene to the muscle cells and allow those muscle cells to encode it. The answer right now is not yet, actually, because the dystrophin gene is massive. Researchers have looked at all the critical components of this massive gene, leaving out the less-critical parts, and packaged them into a smaller microdystrophin that can ben incorporated into our known viral vectors.”

In the latest episode of Cleveland Clinic’s Neuro Pathways podcast, Dr. Bonner shares some insights from this research as well as questions that remain. Along the way, she provides a general update of DMD for non-subspecialists, touching on the following:

• Genetics of DMD
• Diagnostic testing, including initial adoption of newborn screening
• Standard treatments before gene therapy
• Supportive care, including cardiac and respiratory management
• Improvements in lifespan
• The rationale for a comprehensive gene therapy program for DMD

Click the podcast player above to listen to the 21-minute episode now or read on for an edited excerpt. Check out more Neuro Pathways episodes at clevelandclinic.org/neuropodcast or wherever you get your podcasts.

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Excerpt from the podcast

Podcast host Glen Stevens, DO, PhD: Tell us about the genetics of DMD.

Alexandra Bonner, MD: It’s is an X-linked recessive disorder, so females tend to be carriers. They tend not to manifest symptoms, although a small percentage of females can manifest some cardiac symptoms later in life, so it’s good to have that on your radar and know that females can be screened. But it's really males who manifest symptoms.

Dr. Stevens: What percentage of patients inherit this condition from a parent versus developing it from a spontaneous mutation?

Dr. Bonner: About one-third of mutations are de novo, while the other two-thirds will be inherited from a parent.

Dr. Stevens: So if a newborn had an increased creatine kinase level and it remained elevated upon follow-up so that your suspicion for DMD was very high, would you consider genetic testing at that point?

Dr. Bonner: I would. Right now, depending on the level, I would consider sending a screen of the dystrophin protein first. Which testing you choose to order might depend on where you’re practicing. But if the level is frankly high, I would consider sending that dystrophin screen first. Of course, an elevated CK level is not specific to Duchenne; it’s just a marker of muscle breakdown. So there are a lot of other disorders that are potentially being captured with a newborn screen.

Dr. Stevens: Do patients in this situation have to be sent to medical genetics, or can the neurologist order the testing?

Dr. Bonner: It’s a changing landscape right now. For targeted testing, I’m able to send that testing myself. For broader testing, if that’s needed, insurance providers are not always covering tests like whole exome sequencing or whole genome sequencing unless there’s involvement of a genetic counselor or other hoops to jump through. So, from a targeted testing standpoint, I can and do initiate that testing. If we have to expand to further testing, I’ll pull in our medical genetics team.