DMD Treatment Toolkit: Corticosteroids, Exon Skipping, and Gene Therapy

In this episode, Dr. Jayaraman offers a structured overview of the DMD treatment landscape as she would present it to a newly diagnosed family. She divides therapies into two categories: non-mutation-specific treatments, available to any patient with DMD, and mutation-specific treatments, which depend on the individual's genetic profile.

Non-mutation-specific options include corticosteroids—prednisolone, deflazacort, and vamoralone (a dissociative corticosteroid analog)—as well as givinostat, a histone deacetylase inhibitor that is non-steroidal. Mutation-specific therapies include commercially available and investigational gene therapies (microdystrophin replacement) and exon skipping agents. Dr. Jayaraman clarifies an important nuance: exon skip amenability refers to the mutation's potential for correction via skipping, not to the actual absence of the exon in question.

The conversation then pivots to corticosteroids as the cornerstone of DMD management. Dr. Chrzanowski traces the history from Jerry Mendell's landmark 1989 publication on prednisone to the emergence of deflazacort in the 2010s. He notes that while deflazacort offers superior functional outcomes and slightly better bone protection compared to prednisone, accessibility challenges often necessitate prednisone as a bridge. A shift toward deflazacort is occurring across the field.

Dosing regimens are discussed at length. Daily dosing remains standard, but alternative schedules—such as weekend dosing or 10-days-on/10-days-off—are being explored to mitigate the often significant side effects of chronic corticosteroid use. The panel agrees that dosing must be individualized, and that finding the right steroid regimen is a balancing act between functional benefit and tolerability.

In the next episode, "Evaluating a Newer Corticosteroid Option, Vamoralone, in DMD," the panel dives deeper into the efficacy, safety profile, and clinical use of vamoralone, the newest addition to the corticosteroid toolkit.