Background: Duchenne muscular dystrophy (DMD) is a X-linked recessive neuromuscular disorder characterized by progressive muscle degeneration and weakness. For males diagnosed with this condition, death often occurs around 20 years of age, usually due to cardiorespiratory complications. Until 2017, the only treatment for DMD was the use of corticosteroids to delay the onset of symptoms and maximize quality of life. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (EXONDYS 51), a targeted oligonucleotide designed to skip exon 51 and the defective variants to restore the gene’s translational reading frame. The expected result is the production of a partially functional dystrophin protein. Only 14% of patients diagnosed with DMD have mutations amenable to exon 51 skipping. Clinical studies have shown the drug slows natural disease progression as evidenced by a decreased slope in both pulmonary function and functional (6MWT) decline over time. Here we present data from a single-site, retrospective chart-review study on three DMD patients who underwent and initiated weekly eteplirsen infusions post-heart transplantation.
Objective: Describe the response of eteplirsen therapy in three DMD post-heart transplant patients.
Results: Three patients with out-of-frame deletions amenable to exon 51 skipping were treated for DMD-cardiomyopathy with cardiac transplantation. Post-transplant, these patients were initiated on eteplirsen infusions at 30 mg/kg/week in addition to their immunosuppression therapy. To date, none of the patients have exhibited any adverse reactions related to eteplirsen. All lab values have remained within normal limits in accordance to each patient’s baseline. These patients displayed slower respiratory and functional decline as evidenced by stable Brooke/Vignos scores and pulmonary function testing. For all but one patient who developed coronary artery disease and donor specific antibodies post-transplant, cardiac function has remained stable.
Conclusion: We suggest eteplirsen provides the same clinical benefit to exon 51-skip amenable post-heart transplant patients as it does to all non-transplanted patients. A future consideration would be to perform histological analysis of the newly transplanted tissue post-eteplirsen initiation to assess for the disruption of the gene’s translational reading frame.