Late Breaking: Real-world Challenges of Exon Skipping Treated DMD Patients; One Center’s Experience


Topic:

Clinical Management

Poster Number: 52

Author(s):

Elicia Estrella, MS, LCGC, Department of Neurology, Division of Genetics and Genomics, Boston Children's Hospital, Alyssa Rohan, BS, Boston Children's Hospital, Regina Laine, NP, Boston Childrens Hospital, Basil Darras, MD, Boston Children's Hospital, Partha Ghosh, MD, Boston Childrens Hospital

Duchenne Muscular Dystrophy (DMD) is an X-linked progressive muscle disease. Mutations in the DMD gene cause loss of the protein dystrophin. Without dystrophin the muscle fibers are fragile and prone to damage. Over time muscles accumulate progressive damage manifesting as the progressive loss of motor function. Becker Muscular Dystrophy (BMD) is an allelic condition to DMD. Mutations differ by maintaining the reading frame of the DMD gene allowing some production of dystrophin. This results in a milder, more slowly progressive phenotype. Natural history studies of BMD patient show marked clinical variability. Antisense oligonucleotides were designed to induce alternative splicing, or ‘exon skipping’. This technology expands a deletion to restore the open reading frame allowing some dystrophin protein in muscle, slowing the progression of disease in the DMD patient.

Now that exon skipping is a treatment option for DMD, the varied clinical response of this therapy has become a focus of attention. We report the follow up of 14 DMD patients on exon skipping treatment. Eight patients treated with Eteplersin, three patients with Golodirsen and three patients with Casmirsen. Chart review of time on treatment ranges from 1 -7 years. Comparison of ambulation, pulmonology, and cardiac measures are reviewed. Physical therapy measures including North Star, 6MW, timed floor to stand, 10MWR, and PUL are reported over time for all patients. Treated patients are compared to the DMD natural history study to show overall efficacy. Our center shows the significant variability in slowing progression of DMD in our patient cohort using exon skipping treatment. Additional challenges of this treatment include repeated insurance approvals to continue treatment and providing a weekly infusion during the COVID 19 pandemic. As prenatal and newborn screening discussions become a reality, further understanding of this therapy is important in healthcare decisions for patients and families.