Early Exposure to Exon-Skipping Therapy: A Case Report


Clinical Management

Poster Number: T319


Anna Jesus, MD, University of Virginia, Casey Little, BS, University of Virginia, Chelsea Masterson, BA, University of Virginia, Rebecca J. Scharf, MD, University of Virginia

Background: Exon skipping to therapeutically restore the frame of an out-of-frame dystrophin mutation in Duchenne Muscular Dystrophy (DMD) has been the primary genetic treatment for DMD since 2016. Since the average age of diagnosis of DMD is five years and clinical trials for exon-skipping therapies typically included only boys over five years, little has been observed regarding the clinical progression of boys treated with exon-skipping prior to age three years.

Objectives: This case report illustrates the clinical progression of one child diagnosed with DMD and exposed to exon skipping comparatively early in his disease.

Results: ST is a 3-year 9-month-old boy who was born at 32 weeks 6 days due to pre-term labor. At 17 months of age, corrected to 15 months, ST was found to have mild hypotonia and relatively delayed gross motor skills as compared other age-appropriate developmental skills, at a routine NICU Developmental Follow-up Clinic. Creatine Kinase was found to be elevated at 25,688 U/L. PerkinElmer DMD Deletion/Duplication and Sequencing testing pathogenic hemizygous deletion of DMD Exons 48-50. This mutation is 51 exon skipping amenable, therefore ST was a candidate for Eteplirsen.

At 20 months of age, ST began weekly intravenous infusions of Eteplirsen. He has been receiving weekly Eteplirsen infusions for 25 months. ST learned how to walk independently at 19 months of age, prior to treatment with Eteplirsen. He can jump with two feet off of the ground and pedal a tricycle. Most recent North Star Ambulatory Assessment was 15/34.

Conclusions: Understanding of clinical benefit for exon-skipping therapy has been predominantly in boys older than 5 years of age, after boys have experienced clinical decline. This case illustrates improved clinical outcomes that could be associated with early access to exon-skipping therapy. As additional genetic therapies become available, early identification is critical.