Exon skipping therapies in Duchenne muscular dystrophy: a case series of children who initiated before 3 years of age


Clinical Management

Poster Number: T322


Niki Armstrong, MS, CGC, Parent Project Muscular Dystrophy, Andrea O'Brien, MSN, CNRP, Children's Hospital of Philadelphia, Omer Abdul Hamid, MD, Nemours Children's Hospital, Arpita Lakhotia, MD, Norton Children’s, Leigh Maria Ramos-Platt, MD, CHLA MDA clinic

Background: Duchenne muscular dystrophy (DMD) currently has four FDA-approved exon skipping therapies (EST) available to amenable individuals of all ages. Given the pathophysiology of DMD with loss of muscle over time, there is expected benefit of initiation of ESTs early in life, prior to significant muscle loss.
Methods: DMD clinicians were invited to submit case reports of individuals who initiated EST before age 3 years, had received at >1 year of EST, and had outcome measures (OM) available (N=5, from 4 centers). Reported OM varied and included Bayley IV, time function tests, and NSAA.
Results: Patient 1 was diagnosed at 4 months, initiated eteplirsen at 10 months and corticosteroids at 3 years, and transitioned to viltolarsen at 3 years; he is currently 4 years. Patient 2 was diagnosed prenatally, initiated casimersen at 14 months; he is currently 40 months. Patient 3 was diagnosed at 2 months, initiated casimersen at 7 months; he is currently 25 months. Patient 4 was diagnosed at 34 months, initiated eteplirsen at 35 months and corticosteroids at 59 months; he is currently 6 years. Patient 5 was diagnosed at 5 months, initiated eteplirsen at 10 months and low dose twice-weekly corticosteroids at 4 years; he is currently 6.5 years. All have tolerated EST well.
Time on treatment ranges from 18-60 months. Gross motor delays were common, with only Patients 3 and 5, who both initiated EST before age 1, meeting typical milestones including walking at 15 months. Patient 5, who initiated EST <1 year and who has had >5 years of exposure, had an NSAA at age 6 of 31.
Discussion: Determination of efficacy is complicated by slow progression of disease, long time course of interventions required, variable expression, and lack of standardized OM. These cases illustrate initiation of EST <3 is feasible and is likely to provide long-term benefits.