Increase in Full-Length Dystrophin by Exon Skipping in Duchenne Muscular Dystrophy Patients with Single Exon Duplications: An Open-label Study
Nicolau, Stefan | Malhotra, Jyoti | Kaler, Maryann | Magistrado-Coxen, Pamela | Iammarino, Megan A. | Reash, Natalie F. | Frair, Emma C. | Wijeratne, Saranga | Kelly, Benjamin J. | White, Peter | Lowes, Linda P. | Waldrop, Megan A. | Flanigan, Kevin M.
Single exon duplications account for disease in a minority of Duchenne muscular dystrophy patients. Exon skipping in these patients has the potential to be highly therapeutic through restoration of full-length dystrophin expression. We conducted a 48-week open label study of casimersen and golodirsen in 3 subjects with an exon 45 or 53 duplication. Two subjects (aged 18 and 23 years) were non-ambulatory at baseline. Upper limb, pulmonary, and cardiac function appeared stable in the 2 subjects in whom they could be evaluated. Dystrophin expression increased from 0.94?% +/-0.59% (mean+/-SD) of normal to 5.1% +/-2.9% by western blot. Percent dystrophin positive fibers also rose from 14% +/-17% at baseline to 50% +/-42% . Our results provide initial evidence that the use of exon-skipping drugs may increase dystrophin levels in patients with single-exon duplications.