{Reference Type}: Clinical Study
{Title}: Increase in Full-Length Dystrophin by Exon Skipping in Duchenne Muscular Dystrophy Patients with Single Exon Duplications: An Open-label Study.
{Author}: Nicolau S;Malhotra J;Kaler M;Magistrado-Coxen P;Iammarino MA;Reash NF;Frair EC;Wijeratne S;Kelly BJ;White P;Lowes LP;Waldrop MA;Flanigan KM;
{Journal}: J Neuromuscul Dis
{Volume}: 11
{Issue}: 3
{Year}: 2024 Mar 8
{Factor}: 4.693
{DOI}: 10.3233/JND-230107
{Abstract}: 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.