Nonclinical pharmacokinetic evaluation of Eteplirsen, SRP-4045, and SRP-4053: Three Phosphorodiamidate morpholino oligomers (PMOs) for the treatment of patients with Duchenne muscular dystrophy (DMD)

DMD, a rare, X-linked recessive, degenerative neuromuscular disorder, results in severe progressive muscle loss, disability, and premature death. The disease is most commonly caused by frame-shift mutations in the DMD gene that disrupt the reading frame, resulting in a lack of dystrophin, a protein that plays a key structural role in muscle fibers. PMOs can direct alternative splicing of dystrophin pre-mRNA, restore the mRNA reading frame and enable translation of an internally deleted yet functional dystrophin protein.