Long-Term Morpholino Oligomers in Hexose Elicits Long-Lasting Therapeutic Improvements in mdx Mice.

ABSTRACT: Approval of antisense oligonucleotide eteplirsen highlights the promise of exon-skipping therapeutics for Duchenne muscular dystrophy patients. However, the limited efficacy of eteplirsen underscores the importance to improve systemic delivery and efficacy. Recently, we demonstrated that a glucose and fructose (GF) delivery formulation effectively potentiates phosphorodiamidate morpholino oligomer (PMO). Considering the clinical potential of GF, it is important to determine the long-term compatibility and efficacy with PMO in mdx mice prior to clinical translation. Here, we report that yearlong administration of a clinically applicable PMO dose (50 mg/kg/week for 3 weeks followed by 50 mg/kg/month for 11 months) with GF elicited sustainably high levels of dystrophin expression in mdx mice,

SUBMITTER: Han G 

PROVIDER: S-EPMC6070676 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature