Casimersen

Zakeri SE, et al. Trends in Pharmacological Sciences, 2022, 43(7), 607-608.

Casimersen is a breakthrough antisense therapy designed to treat Duchenne muscular dystrophy (DMD) caused by mutations amenable to exon 45 skipping. The drug targets the DMD gene, restoring the open reading frame to produce a partially functional dystrophin protein, akin to that observed in Becker's muscular dystrophy.
DMD arises from frame-shift mutations leading to truncated dystrophin proteins that lack functional domains, causing muscle degradation and loss of sarcolemma integrity. Casimersen binds to the splice site of intron 44 in DMD pre-mRNA, inducing the skipping of exon 45 during splicing. This restores the translational frame, yielding dystrophin with retained N- and C-terminal domains and fewer spectrin-like repeats. The partially functional protein compensates for dystrophin deficiency, slowing disease progression.
Administered intravenously, the therapy is recommended at 30 mg/kg weekly via infusion. Casimersen has a robust molecular profile with enhanced stability against enzymatic degradation, facilitating cellular uptake and nuclear targeting. Clinical use aims to elevate dystrophin levels in skeletal muscles, improving structural integrity and functional outcomes.
In trials, upper respiratory tract infections were the most frequent adverse event (65%), followed by cough, headache, pyrexia, and oropharyngeal pain. Nephrotoxicity is a concern requiring regular monitoring.