IONIS-486178

IONIS-486178 is a **constrained ethyl-modified antisense oligonucleotide** designed to inhibit the expression of the dystrophia myotonica protein kinase (DMPK) gene. Developed as a potential treatment for *myotonic dystrophy type 1* (DM1), it binds specifically to DMPK mRNA transcripts carrying expanded CUG repeats, which are the pathogenic driver in DM1. The compound operates via the antisense gapmer mechanism, inducing **RNase H-mediated degradation** of the mutant DMPK mRNA to reduce toxic RNA foci and restore normal cellular function. In preclinical models, IONIS-486178 reduced mutant DMPK transcript levels in skeletal (up to 70%) and cardiac muscle (up to 50%), as well as in brain tissue with direct administration, and produced functional improvements without overt toxicity. The drug uses a **2',4'-constrained ethyl (cEt) modification**, which enhances RNA binding affinity and tissue potency relative to earlier antisense technologies[1][3][4][5].

Other names

ISIS 486178ISIS486178ISIS-486178