GS-PPMO

GS-PPMO is a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) antisense oligonucleotide designed to selectively suppress the expression of the glycogen synthase 1 (GYS1) gene by targeting Gys1 mRNA, leading to reduced glycogen synthase activity in skeletal muscle and heart. In preclinical models of Pompe disease, systemic administration of GS-PPMO resulted in dose-dependent knockdown of Gys1 mRNA and protein, with substantial reductions in glycogen synthase activity and lysosomal glycogen accumulation in muscle tissues. The drug exhibited high specificity for Gys1 mRNA, without affecting the liver isoform Gys2, and showed a favorable tolerability profile in treated mice without overt toxicity or histopathological changes. GS-PPMO represents a targeted RNA therapy aimed at modulating glycogen metabolism for the treatment of Pompe disease[1][3].