VP48 AOC 1001 demonstrates DMPK reduction and spliceopathy improvement in a phase 1/2 study in myotonic dystrophy type 1 (DM1) (MARINA)

DM1 is a rare, autosomal dominant, progressive neuromuscular disease with no approved therapies. DM1 is caused by a toxic CTG repeat expansion (>50) in the myotonic dystrophy protein kinase (DMPK) gene. Mutant DMPK expression leads to the accumulation of toxic gain-of-function mRNA in the nucleus where it sequesters splicing factors resulting in global splicing dysregulation. AOC 1001 is a humanized anti-transferrin receptor 1 (TfR1) antibody conjugated to a siRNA targeting the DMPK mRNA (siDMPK) designed to reduce DMPK mRNA in muscle tissue and correct mis-spliced events that are responsible for DM1 pathogenesis.

Source: Neuromuscular Disorders - October 1, 2023 Category: Neurology Authors: Y. Zhu, T. Kwan, Q. Meng, L. Tai, H. Cho, M. Lee, H. Younis, A. Levin, M. Flanagan Source Type: research