Researchers at Carnegie Mellon University have identified a way to target disease-causing RNA structures that may open new treatment possibilities for myotonic dystrophy type 1 (DM1) and related RNA-repeat expansion disorders, including spinocerebellar ataxias, Friedreich’s ataxia, and ALS.
DM1, the most common adult-onset form of muscular dystrophy, is caused by an abnormal expansion of CTG repeats in the DMPK gene. When transcribed into RNA, these repeats form a hairpin loop that traps essential proteins involved in RNA splicing, disrupting normal cell function and causing progressive muscle weakness, myotonia, and symptoms affecting the heart, lungs, and eyes. There is currently no effective treatment.
The research team, led by Professor Danith Ly, developed small synthetic molecules called nucleic acid ligands that selectively bind to pathogenic RNA repeats without interfering with healthy RNA. The lead ligand, LG2b, uses a bifacial recognition mechanism, inserting itself between the two RNA strands rather than unwinding them, unlike conventional antisense therapies. In laboratory models, it displaced harmful protein-RNA complexes while leaving normal gene function intact.
The approach is intended to be more precise and produce fewer off-target effects than existing small-molecule drugs or antisense therapies currently under development, though further validation is needed.
The study was published in the Proceedings of the National Academy of Sciences. The team is continuing to optimize the ligands for cellular uptake and delivery, with preclinical evaluation ongoing.
Source: Carnegie Mellon University | PNAS, 2026
