Myotonic dystrophy type 1 (DM1) is a complex rare disorder characterized by progressive muscle dysfunction, involving weakness, myotonia, and wasting, but also exhibiting addnl. clin. signs in multiple organs and systems.Central dysregulation, caused by an expansion of a CTG trinucleotide repeat in the DMPK gene's 3' UTR, has led to exploring various therapeutic approaches in recent years, a few of which are currently under clin. trial.However, no effective disease-modifying treatments are available yet.In this study, we demonstrate that treatments with boldine, a natural alkaloid identified in a large-scale Drosophila-based pharmacol. screening, was able to modify disease phenotypes in several DM1 models.The most significant effects include consistent reduction in nuclear RNA foci, a dynamic mol. hallmark of the disease, and noteworthy anti-myotonic activity.These results position boldine as an attractive new candidate for therapy development in DM1.