The project aims to advance therapeutic strategies for myotonic dystrophy type 1 (DM1) and other muscle atrophies by targeting MSI2, a critical regulator of miR-7 biogenesis implicated in muscle wasting. Our work focuses on developing gapmers—antisense oligonucleotides that trigger RNA degradation—to silence MSI2 and mitigate its pathological effects. Previous studies have shown promising results in DM1 cellular and animal models, validating MSI2 as a therapeutic target.

The proposal emphasizes chemical optimization, preclinical testing, and safety validation of gapmers in DM1 models, while exploring their applicability in related muscle atrophies such as DM2 and LGMDD2. Our approach integrates advanced technologies, such as subcellular proteomics and transcriptomic profiling, to assess specificity and efficacy. Additionally, innovative delivery methods are being explored to enhance tissue targeting.

In collaboration with clinical and industrial partners, this project aims to bridge the gap between laboratory findings and clinical application, ensuring a robust pipeline for drug development. The creation of a spin-off company and intellectual property protection strategies further underscore the project’s translational potential, contributing to both scientific innovation and societal impact in the fight against rare muscular diseases.

Grant PDC2022-133103-I00 funded by MICIU/AEI/10.13039/501100011033 and by “European Union NextGenerationEU/PRTR”