STRIDE-DMD – Uncover STK11IP Role in trIggering fibrosis anD mEchanical-metabolic uncoupling in Duchenne muscular dystrophy

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2025.

The STRIDE-DMD project aims to better understand a little-known protein called STK11IP and its role in Duchenne Muscular Dystrophy (DMD), a rare and severely debilitating muscle disorder. DMD is caused by the lack of dystrophin, a protein that is essential for normal muscle function. Without dystrophin, muscle fibers cannot produce enough energy when needed, leading to muscle damage over time. Normally, a protein called AMPK helps manage the energy supply in muscle cells. In DMD, however, AMPK does not work properly because another protein, LKB1—which activates AMPK—is often found in the wrong location inside the cell. Since STK11IP helps control where LKB1 is positioned, we suspect that problems with STK11IP might be a key factor in the energy management issues seen in DMD. In addition, STK11IP appears to play a role in the prevention of fibrosis—a process where healthy muscle tissue is replaced by scar tissue, further deteriorating muscle function. By investigating STK11IP, we aim to better understand its role in both energy management and fibrosis in dystrophic settings. To achieve this, our project will study both animal models and cells derived from DMD patients using a variety of laboratory techniques, including molecular biology’s analyses, advanced imaging, and 3D muscle models. Ultimately, our goal is to determine whether targeting STK11IP can help to restore normal LKB1 localization and the proper management of energy metabolism in DMD. This research could also pave the way for new therapeutic strategies to treat this debilitating disease.