Duchenne muscular dystrophy is a rare but devastating genetic disorder that primarily affects young boys. It is caused by mutations in the DMD gene, resulting in the absence of dystrophin, a protein critical for muscle integrity. This deficiency leads to progressive muscle wasting, loss of mobility, and premature death, often in early adulthood. While currently treatments may slow disease progression, they offer limited benefits and often accompanied by serious side effects. As no curative therapies are available, there is an urgent need for supportive treatments that can improve quality of life and complement existing interventions. Most experimental therapies are tested in the mdx mouse model, which exhibits a relatively mild disease phenotype and does not fully recapitulate the severity of human DMD. This limits the ability to evaluate new drugs effectively and delays the therapeutic progress. This study investigated the sapje zebrafish model, which closely mimics the severe muscle damage seen in human DMD patients. Our results demonstrate that sapje zebrafish not only display significant locomotor impairments but also show molecular alterations linked to impaired autophagy, a key cellular process dysregulated in DMD. These findings support the use of sapje zebrafish as a powerful model for screening supportive therapies, including osmolyte and amino acid-based interventions.