Juvenile dermatomyositis (JDM) is a highly morbid autoimmune disease that causes progressive muscle weakness in children. As the most common childhood-onset inflammatory muscle disease, it affects approximately 250 children annually in the U.S. If untreated, JDM can lead to severe disability, including loss of mobility, difficulty swallowing, and respiratory failure. Despite its severity, the underlying causes remain unknown, and current treatments rely on broad immunosuppressants that increase infection risk, cause toxic side effects, and often fail to prevent long-term impairment. In fact, two out of three children with JDM continue to experience chronic disability despite standard treatment. For over six decades, therapy has remained imprecise, with no FDA-approved medications for JDM. Progress has been hindered by the lack of an adequate disease model, the impracticality of large-scale pediatric clinical trials, and the reliance on treatment strategies based on adult studies rather than pediatric-specific research. These challenges underscore the urgent need for innovative approaches to studying and treating JDM. To overcome these barriers, I propose using myobundles, a human tissue-derived muscle model that replicates skeletal muscle structure, function, and drug responses. By characterizing patient-derived myobundles, I will investigate key disease mechanisms and accelerate translational research. This project aims to gather initial patient samples and preliminary data to establish a validated JDM muscle model and define the effects of type I interferons—cytokines highly elevated in JDM—on muscle mitochondria, the cell’s energy source. This work will fill critical gaps in our understanding of JDM, providing an urgently needed human tissue-based disease model to fast-track the discovery of more effective, less toxic treatments. By bridging the gap between basic science and clinical care, this research has the potential to transform the lives of children with JDM, offering new hope to patients and their families.