Alternative approaches targeting Duchenne Muscular Dystrophy treatment

Abstract

The main goal of this project is to advance for an efficient therapy for Duchenne Muscular Dystrophy (DMD) based on a novel therapeutic approach. DMD is the most common and severe muscular dystrophy, affecting 1 in 3.500 to 5000 newborn male children. DMD is caused by the absence of dystrophin, an intracellular membrane-associated protein responsible for damping the mechanical stress from myofibril work. The lack of dystrophin increases the chances of membrane rupture, leading to homeostasis unbalance, atrophy and apoptosis of muscle fibers. Since there is no effective treatment for DMD affected boys have a progressive muscular weakness and a short lifespan. Without special care, most patients do not live beyond age 20. The current therapeutic trials, which aim to increase dystrophin expression, are not showing any significant clinical improvement. This shows the need for alternative treatments, not focused on dystrophin, which is the aim of the current project. Recently, a study led by Dr. Zatz in collaboration with researchers from Harvard University have associated the over-expression of Jagged1 with a mild phenotype of two outstanding Golden Retriever Muscular Dystrophy (GRMD) dogs. GRMD dogs are severely affected and represent the best animal model for DMD. The high levels of Jagged1 allowed a normal muscle function and a long lifespan in these two exceptional GRMD dogs. This groundbreaking study outlined a novel way for therapy aiming to investigate the clinical effect of Jagged1 increased expression in different DMD animal models. Data obtained from the proposed study may, in the future, guide a safe and effective treatment for humans. (AU)