Targeting NADPH oxidase 4 in models of Duchenne muscular dystrophy

Dr. Hesham Hamed, University of Geneva

Abstract (Lay summary: see project 2016)


Duchenne muscular dystrophy is a devastating muscle disease to which no cure exist. The current understanding is that multiple therapeutic approaches that show additive or synergistic actions would be necessary to achieve a robust therapeutic effect capable of improving the quality of life and extending the life expectancy of DMD patients [1]. This highlights the urgent need to increase our battery of pharmacological interventions that should serve to ameliorate the condition and to improve the quality of life of DMD patients. 

The current proposal and the previous one address this by exploring the role of NADPH oxidases (NOXes), a reactive oxygen species generating enzymes reported to play an important role in this pathology, and the therapeutic potential of targeting them in DMD mouse models. It will also test both newly designed and clinically validated NOX inhibitors from our collaborators, GenKyoTex, the market leader in developing NOX inhibitors. This will enable us to both genetically and chemically validate of NOXes, and in particular NOX4, as a promising therapeutic target not only for DMD, but also for other muscular dystrophies that share common pathological features due to ROS and Ca2+ dysregulation. Our expertise together with the network established within the framework of this project puts us in a unique position to drive the aims to completion. We believe this work will contribute to the delivery of novel pharmacological therapies highly needed for DMD patients and other similar pathologies.