Nitric Oxide (NO) and Duchenne Muscular Dystrophy: NO Way to Go?

• Main Authors: Cara A. Timpani, Kamel Mamchaoui, Gillian Butler-Browne, Emma Rybalka
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: Antioxidants
• Subjects: Duchenne muscular dystrophy; metabolism; nitric oxide; nitrite; reactive oxygen species; superoxide
• Online Access: https://www.mdpi.com/2076-3921/9/12/1268

The discordance between pre-clinical success and clinical failure of treatment options for Duchenne Muscular Dystrophy (DMD) is significant. The termination of clinical trials investigating the phosphodiesterase inhibitors, sildenafil and tadalafil (which prolong the second messenger molecule of nitric oxide (NO) signaling), are prime examples of this. Both attenuated key dystrophic features in the <i>mdx</i> mouse model of DMD yet failed to modulate primary outcomes in clinical settings. We have previously attempted to modulate NO signaling via chronic nitrate supplementation of the <i>mdx</i> mouse but failed to demonstrate beneficial modulation of key dystrophic features (i.e., metabolism). Instead, we observed increased muscle damage and nitrosative stress which exacerbated MD. Here, we highlight that acute nitrite treatment of human DMD myoblasts is also detrimental and suggest strategies for moving forward with NO replacement therapy in DMD.