Pharmacological prospects in the treatment of Duchenne muscular dystrophy

The most encouraging recent advances regarding pharmacological agents for treating Duchenne muscular dystrophy (DMD) are summarized. Emphasis is given to compounds acting downstream of dystrophin, the protein lacking in DMD, on cellular pathways leading to pathological consequences. The author highlights the progress that may have the greatest potential for clinical use in DMD.

Modifying the transcripts of the mutated gene by exon skipping has led to expression of shortened dystrophins in DMD patients. Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen. Biglycan and SMTC1100 upregulate utrophin. The steroid receptor modulating compounds VBP15 and tamoxifen, and specific antioxidants appear promising agents for symptomatic therapy.

The past 18 months have seen a strong increase in the number of exciting reports on novel therapeutic agents for DMD. Exon-skipping agents have been fine-tuned to improve tissue delivery and stability. Impressive discoveries regarding pathogenic events in cellular signalling have revealed targets that were unknown in the context of DMD, thus enabling approaches that limit inflammation, fibrosis and necrosis. The targets are nuclear hormone receptors, NADPH-oxidases and Ca channels. Inhibition of NF-KB, transforming growth factor-alpha (TGF-α) and transforming growth factor-beta (TGF-β)/myostatin production or action are also promising routes in counteracting the complex pathogenesis of DMD.