DMD is a devastatingly progressive muscle wasting disorder of childhood that significantly shortens life expectancy.
Despite efforts to develop an effective therapy that dates back over a century, clinical interventions are still restricted
to management of symptoms rather than a cure. The rationale to develop effective therapies changed in 1986 with
the discovery of the dystrophin gene. Since then extensive research into both the molecular basis and pathophysiology of
DMD has paved the way not only for development of strategies which aim to correct the primary defect, but also towards
the identification of countless therapeutic targets with the potential to alleviate the downstream pathology. In addition to
gene and cell-based therapies, which aim to deliver the missing gene and/or protein, an exciting spectrum of pharmacological
approaches aimed at modulating therapeutic targets within DMD muscle cells through the use of small drugs are
also being developed. This review presents promising pharmacological approaches aimed at targeting the primary defect,
including suppression of nonsense mutations and functional compensation by upregulation of the dystrophin homologue,
utrophin. Downstream of the primary membrane fragility, inflammation and fibrosis are reduced by blocking NF-κB,
TGF-α and TGF-β, and free radical damage has been targeted using antioxidants and dietary/nutritional supplements.
There are new hopes that ACE and PDE5 inhibitors can protect against skeletal as well as cardiac pathology, and modulating
Ca2+ influx, NO, BMP, protein degradation and the mitochondrial permeability pore hold further promise in tackling
the complex pathogenesis of this multifaceted disorder.
Keywords: Cardiac, duchenne, dystrophy, fibrosis, inflammation, muscular, pharmacological, utrophin, DMD, mdx
Rights & PermissionsPrintExport