Absence of dystrophin makes skeletal muscle more susceptible to injury, 
resulting in breaches of the plasma membrane and chronic inflammation in 
Duchenne muscular dystrophy (DMD). Current management by glucocorticoids has 
unclear molecular benefits and harsh side effects. It is uncertain whether 
therapies that avoid hormonal stunting of growth and development, and/or 
immunosuppression, would be more or less beneficial. Here, we discover an oral 
drug with mechanisms that provide efficacy through anti-inflammatory signaling 
and membrane-stabilizing pathways, independent of hormonal or immunosuppressive 
effects. We find VBP15 protects and promotes efficient repair of skeletal muscle 
cells upon laser injury, in opposition to prednisolone. Potent inhibition of 
NF-κB is mediated through protein interactions of the glucocorticoid receptor, 
however VBP15 shows significantly reduced hormonal receptor transcriptional 
activity. The translation of these drug mechanisms into DMD model mice improves 
muscle strength, live-imaging and pathology through both preventive and 
post-onset intervention regimens. These data demonstrate successful improvement 
of dystrophy independent of hormonal, growth, or immunosuppressive effects, 
indicating VBP15 merits clinical investigation for DMD and would benefit other 
chronic inflammatory diseases.