Duchenne muscular dystrophy is a relatively common disease that affects skeletal muscle, leading to progressive
paralysis and death. There is currently no resolutive
therapy. We have developed a treatment in which we combined the effects of
nitric oxide with nonsteroidal antiinflammatory activity by using
HCT 1026, a
nitric oxide-releasing derivative of
flurbiprofen. Here, we report the results of long-term (1-year) oral treatment with
HCT 1026 of two murine models for limb girdle and Duchenne
muscular dystrophies (
alpha-sarcoglycan-null and mdx mice). In both models,
HCT 1026 significantly ameliorated the morphological, biochemical, and functional phenotype in the absence of secondary effects, efficiently slowing down
disease progression.
HCT 1026 acted by reducing
inflammation, preventing muscle damage, and preserving the number and function of satellite cells.
HCT 1026 was significantly more effective than the
corticosteroid prednisolone, which was analyzed in parallel. As an additional beneficial effect,
HCT 1026 enhanced the therapeutic efficacy of arterially delivered donor stem cells, by increasing 4-fold their ability to migrate and reconstitute muscle fibers. The therapeutic strategy we propose is not selective for a subset of mutations; it provides ground for immediate clinical experimentation with
HCT 1026 alone, which is approved for use in humans; and it sets the stage for combined
therapies with donor or autologous, genetically corrected stem cells.