Therapeutic Potential of SAT-3247 in a Canine Model of Duchenne Muscular Dystrophy

Abstract Background Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the loss of functional dystrophin protein, resulting in progressive muscle degeneration in skeletal muscle due to myofiber fragility and muscle stem cell dysfunction. Satellos Biosciences developed an orally available small molecule SAT-3247 to promote repair and regeneration of injured skeletal muscle. SAT-3247 inhibits the kinase AAK1 to increase membrane localization of NUMB, resulting in enhanced polarity, increased numbers of asymmetric divisions, and increased generation of progenitors. Therefore, a pilot study was conducted with a mixed breed DMD canine model to explore the potential for SAT-3247 treatment to impact repair and regeneration of injured skeletal muscle. Case presentation: Two 9-month-old DMD dogs were treated for a period of 18 weeks, with oral delivery of SAT-3247 for 4 consecutive days per week (i.e., 3 days off) at 10 mg/kg dose. SAT-3247 treatment resulted in improved muscle morphology, decreased infiltration of inflammatory cells, increased regenerative index (measuring the ratio of regenerating to necrosing cells) in multiple muscles, improvement in locomotory parameters in both forelimb and hindlimbs including greater force generation, and stable cardiac function. Conclusions Overall, this proof-of-concept pilot study in a canine model highlights the therapeutic potential of SAT-3247 to repair and regenerate injured muscle and serve as a treatment for DMD. Together, these data provide a compelling preclinical groundwork for advancing SAT-3247 towards clinical evaluation in DMD patients.