Improved Perfusion and Wound Healing in Healthy Pigs With MRG-110, an Inhibitor of MicroRNA-92a
Rusty L. Montgomery, Linda A. Pestano, Corrie L. Gallant-Behm, Paul Rubin.
miRagen Therapeutics, Boulder, CO, USA.
miR-92a has previously been shown to inhibit angiogenesis. Conversely, inhibitors of miR-92a accelerate angiogenesis, improving function following myocardial infarction and vascular injury. The current study suggests miR-92a inhibitors can accelerate wound healing in normal healthy skin as well. The effect of a miR-92a inhibitor on wound healing was investigated in a GLP pig wound healing study. Vehicle or 3 dose levels of a locked nucleic acid (LNA)-modified inhibitor of miR-92a, MRG-110, were administered three times a week for two weeks by intradermal injection around the periphery of 2.5 x 2.5 cm full thickness excisional wounds. Treatments were randomized across eight wound sites on each of six pigs (12 wounds/MRG-110 dose level). Two control pigs with 8 wounds each were treated with either standard of care (SOC; wound dressing changes only) or phosphate buffer vehicle control. Wound healing and perfusion were assessed by photography, wound area measurements, laser Doppler imaging, and histology over a 7-week period until complete wound closure was achieved. MRG-110 significantly (p<0.05) increased vascularization within the dermal portion of the wound bed which was associated with significant (p<0.05) increases in perfusion in drug treated wounds compared to controls on Day 14. Additionally, MRG-110 significantly (p<0.01) increased granulation tissue formation. These effects led to a ~5-day improvement in achieving 50% wound closure in healthy pigs compared to SOC or vehicle. The lowest dose tested had maximal benefit indicating even lower doses may be effective. These data suggest that MRG-110 has the potential to accelerate wound healing in healthy skin and provide support for future clinical trials of antimiR-92a therapeutics in acute wound healing indications.
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