Aim
Epidermolysis Bullosa is a chronic inheritable disease linked to severe blistering and fibrosis. Patients with EB have increased levels of Flightless I protein (Flii), a negative regulator of wound healing. Previous studies have demonstrated that topical application of Flii-neutralising antibodies (FnAb) improves healing outcomes in murine wounded and blistered skin. This study aimed to explore if systemically-administered FnAb could target skin wounds and similarly improve healing in wounded and blistered skin.
Methods
Using an incisional wound model in wild-type mice we investigated the effect of intraperitoneally (IP) injected FnAb, saline or IgG control antibody at the time of injury, on acute wound healing. Using fluorescently-labelled FnAb we further investigated FnAb biodistribution in this in-vivo wound model. Finally, we determined the effect of systemic FnAb administration on the survival of Collagen7a1-/- RDEB mice, which form EB-like blisters.
Results
Systemic administration of FnAbs resulted in significantly improved healing responses compared to saline or IgG controls as evidenced by reduced macroscopic and microscopic wound area, reduced wound length and increased wound re-epithelialisation. Biodistribution analysis showed direct homing of systemically administered FnAb antibody to the wound area which was maintained up to 7 days post-injury. Daily IP injections of FnAb to Collagen7a1-/- RDEB mouse pups significantly increased their mean survival rate (8 days) compared to control Ab administration (17 days).
Conclusion
Systemically administered FnAbs home to the site of injury and improve wound healing. The antibodies remain localised to the site of injury for at least 7 days. Systemic treatment of Collagen7a1-/- RDEB mice with FnAbs increases their lifespan suggesting that FnAbs reduce the symptoms of RDEB and may be a potential new and effective treatment strategy for the management of EB-related wounds and blisters.