Development of systemic antibody therapy for burns.
Dr Allison Cowin
University of South Australia
Burns are one of the most painful injuries a child can sustain and survive. Unfortunately current treatments are still a long drawn out process relying heavily on wound dressings that need regular and painful changes and still result in horrific scarring and contractures. We have taken the novel approach to develop a systemic, injectable antibody therapy that heals wounds from the “inside out”. This ground breaking approach could be life changing for the many children who suffer extensive burns.
Professor Allison Cowin, Professor Fiona Wood.
The aim of this project was to develop a simple systemic, injectable antibody therapy that specifically targets a wound inhibitory protein, Flightless I (Flii) improving healing and reducing scar formation after burn injury. Specifically we aimed to:
Aim 1: Evaluate the effectiveness of systemic Flii neutralising antibodies in a preclinical porcine model of burn injury and scar formation.
Aim 2: Determine the mechanism of action and biodistribution of Flii neutralising antibodies in burn wounds.
To date we have been able to successfully complete the studies outlined in our application which address Aim 2. We have investigated domain specific Flii antibody effects on Flii function (aim 2.1) comparing the effects of neutralising different flii epitopes on Flii function using specific antibodies raised against the LRR domain, the middle domain and the gelsolin domain. Our studies have shown that the middle domain of the Flii protein is critical for Flii functionality and that antibodies that specifically target this region are the most efficacious at neutralising the functional activity of this protein. We have also performed extensive studies to determine the biodistribution of Flii neutralising antibodies (Aim 2.2) when injected systemically into mice with burns and acute excisional wounds. These studies have shown that fluorescently-conjugated FnAbs when injected at the time of injury home to the site of burn injury as assessed using live animal imaging and analysis of ex vivo tissue samples. Wounded mice showed more antibody accumulation around the injured area which persisted for six days following wounding suggesting that a single injection at time of injury would enable antibody functionality for up to 1 week.
However, our studies to assess the effect of efficacy of systemic FnAb and the optimal treatment regime required to improve healing and reduce scarring in a porcine model of burn injury repair have been delayed. We obtained animal ethics to perform the pig studies in 09/04/2018 but it was important that we identify the optimal Flii antibody from our panel using the in vitro and in vivo mouse studies described above. We are now ready to commence these studies and our collaborator A/Prof Mark Fear who works with Co-CI Fiona Wood has offered to come from Perth to Adelaide to instruct us on the best way to perform this complex burn model. I expect these in vivo studies to be completed by July 2019, with the following assessment, analysis and publications to be completed by Dec 2019.
An extension to the project period has been granted to December 2019 to allow pig studies to be undertaken at SAHMRI’s large animal facility at Gilles Plains with the assistance of their highly skilled animal staff.