Endocrine Abstracts

Ulceration is a common and severe complication of diabetes affecting 15% of the 200 million patients with diabetes worldwide. A significant proportion of these chronic wounds fail to respond to conventional treatment, hence major amputation is a feared outcome of diabetes. More than 60% of non-traumatic amputations in the western world are performed in the diabetic population. There exists a growing need for effective therapeutic agents to improve healing in these wounds.

The manipulation of actin-remodelling protein Flightless I revealed its important role as a negative regulator of wound healing. Reductions in Flightless produce improvements, whereas elevated expression impairs wound outcomes. We have studied the biopsy tissue recovered from patients with diabetic ulcers. Immunohistochemistry showed increased expression of Flightless in diabetic wounds compared to unwounded skin samples.

Both diabetic wound fluid and Flightless have previously been shown to inhibit cell proliferation and migration. Therefore to determine if the inhibitory effect of wound fluid could be due in part to Flightless, chronic fluids were preincubated with Flightless neutralizing antibodies (FliiAb) and the effect on fibroblast proliferation determined. FliiAb treated chronic wound fluid ablated the inhibitory effect of chronic wound fluid with fibroblast proliferation being restored to untreated control levels.

It is hypothesized that reduction of Flightless expression in the skin will create permissive environment for improved diabetic wound healing. Using in vivo wound healing models, wounds were created on the back of Type 1 diabetic and non diabetic mice. Diabetic mouse wounds healed faster when Flightless gene expression was reduced. Indeed neutralization of Flightless activity by Flightless specific monoclonal antibodies in WT diabetic wounds lead to higher rate of re-epithelialisation and acceleration of diabetes-impaired wound healing. These results suggest that reducing the activity of Flightless improves diabetic wound healing, which is promising for future development of new therapies for diabetic ulcers.

Comments/keywords: I am a podiatrist with 5 years of experience of working with both Type 1 and Type 2 diabetes patients. I am especially interested in the treatment of non healing diabetic wounds. I am currently undertaking a PhD by research at the University of Adelaide, South Australia. I am in my last year of PhD and I expect to submit my thesis in 3 months. I would be honoured to present the findings of my research results as part of the ‘nurse session’ of the 15th International Congress of Endocrinology.

Keywords: Wound healing, Flightless protein, diabetes, Flightless neutralizing antibodies, diabetic foot ulcers.