Stress hormone metabolism - a novel anti-fibrotic therapeutic pathway for chronic wounds

Chronic wounds, such as DFU, fail to heal within 2-8 weeks (Kwaw et al., 2017) and often takes months to resolve. This results in burden to the patient (clinic visits, potential amputation) and cost to the NHS. Treatments have not improved for many years and so there is an unmet need to address this issue. Novel treatments may be derived from anti-fibrotic mechanisms.

The overarching aim of this project is to generate essential pre-clinical mechanistic data in human primary tissue to support ongoing development of 11β-HSD1 inhibitors as a novel therapy for chronic wounds. The project will explore new mechanistic links between stress hormone (cortisol) activation by 11β-HSD1 and molecular targets of skin fibrosis as key mediators of delayed wound healing. Novel pro-fibrotic 11β-HSD1 targets will be identified as molecular markers of 11β-HSD1 inhibitor efficacy for future clinical trials.

Outputs will provide a new dimension to our ongoing wound healing studies primarily aimed at identifying novel therapeutic targets to mitigate fibrosis and improve healing in diabetes. However, this project provides scope to explore additional therapeutic benefits in SSc, which also presents with delayed wound healing. As an emerging field, investment in early career research (such as this proposal) is vital for longevity of this promising therapy.

Collaborations cemented here between the PhD student, scientists in diabetes, skin fibrosis, cortisol metabolism and wound healing, clinicians, and industry partners (AstraZeneca) will support ongoing development of novel therapeutics for wound healing