Investigating the dysregulation of cellular metabolism in hidradenitis suppurativa patients and whether metformin can reverse this altered metabolism
British Skin Foundation
Trinity College Dublin
Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting approximately 1% of the population. It is characterised by painful nodules and lesions in intertriginous areas of skin. Despite having similar prevalence to psoriasis, the disease is under-recognised, under-diagnosed and its pathogenesis is poorly understood. As a result, treatment options are limited and inadequate, and there is a pressing need for research into its pathogenesis to yield better treatment options. In recent years, immunometabolism has emerged as a major research field, since it became apparent that immune cell function is regulated via metabolic pathways. Although at the centre of other inflammatory diseases, no studies have investigated a dysregulated cellular metabolism in HS. Hence novel therapeutic targets may be uncovered. Furthermore, metformin, which can modulate cellular metabolism has demonstrated efficacy in treating HS. Our preliminary data showed that metabolism was dysregulated in the peripheral blood of HS patients. In addition, transcriptomic analysis of skin samples revealed striking differences in metabolic pathways in lesional HS skin compared with healthy skin. We will confirm our preliminary data showing dysregulated metabolism in peripheral blood of HS patients and identify the specific immune cell type/s responsible. We will then determine whether metformin treatment is associated with a reversal of the altered metabolism in HS. Finally, using available single cell RNA-sequencing data, we will further analyse altered expression of metabolic genes and pathways in HS lesional skin. This study will identify metabolic pathways that may be dysregulated in HS and represent potential therapeutic targets.
2.1 Biological and endogenous factors