Grant: Travel Awards - Institute Community Support

Pressure injuries (PI's), also known as bedsores or pressure ulcers, are areas of localized damage to the skin and underlying tissue due to pressure, shear or friction. They are common in the elderly and costly in financial and human terms. Critically, treatment options are limited. Granzyme B (GzmB) is a protein-degrading enzyme present in normal skin at minimal amounts. However, GzmB becomes elevated skin cut, burnt, damaged by the sun, or afflicted by various skin diseases. Here, GzmB prevents the skin from repairing itself and this leads to scarring. In addition, GzmB progressively accumulates in skin as it ages, with this predicted to contribute to skin thinning and the enhanced likelihood of tearing. Previously, wounds in laboratory mice where GzmB was genetically knocked out showed improved healing and reduced visible signs of skin damage. In collaboration with viDA Therapeutics, the Granville Lab are developing novel inhibitors of GzmB that can be applied topically to the skin, showing emerging evidence of improved healing outcomes. Studies by our lab indicate wound fluid obtained from PI's have significantly elevated GzmB, an observation recent supported by the observation of GzmB's elevation in PI-affected skin. GzmB is therefore predicted to have an important role in the severity of PI's. The aim of the current study is to investigate the contribution of GzmB to the development, severity and healing potential of PI's. We propose that the inhibition of GzmB, using topically applied drug formulations, will reduce wound severity and decrease recurrence. PI's are predicted to become more common in response to an aging and more obese population. The development of new therapeutic options for PI's would have an enormous public health benefits.