Replicating peeling skin diseases in a living skin model

A number of chronic skin conditions have peeling of the skin as the dominant expression; akin to skin peeling following severe sunburns. In the chronic conditions, peeling is cyclical or continuous, often affecting hands, feet, or the body. Today, there is no effective treatment for these conditions, leaving patients subjected to trial and error with a variety of non-effective and often also expensive therapies.

A number of abnormal gene variants have been found to disrupt the normal maturation of the skin. Using a gene manipulation tool known as CRISPR, the team led by Dr Hull will build understanding of the role of four known genes causing skin peeling syndromes. This will be done by replicating the diseases in cell cultures grown into full thickness skin and studying the cellular and biochemical changes caused by the induced gene modifications.

Of particular interest is cathepsin B, an enzyme that has been found to play an important role in peeling associated with the skin disorder, keratolytic winter erythema.

The team’s hypothesis is that there is an important and dynamic interplay and balance between a number of enzymes in the outer layers of the skin and that if this balance favours the activity of cathepsin B, peeling results.

If this is shown, it may be clinically very relevant as there are a number of known compounds that inhibits cathepsin B and which then could be used to treat patients with chronic peeling as a consequence of their skin disorder.