Development of a Protein Replacement Therapy for Peeling Skin Syndrome
First published: 06 June 2021
Linked article: Valentin et al. Br J Dermatol 2021; 184:1123–1131.
Peeling skin syndrome type 1 is a severe form of congenital ichthyosis. Patients have severe itch and generalized peeling of the skin. Current therapeutic approaches are very unsatisfactory. The disease is the result of mutations (mistakes) in the CDSN gene, which cause a lack of the protein corneodesmosin (CDSN) in the skin.
We wanted to develop the first steps towards a specific protein replacement therapy for CDSN deficiency. The aim is to improve the cell–cell connection in two layers of the epidermis (the granular and corneal layers). Human CDSN was produced in bacterial cells. A liposomal carrier system was developed to transport the CDSN to the outer membrane of the epidermal cells. The liposomal carrier system was checked for stability and toxicity. Also, the effect on epidermal cells and artificial skin models was investigated.
The liposomes were found to be successfully present at the epidermal cell membranes. The CDSN-deficient skin models were treated with liposomal CDSN and demonstrated the presence of the replaced protein within the granular layer. Finally, the skin barrier test and microscopy showed improved skin integrity (skin that functioned better), if the skin models were treated with liposomal CDSN.
We believe that this study presents helpful laboratory results to develop a protein replacement therapy for patients with peeling skin syndrome and other diseases where there is also a lack of CDSN.