Therapies for genetic extracellular matrix diseases of the skin

Abstract

A specialized, highly developed dermal extracellular matrix (ECM) provides the skin with its unique mechano-resilient properties and is vital for organ function. Accordingly, genetically acquired deficiency of dermal ECM proteins or proteins essential for the post-translational modification and homeostasis of the dermal ECM, results in diseases affecting the skin. Some of these diseases are lethal or lead to severe complications for the affected individuals. At present limited efficient and evidence-based treatment options exist for genetic ECM diseases of the skin. There is thus a high unmet medical need, creating an urgent demand to develop improved care for these diseases. Here, by drawing examples from the wealth of research on epidermolysis bullosa, we present the current status of biological and small molecule therapies for genetic ECM diseases with skin manifestations. We discuss challenges, and using existing data to propose strategies and future directions allowing development of more efficacious therapies and advancement of them into clinical practice.

Keywords: Cell therapy; Collagen; Dystrophic epidermolysis bullosa; Gene therapy; Laminin; Small molecules.