Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects

Abstract

Ping-Chen Hou,1,* Nathalie del Agua,2,3,* Su M Lwin,4 Chao-Kai Hsu,1– 3 John A McGrath1,3,4 1Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3International Center for Wound Repair and Regeneration (iWRR), National Cheng Kung University, Tainan, Taiwan; 4St John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College London, London, UK*These authors contributed equally to this workCorrespondence: Chao-Kai Hsu, Department of Dermatology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan City, Taiwan, Tel [phone] Ext.5415, Fax [phone], Email [email protected] John A McGrath, St John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College London, London, UK, Tel [phone], Fax [phone], Email [email protected]: Dystrophic epidermolysis bullosa (DEB) is one of the major types of EB, a rare hereditary group of trauma-induced blistering skin disorders. DEB is caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis. DEB can be subclassified into dominant (DDEB) and recessive (RDEB) forms. Generally, DDEB has a milder phenotype, while RDEB patients often have more extensive blistering, chronic inflammation, skin fibrosis, and a propensity for squamous cell carcinoma development, collectively impacting on daily activities and life expectancy. At present, best practice treatments are mostly supportive, and thus there is a considerable burden of disease with unmet therapeutic need. Over the last 20 years, considerable translational research efforts have focused on either trying to cure DEB by direct correction of the COL7A1 gene pathology, or by modifying secondary inflammation to lessen phenotypic severity and improve patient symptoms such as poor wound healing, itch, and pain. In this review, we provide an overview and update on various therapeutic innovations for DEB, including gene therapy, cell-based therapy, protein therapy, and disease-modifying and symptomatic control agents. We outline the progress and challenges for each treatment modality and identify likely prospects for future clinical impact.Keywords: skin, blister, gene therapy, cell therapy, inflammation, fibrosis

Keywords

• skin
• blister
• gene therapy
• cell therapy
• inflammation
• fibrosis