Development of Topical Human Recombinant Decorin as an Anti-Scarring Therapy for Dystrophic Epidermolysis Bullosa

Short lay summary

Patients with dystrophic epidermolysis bullosa (DEB), especially those with the recessive form of the disease (RDEB), have extremely fragile skin and oral mucosa which results in severe skin and oral blisters that heal with extensive scarring. Many RDEB patients also suffer from oesophageal strictures, and contracture and fusion of the digits, which results in pseudosyndactyly, (e.g., ‘mitten deformity’ of the hands and feet, in which fingers and toes become fused).  

This research is investigating the potential of an engineered form of the naturally occurring human protein, decorin, as an anti-scarring agent. Decorin helps to provide maintenance and development of the extracellular matrix in the skin which provides support and various functions including the communication between cells.

Previously, DEBRA UK funded research by Professor Zambruno (2013), who identified that TGF-β (Transforming growth factor), a molecule which contributes to the function of cells, seemed to be associated with more severe symptoms, leading to scarring. In this research it was also discovered that decorin inhibited the levels of TGF-β. A case study of identical twin men with RDEB, showed decorin was expressed almost twice as much in the twin, who had a moderate scarring phenotype (the observable traits seen in the body “the clinical picture”), as compared with his identical twin brother who had a severe scarring phenotype. Both had similarly depressed C7 (collagen 7) levels. It was hypothesized that decorin may help to control TGF-β activity which leads to scarring.

Scientific summary

An anti-scarring therapy like decorin, which has a well-elucidated mechanism of action, may have the potential to improve the quality of life for patients affected by DEB by decreasing the scarring associated with the chronic cycles of skin blistering and wound healing.

These data recently led the FIBRX team to hypothesize that a topical (gel) formulation of human recombinant decorin (hrDecorin), an engineered form of the native protein, would be an ideal anti-scarring therapeutic for DEB (both dominant and recessive DEB). This research will begin the process of investigating whether a topical hrDecorin gel will reduce scarring in DEB skin.

Main aims of this stage of the research

·       To manufacture, develop and test a simple, stable, topical gel formulation of hrDecorin suitable for human clinical trials,

·       Conduct critical toxicology and preliminary safety studies to support the submission of an Investigational New Drug (IND) application to US Food and Drug Administration (FDA). An IND is required for advancing to human clinical trials

Funding of this preliminary work will allow FIBRX to proceed with all the activities necessary to file an IND with the FDA, Dermatology & Dental Division, leading to the conduct of a first in man clinical trial with a topical gel formulation of hrDecorin. FIBRX plans to raise funds for this clinical study in the future.  At the current time, the required pre-clinical IND-enabling work is being supported by a number of funders including the PRMRP Program of the US Department of Defense. The proposal meets core PRMPR strategic requirements, “topical therapeutics to enhance wound healing in EB” and “development of novel therapeutics to reduce EB symptoms and improve quality of life”. The core strategies of the PRMPR are a guide to help industry partners work towards finding drugs and treatments for EB.

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