Decorin is a natural anti-scarring protein that is widely expressed in many tissues in the body. Decorin was discovered by our co-founder, Dr. Erkki Ruoslahti, and named after its ability to bind to and ‘decorate’ collagens, major structural proteins of the extracellular matrix (ECM). Scar tissue (fibrotic tissue) is composed of collagen just like normal skin; however, normal skin has higher flexibility and tensile strength because collagen fibers have a highly organized cross-weave structure. In contrast, scar tissue is made of collagen fibers deposited in less organized, horizontally-arranged, parallel sheets which makes scar tissue less flexible than healthy tissue. By binding to collagens, decorin helps organize and normalize the structure of collagens, leading to healthier tissue regeneration by disrupting the horizontal alignment of collagen fibers typically produced in scar formation.
The anti-fibrotic properties of decorin are supported by decades of research. Many publications have demonstrated that mice lacking decorin have scarring of the lung, heart, liver, kidney, and skin. Decorin levels are reduced in raised scars and lost during scar formation. Decorin also has anti-inflammatory properties, which along with its anti-fibrotic activities slow the rate of scar tissue formation and, more importantly, reverse fibrosis through tissue re-modeling. These properties are a product of decorin regulating the production of ECM components, normalizing collagen structure, and inhibiting the main growth factors that drive scarring and promote inflammation (e.g., TGF-beta 1, TGF-beta 2, CTGF, and PDGF).
In a remarkable case study of identical twin men with RDEB, decorin was expressed almost twice as much in the skin of one twin . This twin had a moderate scarring appearance, compared with his identical twin brother whose RDEB caused severe scarring. This is despite the fact that both twins had similarly depressed levels of type VII collagen. We, therefore, hypothesize that decorin could be an effective anti-scarring therapy for those affected by DEB.
We are developing a topical gel formulation of a recombinant (engineered) form of decorin called hr-decorin that retains all the activities of naturally-occurring decorin. In fact, hr-decorin inhibits certain pro-fibrotic growth factors better than natural decorin. Multiple academic groups have demonstrated the anti-fibrotic potential of hr-decorin in animal models of skin wound healing. In these studies, hr-decorin prevented dermal scar formation and promoted tissue regeneration. A gel formulation of hr-decorin applied topically to full thickness wounds of mice caused “scarless healing” . The hr-decorin-treated wounds looked the same as normal skin whereas the placebo-treated group developed dermal scars. Over-expression of decorin in a mouse model of RDEB increased survival in the mice, and the anti-fibrotic activities of decorin greatly reduced scarring, including significantly reduced mitten deformity in the mouse paws. We hope to advance our topical hr-decorin drug into clinical trials in DEB in the near future.
1. Odorisio, T, et al. "Monozygotic Twins Discordant for Recessive Dystrophic Epidermolysis Bullosa Phenotype Highlight the Role of TGF-Beta Signaling in Modifying Disease Severity." Human Molecular Genetics, 23(15), 2014, 3907–3922. [PubMed]
2. Ruoslahti, EI, Border, WA. 1994. Methods of Preventing or Reducing Scarring with Decorin or Biglycan. Sanford-Burnham Prebys Medical Discovery Institute, assignee. Patent 6509314. 13 June 1994.