SUMMARY OF RESEARCH BEING UNDERTAKEN


This project focuses on the use of a cell in the skin called a fibroblast to try to increase stickiness in the skin so that it is better able to withstand injury. The research is relevant to people with the recessive dystrophic form of epidermolysis bullosa (RDEB).

The fundamental abnormality in RDEB is a lack of the protein collagen VII. This protein is the main component of Velcro-like adhesion hooks in the skin called anchoring fibrils. These fibrils bind the outer skin layer (epidermis) to that below (dermis). Efforts to restore collagen VII in the skin of people with RDEB are likely to lead to less blistering and scarring as well as improved wound healing, and possibly a reduced risk of developing skin cancer.

Currently, DebRA is funding projects trying to introduce the collagen VII gene into the principal cells of the epidermis, the keratinocytes. However, although keratinocytes are the main source of collagen VII in the skin, this protein is also made by fibroblasts, cells that reside in the dermis. Fibroblasts help construct the various fibres in skin that give skin its shape and resilience and have a key role in remodeling wounds and in scar formation.

It is known that the collagen VII gene can also be inserted into RDEB fibroblasts and that, in skin grown in the laboratory, this can help improve adhesion in anchoring fibrils. However, there are several technical and safety issues that need to be addressed when it comes to transferring this to individuals living with RDEB. Indeed, clinical trials of collagen VII gene-modified keratinocytes and/or fibroblasts are still perhaps 2-3 years away. Therefore, this project plans to try to improve skin adhesion using a complementary approach that doesn’t involve gene transfer technology.

Recently, it has been shown that fibroblasts from unrelated donors can restore normal levels of collagen VII in RDEB skin (in laboratory cultures) if used at sufficient cell density and if grown under certain conditions. The researchers plan to optimize this approach in skin models called organotypic cultures. They also want to include fibroblasts from the parents of individuals with RDEB. This may make the cells less prone to rejection and therefore more effective.

The final stage of the project is to transfer this laboratory data to clinical trials on people with RDEB.

Financial Summary