SUMMARY OF RESEARCH BEING UNDERTAKEN

Rapid advances in understanding the causes of DEB have allowed scientists to plan novel treatment strategies. However, a significant knowledge gap still exists between laboratory experiments and the successful treatment of an individual with DEB. Many technical problems must still be solved, safety issues addressed and the therapies tested in animals before clinical trials can be planned. So far, one important problem has been the lack of suitable animal models for testing new therapeutic approaches.

Recently, the researchers have developed a mouse model for DEB, which can be used for such tests. The mouse exhibits the characteristic symptoms of recessive non-Hallopeau-Siemens DEB, i.e. trauma induced blistering of the skin and mucous membranes and dystrophy of the nails. The skin blistering is not too severe and the mice live to adulthood. In a similar fashion to the skin of an individual with DEB, the amount of collagen VII and the anchoring fibrils is reduced in the skin of the DEB mouse. This is an advantage for therapy studies, since the mice are unlikely to develop an immune response and reject the therapeutic molecules.

The project proposes to use this newly developed mouse for characterization of the efficacy and possible side effects of collagen VII based protein and cell therapy for DEB. Recombinent collagen VII and cells will be injected into the mouse skin and, during an observation period of about four weeks, multiple skin biopsies will be analysed by a number of different methods to document the curative effects and any side effects, such as inflammation.

From these investigations we expect to obtain significant new information on the quality and quantity of recombinant collagen VII required for the treatment of DEB in humans, as well as on sustainability, functionality and side effects of collagen VII based treatments.