Individuals with recessive
dystrophic EB (RDEB) suffer from widespread blistering and complications such as poor
wound healing, severe scarring and, in some cases, the development of skin cancer. The
condition is caused by loss of type VII collagen but there is currently no specific
treatment. The goal of this research is to provide a treatment that will improve quality
of life.
Although replacing the entire body skin surface is not
feasible, it is aimed to produce specially engineered skin grafts that are genetically
modified to produce normal type VII collagen. As the original skin will be from the same
patient receiving the graft, the new skin should survive, increasing stickiness in the
skin and reduce blistering.
Recently, the researchers have made considerable progress
towards this goal. They have managed to construct copies of the entire type VII collagen
gene and have used a particular delivery technique using viruses to transfer this molecule
to type VII collagen-deficient RDEB skin cells. Significantly, they have shown sustained
re-expression of type VII collagen in treated cells in culture, thus demonstrating the
feasibility of this viral approach for gene therapy in RDEB.
The aim of this project is now to complete all the
essential basic research studies required before clinical trials can take place. These
important steps include: establishing a source of an affected individuals stem cells (the
regenerative units in skin), constructing and producing high quality viral delivery and
packaging systems containing the type VII collagen building blocks, and making sure the
new gene product is expressed appropriately in the long-term. The latter will require
assessment in models of artificial skin as well as a small number of laboratory animal
(mouse) experiments. To achieve these goals, the project will involve the collaborative
expertise of 5 international groups, all experienced in EB research work. The hope is that
this project will provide a robust foundation for the design of clinical trials in gene
therapy in RDEB patients in the not-too-distant future.
