Еpidermolysis bullosa: approaches of gene and cell therapy

Dystrophic epidermolysis bullosa (EB) is an inherited skin
fragility disorder in which blistering occurs in the sublamina
densa zone at the level of anchoring fibrils of the dermoepidermal
junction. EB result from mutations in the type VII
collagen gene (COL7A1) and the nature of these mutations
and their positions correlate with the severity of the resulting
phenotypes. Presently there are not methods of therapy with
the expressed curative effect.
It is known that the development of approaches to the
treatment of EB is based mainly on the protein, gene and cell
therapy.
In mouse model it was shown that protein therapies of EB
is promising since intradermally injected purified human C7
collagen corrected the EB phenotype and markedly prolonged
survival of the animals.
For gene therapy approaches to EB, the use of various
vectors have been developed. In such a way scientists
efficiently delivered cDNA or full-length type VII collagen into
keratinocytes or fibroblasts and achieve correction of the
genetic defect and persistent synthesis and secretion of
functionally active collagen in transduced cells.
The use of stem cell therapy looks like considerable
progress in solving the problems of EB. For this purpose were
found suitable the bone marrow mesenchymal cells as they
were capable to give rise to functional development of skin
cells, including keratinocytes and dermal fibroblasts. Some
investigators are looking at the potential of human umbilical
cord cells as a source of epithelial stem cells with appropriate
ability for epidermal reconstitution. It is also shown that stem
cells from human umbilical cord blood in in vitro experiments
can differentiate into keratinocytes, so, cord blood is a good
source of cells for ex vivo expansion and transplantation in
patients with large defects of the skin. An international team
of researchers recently conducted an initial phase of clinical
trials of donor bone marrow stem cells in patients with the
most severe form of EB. Despite the modest initial successes,
the results showed that treatment with stem cells in the
future will bring hope to extend and improve the quality of life
of patients with EB.