| SUMMARY OF RESEARCH BEING UNDERTAKEN
Junctional EB is a group of recessively
inherited skin disorders caused by a genetic defect at the junction between the layers of
the skin known as the dermis and epidermis. The results are extensive blisters and extreme
fragility of the skin and mucous membranes. In some cases Junctional EB results in death
in infancy from overwhelming skin blistering and secondary infection. Other cases of a
non-lethal form may be associated with a normal life span but produce blister wounds that
are chronically difficult to heal. At present there is no effective treatment for
Junctional EB.
Junctional EB presents
with clinical expression ranging from severe life threatening (Herlitz-JEB) to non-lethal
but disabling disorders. Most patients surviving beyond childhood are affected by various
forms of involvement compromising life quality. The identification of mutations in the
candidate genes for the various clinical forms of Junctional EB has been crucial for the
development of somatic gene therapy in these devastating diseases.
The patients with mild forms of Junctional EB are faced with disabling disorders that
compromise quality of life. Finding the faulty genes responsible for causing Junctional EB
has paved the way for the development of somatic gene therapy in these devastating
conditions. Prof Meneguzzi's group has recently shown that transfer of a gene restoring
the expression of laminin-5 in Junctional EB keratinocytes regenerates artificial
epithelia presenting the expression of healthy skin. This is the first evidence that a
genetic treatment of EB is a realistic goal.
Using animals presenting with a mild form of Junctional EB, the group is now perfecting
a model system of somatic gene therapy. Their studies are aimed at the cure of wounds and
erosions of the skin of Junctional EB animals by transplantation of artificial epidermis
obtaining using the keratinocytes of the host cured in vitro by gene therapy. The
knowledge gained from these studies will be of invaluable importance to the application of
gene therapy to patients with EB |
