Construction of Transplantable Skin Grafts

DebRA International Completed Research Projects

DebRA Research

Other DebRA Research

Construction of Transplantable Skin Grafts using Phenotypically Reverted Junctional EB Keratinocytes

Name of Researchers:		Professor Guerrino Meneguzzi

Places of Research:		UFR de Médecine INSERM U 385 Nice

Approved by DebRA Medical & Scientific Advisory Panel:		15 December 1997

Budget approved by DebRA central Committee:		17 Jan 1998

Date Commenced		1 December 1998 - 2 years

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.

Using genetically modified lethal Junctional EB keratinocytes, Professor Meneguzzi’s group have recently achieved the construction of artificial skin with the adhesion properties of the normal counterpart. The construction of keratinocyte engraftments containing transfected genes correcting the mutation is therefore conceivable. Their investigations are now devoted to the somatic gene therapy of the non-lethal form of EB, in the perspective of the construction of artificial epithelia for autologous skin grafting.