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Gene therapy for Epidermolysis Bullosa: a model system for treatment of inherited skin diseases

Final Report Summary - SKINTHERAPY (Gene therapy for Epidermolysis Bullosa: a model system for treatment of inherited skin diseases)

Epidermolysis bullosa (EB) is a rare genetic skin disease, affecting approximately 30 000 individuals in Europe (prevalence of about 60 / million) and approximately 400-500 000 people worldwide. Most patients are children and there is no treatment available yet. EB is characterised by an extreme fragility of the skin, which results in unremitting blisters and erosions with unceasing wound healing. The skin lesions result from the poor adhesion of the epidermis to the underlying mesenchyme, which makes the skin vulnerable to damage caused by mild friction and trauma. The genetic bases of the different clinical forms of EB have been elucidated, and a precise correlation has now been made between genetic defects of the basement membrane components and the types of EB, which have been classified within the Simplex (EBS), Junctional (JEB), and Dystrophic (DEB) forms.

In DEB, generalised blisters heal with scarring. Extensive and progressive mutilating scarring results in increasing disability and deformity of the fingers, and joint contractures. The disease may also affect other areas of the body (mouth, throat, eyes) causing discomfort and, in most of cases, difficulties in carrying out vital activities, like eating. The most severe cases are often complicated by the development of aggressive skin cancer and premature death. The physical suffering can be compared to that of severely burnt people. In addition to suffering, patients are faced with social difficulties: they cannot perform physical activities, need permanent assistance and regular medical treatments. Additionally, EB patients are excluded from the workforce not only because of their physical appearance but also because people are not well informed and aware of the condition.

The project's goal was to develop a gene therapy approach to DEB, which is caused by inherited genetic defects of collagen type VII (encoded by the COL7A1 gene), and design appropriate phase I/II clinical trials to exploit the knowledge generated by the preclinical studies proposed by the SKINTHERAPY consortium.

Specifically, the project aimed at developing a gene therapy technology model based on autologous transplantation of skin made in vitro using genetically modified epidermal stem cells. This includes the development of vectors, gene transfer technologies, and preclinical models of cutaneous gene therapy.

The overall expected result was a model system for DEB treatment using ex vivo gene therapy. This model can be extended to other genetic skin diseases. The model system addressed the current weaknesses in related research and aimed particularly at the development of significantly improved, efficient and safe delivery systems, which are urgently needed.