Type_7_collagen_expressionRecessive Dystrophic epidermolysis bullosa (RDEB) (OMIM #226600) is a rare and severe genetic skin disease of children and adults responsible for blistering of the skin after mild trauma. The skin (epithelium) of people suffering of this disease is so fragile that even minor rasping could produce blistering. Prevalence of DEB in Europe is estimated between 0.03 and 0.24 in 10,000. It is caused by recessive mutations in COL7A1 encoding type VII collagen, the constituent of anchoring fibres which form essential structures for dermal-epidermal adherence (Varki et al., 2007).

Type VII collagen expression



To date, only medical care protocols involving symptomatic treatment of recurrent and severe blistering can decrease or delay complications of the disease: local and systemic infections, syndactyly, malnutrition, joint contractures, and aggressive skin cancers. No drug is known to compensate the underlying molecular defects in EB disease. Prolonged use of steroids is contraindicated because of their lack of efficiency on dermal-epidermal adhesion and their side effects. No other drugs, including phenytoin and tetracycline, which often are associated with serious adverse complications, have improved the blistering or epithelial disadhesion in RDEB significantly or consistently.

Surgical treatment mainly includes removal of squamous cell carcinomas and hand surgery to treat fusion of the digits in severely affected patients. Unfortunately, this particularly heavy and painful surgery only delays the loss of function of hands in these patients.

Other surgical procedures include:


a. Skin bioequivalents

Artificial skin bioequivalents made using allogeneic cells, such as Apligraf (Organogenesis, Canton, MA, USA) have been used in small numbers of DEB patients on acute and chronic wounds (Falabella et al., 2000). Initial results have been encouraging; however, the duration of survival of such grafts has not been fully determined.


b. Allogeneic or autologous skin graft

Grafts of skin equivalent made of allogeneic cultured keratinocytes have been used with limited success. It is tempting to consider autologous skin grafting, but this has proved to be of limited value in ensuring permanent healing (Terrill et al., 1992). Indeed, autologous grafting of either full-split skin (taken in non blistering areas) or grafting of epithelia made from cultured autologous keratinocytes have so far failed to produce lasting benefit (McGrath et al., 1993). The cost of such treatments, considering covering of large areas for only a limited time means that this is not an option for most DEB patients.


Overall, these palliative treatments of RDEB cannot prevent the recurrence of the lesions arising from loss of dermo-epidermal adherence caused by defective expression of type VII collagen and none of these treatments are curative.



Figure 1: Skin equivalent preparation. © INSERM



The GENEGRAFT research program aims to fill the serious therapeutical void by developing ex vivo gene therapy protocols for RDEB by:

  • Grafting of genetically corrected autologous skin equivalent re-expressing type VII collagen over the most affected areas of the body,
  • Restoring dermal-epidermal cohesion.


It is expected that the clinical benefits of a novel and effective therapy for RDEB would prevent the occurrence of the most severe complications of the disease, thus improving the functional and vital prognosis of these young patients.