Epidermolysis Bullosa is a set of genetically inherited conditions affecting 1 in 17,000 of the population. A fault in a gene causes the skin to be extremely fragile. The layers of the skin do not adhere properly and painful widespread blisters occur very easily. These can lead to increasing disfigurement, disability and in the most severe forms death in early childhood.

Several gene therapy strategies are currently under development for a wide spectrum of hereditary disorders, including EB. Most systems used for therapy of autosomal recessive disorders (including most forms of EB) are based on introducing a correct copy of the responsible gene. All have a number of drawbacks eg inflammatory & immunological reactions, mostly caused by the viral delivery systems used or the inefficacy of the gene transfer in the case of gene delivery systems using liposomes.

This research aims at correction of a specific pathogenic mutation at the cellular level by RNA/DNA mediated homologous recombination. The advantage of this approach is that once a defect gene copy has been corrected, its transcription and translation are under control of their natural regulatory elements. This is in contrast with the artificial regulation obtained in current gene therapy strategies. The proposed approach has the additional advantage that it could also be applied to autosomal dominant hereditary disorders including particular forms of EB.

The researchers recently reported a case of "natural gene therapy" or more accurately natural allele correction. Understanding this process and then mimicking and adapting it for application to EB patients is one of the aims of this research.

Dr Hans Scheffer is a scientist who has been working in the field of medical genetics since 1983, initially in cancer, then cystic fibrosis and EB. Since 1994 he has been a member of the Medical & Scientific Advisory Commission for the Dutch EB Association.