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.

The different forms of EB are caused by molecular abnormalities (mutations) in many genes encoding the proteins which provide the strength to hold the layers of the skin together at the junction between the dermis and the epidermis, called the cutaneous basement membrane.

Lay Summary of Research

EB Simplex is caused by defects in keratin genes. Keratins are filamentous proteins which are found in a number of tissues including the skin. They are important for its structural integrity and alterations in these proteins can make the cells fragile and less resilient to mechanical stress. A great deal of progress has been made in recent years in identifying the mutations (changes in DNA) which are responsible for EB Simplex and in some cases it is now possible to carry out prenatal testing for the disorder. However there is still no treatment or cure.

The aim of this research is to investigate the possibility of correcting the genetic mutation in the cell by using small stretches of synthetic nucleic acids (the substance which DNA is made of), which correspond to the region of DNA in which a mutation has been identified. The presence of this synthetic molecule stimulates repair mechanisms within the cell which corrects the defect. This technique has been used to alter DNA in other systems and would appear to be an attractive gene therapy for EB Simplex since the agents involved are non-toxic. The project will involve developing model systems in which to test the viability of this approach.

Abstract of Research

Epidermolysis Bullosa Simplex results in mutations in the genes for keratins K5 and K14. The primary aim of this research is to investigate the use of chimeric RNA/DNA oligonucleotides to correct known pathogenic point mutations. Assay systems based on cultured keratinocytes and animal models will be developed in which the viability of this approach can be assessed and refined. If successful, this work will be applicable to the treatment of other forms of EB and related skin disorders.

Dr Rugg is an experienced and successful EB Researcher. DebRA has funded her previously when she was part of Prof Birgitt Lane's group in Dundee. Her move south coincides with her husband's job and the invitation by Prof Irene Leigh who is one of the leaders in EB Simplex research. This project will further enable the development of successful treatments and combine collaboration, which is one of the hallmarks of EB research throughout Europe.