Prospects for treatment of skin disorder epidermolysis bullosa

It is extremely important to inspect every patient with the serious skin condition epidermolysis bullosa (EB) very carefully for healthy skin patches. In these healthy patches, the body itself appears to correct the effect of a pathogenic DNA mutation. The healthy skin cells from these skin patches can be reprogrammed to become stem cells, which can be used to generate healthy skin transplants or bone marrow cells. This may lead to a breakthrough in the treatment of patients. These healthy skin patches may be expected in all patients with EB. This was demonstrated by PhD research carried out by the clinical geneticist Peter van den Akker from the University Medical Center Groningen. He will be awarded a PhD for his research on 6 November by the University of Groningen.

Epidermolysis bullosa is a collective term for a large group of serious hereditary skin conditions. The common characteristic is that patients very easily form blisters and other types of damage to the skin and mucous membranes. The blister formation is usually present from birth. In extreme cases, patients can die from this condition. Young patients suffering from EB are often referred to as ‘butterfly children’.

Van den Akker focused his research primarily on one of the four EB variants, dystrophic epidermolysis bullosa. The blister formation associated with this disease originates from mutations in a gene called COL7A1. One of the things Van den Akker studied in his PhD research was the phenomenon that the body itself corrects the effect of these pathogenic gene mutations, which is called revertant mosaicism or natural gene therapy. This phenomenon is recognizable as a healthy skin patch surrounded by affected skin. Based on mathematical calculations, Van den Akker’s research shows that this phenomenon can be expected in all EB patients. This prediction proved to be true for junctional EB, another EB variant, where healthy skin patches appeared in all patients. Further research will show if this is true for the other variants as well.

According to Van den Akker, the natural gene therapy offers the prospect of a breakthrough in the treatment of patients. These healthy skin cells can be reprogrammed to become specific stem cells using a method, the induced pluripotent stem cell method, for which the Japanese Prof. Yamanaka and the British Prof. Gurdon won the Nobel Prize in 2012. In doing so, an endless source of endogenous stem cells is produced, which researchers can grow into skin or bone marrow stem cells. These can be used for skin and bone marrow transplants. Dermatologists and geneticists from the Centre for Blistering Diseases at the UMCG are collaborating with two laboratories in the US in order to develop this technique further. It will take many years before this technique can be applied to patients in clinical practice.

Van den Akker’s advice is therefore to inspect all EB patients very carefully for healthy skin patches.

P.C. van den Akker (Rotterdam, 1979) studied medicine at the University of Groningen. He conducted his PhD research at the Genetics and Dermatology departments at the UMCG. Van den Akker’s research was supported by ZonMw. His thesis is entitled ‘Dystrophic epidermolysis bullosa. Novel insights into the genotype-phenotype correlation and somatic mosaicism’. He works as a clinical geneticist at the UMCG where his area of interest is hereditary skin disorders.