There are about 5400 human genetic diseases and in principle the mutation cause of the majority of them would be correctable by genome editing and other forms of gene therapy. This is approximately 10% of people. 30 Million in Europe alone. These are all the silent sufferers of presently incurable conditions.
Basic research over some 30 years has elucidated the genes causing various types of EB and has led to effective, accurate and early prenatal diagnosis. Acquired knowledge and scientific advance have brought us to treatment trials. There have also been some pivotal events which led to new avenues of research.
In Minnesota in 2007, John E Wagner, a respected and experienced transplant surgeon, performed a Bone Marrow Transplant on Nate Liao (who suffers from RDEB). This trial marked a revolution in EB research and due to positive results, led to full BM transplants in other children.
The results of this trial, whilst positive, highlighted the significant risks associated with full Bone Marrow Transplants in RDEB patients. Two of the 7 children transplanted died. One as a result of pre transplant treatment and the second because of transplant rejection 6 months after transplant.
Whilst it seemed clear that Bone Marrow cells could prove to be very valuable in the repair of damaged skin, a safer approach is being sought.
Shinya Yamanake 2006 discovers he could reprogram mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body. He wins a Nobel Prize in 2012 for this discovery
Research published (Tamai, McGrath April 2011) by Professor John McGrath (Guys and St Thomas’s Hospital, London) and colleagues from the group of Professor Katsuto Tamai in Osaka, Japan, marked a huge step in this direction. They identified, for EB, which cells in the bone marrow are important in repairing wounds in skin and also pinpointing the signalling mechanism that directs cells to the wounded areas.
Gene editing a cure for leukaemia: In 2015, Professor Waseem Qasim of UCL uses gene editing to disable a gene in donor cells that makes a receptor that recognises other cells as foreign.
In 2017, a young boy with Junctional EB was given ‘a new skin’ by using transgenic stem cells to regenerate an epidermis. (click here to see BBC News report)
There are treatment options now being developed. We are engaged in ‘first in man’ clinical trials, additional preclinical studies, phase two trials for forms of gene therapy involving skin sheets, trying to elucidate fully disease mechanisms and how potential therapies might work. The results are expected to lead to varying levels of treatment for RDEB and ultimately a cure.