The clinical trial, led by King’s College London in collaboration with Great Ormond Street Hospital (GOSH), recruited 10 children with recessive dystrophic epidermolysis bullosa (RDEB).
RDEB is a painful skin disease in which very minor skin injury leads to blisters and poorly healing wounds. About 1,000 people in the UK live with RDEB. The fragile skin in RDEB also scars, develops contractures and is prone to life-shortening skin cancers. There is currently no cure for RDEB.
The Phase I/II EBSTEM trial, funded by the Sohana Research Fund with donations from Goldman Sachs Gives, tested the safety of the treatment and also sought to establish whether it could help to reduce the severity of the disease and improve quality of life for these patients.
During the first six months of the trial, participants were given three infusions of mesenchymal stromal cells (stem cells) grown from the bone marrow of unrelated donors. Mesenchymal stem cells (MSCs) have been shown to home to wounded tissue and mediate wound healing in previous studies. Although the cells do not survive permanently, they may still deliver clinical benefits.
The children were then monitored for a year after the cell infusions. A range of monitoring tests showed no serious adverse effects in patients who received the therapy. The pain score (level of pain) reported was on average lower than before treatment, and the severity of the condition was also reported to have lessened following the infusions. Parents also reported better wound healing, less skin redness and fewer blisters.
Overall, the paper concludes that the outcomes of the trial are promising, although this is an unblinded study of participants which may introduce a positive bias in the information reported. In interviews families reported a range of benefits from having better sleep, a parent being able to return to work part-time because of reduced caring needs, and a family being able to plan their first vacation together.
However, further work is needed to better understand the mechanisms involved – for example, whether the stem cells trigger the production of a variety of growth factors and cytokines – immune system regulators – to stimulate wound healing and reduce inflammation in the skin. Further studies are also needed to confirm the efficacy of the treatment and establish the optimal dose of cells to give RDEB patients.
Dr Gabriela Petrof, lead author from St John’s Institute of Dermatology at King’s College London, said: ‘We found that wound healing improved in all 10 children and the skin was less inflamed. Many of the kids also mentioned their skin was less painful and itchy, and their parents noted how much more energetic they were.’
Professor John McGrath, senior author from St John’s Institute of Dermatology at King’s College London and honorary consultant dermatologist at Guy’s and St Thomas’ NHS Foundation Trust, added: ‘In 25 years of my research on RDEB, this is the only time I have seen any treatment change the nature of the condition. The outcomes are truly impressive and injecting the MSCs raised no safety concerns. At the same time, it’s important to note that this is not a cure and that the benefits wear off after about six months.’
‘Moving forward, we are now starting to introduce repeated infusions of MSCs into routine NHS clinical care. But we are also starting new clinical trials – combining cell and gene therapy to give patients with RDEB, children and adults, even better treatments as we search for a cure for this devastating inherited skin condition.’
Dr Anna Martinez, principal investigator from Great Ormond Street Hospital, said: ‘Giving the cells is straightforward, but we now have to fine tune the optimal dose and interval between infusions whilst work continues on more long term-therapies.’
The study was also supported by the UK National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.
Notes to editors
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‘Potential of Systemic Allogeneic Mesenchymal Stromal Cell Therapy for Children with Recessive Dystrophic Epidermolysis Bullosa’ by Petrof et al is published in the Journal of Investigative Dermatology.
This paper summaries research funded by the Sohana Research Fund (SRF; with support from Goldman Sachs Gives) with administrative support from the Dystrophic Epidermolysis Bullosa Research Association (DEBRA, UK). The study is also supported by the UK National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.
About King’s College London
King’s College London is one of the top 20 universities in the world (2014/15 QS World University Rankings) and among the oldest in England. King’s has more than 26,500 students (of whom nearly 10,400 are graduate students) from some 150 countries worldwide, and nearly 6,900 staff. The university is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
For more information, please visit King’s in Brief.
About the Sohana Research Fund
The Sohana Research Fund is a charity registered in the UK which exists to fundraise for targeted medical research and clinical trials into effective treatments for Epidermolysis Bullosa. It was set up by the parents of a 12.5 year old sufferer. EBSTEM was its first commissioned trial. Two further trials have been funded in adults this year, including an adult gene therapy trial. Additional funding has been given to projects at the UCL Institute of Child Health and it has also commissioned work in Dr Jakub Tolar’s lab at the University of Minnesota. SRF aims to continue to help fund breakthrough research and clinical trials, facilitate collaboration and transition to effective treatments and eventually a cure.
The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world.
For further information, visit the NIHR website (www.nihr.ac.uk).