A prospective phase I/II study to evaluate allogeneic mesenchymal stromal cells for the treatment of children with recessive dystrophic epidermolysis bullosa (EBSTEM)

Contents:

• Project information
• Lay summary

Investigator: Professor John McGrath, Professor of Molecular Dermatology and Consultant Dermatologist

Co-applicants: Dr Jemima Mellerio, Dr Anna Martinez, Dr Alya Abdul-Wahab,  Dr Gabriela Petrof, Professor Janet Peacock

Institution: St John’s Institute of Dermatology, Division of Genetics and Molecular Medicine

Grant: £477,872.33 (01/10/2012 – 30/09/2015) – Sohana Research Fund

Lay summary

Recessive dystrophic epidermolysis bullosa (RDEB) is characterised primarily by fragile skin prone to damage in response to even minor trauma. Although skin involvement is the most obvious clinical feature, others include profound anaemia, failure to thrive, delayed growth, scarring of the tissue lining the digestive system (sometimes causing a ‘closing down’ of the oesophagus), and corneal (eye) erosions and scarring. Although not completely understood many of these effects are due to increased inflammation. Currently there is no effective treatment for RDEB and we are unable to prevent the complications.

Mesenchymal stromal cells (MSCs) are cells isolated from umbilical cord blood, bone marrow and other sources. They are sometimes termed stem cells and they can mature into different cell types, but importantly here, are able to stimulate anti-inflammatory responses and have been shown to benefit people with a number of inflammatory conditions.

This study will evaluate whether MSCs can produce benefit in the skin of children with RDEB. Developing new therapeutic treatments is a slow process and after laboratory evaluation, the first stage of development in people is to make sure the treatment is safe and does not produce any unwanted side effects. This study is an early evaluation in patients. Ten study participants are receiving three intravenous (into the blood stream) MSC infusions over a month with cells taken from the bone marrow of healthy donors. People in the study are being followed up for a 12 month period.

Those taking part are being assessed for any immediate effects associated with the infusion of the MSCs and subsequently their skin condition (blistering and skin strength), experience of pain, sleep, fatigue and quality of life. Markers involved in the inflammatory responses in tissues will be investigated.

To date all the infusions have been made without any serious untoward effects. Some parents have reported an improvement in their child’s skin condition, and positive effects on family life. However, these are interim anecdotal reports and the study is continuing to expand the scientific assessment of the results.  This study will help to understand the inflammatory processes in RDEB and in providing potential therapeutic options.

What is important about this research?

“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 6 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.” 

Investigator biography John McGrath MD FRCP FMedSci is Professor of Molecular Dermatology at King’s College London and Head of the Genetic Skin Disease Unit, as well as Honorary Consultant Dermatologist at St John’s Institute of Dermatology, the Guy’s and St Thomas’ NHS Foundation Trust in London. He was previously a DEBRA-funded junior EB research fellow and has worked on EB research for more than 25 years. He now leads and collaborates on several National and International projects to develop gene, cell, protein and drug therapies that can lead to better treatments for people living with EB.