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A prospective phase I/II study to evaluate allogeneic mesenchymal stromal cells for the treatment of children with Recessive Dystrophic Epidermolysis Bullosa (EBSTEM)

Completed
Project lead Prof. John McGrath
Organisation King’s College London
Project budget GBP 477,872.33
Start date / Duration 01. Oct 2012 / 36 months
Funder(s) / Co-Funder(s) DEBRA UK, Others
Other funder(s) cofunded by Cure EB (previously Sohana Research Fund)
Research area Cellular therapy

Project details

Short lay summary

About Mesenchymal Stem Cells

Mesenchymal stromal cells (MSC) are multipotent cells capable of maturing into a variety of cell types, but they also have anti-inflammatory properties. Intravenous infusion of MSCs, (introducing the cells directly into the person’s blood stream) has shown to benefit patients who have had heart attacks, renal failure, stroke, diabetes, Crohn’s and Parkinson’s disease. However, we do not fully understand how this is achieved. The cells do not become incorporated into the recipient’s tissue – in fact they seem to be removed within days, and disappear harmlessly, but they seem to be stimulating anti-inflammatory responses in the recipient that persist for many days or weeks.

People with Recessive Dystrophic Epidermolysis Bullosa (RDEB) have a number of complications closely linked to inflammatory reactions; these include anaemia, bone thinning (osteoporosis), poorly healing wounds, itching, loss of appetite and a general failure to thrive. This group wished to further investigate the anti-inflammatory actions of MSCs in adults with RDEB. Having started an investigation in children, Professor McGrath and team planned to give intravenous MSC infusions to 10 adults with RDEB to examine in detail important markers in the blood and tissues. Their clinical responses (skin blisters, wound healing, itching and pain) were also recorded.

EBSTEM – A Previous Clinical Trial with MSCs

Early results from EBSTEM showed that the infusions appeared safe and may have some beneficial effect in children. An important observation is that individuals can respond differently to MSCs, leading researchers to believe that people may have some factors in their inherent biological make-up that makes them good or poor responders. ADSTEM planned to assess the safety of MSCs in adults. This study was needed because compared with children, scarring in adults with RDEB is often greater and there is an increased risk of skin cancer, so it is important to study the safety profile of intravenous MSCs in older subjects too.

Aims of this project

This project aimed to increase understanding of the inflammatory responses in RDEB, help evaluate whether MSCs have the potential to be a useful therapy, and consolidate how this kind of therapy can be given and aid development of future studies in RDEB.

Strategic relevance

Professor John McGrath, Principal Investigator for ADSTEM, said “This clinical trial has given us a great opportunity to look at the safety and potential benefits of cell therapy in people with dystrophic EB. We hope these cells will improve wound healing as well as reduce itch and pain, and that in the longer term the trial will lead to positive changes in the way we treat EB in the clinic”

What did this project achieve?

Professor McGrath and team invited people with the recessive dystrophic form of EB who were over the age of 18 to take part in a clinical trial of this form of cell therapy. This involved receiving intravenous infusions of cells from an unrelated individual who did not have EB. The team have now investigated whether giving these cells is safe and if this type of treatment might improve the condition of the EB in adults.

Ten adults with recessive dystrophic EB took part in the clinical trial. The researchers found that giving the cells was a “safe” procedure in that no-one had any significant adverse reactions or side-effects.

They also found that giving MSCs led to some clinical improvements such as reducing itch, having fewer blisters and improving quality of life. These personal benefits lasted for a few months before wearing off. They also looked for changes in the skin and blood before and after receiving MSCs and identified some genes and proteins related to wound healing that were altered by the MSCs.

Next steps

These findings have provided new ideas about how to reduce inflammation and accelerate wound healing in EB skin. The plan now is to try to introduce MSC therapy into regular clinical care as well as using the new laboratory data to develop even better treatments for people with EB.


Keywords

McGrath
Mellerio
Martinez
Abdul-Wahab
Petrof
Peacock
Cure EB
mesenchymal stem cells
clinical Trial Phase 1/2
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