Evaluation of the early efficacy of intravenously administered allogeneic mesenchymal stromal cells on itching in adults with Epidermolysis Bullosa Pruriginosa (McGrath 21 Itch, PRUMEC - PRUSTEM)

Short lay summary

This research is about itch in Epidermolysis Bullosa (EB). We know that itching is a common and distressing symptom, and that better control of itch is an important research priority for people living with EB. At the moment, it is not understood why the skin is itchy in EB and we know that most current treatments are not particularly effective.

Previous clinical trials of a form of cell therapy took bone marrow cells (mesenchymal stromal cells, MSCs) from unrelated healthy donors and infused them via a vein into children and adults with Recessive Dystrophic EB; these trials were called EBSTEM and ADSTEM and showed that the cells were safe and that in most people the cell infusions had positive benefits for wound healing, skin pain and itching.

This project will investigate the underlying mechanisms and potential treatment for itch in EB will be divided in to two stages, PRUMEC and PRUSTEM.

Scientific summary

Stage 1 - PRUMEC

This is a case control study, (a type of observational study involving 2 or more groups) which aims to determine whether the groups have different outcomes after the study. As this is a mechanistic study, this means the research aims to understand the biological processes behind pruritus (itch) and identify treatment targets for this.

Since this research involves studying the underlying mechanisms of pruritus, there will be 3 distinct groups:

1. 10-30 adults with dystrophic epidermolysis bullosa pruriginosa (DEB-P), which will have skin and blood samples taken and compared to,
2. 10-30 adults with DEB non-pruriginosa subtype (DEB-NP), and
3. 10-30 healthy volunteers as control groups.

Recruited patients will be matched if possible, as closely as what is practical clinically and logistically feasible, based on age, gender, ethnicity, EB severity, time of biopsy and site of biopsy. Questionnaires as well as the blood and skin samples will be taken from each group over a 12 month period. This will allow comparison between groups.

Stage 2 - PRUSTEM (Phase I/II trial)

This stage will follow the completion of PRUMEC, where the sub group of DEB-P patients enrolled will be given a medicinal product depending on the results of the PRUMEC. The blood tests, questionnaires and biopsies will be repeated and carried out as they were in the PRUMEC study and compared with the baseline assessments carried out in the first stage.

The medicinal product will be in the form of cell therapy where up to 10 adults with EB pruriginosa will each receive 3 infusions of MSCs. This work will measure the itch using a detailed scoring system called the Leuven Itch Scale, which has been previously tested in EB. Skin and blood will be examined after the cell therapy has been administered to investigate how the cells might be working in reducing itch and compared with results taken before.

The results will also be compared with the blood of 10 people with DEB - NP and 10 control subjects who do not have EB from the PRUMEC study. Those individuals will not receive MSC cell therapy, but their samples will be helpful in trying to work out what causes the very itchy EB pruriginosa in the first place.

The overall aim of this work is to improve understanding about (a) what causes itch in EB pruriginosa (and potentially other forms of EB), (b) whether intravenous infusions of MSCs offer a helpful treatment for people with EB pruriginosa and, (c) how do the MSCs work in reducing pruritus in EB pruriginosa. It is hoped that the combined results of EBSTEM, ADSTEM and PRUSTEM/PRUMEC will define the potential benefits of this form of cell therapy for people with DEB (and potentially other forms of EB) and provide momentum for the development of MSC cell therapy as part of routine clinical care for DEB.

Strategic relevance

“One of the most troubling symptoms in people with EB is itch. At the moment, we know little about what causes the itch and even less about how to treat it. We are delighted to receive DEBRA funding to work on itch. We will be studying people with a very itchy form of EB called EB pruriginosa. We also plan to carry out a clinical trial of intravenous bone marrow cells that we hope will lessen the itch and improve EB skin”. John McGrath

More on DEBRA UK's website.