A phase I/II study to evaluate allogeneic mesenchymal stromal cells for the treatment of skin disease in adults with Recessive Dystrophic Epidermolysis Bullosa
Lay summary
Ten adults with Recessive Dystrophic Epidermolysis Bullosa (RDEB) took part in the trial. This involved receiving intravenous infusions of cells from an unrelated individual who did not have EB. The cells were a special type of bone marrow cell called mesenchymal stromal cells (MSCs). MSCs can transform into other types of cells including skin and corneal cells.
The aim of the study was to check whether giving MSCs would be safe and whether it would improve the condition of the EB.
The study found that giving the cells was a safe procedure in that no-one had any significant adverse reactions or side-effects.
It also found that receiving MSCs led to some clinical improvements in reducing itch, having fewer blisters, and improving quality of life. The personal benefits lasted for a few months before wearing off.
The researchers also looked for chemical and gene 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. These findings have given new ideas about how to reduce inflammation and accelerate wound healing in EB skin which can be investigated in new research.
Scientific Summary
The overall objective of this phase I/II open label study was to perform a clinical trial of intravenous mesenchymal stromal cells (MSCs) in 10 adults with RDEB and to determine whether the use of such cells is safe in the adult RDEB population. Each participant in the trial received two separate intravenous infusions of same donor MSCs on Day 0 and Day 14 at a dose of 2-4 x 106 cells / kg.
This proved to be a safe intervention as no serious adverse events were reported up to 12 months post-MSCs.
Regarding efficacy, one individual showed a slight transient increase in collagen VII (days 28-60 only). However, clinical burden of RDEB improved in 8 subjects with a decrease in disease activity at day 28 and day 60 post-MSCs compared to baseline for the Birmingham Epidermolysis Bullosa Severity Score (BEBSS), Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) activity and the Quality of Life in EB (QOLEB) scores. Leuven Itch Score (LIS) subscales of frequency, severity and consequences of itch showed a significant reduction at days 28 and 60 post MSCs.
In serum, HMGB1 levels were reduced after MSCs at day 28 and day 60 compared to baseline. RNA-seq data from both blood and skin revealed upregulated MAPK, Death receptor signalling and JAK stat pathways after cell therapy. Cell therapy led to an up-regulation of CXCL8, CXCR1 and CXCR2 genes with roles germane to wound healing.
This clinical trial demonstrates that MSC infusion is safe in adults with RDEB and can lead to clinical benefits that persist for at least 2 months. Our data also highlight HMGB1 as a potential biomarker for cell therapy intervention and identifies key genes and signalling pathway changes that occur in response to MSC infusion.
Publications
Rashidghamat E., et al., 2020. Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa. J. Am. Acad. Dermatol. 2020;83:447-454
Related publications
Rashidghamat E, et al. Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa. Intractable Rare Dis. Res. 2017;6(1):6-20
Rashidghamat E. & Mellerio, J.E. Management of chronic wounds in patients with dystrophic epidermolysis bullosa: challenges and solutions. Chronic Wound Care Management and Research 2017;4:45-54
Rashidghamat E, et al. Mesenchymal stem cell therapy for recessive dystrophic epidermolysis bullosa: prospects and clinical progress. Expert Opinion on Orphan Drugs, 2016;4(4):343-345
