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MesemSistem-EB: Safety and preliminary efficacy study of infusing mesenchymal stem cells derived from bone marrow for treating Recessive Dystrophic Epidermolysis Bullosa

Ongoing
Project leadR de Lucas and MJ Escámez
Organisation University Hospital La Paz, Madrid
Partner organizations & collaboratorsUC3M – Universidad Carlos III de Madrid
Project budgetEUR 318,000.00
Start date / Duration01. Jul 2015 / 54 months
Funder(s) / Co-Funder(s) Others
Other funder(s)Carlos III Health Institute-ERDF (European Regional Development Fund), Berritxuak and DEBRA Spain
Research area Cellular therapy, Symptom prevention & relief

Project details

Short lay summary

People with Recessive Dystrophic Epidermolysis Bullosa (RDEB) have fragility and blistering of the skin and mucosa and, complications derived from inflammation: non-healing wounds, anemia, itching and skin carcinomas, among others. Mesenchymal stromal cells (MSCs) injected into the patient’s bloodstream could display their anti-inflammatory potential. In fact, no adverse effects and transient beneficial effects of MSC were associated to RDEB and other diseases linked to inflammation. However, there are still remaining questions: 1) how MSCs accomplish their beneficial effect for weeks since they apparently disappear within a few days after injection and 2) Why only some of the patients improve their clinical condition after MSC treatment. MesenSistem-EB, a clinical trial conducted in Spain, aims to address these questions by examine the response of 9 children with RDEB to the injection of MSCs from the bone marrow of one of their progenitors (haploidentical). Thus, beside to assess that this treatment is safe and efficient, changes in blood inflammatory markers (proteins, metabolites and genes) and in white cell populations that go along with the clinical response are being studied (see projects Omic-MesenSistem-EB and Avancell-CA).

Scientific summary

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is an incurable genodermatosis with extensive muco-cutaneous blistering and systemic complications closely related to inflammation and fibrosis (chronic wounds, esophageal strictures, mutilating scars, aggressive squamous cell carcinoma, osteoporosis, and failure to thrive among others). RDEB is due to mutations in COL7A1 gene resulting in reduced or no collagen type VII (C7). One promising cell therapy for symptom prevention and relief is the use of mesenchymal stromal cells (MSCs) from healthy donors that in addition of being well tolerated by the patient's immune system, have anti-inflammatory properties and are able to produce C7. When administered intravenously, they could display their anti-inflammatory potential modulate the behavior of the cells involved in healing, stimulate tissue remodeling, reduce fibrosis, control itching and pain and, perhaps, improve dermo-epidermal adhesion. In the absence of serious adverse events, transient beneficial effects of the systemic use of MSCs were reported in the treatment of patients with RDEB and other diseases related to inflammation (diabetes, cardiovascular and renal failures, Crohn’s, Parkinson’s disease and multiple sclerosis). However, the therapeutic mechanism and the different responses of patients to the treatment are poorly understood. A phase I/II Spanish single-center clinical trial of systemic MSCs therapy, MesenSistem-EB, (EudraCT 2017-000606-37) is being conducted in Spain for the treatment of 9 pediatric patients with RDEB. MesenSistem-EB has been designed to evaluate the safety and efficacy of the systemic administration of MSCs mesenchymal stem cells derived from haploidentical bone marrow donors but also to decipher the inflammatory, immunological, transcriptomic and metabolic responses (see projects Omic-MesenSistem-EB & Avancell-CA).

Strategic relevance

The exhaustive characterization of individual responses (inflammatory, immunological, transcriptomic and metabolic) may contribute to the better understanding of the molecular mechanisms by which MSCs exert their action and to determine the molecular profile of treatment responding patients. Thus, results could facilitate the translation to the use of MSCs for the management of RDEB in clinical practice and the design of optimized new treatments to control inflammation, stimulate wound healing and tissue remodeling, reduce fibrosis, control itching and pain and, perhaps, improve momentarily dermo-epidermal adhesion.


Keywords

recessive dystrophic epidermolysis bullosa
inflammation
systemic cell therapy
mesenchymal stromal cells
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