Phase I/II efficacy and safety study of mesenchymal stromal cells in recessive dystrophic epidermolysis bullosa Articles uri icon

publication date

  • September 2019

start page

  • S236

end page

  • S236

issue

  • 9, supplement

volume

  • 139

International Standard Serial Number (ISSN)

  • 0022-202X

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

abstract

  • Patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB) have a pronounced muco-cutaneous fragility, which triggers the formation of blisters spontaneously or in response to minimal trauma. RDEB is also associated with chronic inflammation; patients have wounds that do not close and aggressive squamous cell carcinomas. The disease is due to mutations in the COL7A1 gene that codifies for collagen VII (C7). One of the most promising therapeutic options is the use of mesenchymal stromal cells (MSCs) from healthy donors that, in addition to producing C7 and having anti-inflammatory properties, are well tolerated by the patient"s immune system. When administered systemically, they could display their anti-inflammatory potential in the skin and mucous membranes, modulate the behavior of the cells involved in healing, stimulate tissue remodeling, reduce fibrosis and, perhaps, improve dermo-epidermal adhesion. Transient beneficial effects of the systemic use of MSCs have been reported in the treatment of patients with RDEB. For this purpose, we are conducting a phase I/II Spanish single-center clinical trial of systemic MSCs therapy, MesenSistem-EB (EudraCT 2017-000606-37), with 9 pediatric patients with RDEB. MesenSistem-EB has been designed to evaluate the safety and preliminary efficiency of the systemic administration of MSCs derived from haploidentical bone marrow donors. Understanding the molecular mechanisms by which these cells exert their action will contribute to optimize the treatment and increase the persistence of the therapeutic benefits. We are also carrying out a nested study consisting in a transcriptomic-metabolomic analysis of the patient response to the treatment.

subjects

  • Biology and Biomedicine