Clinical trial of ABCB5(+) mesenchymal stem cells for recessive dystrophic epidermolysis bullosa

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and life-threatening inherited skin fragility disorder that comes about due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5(+) dermal mesenchymal stem cells (ABCB5(+) MSCs) possess immunomodulatory, inflammation-dampening, and tissue-healing capacities. In a Col7a1(–/–) mouse model of RDEB, treatment with ABCB5(+) MSCs markedly extended the animals’ lifespans. METHODS: In this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4–36 years) enrolled into 4 age cohorts received 3 i.v. infusions of 2 × 10(6) ABCB5(+) MSCs/kg on days 0, 17, and 35. Patients were followed up for 12 weeks regarding efficacy and 12 months regarding safety. RESULTS: At 12 weeks, statistically significant median (IQR) reductions in the Epidermolysis Bullosa Disease Activity and Scarring Index activity (EBDASI activity) score of 13.0% (2.9%–30%; P = 0.049) and the Instrument for Scoring Clinical Outcome of Research for Epidermolysis Bullosa clinician (iscorEB‑c) score of 18.2% (1.9%–39.8%; P = 0.037) were observed. Reductions in itch and pain numerical rating scale scores were greatest on day 35, amounting to 37.5% (0.0%–42.9%; P = 0.033) and 25.0% (–8.4% to 46.4%; P = 0.168), respectively. Three adverse events were considered related to the cell product: 1 mild lymphadenopathy and 2 hypersensitivity reactions. The latter 2 were serious but resolved without sequelae shortly after withdrawal of treatment. CONCLUSION: This trial demonstrates good tolerability, manageable safety, and potential efficacy of i.v. ABCB5(+) MSCs as a readily available disease-modifying therapy for RDEB and provides a rationale for further clinical evaluation. TRIAL REGISTRATION: Clinicaltrials.gov NCT03529877; EudraCT 2018-001009-98. FUNDING: The trial was sponsored by RHEACELL GmbH & Co. KG. Contributions by NYF and MHF to this work were supported by the NIH/National Eye Institute (NEI) grants RO1EY025794 and R24EY028767.