Abstract
BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and lifethreatening 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 × 106ABCB5+ 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.
RAS ID
42654
Document Type
Journal Article
Date of Publication
11-22-2021
Volume
6
Issue
22
Funding Information
RHEACELL GmbH & Co. KG. NIH/National Eye Institute
PubMed ID
34665781
School
School of Medical and Health Sciences
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Publisher
American Society for Clinical Investigation (ASCI)
Recommended Citation
Kiritsi, D., Dieter, K., Niebergall-Roth, E., Fluhr, S., Daniele, C., Esterlechner, J., Sadeghi, S., Ballikaya, S., Erdinger, L., Schauer, F., Gewert, S., Laimer, M., Bauer, J. W., Hovnanian, A., Zambruno, G., El Hachem, M., Bourrat, E., Papanikolaou, M., Petrof, G., Kitzmüller, S., Ebens, C. L., Frank, M. H., Frank, N. Y., Ganss, C., Martinez, A. E., McGrath, J. A., Tolar, J., & Kluth, M. A. (2021). Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. DOI: https://doi.org/10.1172/jci.insight.151922
Comments
Kiritsi, D., Dieter, K., Niebergall-Roth, E., Fluhr, S., Daniele, C., Esterlechner, J., . . . Kluth, M. A. (2021). Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. JCI Insight, 6(22), article e151922. https://doi.org/10.1172/jci.insight.151922