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

被引：34

作者：

Kiritsi, Dimitra ^{[1
]}

Dieter, Kathrin ^{[2
]}

Niebergall-Roth, Elke ^{[3
]}

Fluhr, Silvia ^{[2
]}

Daniele, Cristina ^{[2
]}

Esterlechner, Jasmina ^{[3
]}

Sadeghi, Samar ^{[3
]}

Ballikaya, Seda ^{[3
]}

Erdinger, Leoni ^{[2
]}

Schauer, Franziska ^{[1
]}

Gewert, Stella ^{[1
]}

Laimer, Martin ^{[4
]}

Bauer, Johann W. ^{[4
]}

Hovnanian, Alain ^{[5
,6
]}

Zambruno, Giovanna ^{[7
]}

El Hachem, May ^{[7
,8
]}

Bourrat, Emmanuelle ^{[9
]}

Papanikolaou, Maria ^{[10
]}

Petrof, Gabriela ^{[11
]}

Kitzmuller, Sophie ^{[4
]}

Ebens, Christen L. ^{[12
]}

Frank, Markus H. ^{[13
,14
,15
,16
]}

Frank, Natasha Y. ^{[14
,15
,17
,18
]}

Ganss, Christoph ^{[2
,3
]}

Martinez, Anna E. ^{[11
]}

McGrath, John A. ^{[10
]}

Tolar, Jakub ^{[12
]}

Kluth, Mark A. ^{[2
,3
]}

机构：

[1] Univ Freiburg, Fac Med, Dept Dermatol, Med Ctr, Freiburg, Germany

[2] RHEACELL GmbH & Co KG, Heidelberg, Germany

[3] TICEBA GmbH, Neuenheimer Feld 517, D-69120 Heidelberg, Germany

[4] Paracelsus Med Univ Salzburg, Dept Dermatol & Allergol, Univ Hosp, EB House Austria, Salzburg, Austria

[5] Univ Paris, Necker Hosp, Dept Genet, Paris, France

[6] Univ Paris, St Louis Hosp, INSERM UMR 1163, Lab Genet Skin Dis,IMAGINE Inst Genet Dis, Paris, France

[7] Bambino Gesu Pediat Hosp, IRCSS, Genet & Rare Dis Res Div, Genodermatosis Unit, Rome, Italy

[8] Bambino Gesu Pediat Hosp, Genet & Rare Dis Res Div, Dermatol Unit, IRCSS, Rome, Italy

[9] St Louis Hosp, Dept Dermatol, Reference Ctr Rare Skin Dis MAGEC, Paris, France

[10] Kings Coll London, Guys Hosp, St Johns Inst Dermatol, London, England

[11] Great Ormond St Hosp NHS Fdn Trust, Dept Dermatol, London, England

[12] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat & Cellular Therap, M Hlth Fairview Masonic Childrens Hosp, Minneapolis, MN 55455 USA

[13] Harvard Med Sch, Boston Childrens Hosp, Dept Dermatol, Boston, MA 02115 USA

[14] Harvard Med Sch, Boston Childrens Hosp, Transplant Res Program, Boston, MA 02115 USA

[15] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[16] Edith Cowan Univ, Sch Med & Hlth Sci, Perth, WA, Australia

[17] VA Boston Healthcare Syst, Dept Med, Boston, MA USA

[18] Harvard Med Sch, Div Genet, Brigham & Womens Hosp, Boston, MA 02115 USA

来源：

JCI INSIGHT | 2021年 / 6卷 / 22期

关键词：

DIMETHYL-SULFOXIDE; DISEASE SEVERITY; PRECURSOR CELLS; CHILDREN; MOBILITY; THERAPY; SAFETY;

D O I：

10.1172/jci.insight.151922

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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. © 2021 American Society for Clinical Investigation. All rights reserved.

引用

页数：17

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