Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa

被引：55

作者：

Rashidghamat, Ellie ^{[1
]}

Kadiyirire, Tendai ^{[1
]}

Ayis, Salma ^{[2
]}

Petrof, Gabriela ^{[5
]}

Liu, Lu ^{[6
]}

Pullabhatla, Venu ^{[7
]}

Ainali, Chrysanthi ^{[1
,9
]}

Guy, Alyson ^{[6
]}

Aristodemou, Sophia ^{[6
]}

McMillan, James R. ^{[6
]}

Ozoemena, Linda ^{[6
]}

Mee, John ^{[10
]}

Pramanik, Rashida ^{[1
]}

Saxena, Alka ^{[7
]}

Nuamah, Rosamund ^{[7
]}

de Rinaldis, Emanuele ^{[11
]}

Serrano, Sonia ^{[8
]}

Maurin, Clarisse ^{[8
]}

Martinez-Queipo, Magdalena ^{[1
]}

Lwin, Su M. ^{[1
]}

Ilic, Dusko ^{[3
]}

Martinez, Anna ^{[5
]}

Dazzi, Francesco ^{[4
]}

Slaper-Cortenbach, Ineke ^{[12
]}

Westinga, Kasper ^{[12
]}

Zeddies, Sabrina ^{[12
]}

van den Broek, Marcel ^{[12
]}

Onoufriadis, Alexandros ^{[1
]}

Mellerio, Jemima E. ^{[1
]}

McGrath, John A. ^{[1
]}

机构：

[1] Kings Coll London, St Johns Inst Dermatol, Sch Basic & Med Biosci, London, England

[2] Kings Coll London, Sch Populat Hlth & Environm Sci, London, England

[3] Kings Coll London, Fac Life Sci & Med, Dept Women & Childrens Hlth, Guys Assisted Concept Unit,Stem Cell Labs, London, England

[4] Kings Coll London, Rayne Inst, Dept Haematol Med, London, England

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

[6] Guys Hosp, Robin Eady Natl Diagnost Epidermolysis Bullosa La, Viapath, London, England

[7] Guys & St Thomas NHS Fdn Trust, UK NIHR GSTFT KCL Comprehens Biomed Res Ctr, London, England

[8] Guys & St Thomas NHS Fdn Trust, Clin Trial Management Res Platform, NIHR Biomed Res Ctr, London, England

[9] Dignosis Ltd, London, England

[10] St Thomas Hosp, Viapath, Immunodermatol Lab, London, England

[11] Sanofi, I&I Precis Immunol, Cambridge, MA USA

[12] Univ Med Ctr Utrecht, Dept Clin Pharm, Cell Therapy Facil, Utrecht, Netherlands

来源：

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY | 2020年 / 83卷 / 02期

关键词：

BM-MSC; epidermolysis bullosa; mesenchymal stromal cells; RDEB; IIND INTERNATIONAL-SYMPOSIUM; BONE-MARROW; STEM-CELLS; MANAGEMENT; CARCINOMA; SEVERITY; SANTIAGO; CHILE; ITCH; EB;

D O I：

10.1016/j.jaad.2019.11.038

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to a lack of type VII collagen. At present, treatment is mainly supportive. Objectives: To determine whether intravenous allogeneic bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the cells improve wound healing and quality of life. Methods: We conducted a prospective, phase I/II, open-label study recruiting 10 RDEB adults to receive 2 intravenous infusions of BM-MSCs (on day 0 and day 14; each dose 2-4 3 106 cells/kg). Results: BM-MSCs were well tolerated with no serious adverse events to 12 months. Regarding efficacy, there was a transient reduction in disease activity scores (8/10 subjects) and a significant reduction in itch. One individual showed a transient increase in type VII collagen. Limitations: Open-label trial with no placebo. Conclusions: MSC infusion is safe in RDEB adults and can have clinical benefits for at least 2 months.

引用

页码：447 / 454

页数：8

共 50 条

[21] Phase I clinical trial for Recessive Dystrophic Epidermolysis Bullosa using genetically corrected autologous keratinocytes
Siprashvili, Z.
Nguyen, N. T.
Gorell, E. S.
Loutit, K.
Khuu, P.
Furukawa, L. K.
Lorenz, H. P.
Leung, T. H.
Keene, D.
Rieger, K.
Khavari, P. A.
Lane, A.
Tang, J.
Marinkovich, P.
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2016, 136 (05) : S65 - S65
[22] Patient pre-selection outcomes for the European GENEGRAFT ex vivo phase I/II gene therapy trial for recessive dystrophic epidermolysis bullosa
Lwin, S. M.
Gaucher, S.
Titeux, M.
Abdul-Wahab, A.
Pironon, N.
Miskinyte, S.
Ganier, C.
Duchatelet, S.
McGrath, J.
Hovnanian, A.
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2017, 137 (10) : S231 - S231
[23] Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa
Eichstadt, Shaundra
Barriga, Melissa
Ponakala, Anusha
Teng, Claudia
Nguyen, Ngon T.
Siprashvili, Zurab
Nazaroff, Jaron
Gorell, Emily S.
Chiou, Albert S.
Taylor, Lisa
Khuu, Phuong
Keene, Douglas R.
Rieger, Kerri
Khosla, Rohit K.
Furukawa, Louise K.
Lorenz, H. Peter
Marinkovich, M. Peter
Tang, Jean Y.
JCI INSIGHT, 2019, 4 (19)
[24] PHASE 1/2A CLINICAL TRIAL OF GENE-CORRECTED AUTOLOGOUS CELL THERAPY FOR RECESSIVE DYSTROPHIC EPIDERMOLYSIS BULLOSA
Gorell, E.
Eichstadt, S.
Barriga, M.
Ponakala, A.
Teng, C.
Nguyen, N.
Siprashvili, Z.
Nazaroff, J.
Chiou, A.
Taylor, L.
Khuu, P.
Keene, D.
Rieger, K.
Khosla, R.
Lorenz, H. P.
Furukawa, L.
Marinkovich, M. P.
Tang, J. Y.
ACTA DERMATO-VENEREOLOGICA, 2020, 100 : 75 - 75
[25] Phase I/IIa clinical trial for recessive dystrophic epidermolysis bullosa using genetically corrected autologous keratinocytes
Siprashvili, Z.
Nguyen, N.
Gorell, E.
Loutit, K.
Dutt-Singkh, Y.
Nazaroff, J.
Khuu, P.
Furukawa, L.
Lorenz, H.
Leung, T.
Keene, D.
Rieger, K.
Khavari, P. A.
Lane, A.
Tang, J. Y.
Marinkovich, M.
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2017, 137 (05) : S89 - S89
[26] Characterization and selection of a patient cohort for a phase I/II study of ex vivo gene therapy for recessive dystrophic epidermolysis bullosa (GENEGRAFT)
Abdul-Wahab, A.
Titeux, M.
Mellerio, J.
McGrath, J.
Hovnanian, A.
BRITISH JOURNAL OF DERMATOLOGY, 2015, 173 : 80 - 80
[27] Chemoprevention of squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: Results of a phase 1 trial of systemic isotretinoin
Fine, JD
Johnson, LB
Weiner, M
Stein, A
Suchindran, C
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2004, 50 (04) : 563 - 571
[28] Kinetics of Wound Development and Healing Suggests a Skin-Stabilizing Effect of Allogeneic ABCB5+ Mesenchymal Stromal Cell Treatment in Recessive Dystrophic Epidermolysis Bullosa
Niebergall-Roth, Elke
Dieter, Kathrin
Daniele, Cristina
Fluhr, Silvia
Khokhrina, Maria
Silva, Ines
Ganss, Christoph
Frank, Markus H.
Kluth, Mark A.
CELLS, 2023, 12 (11)
[29] Investigation of cell therapy for generalized severe recessive dystrophic epidermolysis bullosa by intradermal allogeneic fibroblasts randomized against placebo injections
Yan, W. F.
Venugopal, S.
Frew, J. W.
Tran, K.
Sturm, M.
Fogarty, J.
Marinkovich, P.
Igawa, S.
Ishida-Yamamoto, A.
Murrell, D. F.
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 : S28 - S28
[30] Investigation of cell therapy for generalized severe recessive dystrophic epidermolysis bullosa by intradermal allogeneic fibroblasts randomized against placebo injections
Venugopal, S. S.
Yan, W. F.
Tran, K.
Sturm, M.
Fogarty, J.
Frew, J. W.
Marinkovich, P.
Igawa, S.
Ishida-Yamamoto, A.
Murrell, D. F.
AUSTRALASIAN JOURNAL OF DERMATOLOGY, 2010, 51 : A8 - A9

← 1 2 3 4 5 →