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

Elham Rashidghamat; Tendai Kadiyirire; Salma Ayis; Gabriela Petrof; Lu Liu; Venu Pullabhatla; Chrysanthi Ainali; Alyson Guy; S Aristodemou; James R. McMillan; L Ozoemena; John Mee; Rashida Pramanik; Alka Saxena; Rosamond Nuamah; Emanuele de Rinaldis; Sonia Serrano; Clarisse Maurin; Magdalena Martinez-Queipo; Su Lwin; Dusko Ilic; Anna E. Martinez; Francesco Dazzi; Ineke Slaper-Cortenbach; Kasper Westinga; Sabrina Zeddies; Marcel van den Broek; Alexandros Onoufriadis; J Mellerio; John A. McGrath

doi:10.1016/j.jaad.2019.11.038

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

Elham Rashidghamat, Tendai Kadiyirire, Salma Ayis, Gabriela Petrof, Lu Liu, Venu Pullabhatla, Chrysanthi Ainali, Alyson Guy, S Aristodemou, James R. McMillan, L Ozoemena, John Mee, Rashida Pramanik, Alka Saxena, Rosamond Nuamah, Emanuele de Rinaldis, Sonia Serrano, Clarisse Maurin, Magdalena Martinez-Queipo, Su LwinDusko Ilic, Anna E. Martinez, Francesco Dazzi, Ineke Slaper-Cortenbach, Kasper Westinga, Sabrina Zeddies, Marcel van den Broek, Alexandros Onoufriadis, J Mellerio, John A. McGrath

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Abstract

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 × 10 ⁶ 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.

Original language	English
Journal	Journal of the American Academy of Dermatology
Early online date	28 Nov 2019
DOIs	https://doi.org/10.1016/j.jaad.2019.11.038
Publication status	E-pub ahead of print - 28 Nov 2019

Keywords

BM-MSC
RDEB
epidermolysis bullosa
mesenchymal stromal cells

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10.1016/j.jaad.2019.11.038Licence: CC BY-NC-ND

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A Phase I/II open-label trial_rashidghamat_Accepted4November2019_GREEN AAM
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Embargo ends: 1/01/2099

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Rashidghamat, E., Kadiyirire, T., Ayis, S., Petrof, G., Liu, L., Pullabhatla, V., Ainali, C., Guy, A., Aristodemou, S., McMillan, J. R., Ozoemena, L., Mee, J., Pramanik, R., Saxena, A., Nuamah, R., de Rinaldis, E., Serrano, S., Maurin, C., Martinez-Queipo, M., ... McGrath, J. A. (2019). Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa. Journal of the American Academy of Dermatology. Advance online publication. https://doi.org/10.1016/j.jaad.2019.11.038

@article{970f9dbeddea4328bfabc8e1ec205517,

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

abstract = "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 × 10 6 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. ",

keywords = "BM-MSC, RDEB, epidermolysis bullosa, mesenchymal stromal cells",

author = "Elham Rashidghamat and Tendai Kadiyirire and Salma Ayis and Gabriela Petrof and Lu Liu and Venu Pullabhatla and Chrysanthi Ainali and Alyson Guy and S Aristodemou and McMillan, {James R.} and L Ozoemena and John Mee and Rashida Pramanik and Alka Saxena and Rosamond Nuamah and {de Rinaldis}, Emanuele and Sonia Serrano and Clarisse Maurin and Magdalena Martinez-Queipo and Su Lwin and Dusko Ilic and Martinez, {Anna E.} and Francesco Dazzi and Ineke Slaper-Cortenbach and Kasper Westinga and Sabrina Zeddies and {van den Broek}, Marcel and Alexandros Onoufriadis and J Mellerio and McGrath, {John A.}",

year = "2019",

month = nov,

day = "28",

doi = "10.1016/j.jaad.2019.11.038",

language = "English",

journal = "Journal of the American Academy of Dermatology",

issn = "1097-6787",

publisher = "Elsevier",

}

Rashidghamat, E, Kadiyirire, T, Ayis, S , Petrof, G , Liu, L, Pullabhatla, V, Ainali, C, Guy, A, Aristodemou, S, McMillan, JR, Ozoemena, L, Mee, J , Pramanik, R, Saxena, A, Nuamah, R, de Rinaldis, E, Serrano, S, Maurin, C, Martinez-Queipo, M, Lwin, S , Ilic, D, Martinez, AE, Dazzi, F, Slaper-Cortenbach, I, Westinga, K, Zeddies, S, van den Broek, M, Onoufriadis, A, Mellerio, J & McGrath, JA 2019, 'Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa', Journal of the American Academy of Dermatology. https://doi.org/10.1016/j.jaad.2019.11.038

TY - JOUR

T1 - Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa

AU - Rashidghamat, Elham

AU - Kadiyirire, Tendai

AU - Ayis, Salma

AU - Petrof, Gabriela

AU - Liu, Lu

AU - Pullabhatla, Venu

AU - Ainali, Chrysanthi

AU - Guy, Alyson

AU - Aristodemou, S

AU - McMillan, James R.

AU - Ozoemena, L

AU - Mee, John

AU - Pramanik, Rashida

AU - Saxena, Alka

AU - Nuamah, Rosamond

AU - de Rinaldis, Emanuele

AU - Serrano, Sonia

AU - Maurin, Clarisse

AU - Martinez-Queipo, Magdalena

AU - Lwin, Su

AU - Ilic, Dusko

AU - Martinez, Anna E.

AU - Dazzi, Francesco

AU - Slaper-Cortenbach, Ineke

AU - Westinga, Kasper

AU - Zeddies, Sabrina

AU - van den Broek, Marcel

AU - Onoufriadis, Alexandros

AU - Mellerio, J

AU - McGrath, John A.

PY - 2019/11/28

Y1 - 2019/11/28

N2 - 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 × 10 6 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.

AB - 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 × 10 6 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.

KW - BM-MSC

KW - RDEB

KW - epidermolysis bullosa

KW - mesenchymal stromal cells

U2 - 10.1016/j.jaad.2019.11.038

DO - 10.1016/j.jaad.2019.11.038

M3 - Article

SN - 1097-6787

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

ER -

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

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Keywords

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