Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa - 29/01/20

Doi : 10.1016/j.jaad.2019.11.038

Ellie Rashidghamat, MBBS, MRCP(UK) ^a, Tendai Kadiyirire, MRes, BSc ^a, Salma Ayis, PhD ^b, Gabriela Petrof, PhD, MRCP(UK) ^c, Lu Liu, PhD ^d, Venu Pullabhatla, PhD ^e, Chrysanthi Ainali, PhD ^a,^f, Alyson Guy, BSc ^d, Sophia Aristodemou, BSc ^d, James R. McMillan, MSc, MBA, PhD ^d, Linda Ozoemena, PhD ^d, John Mee, PhD ^g, Rashida Pramanik, BSc ^a, Alka Saxena, PhD ^e, Rosamund Nuamah, PhD ^e, Emanuele de Rinaldis, PhD ^h, Sonia Serrano, BSc ⁱ, Clarisse Maurin, PhD ⁱ, Magdalena Martinez-Queipo, MSc ^a, Su M. Lwin, MBBS, MRCP(UK) ^a, Dusko Ilic, MD, PhD ^j, Anna Martinez, MBBS, FRCP ^c, Francesco Dazzi, MD, PhD ^k, Ineke Slaper-Cortenbach, PhD ^l, Kasper Westinga, PhD ^l, Sabrina Zeddies, PhD ^l, Marcel van den Broek, PhD ^l, Alexandros Onoufriadis, PhD ^a, Jemima E. Mellerio, MD, FRCP ^a, John A. McGrath, MD, FRCP, FMedSci ^a,^⁎
^a St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK
^b School of Population Health and Environmental Sciences, King's College London, London, UK
^c Department of Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
^d The Robin Eady National Diagnostic Epidermolysis Bullosa Laboratory, Viapath, Guy's Hospital, London, UK
^e UK NIHR GSTFT/KCL Comprehensive Biomedical Research Centre, Guy's & St Thomas' NHS Foundation Trust, London, UK
^f Dignosis Ltd, London, UK
^g Immunodermatology Laboratory, Viapath, St Thomas' Hospital, London, UK
^h I&I Precision Immunology, Sanofi, Cambridge, Massachusetts
ⁱ Clinical Trial Management Research Platform, NIHR Biomedical Research Centre, Guy's & St Thomas' NHS Foundation Trust, London, UK
^j Stem Cell Laboratories, Guy's Assisted Conception Unit, Department of Women & Children's Health, Faculty of Life Sciences & Medicine, King's College London, London, UK
^k Department of Haematological Medicine, The Rayne Institute, King's College London, London, UK
^l Cell Therapy Facility, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands

^∗Correspondence to: John A. McGrath, MD, FRCP, FMedSci, St John's Institute of Dermatology, 9th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.St John's Institute of Dermatology9th Floor Tower WingGuy's HospitalGreat Maze PondLondonSE1 9RTUK

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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 × 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.

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Key words : BM-MSC, epidermolysis bullosa, mesenchymal stromal cells, RDEB

Abbreviations used : BM, C7, CI, EB, HMGB-1, MSC, RDEB, SCC, SD, SEM

Plan

Methods

Patient selection

Donor and allogeneic MSCs

Clinical procedures

Laboratory assessments

Results

Patients

Safety data and adverse events

Quality of life and clinical severity assessments

Direct immunofluorescence and ultrastructural microscopy assessment

Laboratory results

Discussion

	Funding sources: Supported by Debra UK and the Sohana Research Fund (now known as Cure EB). The research was funded/supported by the National Institute for Health Research Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London, with the trial undertaken in the Clinical Research Facility at Guy's Hospital.
	Conflicts of interest: None disclosed.
	Reprints not available from the authors.