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Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa
Shaundra Eichstadt, … , M. Peter Marinkovich, Jean Y. Tang
Shaundra Eichstadt, … , M. Peter Marinkovich, Jean Y. Tang
Published October 3, 2019
Citation Information: JCI Insight. 2019;4(19):e130554. https://doi.org/10.1172/jci.insight.130554.
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Clinical Medicine Dermatology

Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa

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Abstract

BACKGROUND Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy.METHODS Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 × 7 cm (35 cm2) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years.RESULTS No participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019).CONCLUSION C7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene–corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01263379.FUNDING Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH R01 AR055914, Office of Research and Development at the Palo Alto Veteran’s Affairs Medical Center, and the Dermatology Foundation.

Authors

Shaundra Eichstadt, Melissa Barriga, Anusha Ponakala, Claudia Teng, Ngon T. Nguyen, Zurab Siprashvili, Jaron Nazaroff, Emily S. Gorell, Albert S. Chiou, Lisa Taylor, Phuong Khuu, Douglas R. Keene, Kerri Rieger, Rohit K. Khosla, Louise K. Furukawa, H. Peter Lorenz, M. Peter Marinkovich, Jean Y. Tang

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Figure 1

Representative clinical photographs of C7 gene–corrected cell therapy in participants.

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Representative clinical photographs of C7 gene–corrected cell therapy in...
(A) Participant 7, C7 gene–corrected treated sites A, C, and D, upper back. (B) Participant 5, untreated control wound, right antecubital fossa. (C) Participant 5, C7 gene–corrected treated sites A and B, left upper arm. Photographs of RDEB wounds at baseline and at designated time points after treatment. In A and C, purple marker outlines gene-corrected autologous cellular sheet edges; each treated wound is denoted with a letter. Participant 7’s sites A, C, and D demonstrate persistent healing at 2 years after treatment (A). Participant 5’s sites A and B (C) demonstrated wound healing at months 3 and 6. Participant 5’s untreated control wound (B) did not close during the measured time points.

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