Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, netherton syndrome

Wei-Li Di; Jemima E Mellerio; Catina Bernadis; John Harper; Alya Abdul-Wahab; Sumera Ghani; Lucas Chan; Magdalena Martinez-Queipo; Havinder Hara; Anne-Marie McNicol; Farzin Farzaneh; John McGrath; Adrian Thrasher; Waseem Qasim

doi:10.1089/humc.2013.195

Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, netherton syndrome

Wei-Li Di, Jemima E Mellerio, Catina Bernadis, John Harper, Alya Abdul-Wahab, Sumera Ghani, Lucas Chan, Magdalena Martinez-Queipo, Havinder Hara, Anne-Marie McNicol, Farzin Farzaneh, John McGrath, Adrian Thrasher, Waseem Qasim

Dermatology

1 UCL Institute of Child Health & Great Ormond Street Hospital , London WC1N 1EH, United Kingdom .

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the serine protease inhibitor Kazal type 5 gene (SPINK5), which encodes for a serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI). Patients with NS have defective keratinization, hair shaft defects, recurrent infections, atopy, and a predisposition to skin malignancies. Historically, 1 in 10 infants has died before their first birthday. Currently, there are no proven treatments to cure this condition. A SIN-lentiviral vector encoding the codon-optimized SPINK5 gene under the control of a 572 bp element derived from the human involucrin promoter can confer compartment-specific LEKTI expression in NS keratinocytes with restoration of normal skin architecture. Here we detail a study protocol for a phase I trial for feasibility and safety evaluations of autologous epidermal sheets generated from ex vivo gene-corrected keratinocyte stem cells, which will be grafted onto patients with mutation-proven NS.

Original language	English
Article number	N/A
Pages (from-to)	182-190
Number of pages	9
Journal	Human Gene Therapy
Volume	24
Issue number	4
DOIs	https://doi.org/10.1089/humc.2013.195
Publication status	Published - 11 Dec 2013

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Di, W.-L., Mellerio, J. E., Bernadis, C., Harper, J., Abdul-Wahab, A., Ghani, S., Chan, L., Martinez-Queipo, M., Hara, H., McNicol, A.-M., Farzaneh, F., McGrath, J., Thrasher, A., & Qasim, W. (2013). Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, netherton syndrome. Human Gene Therapy, 24(4), 182-190. Article N/A. https://doi.org/10.1089/humc.2013.195

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title = "Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, netherton syndrome",

abstract = "Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the serine protease inhibitor Kazal type 5 gene (SPINK5), which encodes for a serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI). Patients with NS have defective keratinization, hair shaft defects, recurrent infections, atopy, and a predisposition to skin malignancies. Historically, 1 in 10 infants has died before their first birthday. Currently, there are no proven treatments to cure this condition. A SIN-lentiviral vector encoding the codon-optimized SPINK5 gene under the control of a 572 bp element derived from the human involucrin promoter can confer compartment-specific LEKTI expression in NS keratinocytes with restoration of normal skin architecture. Here we detail a study protocol for a phase I trial for feasibility and safety evaluations of autologous epidermal sheets generated from ex vivo gene-corrected keratinocyte stem cells, which will be grafted onto patients with mutation-proven NS.",

author = "Wei-Li Di and Mellerio, {Jemima E} and Catina Bernadis and John Harper and Alya Abdul-Wahab and Sumera Ghani and Lucas Chan and Magdalena Martinez-Queipo and Havinder Hara and Anne-Marie McNicol and Farzin Farzaneh and John McGrath and Adrian Thrasher and Waseem Qasim",

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Di, W-L, Mellerio, JE, Bernadis, C, Harper, J, Abdul-Wahab, A, Ghani, S, Chan, L, Martinez-Queipo, M, Hara, H, McNicol, A-M, Farzaneh, F , McGrath, J, Thrasher, A & Qasim, W 2013, 'Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, netherton syndrome', Human Gene Therapy, vol. 24, no. 4, N/A, pp. 182-190. https://doi.org/10.1089/humc.2013.195

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AU - Di, Wei-Li

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AU - Bernadis, Catina

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AU - Abdul-Wahab, Alya

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AU - Chan, Lucas

AU - Martinez-Queipo, Magdalena

AU - Hara, Havinder

AU - McNicol, Anne-Marie

AU - Farzaneh, Farzin

AU - McGrath, John

AU - Thrasher, Adrian

AU - Qasim, Waseem

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AB - Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the serine protease inhibitor Kazal type 5 gene (SPINK5), which encodes for a serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI). Patients with NS have defective keratinization, hair shaft defects, recurrent infections, atopy, and a predisposition to skin malignancies. Historically, 1 in 10 infants has died before their first birthday. Currently, there are no proven treatments to cure this condition. A SIN-lentiviral vector encoding the codon-optimized SPINK5 gene under the control of a 572 bp element derived from the human involucrin promoter can confer compartment-specific LEKTI expression in NS keratinocytes with restoration of normal skin architecture. Here we detail a study protocol for a phase I trial for feasibility and safety evaluations of autologous epidermal sheets generated from ex vivo gene-corrected keratinocyte stem cells, which will be grafted onto patients with mutation-proven NS.

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Phase I study protocol for ex vivo lentiviral gene therapy for the inherited skin disease, netherton syndrome

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