TY - JOUR
T1 - Phase i study protocol for Ex vivo lentiviral gene therapy for the inherited skin disease, netherton syndrome
AU - Di, Wei Li
AU - Mellerio, Jemima E.
AU - Bernadis, Catina
AU - Harper, John
AU - Abdul-Wahab, Alya
AU - Ghani, Sumera
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
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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.
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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U2 - 10.1089/humc.2013.195
DO - 10.1089/humc.2013.195
M3 - Article
C2 - 24329107
AN - SCOPUS:84907241768
SN - 2324-8637
VL - 24
SP - 182
EP - 190
JO - Human gene therapy. Clinical development
JF - Human gene therapy. Clinical development
IS - 4
ER -