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.
authors: 1 UCL Institute of Child Health & Great Ormond Street Hospital , London WC1N 1EH, United Kingdom .
authors: Wei-Li
authors: WL
authors: Di
authors: Jemima E
authors: JE
authors: Mellerio
authors: Catina
authors: C
authors: Bernadis
authors: John
authors: J
authors: Harper
authors: Alya
authors: A
authors: Abdul-Wahab
authors: Sumera
authors: S
authors: Ghani
authors: Lucas
authors: L
authors: Chan
authors: Magdalena
authors: M
authors: Martinez-Queipo
authors: Havinder
authors: H
authors: Hara
authors: Anne-Marie
authors: AM
authors: McNicol
authors: Farzin
authors: F
authors: Farzaneh
authors: John
authors: J
authors: McGrath
authors: Adrian
authors: A
authors: Thrasher
authors: Waseem
authors: W
authors: Qasim
mesh_terms: D017321:Clinical Trials, Phase I as Topic / Q000379:methods; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000637:transplantation; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D056770:Netherton Syndrome / Q000628:therapy*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics / Q000378:metabolism; D000074163:Serine Peptidase Inhibitor Kazal-Type 5
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5