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 gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor). Patients with NS have defective keratinization, hair shaft defects, recurrent infections, atopy and a predisposition to skin malignancies. Historically, one in ten 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 572bp element derived from the human involucrin promoter (INVO) 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.affiliation: UCL Institute of Child Health, London, UK, London, United Kingdom ; w.di@ucl.ac.uk.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Di
authors.forename: Jemima E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: Catina
authors.initials: C
authors.lastname: Bernadis
authors.forename: John
authors.initials: J
authors.lastname: Harper
authors.forename: Alya
authors.initials: A
authors.lastname: Abdul-Wahab
authors.forename: Sumera
authors.initials: S
authors.lastname: Ghani
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinez-Queipo
authors.forename: Havinder
authors.initials: H
authors.lastname: Hara
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: McNicol
authors.forename: John
authors.initials: J
authors.lastname: McGrath
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim