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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.
AuthorsWei-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
JournalHuman gene therapy. Clinical development (Hum Gene Ther Clin Dev) Vol. 24 Issue 4 Pg. 182-90 (Dec 2013) ISSN: 2324-8645 [Electronic] United States
PMID24329107 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Proteinase Inhibitory Proteins, Secretory
  • SPINK5 protein, human
  • Serine Peptidase Inhibitor Kazal-Type 5
Topics
  • Clinical Trials, Phase I as Topic (methods)
  • Female
  • Genetic Therapy
  • Humans
  • Keratinocytes (metabolism, transplantation)
  • Lentivirus (genetics)
  • Male
  • Netherton Syndrome (therapy)
  • Proteinase Inhibitory Proteins, Secretory (genetics, metabolism)
  • Serine Peptidase Inhibitor Kazal-Type 5

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