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.
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Authors | 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 |
Journal | Human gene therapy. Clinical development
(Hum Gene Ther Clin Dev)
Vol. 24
Issue 4
Pg. 182-90
(Dec 2013)
ISSN: 2324-8645 [Electronic] United States |
PMID | 24329107
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Proteinase Inhibitory Proteins, Secretory
- SPINK5 protein, human
- Serine Peptidase Inhibitor Kazal-Type 5
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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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