Clinical Trials Logo

Clinical Trial Summary

Netherton Syndrome is a serious skin disorder caused by damage in a gene called SPINK5. This gene controls the formation of a protein called LEKTI, which important for skin barrier function. LEKTI inhibits certain enzymes (serine proteinases) in the outermost layer of the skin (epidermis). The function of the serine proteinases is to break down the intracellular cement that holds together the horny cells in the epidermis, in order for the skin to be able to shed cells (known as cell desquamation). LEKTI deficiency leads to an uninhibited desquamation of horny cells, and as a result the skin becomes red and scaly. The barrier function of the skin is also affected. The permeability of the skin increases, and its capacity to bind water decreases, which causes dryness. The thinness of the barrier also results in over absorption of chemicals, for example topical medical treatments. Historically one in ten infants dies before their first birthday. Currently there are no proven treatments to cure this condition.

The investigators have been developing a gene therapy approach to treat this disorder. The investigators have used a disabled virus (vector) to carry a functional copy of the SPINK5 gene into skin stem cells. Proof-of-principle experiments have shown the investigators can restore almost normal shape and size of the upper layer of the skin in skin grafts grown in the lab. Even if only a small number of cells are genetically modified to carry the corrected SPINK5 gene, there seems to be a correction over a wide area of the graft.

In this trial the investigators propose grafting of autologous epidermal sheets generated from genetically modified skin stem cells for the treatment of patients with Netherton Syndrome. The investigators anticipate production and release of LEKTI protein from even a small patch of skin will be beneficial.


Clinical Trial Description

Netherton Syndrome is a serious skin disorder caused by damage in a gene called SPINK5. This gene controls the formation of a protein called LEKTI, which important for skin barrier function. LEKTI inhibits certain enzymes (serine proteinases) in the outermost layer of the skin (epidermis). The function of the serine proteinases is to break down the intracellular cement that holds together the horny cells in the epidermis, in order for the skin to be able to shed cells (known as cell desquamation). LEKTI deficiency leads to an uninhibited desquamation of horny cells, and as a result the skin becomes red and scaly. The barrier function of the skin is also affected. The permeability of the skin increases, and its capacity to bind water decreases, which causes dryness. The thinness of the barrier also results in over absorption of chemicals, for example topical medical treatments. Historically one in ten infants dies before their first birthday. Currently there are no proven treatments to cure this condition.

The investigators have been developing a gene therapy approach to treat this disorder. The investigators have used a disabled virus (vector) to carry a functional copy of the SPINK5 gene into skin stem cells. Proof-of-principle experiments have shown the investigators can restore almost normal shape and size of the upper layer of the skin in skin grafts grown in the lab. Even if only a small number of cells are genetically modified to carry the corrected SPINK5 gene, there seems to be a correction over a wide area of the graft.

In this trial the investigators propose grafting of autologous epidermal sheets generated from genetically modified skin stem cells for the treatment of patients with Netherton Syndrome. The investigators anticipate production and release of LEKTI protein from even a small patch of skin will be beneficial. ;


Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT01545323
Study type Interventional
Source Great Ormond Street Hospital for Children NHS Foundation Trust
Contact Waseem Qasim, Dr
Phone 00442079052764
Email w.qasim@ucl.ac.uk
Status Recruiting
Phase Phase 1
Start date April 2014
Completion date April 2018

See also
  Status Clinical Trial Phase
Recruiting NCT05979831 - A Study to Explore Safety, Pharmacokinetics, and Early Clinical Signal of Efficacy of DS-2325a in Patients With Netherton Syndrome Phase 1/Phase 2
Completed NCT00208026 - Safety Study of Elidel (Pimecrolimus) 1% Cream to Treat Netherton Syndrome Phase 1/Phase 2
Completed NCT05583669 - A Study to Assess the Safety and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of DS-2325a in Healthy Subjects Phase 1
Completed NCT01428297 - A Study Evaluating the Safety and Efficacy of Topical BPR277 for the Treatment of Atopic Dermatitis and Netherton Syndrome Phase 1
Recruiting NCT05856526 - A Study to Test Whether Spesolimab Helps People With a Skin Disease Called Netherton Syndrome Phase 2/Phase 3
Recruiting NCT05789056 - Open Label, Safety and Efficacy Study of QRX003 Lotion in Subjects With Netherton Syndrome Phase 2/Phase 3
Recruiting NCT05521438 - Safety, Tolerability and Efficacy of QRX003 Lotion in Subjects With Netherton Syndrome Phase 2/Phase 3
Completed NCT05388903 - A Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous Doses of DS-2325a in Healthy Subjects Phase 1
Recruiting NCT06137157 - Evaluation of Topical ATR12-351 in Adults With Netherton Syndrome Phase 1
Not yet recruiting NCT05902663 - Natural History of Netherton Syndrome
Recruiting NCT04244006 - A Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome Phase 2/Phase 3
Recruiting NCT03417856 - Defining the Skin and Blood Biomarkers of Ichthyosis
Completed NCT02113904 - Clinical Trial Using Humira in Netherton Syndrome Phase 2
Recruiting NCT05211830 - A Study to Evaluate Topically Applied SXR1096 Cream in Patients With Netherton Syndrome Phase 1/Phase 2
Completed NCT03041038 - The Efficacy and Safety of Secukinumab in Patients With Ichthyoses Phase 2
Recruiting NCT02081313 - Natural History and Biological Study of Netherton Syndrome N/A