Netherton Syndrome Clinical Trial
Official title:
Phase I Study of Ex-vivo Lentiviral Gene Therapy for the Inherited Skin Disease Netherton Syndrome
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.
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.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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