Gene Therapy for genetic skin disease Netherton syndrome

Update 2012

Gene therapy for inherited skin disease Netherton syndrome

We have been developing gene therapy for the inherited skin disease Netherton syndrome. The therapeutic process involves taking skin stem cells from a patient with Netherton syndrome which are cultured in the laboratory and modified by introducing a new gene called SPINK5 (therapeutic gene). These modified cells are further cultured in the laboratory to form a skin-like sheet and then grafted back to the patient. We expect the modified skin cells to produce a functioning SPINK5 gene to resolve the genetic problem seen in patients with Netherton syndrome. We also expect the therapeutic gene to be introduced into a special cell called a skin stem cell, which will pass the new gene onto its daughter cells to provide a lifelong source of corrected cells. Our previous pre-clinical study data showed the treatment to be feasible and the patient cells introduced with the therapeutic gene is able to correct the abnormal skin structure seen in Netherton syndrome.

Recently, we have further modified the gene delivery system known as  the ‘vector’ to ensure that the production of the therapeutic gene is durable and the production pattern is the same as seen in normal human skin, i.e. the gene SPINK5 is stably produced in the outermost layers of the skin. The re-configured vector has been tested and results showed high, stable and specific production of the corrected gene products in the skin. Furthermore, the skin sheet generated by gene corrected patient’s skin cells corrects skin structure. These studies have been published in the Journal of Molecular Therapy (Di et al, 2011, 19:408-16) and the Journal of Human Gene Therapy (Di et al, 2012, 23: 83-90).

Based on this research work, we are currently setting up a first-in-man study for gene corrected skin grafts for NS patients. This study is supported by the UK charities of the Moulton Foundation and ICH/GOSH Biomedical Research Centre. One batch of clinical grade vectors has been produced and is under evaluation. Preliminary data suggests that the vector is able to correct patients’ cells. Production of gene corrected skin grafts has been optimised using specialised culture conditions that are suitable for clinical application. We have submitted the protocol of the clinical trial to The Gene Therapy Advisory Committee (GTAC) for study approval. Recruitment of candidate patients for the gene therapy will commence after GTAC approval.

reported by Dr Wei-Li Di

Dermatology and Molecular Immunology