Key Points

Stanford, Calif. — After 15 years of intensive research and having to overcome multiple regulatory hurdles, the first clinical trial of ex vivo gene delivery in patients with recessive dystrophic epidermolysis bullosa (RDEB) is underway at Stanford University, according to Alfred T. Lane, M.D.

Demonstration in an RDEB preclinical model that ex vivo gene therapy achieved long-term genetic and phenotypic correction provided the foundation for finally advancing forward into clinical testing, says Dr. Lane, who is principal investigator for the gene therapy trial and professor of dermatology and pediatrics, Stanford University School of Medicine.

"This is a phase 1, proof-of-concept study investigating the feasibility of gene therapy in patients with one of the most severe types of EB," Dr. Lane says. "If it is successful, it will set the stage for further therapeutic extension of this approach in patients with RDEB and hopefully in patients with other forms of EB as well."

Dr. Lane 

The study

The trial is funded to enroll 12 adults with biopsy-confirmed RDEB who will undergo grafting with tissue derived from their own keratinocytes that has been genetically engineered using a retroviral carrier (LZRSE) to express the gene for type VII collagen (Col7A1).

Eligible patients and their parents must have RDEB type VII collagen mutations, but the patients must show evidence of making the antigenic portion (NC1) of the protein and have no antibodies to collagen VII.

In addition, they must have at least 100 cm² to 200 cm² areas of open erosions on the trunk and/or extremities to receive the LZRSE-Col7A1 engineered autologous epidermal sheet grafts.

The study, which is being sponsored by Stanford University and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, has one year of planned follow-up. Outcome measures include safety assessments and identification of the presence of anchoring fibrils and type VII collagen.