Our research Completed projects Bauer 5 (2017) To develop therapies which combine ex vivo gene therapy with stem cell transplantation for Junctional EB Contents: Project information Lay summary Combining ex vivo gene therapy with stem cell transplantation for Junctional Epidermolysis Bullosa Investigator: Professor Johann W Bauer, Head, EB House/Division of Experimental Dermatology Institution: Division of Experimental Dermatology and EB House Austria, Department of Dermatology, Austria Grant: €260,000 - Completed Lay Summary This group has brought together three prestigious research units in Europe: The EB House, University of Salzburg in Austria; The Centre for Regenerative Medicine, University of Modena in Italy and Medizinische Hochschule Hanover, Germany’s largest transplantation medicine centre to collaborate on important research in EB. The centres have sound expertise in growing human tissues in the laboratory including growing human skin to produce sheets of skin cells that can be used for the treatment of large full-thickness skin burns. They are also experts in gene technology, which involves using harmless viruses to carry genes into a cell which then become incorporated into the cell’s own DNA. Viruses capable of carrying DNA into cells are called vectors. The aim of the project entitled “Combining ex vivo gene therapy with stem cell transplantation for junctional epidermolysis bullosa” was to develop safe tools for implication of a clinical trial for nH-JEB patients with mutations in the COL17A1 gene. Similar trials in Italy and Austria showed the success of this approach for the Laminin B3 gene. Clinical evaluation showed stable skin for up to 7 years and molecular biological analysis revealed that the protein introduced by the therapy also was still expressed (indicating a long-term effect of the correction of skin stem cells). One of the first steps of this project was to develop a safe way of integrating the correct gene sequence into patient cells. Viral vectors are a technology used to do this and safety testing for potential vector candidates for the clinical trial was carried out and vectors were selected for their high safety profile. A particular retroviral vector carrying the COL17A1 DNA was designed. This was a type of vector that has already been used in previous studies and shown to be efficient and safe. JEB keratinocytes (type XVII collagen protein-deficient) in cell cultures treated with this vector showed restoration of protein expression comparable to non-EB cells. However, this correction did not influence the cells vitality or growth. To assess whether this vector would be suitable for the aspired clinical trial, safety validation was done. Also cells -involved with this vector type showed a very high safety profile. Based on these results the retroviral vector carrying the COL17A1 cDNA was selected for the clinical trial. With this vector, patient cells were corrected which means the DNA sequence enables them to produce a stable and functional protein. These corrected cells will be used to grow skin sheets, which are transplanted onto highly affected areas of the patient and form stable and healthy skin there. Related documents were submitted to several regulatory authorities and the results are expected in the coming months. A small number of patients meeting the inclusion criteria have already been informed about the study. Screening is estimated to start towards the end of 2017 and first transplantations are planned for 2018. In summary, this work established a safe and efficient way to correct JEB patient cells and achieved a clinical trial protocol, which is likely to start recruit patients within this year with the hope to improve their quality of life with partial repair of the skin stability. What is important about this research? “This preliminary work has enabled us to include novel safety tests for our patients that are treated with ex vivo stem cell/-gene therapy. In addition, knowledge about an efficient gene therapy vector for correction of type XVII collagen deficient JEB patients has been established. Based on this knowledge we are now ready to move ahead with further trials.” Investigator Biography Prof. Johann Bauer is head of the Department of Dermatology of the University Hospital Salzburg. He built up and has headed the research group of the EB-house Salzburg, which consists of more than 20 scientists working on EB-research, up to now. His main interest is the development of a safe and applicable gene therapy for all forms of EB. Moreover the group in Salzburg works on Small Molecule based approaches to alleviate the symptoms of EB in order to enhance the quality of life of the patients and on developing therapies for RDEB associated aggressive squamous cell carcinomas.