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A prospective phase I study of lentiviral-mediated COL7A1 gene-corrected autologous fibroblast therapy in adults with recessive dystrophic epidermolysis bullosa (LENTICOL-F)

Investigator: Professor John McGrath, Professor of Molecular Dermatology and Consultant Dermatologist

Co-applicants: Dr Jemima Mellerio, Dr Waseem Qasim, Dr Wei-Li Di, Professor Adrian Fletcher

Institution: St John’s Institute of Dermatology, Division of Genetics and Molecular Medicine

Grant: £499,320 (01/02/2015 – 31/01/2018) Sohana Research Fund

Lay summary

In Recessive Dystrophic Epidermolysis Bullosa (RDEB) there are inherited mutations (mistakes) in the gene COL7A1 that produces a specific type of protein (collagen VII). The mutations mean that the C7 produced cannot fulfil its normal function of holding the skin layers together to maintain normal skin integrity, so the skin blisters. If normal C7 structure could be restored, this would lead to fewer blisters and stronger skin.

Previously, using grants from DEBRA and the Sohana Research Fund (SRF), this group have shown that they can take the collagen-producing cells (called fibroblasts) from RDEB patients, grow them in the laboratory and introduce a perfect version of the COL7A1 gene using a harmless virus (lentivirus). These treated cells are called “gene-corrected fibroblasts” and can produce perfect C7. Following safety checks, the group is now in a position to take this therapy into a small clinical study in people.

This study proposes to take skin samples from 6-10 adults with RDEB to produce “person-specific” gene-corrected fibroblasts. When sufficient cells have been grown, they will be injected back into the donor’s skin. Three injections will be given 1-2 millimetres under the skin surface, covering an area about the size of a once pence piece.

Skin samples will be taken from the injected areas over 12 months to make sure that the gene-corrected cells do not cause any serious side effects. The skin will be monitored and blood samples collected for up to 3 years. The study is focusing primarily on safety; however, scientific information on C7 production will also be collected.

The results from this work will help in planning further clinical trials. If the gene-corrected cells are safe and show some improvement in the skin structure then the research will progress to other studies – such as comparing gene corrected and uncorrected fibroblasts cells.

This technology could be used to correct other cell types such as bone marrow stem cells which could be delivered by intravenous injections and thus could show benefit throughout the body and not just in the local area of skin.

What is important about this research?

“If safety can be established, future trials will compare the genetically corrected cells with uncorrected cells injected into the skin, but the data will also help plan trials of delivering gene therapy to other cells that can be delivered via the bloodstream to help target the whole body. Such work is likely to edge us closer to more effective treatments for RDEB.”

Prof McGrathInvestigator biography

John McGrath MD FRCP FMedSci is Professor of Molecular Dermatology at King’s College London and Head of the Genetic Skin Disease Unit, as well as Honorary Consultant Dermatologist at St John’s Institute of Dermatology, the Guy’s and St Thomas’ NHS Foundation Trust in London. He was previously a DEBRA-funded junior EB research fellow and has worked on EB research for more than 25 years. He now leads and collaborates on several National and International projects to develop gene, cell, protein and drug therapies that can lead to better treatments for people living with EB.

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