Kings College London: A Novel Gene Therapy Addressing Recessive Dystrophic Epidermolysis Bullosa (RDEB) Shows Promise

Jul 27, 2019 | Gene-Modified Autologous Fibroblasts, Kings College London, Recessive Dystrophic Epidermolysis Bullosa, Stem Cell

Smart geneticist looking at the DNA model and thoughtfully touching it

King’s College London, in collaboration with University College, London conducted a Phase I clinical trials focused on recessive dystrophic epidermolysis bullosa (RDEB), a severe form of blistering skin disease caused by mutations in COL7A1 gene. The UK-based study aimed to assesses the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB. The study evidenced a positive outcome and investigators suggest the data offers a rationale for Phase II studies for further evaluation.

The Study

Titled “Phase I Study of Lentiviral-mediated COL7A1 Gene-modified Autologous Fibroblasts in Adults with Recessive Dystrophic Epidermolysis Bullosa” the study commenced in 2015 and concluded in 2018. RDEB is a severe form of blistering skin disease caused by mutations in COL7A1gene. The study sought to assess the safety of intradermal injections of gene-modified autologous fibroblasts in 5-10 adults with RDEB.

It was an open-label, single-center Phase I study with the primary objective to evaluate the adverse and serious adverse events over 12 months’ follow-up period. Secondary objectives including (1) analysis of type VII collagen (C7) expression and morphology of anchoring fibrils in the injected areas of the skin; (2) analysis of immune response to newly expressed C7.

Each study participant will receive three intradermal injections of COL7A1 gene-modified autologous fibroblasts on Day 0 only. Each subject will undergo an initial screening including a physical examination and assessment of disease severity. Blood analyses and skin biopsies will be performed at various time points per the monitoring schedule over 12 months. John A. McGrath, FRCP, Kings College London served as Principal Investigator.

The Results

Epidermolysis Bullosa News’ Iqra Mumal reported on the Phase I results. The clinical trial included four adults with RDEB, who received three into-the-skin injections of their fibroblasts, genetically engineered to express a healthy COL7A1 gene. The investigators injected fibroblasts into the left upper arm, where all patients had intact, non-blistering skin. The participants were thereafter evaluated for safety and efficacy signals over the 12 months.

The study team reported on the primary outcome, safety, including autoimmune reactions against foreign C7. Secondary outcomes included C7 expression, the structure of anchoring fibrils, and presence of COL7A1 in the injected skin. The outcomes pointed out that gene-modified fibroblasts were well-tolerated and there were no serious adverse reactions of autoimmune reactions against recombinant C7.

Investigators pointed out that a significant increase (ranging from 1.26-fold to 26.10-fold) in C7 expression in the injected skin compared with non-injected skin In three out of four participants. The increase in C7 was sustained for up to 12 months in two patients reported Iqra Mumal.

Investigators were quoted by Epidermolysis Bullosa News “To our knowledge, this is the first human study demonstrating safety and potential efficacy of lentiviral fibroblast gene therapy with the presence of COL7A1 transgene and subsequent C7 restoration in vivo in treated skin at one year after gene therapy.” They continued “These data provide a rationale for Phase II studies for further clinical evaluation.”


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