Recessive Dystrophic Epidermolysis Bullosa (RDEB) sufferers have a faulty version of a gene (COL7A1) that produces a protein called Collagen VII. Collagen VII should help skin layers hold together, giving skin its strength. In RDEB, the lack of Collagen VII leads to blisters. Restoring Collagen VII should lead to fewer blisters and stronger skin.
In this study, researchers took samples of the collagen-producing cells from RDEB sufferers, grew them in the laboratory, and introduced a corrected version of the collagen gene using a harmless virus called a lentivirus. When enough cells with the corrected gene had been grown, they were injected back into the sufferer’s skin.
This study was carried out primarily to assess the safety of this approach. Over the 12-month assessment period, there were no serious adverse effects seen in the four adult patients enrolled in the study.
The main aim of the project was to conduct a phase I clinical trial to evaluate the safety of SIN lentiviral mediated COL7A1 modified autologous fibroblasts in 5 to 10 adults with RDEB over a 12-month follow-up.
Gene-modified fibroblasts were well tolerated without serious adverse reactions or autoimmune reactions against recombinant Collagen VII. Regarding efficacy, there was a significant 1.26-fold to 26.10-fold increase in Collagen VII mean fluorescence intensity in the injected skin compared to non-injected skin in 3 of 4 subjects with sustained increase up to 12 months in 2 of 4 subjects. The presence of transgene (codon-optimised COL7A1 cDNA) was demonstrated in the injected skin at month 12 in one subject but no new mature anchoring fibrils were detected.
Lwin S.M., et al. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. JCI Insight 2019;4(11)