There are 17 genes which may be mutated in epidermolysis bullosa. The three main forms for which targeted therapies are being developed are EB simplex Dowling Meara (silencing the keratin 14 gene), Junctional EB (to replace the defective LAMB3 gene affecting anchoring filaments), and recessive dystrophic EB (to upregulate or replace the collagen VII gene/anchoring fibril protein). Gene therapy has already been successful ex-vivo for in non-Herlitz JEB and gene therapy trials are underway for RDEB.
Cell therapy uses stem cells from the skin or bone marrow which are from normal unrelated donors to replace the defective gene. Bone marrow stem cells, either haemopoietic or mesenchymal, have been tried for RDEB and JEB. Bone marrow transplantation has high mortality in EB related to the immunosuppression or graft rejection and is not a cure. Intralesional injections of mesenchymal stem cells have shown promise in RDEB. Allogeneic cultured fibroblasts injected intradermally were shown to improve wound healing for 4-6 months. Protein therapy to replace the missing collagen VII is in phase I trials for RDEB in the USA. Other new therapy approaches in trial are PTC read-through drugs, which trick the body into ignoring mutations that have stop codons, so that the full length protein is produced. These would have applicability to up to 30% of RDEB cases and most H-JEB cases as well as other recessive forms of EB.