Treatment of Hereditary Epidermolysis Bullosa: Updates and Future Prospects

Chao-Kai Hsu; Sheng-Pei Wang; Julia Yu-Yun Lee; John A. McGrath


Am J Clin Dermatol. 2014;15(1):1-6. 

In This Article

3 Protein Replacement Therapy

Another potentially attractive approach is recombinant protein therapy—if RDEB skin is lacking C7 protein, then why not simply make recombinant C7 and restore this to the defective skin? Woodley et al.[13] first injected human recombinant C7 intradermally into mouse animal models. The injected C7 localized to the basement membrane zone and organized into human anchoring fibril structures, thus reversing the pathological features of RDEB. Of note, the injected C7 remained stably incorporated into the basement membrane zone for at least 3 months after a single injection. However, many RDEB patients typically have widespread blisters and erosions, and effective treatment would require either multiple intradermal injections or systemically delivered C7. Woodley et al. therefore intravenously injected human recombinant C7 in a murine model with grafted murine RDEB skin. C7 was observed homing mainly to the RDEB skin graft, and further restored dermalepidermal adhesion, C7 expression, and anchoring fibril formation.[14] No aggregation of C7 in the blood circulation or any adverse effect was shown in the study. Recombinant C7 protein therapy for RDEB is now being assessed in a dog model of RDEB.[15] Extension of the studies to clinical trials of C7 protein in humans (intradermal or intravenous) is expected within the next 2–3 years. One concern has been whether patients might develop autoantibodies to the new C7 and therefore be at risk of developing EB acquisita on top of their RDEB. However, a recent study showed that, as a baseline finding, although many subjects with RDEB do have circulating anti-C7 antibodies (detected by ELISA), these antibodies do not tend to bind to the dermal–epidermal junction (negative indirect immunofluorescence) and therefore may not be clinically relevant—although clearly this will need to be monitored closely in human trials of recombinant C7.[16]