What would an effective EB therapy look like?
Because EB is caused by a fault in a gene in skin cells, which in turn produces a faulty skin protein, EB therapies must supply either:
- the correct gene able to make the missing protein: gene therapy
- the missing protein: protein therapy
- cells carrying the correct(ed) gene: cell (or cell-gene) therapy
- drugs to reduce production of, or reduce the impact of, the faulty protein, or increase the production of compensatory proteins: drug therapy
Systemic versus localized therapies
Ideally, a therapy for EB would be a one-off safe, systemic treatment that resulted in a lifetime cure. EB is a systemic disease, and ideally, a durable whole-body therapy is required to treat internal body sites as well as skin.
To develop durable therapy, a persistent stem-cell population will need to be provided. The human epidermis consists of a stratified squamous epithelium that is replenished constantly, with a complete turnover every 3–4 weeks by resident stem cells in the epidermis. However, in EB, recurrent blistering depletes the stem cell pool. Epidermal stem cells and other skin stem cell populations and extracutaneous sources of pluripotent stem cells are in development for gene- cell therapy approaches both to modify disease severity and to improve quality of life for people living with RDEB.
Other therapeutic approaches are locally targeted to heal just the treated area. Although EB is a systemic disease, localized therapies that can enhance wound healing and decrease fragility in body locations subject to recurrent trauma can significantly improve quality of life. Symptom-relief (pain, itch) treatments are similarly important to people with EB living with the condition 24/7.
Patient choice
Therapies in development recognize not only differences in genetic defect, but the differences in EB features that impact patients’ lives, and therefore acceptable risks: benefit profiles.
Most people with EB will have an individual approach to deciding what is the right balance of risk versus benefit in choosing a therapeutic approach to improve their own quality of life. It cannot be assumed that all patients with the same EB subtype, symptoms and prognosis will select the same treatment. This impacts on both clinical trial design and patient recruitment, as well as likely markets for treatments. Further research is required to refine concepts and processes to yield safer, more effective and ‘patient-friendly’ treatments.
It is likely that eventual ‘cures’ will combine various approaches currently in development, with novel technologies and therapeutic concepts as yet to emerge from fundamental research into EB.
