An update on molecular therapies and clinical studies for epidermolysis bullosa
New publication from the EB House
EB is still uncurable, since the current treatments, primarily focussing on wound care and symptom relieve, do not target the underlying cause of the disease. Thus, a major focus of EB research lies on the development of approaches with curative potential. In a recently published article, researchers of the EB House provide an updated overview on the different molecular therapies that are explored to treat EB. The authors discuss the status and challenges of these therapies and provide a list of currently ongoing clinical trials involving EB patients (Table 1 in the article).
Most of the approaches focus on the restoration of a healthy protein. This can be achieved by correcting the mutation or by adding a funtional copy of the affected gene or the missing protein into the skin stem cells. Other therapies use small molecular drugs, that aim to modulate the gene copy (RNA), so it can produce a corrected protein.
Currently, severely affected patients that are completely missing an EB protein are often excluded from studies, due to the risk that the patient’s immune system might reject the newly introduced healthy protein.
Such immune reactions could be prevented if small amounts of residual protein are present in the skin, which is the case in some severely affected patients showing patches of healthy skin. This phenomenon, referred to as revertant mosaicism or natural gene therapy, is due to spontaneous correction of the disease causing mutation in some skin cells. As a result, normally functioning protein can be produced in these skin areas. Inital attempts to expand the reverted cells in culture, generate skin sheets and graft them back onto wounds, did not result in long-term closure of the wounds. This might be due to the small number of healthy stem cells in the skin graft, which are responsible to permanently maintain the graft. In order to ensure long-term clinical benefit, protocols must be developed, allowing the production of skin grafts containing adequate numbers of revertant stem cells.
In summary, the increasing number of clinical trials assessing innovative molecular therapies for EB reflects the fast advances in EB research. However, positive study results do not automatically lead to a broad clinical application of the tested therapies, as each EB patient has very individual symptoms and needs. The most realistic scenario for the future thus involves the development of patient-tailored therapies.