An overview of advances on potential therapeutic options for EB
New article of the Koller Working Group
To date, there is no cure for EB, and not every therapy is applicable to any type of EB. Therefore, different approaches have been developed in the last decades, which have been summarized in a review article in the journal "Expert Opinion on Orphan Drugs".
The aim of these therapies is to repair or replace the defective gene DNA or its copy (= RNA) in the skin cells, in order to create a healthy protein for the cohesion of the skin layers.
In gene replacement therapy, already applied in EB patients, skin cells are isolated from a small piece of skin, in which an intact gene is introduced via a virus. The corrected cells are then used to grow a thin skin layer which is transplanted onto wounds.
It is important, that the transplanted skin contains corrected stem cells, as they ensure the permanent regeneration of the healthy new skin. Since harvesting stem cells from the skin is challenging, approaches have been developed to "reprogram" normal skin cells into stem cells in cell culture. However, for their use on patients, safety aspects still need to be clarified.
Although side effects have never occurred in gene replacement therapy in EB patients, the use of a virus carries a residual risk of tumor development. Therefore, much research is being performed to develop virus-free gene therapy methods such as CRISPR or TALEN. These approaches also referred to as gene scissors replace the defective gene segment with a healthy copy, leading to a permanent gene repair in the cell.
Other approaches use repair molecules to correct the gene transcript. These RNA approaches, such as trans-splicing or exon skipping, do not permanently correct the defect and therefore need to be applied repeatedly. At present, possibilities are being investigated to deliver the repair molecules directly into the skin in a most efficient and painless manner.
Each of these therapies has the potential to ease EB symptoms and improve the quality of life of EB patients.
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