Epidermolysis Bullosa Therapeutic Reprogramming Consortium
Induced pluripotent stem (iPS) cells are a type of stem cell generated from other adult cells. Like other stem cells, they have the ability to become another type of cell in the body. Patient iPS cells can be gene-corrected and then differentiated into a skin graft and returned to the patient to treat EB.
The Consortium was formed in 2016* to accelerate scientific discoveries in stem-cell-created grafts into the manufacturing and treatment stages. At the time of forming the Consortium, methods of reprogramming iPS cells were slow and inefficient. However, in 2018, the Consortium reported a more efficient approach to reprogramming the disease skin cells into stem cells.
*Cure EB joined the funding collaboration with EBRP and EBMRF in 2017. The work funded by this funding collaboration has led to significant awards for the Consortium from other parties including the California Institute for Regenerative Medicine and the US Department of Defense.
The discovery of methods to generate human iPS cells brought the possibility of using corrected human autologous iPS cells to generate tissue replacement, a process called Therapeutic Reprogramming. iPS cells can be expanded indefinitely retaining a pluripotent and undifferentiated state and can therefore be used as a constant source of material for cell therapy. The advent of novel genome editing technologies allows the manipulation and correction of iPS cells in a defined environment where the resulting corrected clone can be evaluated. Development of iPS cell-based therapies for RDEB patients represents an ideal paradigm due to the severe and orphan nature of the disease, the demonstration that corrected keratinocytes can have long-term tissue repopulation, and the need for large numbers of stem cells to cover the affected surface area. Moreover, because the skin is visible, any abnormalities in the product can be noticed early and quickly removed, enhancing safety.
While iPS-based therapies represent the ideal goal, the precise techniques representing the optimal manufacturing protocol remain undefined. The overall strategy consists of four major steps:
- Reprogramming patient somatic cells into iPS cells;
- Genome editing to correct the genetic mutation;
- Validating and Sequencing the Cell bank;
- Generating downstream skin tissue for grafting.