Grant Award Details
Pre-IND meeting for autologous COL7A-1 gene corrected iPSC-derived epithelial sheets, aka “DEBCT”, to treat dystrophic epidermolysis bullosa.
Grant Application Details
- DEBCT: Genetically Corrected, Induced Pluripotent Cell-Derived Epithelial Sheets for Definitive Treatment of Dystrophic Epidermolysis Bullosa
DEBCT is an autologous iPS-derived COL7A1-corrected keratinocyte graft indicated for the treatment of all chronic open wounds in patients with RDEB.
Area of Impact
RDEB patients lack type VII collagen and have chronic wounds that lack an abundance of keratinocyte stem cells. DEBCT skin grafts will close wounds.
Mechanism of Action
RDEB patient keratinocytes contain mutations in COL7A1, lack the adhesion protein type VII collagen, and suffer profound skin fragility, chronic open wounds, and stem cell depletion. DEBCT is a COL7A1-corrected autologous keratinocyte stem cell sheet, when grafted onto wounds, adhere tightly and provide long-term wound closure. Autologous, corrected iPS cells can be grown in large quantities and can be induced to produce keratinocyte stem cells, allowing clinical scaling and manufacturing.
Unmet Medical Need
Children with the debilitating inherited blistering disorder Recessive Dystrophic Epidermolysis Bullosa lack the COL7A1 gene and experience painful non-healing wounds over their body, and risk death from cancer later in life. Current therapy is palliation costing thousands of dollars per month.
Pre-IND meeting and DEBCT pivotal study plan
Major Proposed Activities
- Optimize cGMP-compatible one step reprogramming and correction to autologous IPS cells and develop cGMP-compatible nucleic acid reagents
- Optimize coupling efficiency of COL7A1-corrected iPS-derived graftable keratinocytes and develop cGMP-compatible CD49f cell separation protocol
- Perform rodent pilot efficacy and safety studies of DEBCT keratinocyte grafts prior to a Pre-IND FDA meeting
While Epidermolysis Bullosa is a rare orphan disease, many of the common alleles are found in people of Latin American descent, a significant population in California. Children with the debilitating inherited blistering disorder experience painful non-healing wounds over their body, with current palliative therapy costing thousands of dollars per month. Long-term wound closure with DEBCT, a therapy developed in California, would lead to lower overall health costs and improved quality of life.
- Cell Stem Cell (2019) TFAP2C- and p63-Dependent Networks Sequentially Rearrange Chromatin Landscapes to Drive Human Epidermal Lineage Commitment. (PubMed: 30686763)
- Nat Genet (2018) Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment. (PubMed: 30397335)