Epidermolysis bullosa simplex (EBS) is a highly penetrant genetic condition that causes fragility of skin keratinocytes resulting in fluid-filled skin blisters that erode upon scratching or minor pressure on the skin. There is no good cure for EBS, and treatment typically involves preventive and/or supportive care to protect skin from painful blistering.
Researchers from Leipzig and Rutgers Universities have shown that keratinocytes from patients with EBS are protected from injury by the multi-kinase inhibitor PKC412. Treatment with PKC412 improves epithelial sheet integrity of EBS-associated keratinocytes harboring the severe keratin 14 Arg125-to-Cys mutations (K14.R125C) and K14.R125G and reduces their associated keratin aggregation. To further substantiate the efficacy of PKC412 on EBS-associated keratinocytes quantitatively, the researchers performed real-time impedance spectroscopy measurements. Upon PKC412 treatment, EBS keratinocytes showed a significant increase in impedance readings in a concentration-dependent manner. The overall findings provide a potential approach for targeted treatment of EBS.
- Oral drug or topical formulation (predicted to have less systemic toxicity) against EBS conditions
- Other intermediate filament associated diseases that harbor K14-like mutations
- Novel potential treatment of EBS
- Stabilizing keratin filaments in keratinocytes can potentially treat blisters and likely prevent or reduce the frequency of their formation
- PKC412 is an already FDA-approved oral drug for the treatment of acute myeloid leukemia and advanced systemic mastocytosis
- Kwan et al. (2015). PKC412 normalizes keratin mutation-related filament disruption and hepatic injury in mice by promoting keratin-myosin binding. Hepatology 62:1858-69
- Rietscher et al. (2022). Kinase inhibition prevents epithelial damage in epidermolysis bullosa simplex via keratin and cell contact stabilization. J Invest Dermatol, in press
Intellectual Property & Development Status: Patent pending. Available for licensing and/or research collaboration.