PsorTREX2. An innovative keratinocyte-based therapy for psoriasis
Universitat de Barcelona - Fundació Bosch i Gimpera, Spain
Available treatments for psoriasis are mainly focused in targeting key immune players. However, the appearance over time of negative side effects, such as immunosuppression, affects patients health and quality of life.
Keratinocytes actively participate in the inflammatory loops involved in the pathogenesis of psoriasis. Our studies have uncovered TREX2, a keratinocyte-specific exonuclease, as a novel target for innovative skin-site psoriasis treatments. Blocking TREX2 can be as effective as treatments targeting the immune system, while avoiding their adverse immunosuppressive effects.
By means of drug discovery approaches, the team has identified compounds that selectively block TREX2 activity and significantly reduce psoriatic inflammation in the IL23-induced mouse model of psoriasis in a TREX2 dependent manner, as no effects are observed in the TREX2 knockout mice.
The project pursues to develop highly selective, effective and safe TREX2 small molecule inhibitors for a reliable skin-directed psoriasis therapy to be proposed for future clinical trials.