Engineered Peptides Offer Safer Relief for Psoriasis

A newly published study in Pharmacological Research investigates the anti-inflammatory potential of PEPITEM, a 14-amino acid immune-modulatory peptide, and its smaller pharmacophore sequences and engineered peptidomimetic analogues. The study reports that these compounds effectively regulate inflammation in both systemic and topical delivery models.

Researchers identified two independently active tripeptide pharmacophores within PEPITEM and developed peptidomimetic analogues with improved pharmacodynamic profiles. These analogues demonstrated the ability to regulate T-cell trafficking in vitro and significantly reduce T-cell, neutrophil, and macrophage populations in the inflamed peritoneal cavity of treated mice.

In a plaque psoriasis model, topical administration of PEPITEM and its derivatives reduced disease severity, local inflammation, and immune cell infiltration. The compounds also modulated cytokine release from macrophages and fibroblasts and suppressed keratinocyte proliferation. Notably, treatment was associated with decreased Th1 and Th17 cell abundance and lower levels of their associated cytokines in secondary lymphoid organs.

Clobetasol, a topical corticosteroid used as a control, was more effective than PEPITEM in reducing psoriasis severity. However, PEPITEM and its derivatives achieved these effects without the known side effects associated with steroid use.

The identification of smaller, active tripeptide pharmacophores within the full-length PEPITEM sequence offers potential advantages. Additionally, the increased efficacy observed in some peptidomimetics suggests improved pharmacological properties over the parent compound.

These findings support further development of PEPITEM and its derivatives as novel anti-inflammatory agents targeting immune and stromal cell-mediated pathology. The results may have broad implications for the treatment of autoimmune and chronic inflammatory diseases.