PEPITEM, a natural molecule, and the tripeptide sequence derived from it may reduce the severity of psoriasis when applied topically in an emollient cream.
In its native state, PEPITEM consists of a chain of 14 amino acids, but researchers identified the smallest parts of the PEPITEM molecule that influence immune cells and inflammation in psoriasis. The scientists identified two sequences of three amino acids that showed biological activity comparable to the full-length PEPITEM molecule.
Next, they optimized these tripeptides to improve their stability in the body and tested their ability to reduce immune cell activation and migration, which are hallmarks of inflammatory disease. Their findings showed these two sequences had at least the same activity as the original PEPITEM molecule. They then selected the sequence with the greatest biological activity, and researchers trialed its effectiveness in psoriasis using an animal disease model.
A Clear Reduction in Disease
They found that topical application directly to the skin every day for seven days in an emollient cream resulted in a clear reduction in disease compared to untreated animals, and their findings were confirmed using PASI (Psoriasis Area and Severity Index) scoring, which is used in clinical practice to measure the extent and severity of psoriasis.
In addition, the study also showed that both PEPITEM and the tripeptide sequence reduced the PASI score by 50%, making it comparable to the steroid cream clobetasol propionate at 0.05%.
“While there are a number of therapies for psoriasis, there is a clear need for new therapeutic agents that can be used continuously, and without the risk of excessive side effects, to prevent psoriasis flares. Our findings raise the possibility of using PEPITEM-derived peptides for the treatment of psoriasis,” says Professor George Edward Rainger, BSc, PhD, Deputy Director of the Department of Cardiovascular Sciences at the University of Birmingham in Birmingham, UK, in a news release.
“This study also raises the interesting possibility that PEPITEM-derived peptides could be used in combination with other psoriasis therapies, allowing lower dosing for longer durations, for example, a ‘steroid-sparing’ approach, to reduce the side effects associated with prolonged use of such agents.”
Steroids should only be used for short periods due to side effects that occur with continuous use, but as a natural molecule, PEPITEM and the tripeptide sequence that is derived from it are less likely to show these ‘off-target’ effects.
Influence Inflammation
Further investigation showed both the whole PEPITEM molecule and the tripeptide sequences regulate the synthesis of signaling molecules that promote inflammation, leading to the recruitment of immune cells and proliferation of other cell types in skin tissue involved in disease, with some tripeptide sequences showing an order of magnitude increase in efficacy compared to the parent PEPITEM sequence.
“We have identified the parts of the PEPITEM molecule that are responsible for its biological action and delivered peptides that mimic PEPITEM and dramatically influence the skin’s inflammatory processes,” Rainger adds. ”Their significantly smaller size and higher efficacy should result in substantial advantages in synthesis, formulation, and use in therapeutics.”
The study appears in Pharmacological Research.
