Topical Tripeptide in an Emollient-Based Cream May Ease Psoriasis Symptoms

New findings from a study led by University of Birmingham scientists suggest that treatment of psoriasis with a tripeptide, made up of 3 amino acids, may ease symptoms of the disease when applied through a topical emollient-based cream.1,2

Psoriasis is a chronic, inflammatory, autoimmune disease marked by an overproduction of skin cells among those with the condition, resulting in patches of skin that are painful, scaly, and inflamed. These psoriatic lesions can disrupt patients’ focus, sleep, and quality of life, with a cyclical pattern of psoriatic flare-ups persisting for weeks or months in many individuals with the skin disease.

“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,” Ed Rainger, BSc, PhD, University of Birgmingham professor, said in a statement.1 “Our findings raise the possibility of using PEPITEM derived peptides for the treatment of psoriasis.”

The study was led by Rainger Francesco Maione, a professor at the University of Naples Federico II. Rainger and Maione’s findings on this emollient cream for psoriasis were published in Pharmacological Research, with their analysis focusing a naturally occurring peptide within the human body known as PEPITEM.2

It is also known for its role in the modulation of inflammation in such conditions as psoriasis. Standard therapies for psoriasis often include emollients and creams that contain retinoids, vitamin D analogues such as calcipotriol, or corticosteroids.

Such agents, given side effects that can result from prolonged implementation, are typically limited in their duration. The investigators whose analysis led to the findings on PEPITEM were able to isolate the smallest active portion of this 14-amino-acid molecule, finding short sequences that are known to be responsible for the tripeptide’s immune-regulating impact.

The team pinpointed 2 tripeptide fragments of PEPITEM that retained full biological function. The fragments were optimized by the investigators for stability within the body and tested for their ability to suppress immune cell activation and migration, key mechanisms that are identified in chronic inflammation.

Both the full-length PEPITEM and a derived 3-amino-acid sequence substantially reduced the severity of trial participants’ psoriatic disease during the team’s analysis. In fact, the impacts were noted by investigators as comparable to the steroid cream Clobetasol Propionate 0.05%, known for its potency.1,2

One of the tripeptides exhibited the strongest biological activity and it was selected for further testing in a psoriasis animal model. Topical application of this sequence on a daily basis in an emollient over the course of 7 days was shown by the investigative team to lead to notable disease severity reductions compared to untreated controls, with findings quantified via the Psoriasis Area and Severity Index (PASI) scores among subjects.

Both PEPITEM and its most active tripeptide were found to have lowered participants’ PASI scores by 50%, matching the efficacy of Clobetasol Propionate 0.05%.2 The team further highlighted that the peptides they evaluated regulate inflammatory signaling molecule production, specifically those molecules driving immune cell recruitment and promoting the proliferation of skin cells involved in psoriasis.

In 1 notable finding highlighted by the investigators, some of the tripeptides were shown to have demonstrated up to tenfold higher activity than the original PEPITEM sequence. The investigative team summarized that PEPITEM and its tripeptide derivatives are naturally occurring, pointing out that they may consequently provide those with psoriasis a safer long-term therapy alternative. They highlighted the reduced risk of off-target effects.

This study forms part of a broader initiative exploring PEPITEM’s potential as a therapeutic option for a plethora of chronic inflammatory conditions, some of which include lupus, rheumatoid arthritis, diabetes, and psoriasis. Several patent families related to PEPITEM and its immunomodulatory components were noted to have been filed by University of Birmingham Enterprise.

The investigative team is now actively pursuing investment, licensing, and collaborative opportunities for the purposes of advancing the development of such peptide-based medications.1

References

1. PEPITEM sequence shows effects in psoriasis, comparable to steroid cream. University of Birmingham. April 3, 2025. Date accessed: April 7, 2025. https://www.eurekalert.org/news-releases/1078892.

2. Saviano A, Apta B, Tull S, Pezhman L, Fatima A, Sevim M, Mete A, Chimen M, Schettino A, Marigliano N, McGettrick HM, Iqbal AJ, Maione F, Rainger GE. PEPITEM, its tripeptide pharmacophores and their peptidomimetic analogues regulate the inflammatory response through parenteral and topical dosing in models of peritonitis and psoriasis. Pharmacol Res. 2025 Mar;213:107624. doi: 10.1016/j.phrs.2025.107624. Epub 2025 Jan 22. PMID: 39855372.