Gene May Lead to Psoriasis Therapies

A recent study has identified a new gene, PIM1, that may eventually lead to the development of new treatment approaches for psoriasis.

“We have provided profound new scientific insights into the role of interleukin-22 (IL-22) as a key inflammatory cytokine in skin and have discovered the kinase PIM1 a potential drug target for psoriasis in preclinical models,” said Professor Frank O. Nestle, senior author, King’s College London and the National Institute for Health Research Biomedical Research Centre, London, United Kingdom. Further, this is the first time that the gene has been specifically linked to psoriasis.

Psoriasis is a common, chronic skin disease that produces itchy or sore patches of dry, red, thick skin with silvery scales typically on the knees, elbows, scalp, face, back, palms, and feet. Although there is no cure, treatments including creams, light therapy, and medications can help control symptoms and prevent infection. The exact cause of psoriasis is unknown, but it is thought to be related to the immune system and genetics.

“The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap,” the authors write in the study.

For the analysis, the cytokine IL-22 was injected into models of normal human skin in mice, which produced marked inflammatory skin changes that looked similar to human psoriasis. Researchers then injected the mice with an antibody to block the IL-22 cytokine, resulting in a reversal of these skin changes.

Bioinformatic analysis was used to map the IL-22 and the antibody transciptomes onto a psoriasis disease gene coexpression network. With this method, researchers were able to identify key cytokine-dependent hub genes; PIM1, one of these hub genes, was determined to be a critical checkpoint for human skin inflammation and a possible therapeutic target in psoriasis.

The findings demonstrate that a combination of genomic technologies and computational analysis of key cytokines allows for the discovery of novel drug targets in psoriasis, explained Nestle.

When asked how he hopes that this study will eventually affect the care of patients with psoriasis, Nestle stated, “Advancing insight into new mechanism of skin inflammation provide candidate molecules for targeted therapies, to be tested in the clinic.”

Although the results are exciting, Nestle pointed out that the study was performed in preclinical models and need to be validated in patient studies.

The study, which was published in Science Translational Medicine, was supported by the Medical Research Council, Wellcome Trust, and the National Institute for Health Research Biomedical Research Centre (NIHR BRC) at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London.

-Meredith Edwards White

Reference

Perera GK, Ainali C, Semenova E, et al. Integrative biology approach identifies cytokine targeting strategies for psoriasis. Sci Transl Med. 2014 Feb 12;6(223):223ra22. doi: 10.1126/scitranslmed.3007217.