Researchers describe alternative psoriasis target

The group headed by Francesca Capon from King’s College in London believe its findings could pave the way for early-stage clinical trials of IL-36 blockers as therapies for psoriasis. The auto-immune disease affects as many as 3% of people worldwide in the form of raised, itchy, and often painful skin lesions.

Treatment alternatives to IL17 blockers are urgently needed because they don’t always give patients the same relief in real-world settings as observed in clinical trials. (IL)–36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. Seeking new treatment options, Satveer Mahil et al. blocked IL-36, with an antibody and with an recombinant antagonist and saw substantial reduction of psoriasis lesions in a mouse model of disease. Furthermore, the researchers demonstrated that inhibition of IL-36 alleviated inflammatory signaling in cultured skin from psoriasis patients, and led to significant reductions in IL-17 expression, keratinocyte activation, and leukocyte infiltration. Adding IL-36 to skin cells growing in culture activated the expression of hundreds of genes known to be associated with psoriasis.

To determine if inhibition of IL-36 signalling would be safe in human patients, Mahil and colleagues examined 12 persons carrying inactivating mutations in the gene encoding the cytokine’s receptor. They observed that all individuals were healthy; none had skin abnormalities, cardiovascular disease, cancer, or immune disorders. What’s more, they all mounted adequate protective responses after being exposed to pathogens, and did not have any overt immunodeficiency. The authors conclude their results suggest IL-36 inhibitors could be safe and effective psoriasis treatments in humans. 

Anaptysbio, Inc. and Boehringer Ingelheim last year published  patent applications of IL-36 receptor blockers to treat psoriasis. Researchers at College Of The Holy & Undiv. Trinity Of Queen Elizabeth Near Dublin filed a patent on inhibitors of IL-36 proteolytic processing in 2015.