Background

Psoriasis is a chronic skin disease that affects over 100,000 people in Ireland alone and is estimated to affect 2-4% of the population in western countries. Market reports predict that the world psoriasis drug market will be worth $8.9bn in 2018. Those products, treating that indication generated £6bn in 2012 according to ‘Psoriasis Treatment: World Drug report 2013-2023’

Individuals that carry loss-of-function mutations in the IL-36 receptor antagonist (IL-36RA) display a severe and highly debilitating form of psoriasis, called generalized pustular psoriasis.

Technology Overview

Researchers at Trinity College Dublin have identified the proteases that activate IL-36alpha, IL-36beta and IL-36gamma ( Figure 1. ) and demonstrate that inhibition of these proteases (specifically elastase and cathepsin G) greatly attenuates the biology activity of IL-36 family cytokines.

Technology Status:

Following on from this discovery, specific novel polypeptides have been developed that are capable of blocking processing and activation of IL-36 cytokines by neutrophil granule proteases, cathepsin G and elastase.

Applications

These novel small (<400 daltons) polypeptide inhibitors of proteases have a therapeutic potential for inflammatory conditions where excessive or deregulated IL-36 signalling may have a function in disease pathology, such as psoriasis. Specifically, direct therapeutic utility as inhibitors of neutrophil granule protreases (Cathepsin G, Elastase and proteinase 3) in inflammatory diseases.

The application of small molecule inhibitors directly onto affected areas of skin circumvents a major disadvantage of current therapies for psoriasis and related skin diseases, namely the systemic delivery of potent immunosuppressive drugs or neutralizing antibodies that could make patients vulnerable to sporadic infections.

Interleukin-36 Proteolytic Processing Inhibitors

Patents

IP Status