Severe steroid resistant asthma is an allergic disease that affects around 5% of asthmatics, but requires 50% of the total NHS spend to treat. There are no treatments and it is considered as a major unmet need.
IL-33 cytokine release has been shown to be a critical step in a range of allergic diseases, and high IL-33 levels in the lung have been associated with severe asthmatic pathology. IL-33 has been proposed as a potential target for steroid-resistant asthma. Candidates that directly block released IL-33 are in development, but none of these prevent the release of IL-33 from necrotic cells or selectively bind only the active form of IL-33, which is required for therapeutic effect.
Our technology, HpARI, centres around a peptide derived from the secretions of a helminth parasite, and which we have shown blocks the release of IL-33 from cells, and binds to active IL-33 only. This dual strategy is a potentially more efficacious and efficient approach to treatment than current candidates.
HpARI suppresses allergic immune responses, lung pathology, and improves lung function through interference in the IL-33 pathway in in vivo and in vitro models. We have characterised the domains and binding sites necessary for activity, and the design of drugable peptides is currently underway.