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A long-standing puzzle is why some substances – usually proteins – trigger allergic diseases, while others do not. Understanding the bioactivity of allergens in their host sources can shed light on why they are allergenic in humans, and why some are more important than others as triggers of disease.
Professor Clive Robinson is studying the molecular basis of allergenicity and using this knowledge to design innovative drugs for the treatment of allergic asthma, perennial rhinitis and atopic dermatitis.
The Robinson laboratory primarily studies house dust mites (HDM) as allergy triggers. HDM are globally significant causes of allergic diseases and they have a diverse repertoire of allergens, which enables their interactions to be investigated. There is particular interest in group 1 allergens of HDM because they have a key role as allergy initiators – that is to say they promote allergy to themselves and allergens from unrelated sources. The group 1 allergens are powerful digestive enzymes in HDM, but when in contact with humans, this enzyme activity initiates a cascade of innate immune responses which cause and then maintain allergy.
Investigation of the molecular basis of allergenicity has enabled Professor Robinson’s team to translate their discoveries into an unprecedented small-molecule approach which targets the root cause triggers of allergic disease. With multi-million pound support from the Wellcome Trust Seeding Drug Discovery Initiative, they have designed clinically developable inhibitors of key initiator allergens. This work has resulted in more than 50 composition of matter patents and a number of medical use patents. It is hoped that progression of these new drugs through clinical development will eventually improve cost-effective treatment options for the millions of people who live with allergic disease.
Zhang J, Chen J, Mangat SC, Perera Baruhupolage C, Garrod DR, Robinson C. Pathways of airway oxidant formation by house dust mite allergens and viral RNA converge through myosin motors, pannexons and Toll-like receptor 4. Immunity, Inflammation & Disease 2018; 6: 276-296.
Zhang J, Chen J, Newton GK, Perrior TR, Robinson C.Allergen delivery inhibitors: A rationale for targeting sentinel innate immune signaling of group 1 house dust mite allergens through structure-based protease inhibitor design. Mol Pharmacol 2018; 94: 1007-1030.
Allergen Delivery Inhibitors: A potential end to asthma? | A film by the Wellcome Trust
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