PhD defence M.P.M. van den Berg

Arginase and TRPA1 as novel therapeutic targets for the treatment of asthma

Mariska van den Berg investigated novel therapeutic targets for the treatment of asthma. Asthma is a common chronic respiratory disease characterized by recurring symptoms, including shortness of breath, cough and airway inflammation. Current asthma treatment options are not sufficient for all asthmatics, especially for patients suffering from severe asthma, underlining the need for new therapies. Van den Berg focused her research on two potential targets: arginase and TRPA1.

The enzyme arginase is a promising target for the treatment of asthma, as it plays an important role in various aspects of the respiratory disease by influencing the production of NO and ւ-ornithine in the airways. In this thesis, the effectiveness of new arginase inhibitors is tested in different asthma models. Furthermore, it is suggested that treatment of asthma with arginase inhibitors may also lead to the relief of symptoms of common asthma comorbidities. In addition, specific attention was paid to the role of arginase 2 in mast cells, demonstrating that arginase 2 may play a protective role by preventing mast cell differentiation into an allergic phenotype.

The second potential therapeutic target for the treatment of asthma that has been investigated is the ion channel TRPA1. In the airways, TRPA1 contributes to various respiratory symptoms, such as bronchoconstriction, mucous secretion and reflex cough. In this thesis, a novel TRPA1 antagonist is presented. Using this TRPA1 antagonist it is demonstrated that both neuronal and non-neuronal TRPA1 play a role in allergen-induced airway narrowing.

Promotores: Prof.dr. R. Gosens and Prof.dr. H. Meurs