Grant: Project Grant

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases and up to 17% of the Canadian population is affected at some point in their lives. Furthermore, AD often is an entry point for further allergies such as food allergies, hay fever or allergic asthma. As such, AD has a significant socioeconomic impact. Since AD is a highly complex and heterogenic disease, its pathophysiology is still not fully understood. Over the past years, however, the keratinocyte-derived cytokine thymic stromal lymphopoietin (TSLP) has been identified as a key player in skin inflammation and a trigger for the development of further allergies. This has sparked the interest of pharmaceutical companies to develop inhibitors of TSLP. Tezepelumab is the most advanced drug showing promising results, however it is a protein which means that it must be administered systemically and cannot be applied locally, for example as a cream. However, drugs which can be applied locally offer several advantages such as reduced side effects, targeted drug delivery at the site of action as well higher acceptance rates among the patients. Hence, this project aims to develop effective blockers of TSLP which can be applied topically. To achieve this goal, we combine our expertise in drug development and skin research. First, we will develop and synthesize potent low molecular weight TSLP inhibitors which will then be tested with regard to efficacy and tolerability in 2D and 3D cell cultures. Finally, the most promising compounds will be tested in animal models of atopic dermatitis. The overall goal are new topical treatment options for AD and the prevention of the development of further allergic diseases such as asthma.