Pre-clinical develOpment of Rac1-dependent pathway inhiBITors to fight severe asthma – ORBIT

Asthma is one of the most common chronic diseases with an increased prevalence in developed countries. Severe asthmatic patients are resistant to the current therapeutic management, leading to dramatically increased mortality risk. Those patients definitely need new treatments.
We recently unveiled an essential signaling pathway in human bronchoconstriction involving the small GTPase Rac1. We demonstrated that Rac1 is involved in airways hyperreactivity and remodeling, highlighting the essential role of Rac1 in sever asthma.
We have recently carried out a pharmacophore modeling and in silico screening of new Rac1 inhibitors which allow us to identify the lead compound #A4.1.
The challenge of the project STAR is to validate Rac1 hyperactivity in the airways from severe asthmatics, identify the mechanisms leading to its activation and evaluate the therapeutic potential of the Rac1-dependent signalling pathway inhibition to tackle severe asthma.