Grant: Proof of Principle Program Phase I - Drug Development

Cystic fibrosis (CF) is the most common, deadly genetic disease affecting young Canadians. Even today, only half of the people living with CF will survive beyond their mid-30's. New treatments for CF are critically needed. Lung disease is the major cause of disability and death in CF. People with CF are born with normal lungs; soon after birth, however, infection and inflammation begin to cause lung damage. At present, antibiotic treatment targets only the infectious component of CF lung disease; hence, new treatments to target lung inflammation are predicted to substantially improve the health of those living with CF. We have identified a sophisticated immunological alarm system, the Toll-like receptor (TLR) system, as a critical pathway contributing to lung inflammation in CF. We have also discovered girolline, a possible new medication for turning off this damaging inflammation. In the proposed studies, we will perform an in-depth analysis of the anti-inflammatory effects of girolline and we will develop variants of girolline that are more effective and less toxic. These are the essential first-steps in developing a new medicine to safely reduce the damaging inflammation occurring in the lungs of people with CF.