Unresolved inflammation still represents a significant problem for people with cystic fibrosis (CF). Since current anti-inflammatory therapy is of limited efficacy, innovative strategies to combat CF inflammation are needed. Melanocortin-based therapy can offer a fresh and innovative approach to the management of CF inflammation. Using molecules that our body produces to terminate inflammation, the immunosuppression caused by conventional anti-inflammatory drugs will be avoided, potentially limiting recurrent infection.
The efficacy of two molecules, named Afamelanotide and BMS, designed to mimic natural melanocortins, will be tested using a novel CF airway-on-a-chip. In this device, the researchers will seed cells that cover the respiratory tract and cells that cover the vascular wall to mimic the structure of a human respiratory unit. All cells will be from people with CF. Some chips will be infected with bacteria. The efficacy of melanocortins will be evaluated by measuring indices of inflammation and infection, i.e. the reduction in production of inflammatory molecules, the improvement in the fluidity of the mucus and the reduced activation of blood cells. Moreover, the removal of bacteria by melanocortins will be tested.
This work also proposes a new paradigm for testing drugs; the substitution of animal studies will accelerate the introduction of new molecules in the therapeutic lineup of people with CF.
This study represents the prototype of an innovative approach for the development of a better treatment for respiratory inflammation and infection in people with CF. It paves the way for further development of resolution pharmacology in CF as well as for establishing new procedures for testing drugs for treatment people with CF.