Cystic fibrosis (CF) is an inherited disease in which the body makes very thick, sticky mucus. The thick mucus causes problems in the lungs, pancreas, and other organs. People with cystic fibrosis suffer from chronic pulmonary infections and progressive loss of pulmonary function. CF is typically diagnosed in young children mostly within the first years of age. The cause are mutations in the so-called CF transmembrane conductance regulator (CFTR) gene.
The pulmonary symptoms are caused by accumulation of mucus, obstructing the airways and leading to persistent infection, influx of inflammatory cells like neutrophils with subsequent chronic inflammation. High levels of neutrophil elastase (NE) play a central role in the deterioration of pulmonary function associated with CF. Neutrophils produce NE, normally absent in the lung, which causes damage to structural, cellular and soluble components of the pulmonary tissues. Inhibition of NE is expected to stop or slow down the progression of pulmonary function loss, preserve pulmonary independence for longer and help to live longer with an improved overall quality of life for individuals with CF.
More than 80,000 patients in the US and Europe combined have been diagnosed with CF. While treatments have been approved to ameliorate airway obstruction and treat infections, currently no drug has been approved to directly target inflammation in this disease. There remains is a need for treatments to effectively break the vicious cycle of obstruction, infection and inflammation.