It strikes mainly children and young adults by causing abnormal fluid transport mainly in their lungs, pancreas and intestine. At its most advanced stage, cystic fibrosis still leaves no alternative other than lung transplant. But now, 19 years after the identification of mutations in the CFTR gene which cause the disease, European researchers have identified 15 potential repair molecules.
In particular, experiments conducted by the EU project NEUPROCF on an “in vitro” model have pinpointed 4 active molecules. This approach, according to Mr Aleksander Edelman from Inserm in Paris, “may result in real therapeutic progress”. In order to identify potential niches for repair molecules, researchers developed a dynamic model of the CFTR protein fragment, containing one of the most important mutations.
Cystic fibrosis leads to superinfected chronic inflammatory lung disease, which is the main cause of death. NEUPROCF also developed a new method for the analysis of lipids, which will be applied to seek lipid markers of the disease, but which might also be used for other pathologies. “This approach has never been attempted in cystic fibrosis or in any other disease”, Mr Edelman says.
Also, the study of inflammatory cells, neutrophils in particular, has helped the project’s researchers to demonstrate new mechanisms involved in the survival of these cells, which may eventually turn into anti-inflammatory therapy targets.
In addition to defining a predictive clinical score of cystic fibrosis severity, which may allow to tailor therapy to each patient’s clinical outlook, scientists identified two inflammation proteins, such as annexin1 and coronin as potential drug therapy targets.
Improving the prognosis of the disease is particularly important in North-Western Europe, especially in Scotland where the incidence is really high. All in all, cystic fibrosis is the most common life-limiting genetic disorder in white people, with an incidence of 1 case every 3200-3300 newborn in the US. Internationally, the rate is estimated to be one case every 2,000 and 4,000 people.
The disease is characterized by abnormal transport of chloride and sodium across the epithelium in all exocrine tissues, leading to thick, viscous secretions in lungs, sinuses, pancreas, intestine, liver and reproductive tract. Chronic airway obstruction due to these secretions is soon followed by colonization with pathogenic bacteria.