Treatment strategies for cystic fibrosis: what's in the pipeline?

Inhaled hypertonic saline in adults hospitalised for exacerbation of cystic fibrosis lung disease: a retrospective study

“…In the last decade, at least five new agents have shown benefits compared with placebo 28. These valuable, placebo-controlled randomised control trials for new treatments, however, do not analyse synergy or interaction with other therapies.…”

Modulation of expression of IL-8 gene in bronchial epithelial cells by 5-methoxypsoralen

“…However, as far as 5-MOP is concerned, although its use in association with Ultraviolet A irradiation for skin diseases is known from a long time [46], to the best of our knowledge, this is the first report of its direct anti-inflammatory effect in the absence of irradiation, whose mechanisms require further investigation. As far as the clinical indication of the lead compounds identified here to cure the chronic lung disease of patients affected by cystic fibrosis, consensus is growing on the need of intervening in parallel on the three major pathophysiological issues of CF lung pathology [47], that is the basic defect of ion transport regulation and airway surface fluid hydration, the chronic bacterial colonization by P. aeruginosa and the excessive inflammatory response, which contributes to the progressive damage of the respiratory tissue and lung function insufficiency. Thus potential clinical application of molecules such as 5-MOP, an already FDA-approved drug, as an anti-inflammatory molecule for cystic fibrosis patients deserves further investigation in pre-clinical and clinical studies.…”

Emergent Properties of Proteostasis in Managing Cystic Fibrosis

“…Indeed, an extensive therapeutic pipeline has been developed by the CF foundation (http://www.cff.org/research/ DrugDevelopmentPipeline/) to address this challenge. Although this pipeline has been instrumental in moving the median survival age from 5-37 years old, it is largely a consequence of endpoint disease management at clinical centers using therapeutics that include digestive enzyme supplements, hypertonic NaCl inhalation protocols that facilitate increased lung function and mucociliary clearance, and, importantly, antibiotics that prevent recurrent bacterial infections that is the primary cause of premature death of CF patients (Proesmans et al 2008;Frerichs and Smyth 2009;Jones and Helm 2009;Verkman and Galietta 2009;Becq 2010;Belcher and Vij 2010;Kreindler 2010;Zemanick et al 2010). While no drugs to date are known to directly target the basic folding problem in disease, the quest for such drugs is in full force (Amaral and Kunzelmann 2007;Verkman and Galietta 2009;Becq 2010;Belcher and Vij 2010) with the goal of correcting the defects leading to the pathological triad (Fig.…”

“…1) (Proesmans et al 2008;Frerichs and Smyth 2009;Jones and Helm 2009;Verkman and Galietta 2009;Becq 2010;Belcher and Vij 2010;Kreindler 2010;Zemanick et al 2010).…”