New genetic and pharmacological treatments for cystic fibrosis

Massimo Conese, Mario Romano, Maria Lucia Furnari, Elena Copreni, Ida De Fino, Francesca Pardon, Luis V J Galietta

Research output: Contribution to journalArticlepeer-review


Cystic Fibrosis (CF) is a still life-treathening disease, although therapies have augmented the life span of CF individuals. Isolation of the CF gene, named CFTR (CF Transmembrane Conductance Regulator), led to the discovery that it encodes for a protein kinase A-regulated chloride channel, expressed by epithelial cells mainly in mucosal tissues. Mutated or absent CFTR brings about altered muco-ciliary clearance, by a yet disputed mechanism (likely involving over-function of the epithelial sodium channel [ENaC]), and ultimately to colonization and infection of the airways by a few opportunistic bacteria species, including Pseudomonas aeruginosa (P.a.). An exuberant and persistent acute inflammatory reaction is commonly observed in the lung from CF patients, representing a key pathogenetic event of lung damage and respiratory insufficiency. Lung disease is the chief cause of morbidity and mortality in CF patients and current therapies are aimed at controlling the respiratory symptoms by antibiotic and anti-inflammatory treatments. Major improvements in the strategy to fight pulmonary P.a. infection are based on treatment of first colonization with P.a., of chronic infection and of multidrug resistant bacteria. Controlling inflammation is a challenging, however crucial, task in CF therapy. Since classical steroidal and non-steroidal anti-inflammatory drugs are endowed with serious side-effects, alternative antiinflammatory strategies are being developed, including drugs which modulate cytokine expression, nitric oxide production and the oxidation unbalance in the CF airways. Soon after gene identification, gene transfer vectors to replace the defective gene were developed and underwent a number of human trials which have not yet produced a viable clinical gene therapy strategy. Novel gene therapy vectors and strategies for delivering them more efficiently and safely to the lung are being studied. In the last few years various in vitro studies have demonstrated the possibility of pharmacological intervention to correct the primary defect in CF. This may be obtained by directly addressing the CFTR protein (by means of so-called correctors and potentiators) or by modulating the activity of other types of ion transport in epithelial cells (such as with Moli1901 or denufosol). Novel interventions aimed to improve the mucociliary clearance, including hypertonic saline, mannitol and ENaC inhibitors, will be finally discussed.

Original languageEnglish
Pages (from-to)8-27
Number of pages20
JournalCurrent Pediatric Reviews
Issue number1
Publication statusPublished - 2009


  • Bacterial infection
  • CFTR (cystic fibrosis transmembrane conductance regulator)
  • Correctors
  • ENaC (epithelial sodium channel)
  • Gene therapy
  • Inflammation
  • Mucociliary clearance
  • Potentiators

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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