Emerging therapies for cystic fibrosis lung disease.
BACKGROUND
Cystic fibrosis (CF), one of the major respiratory diseases, is caused by mutations in a gene encoding for a chloride channel. Abnormal transepithelial ion transport leads to a reduced volume of the airway surface liquid layer and reduced mucociliary clearance.


METHODS
There is currently no cure for CF and CF lung disease remains a major contributor to morbidity and mortality. However, most current treatments for CF lung disease do not address the underlying pathology. We describe here new therapeutic developments aiming to identify or generate compounds that counteract the effects of cystic fibrosis transmembrane conductance regulator (CFTR) on the airway.


RESULTS
This review summarizes the current state of new developments in the treatment of CF lung disease. These drugs include nebulized and inhaled osmotically active agents, but also modifiers of ion channels other than CFTR, such as activators of alternative chloride channels or inhibitors of sodium absorption, and compounds in development aim to correct or improve impaired CFTR function directly. First clinical trials with new drugs including ion channel modifiers and CFTR pharmacotherapeutics have revealed very promising results.


CONCLUSIONS
CF drug therapy is moving rapidly from symptomatic therapy to treatment of the underlying pathophysiology.
Grasemann
Hartmut
H
Department of Paediatrics, University of Toronto, Division of Respiratory Medicine, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Ratjen
Felix
F
D000818:Animals; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism
C505032:CFTR protein, human; D007473:Ion Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator