Treating cystic fibrosis infection, inflammation and ion channels

chloride and hyperabsorption of sodium ions results in a reduction in the height of airways surface liquid and subsequent dysfunctional mucociliary clearance. This defect results in chronic infection, which drives inflammation and subsequent lung destruction from proteolytic enzymes primarily from host neutrophils [5]. To significantly perturb this pathogenesis the current strategies are to optimize the clearance of infected mucus, reduce inflammation and treat acute and chronic infection [4]. However the ultimate goal is to find therapies that will correct the basic defect using strategies, such as gene therapy or small molecule correctors and potentiators [6,7]. In this edition of Therapy these issues are explored by a number of experts in the field. In most developed countries CF is diagnosed in the neonatal period following newborn screening programs. This allows for early preventative interventions which, if effective, could be disease modifying by preventing early infection [8]. Wainwright and colleagues discuss the importance of developing a proper evidence base for such interventions, in spite of the difficulty of designing studies in infants and small children where surrogate measures of lung function, for example, are difficult [9,10]. Therapies that correct the basic defect are likely to be most effective in this early stage of disease development. It is critically important that clinical trial design and outcome measures are developed to determine whether the exciting new therapies, such as potentiators and correctors, are truly disease modifying. There are a range of exciting new approaches with small molecules to modulate CFTR function, discussed by de Boeck and Cuppens [11]. Disease modifying drugs are currently in In this issue of Therapy, cystic fibrosis (CF), one of the most devastating autosomal recessive disorders in man is discussed. This condition, which was only properly recognized in the 1940s, had a very poor prognosis at that time with most children dying in their first decade of life [1]. Since then the introduction of multidisciplinary center care, the use of effective pancreatic enzyme replacement therapy and antipseudomonal antibiotics has progressively improved outcomes. Median survival in most developed countries is now around 40 years and the anticipated median survival for children born in the current decade is into the sixth decade of life [2]. This success has been achieved by improving nutrition and controlling infection and inflammation by optimizing the clearance of infected mucus from the airway and using aggressive antibiotic therapy. However, CF remains a life-shortening condition with median age of death still stubbornly in the mid-to-late 20s. New and transformative therapies are therefore required for this condition.

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