New and Emerging Treatments for Cystic Fibrosis

Abstract

Recently, a significant number of additional key medications have become licensed in Europe for the treatment of patients with cystic fibrosis (CF), including a number of inhaled antibiotics, such as nebulised aztreonam and dry powder versions of colistin and tobramycin for inhalation; dry powder inhaled mannitol, an agent to improve airway hydration and aid airway clearance; and ivacaftor, an oral therapy that directly acts on dysfunctional CFTR to correct the basic defect encountered in CF patients with the G551D CF gene mutation. The marked success of ivacaftor both in clinical trials and in post-licensing evaluation studies in treating patients with G551D and other gating mutations has greatly encouraged the ongoing development of similar therapies that can directly target the underlying cause of CF. Other therapies, including a number of anti-infectives, anti-inflammatories and replacement pancreatic enzymes, are currently undergoing clinical studies. This article reviews those treatments that have been recently licensed for CF and highlights some of the exciting emerging therapies presently under evaluation in clinical trials. In addition, it discusses some of the potential challenges being encountered by research and clinical teams in developing and delivering treatments for this condition.

A Low-Molecular-Weight Alginate Oligosaccharide Disrupts Pseudomonal Microcolony Formation and Enhances Antibiotic Effectiveness

“…ATP production levels by PAO1 and NH57388A were compared in MH and AS media with or without 2% OligoG CF-5/10. Cultures were prepared as for the growth curve experiments and analyzed using the BacTiter-Glo microbial cell viability assay (Promega) at 0, 2,4,6,8,12,24, and 48 h, with luminescence read on a Fluostar Omega plate reader.…”

“…The acquisition of MDR Pseudomonas in the CF lung has led to a resurgence of clinical interest in the bactericidal antibiotic colistin (24). Overlooked for many years due to associated nephro-and neurotoxicity (25,26), colistin is increasingly used to treat life-threatening infections (24) and as an inhaled therapy in CF to prevent establishment of infection by MDR bacteria (25).…”

“…Overlooked for many years due to associated nephro-and neurotoxicity (25,26), colistin is increasingly used to treat life-threatening infections (24) and as an inhaled therapy in CF to prevent establishment of infection by MDR bacteria (25). While resistance to colistin remains low (27), the emergence of colistin-resistant strains heralds fears of a postantibiotic era (28).…”

Chronic Inflammation in CF Airways - A Persistent Issue for A20

“…Pre-incubation of cells with gibberellin alone did not change p38 mRNA expression. When investigating the response of selected PNECs individually, we observed two different response types of CF PNECs, those in which the pre-treatment with gibberellin lead to an increase of IL-8 release (CF#7, 8,157) and those which showed a decrease in IL-8 release similar to non-CF cells (CF#12, 14,34). Analyses of p38 mRNA in these cells revealed that those in which gibberellin had a pro-inflammatory effect were PNECs with the higher basal p38 expression, while those which responded to gibberellin with a reduction in IL-8 had lower basal p38 mRNA expression.…”

“…However, although successfully improving expression and function of CFTR, airway inflammation was not reduced. In CF patients aged 6 years and above with Gly551Asp-CFTR, 6 months of treatment with Ivacaftor did not reduce inflammatory markers in sputum such as IL-1, IL-6 and IL-8 [7] and heterogeneous responses to the corrector/potentiator treatment have been reported in patients homozygous for Phe508del-CFTR [8]. This suggests that CFTR correction/potentiation may not directly improve the underlying compromised immune response, thus there is still an unmet need to normalise the inflammatory response in CF airways.…”