Progress in cystic fibrosis and the CF Therapeutics Development Network

Abstract

Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised.

Figure 1

Cystic fibrosis transmembrane conductance regulator gene mutation classes and therapeutic approaches under study by the cystic fibrosis Therapeutics Development Network (CF-TDN). Note: approaches to class V (splicing mutations that alter surface CFTR levels), and class VI (mutations in the PDZ binding domain that decrease surface stability and/or alter recycling) CFTR mutations are under development, but have not yet entered clinical testing through the TDN.