Biomarkers for cystic fibrosis drug development

Abstract Purpose To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs. Methods Biomarkers are considered across several are...

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Bibliographic Details
Published in:Journal of cystic fibrosis 2016-11, Vol.15 (6), p.714-723
Main Authors: Muhlebach, Marianne S, Clancy, JP, Heltshe, Sonya L, Ziady, Assem, Kelley, Tom, Accurso, Frank, Pilewski, Joseph, Mayer-Hamblett, Nicole, Joseloff, Elizabeth, Sagel, Scott D
Format: Article
Language:English
Subjects:
Advanced technologies
Biomarker
Biomarkers - analysis
Cystic Fibrosis - diagnosis
Cystic Fibrosis - genetics
Cystic Fibrosis - metabolism
Cystic Fibrosis - microbiology
Cystic Fibrosis Transmembrane Conductance Regulator - physiology
Drug Discovery - methods
Electrophysiology
Humans
Infection
Inflammation
Microbiome
Pulmonary/Respiratory
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Summary:Abstract Purpose To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs. Methods Biomarkers are considered across several areas of CF drug development, including cystic fibrosis transmembrane conductance regulator modulation, infection, and inflammation. Results Sweat chloride, nasal potential difference, and intestinal current measurements have been standardized and examined in the context of multicenter trials to quantify CFTR function. Detection and quantification of pathogenic bacteria in CF respiratory cultures (e.g.: Pseudomonas aeruginosa ) are commonly used in early phase antimicrobial clinical trials, and to monitor safety of therapeutic interventions. Sputum (e.g.: neutrophil elastase, myeloperoxidase, calprotectin) and blood biomarkers (e.g.: C reactive protein, calprotectin, serum amyloid A) have had variable success in detecting response to inflammatory treatments. Conclusions Biomarkers are used throughout the drug development process in CF, and many have been used in early phase clinical trials to provide proof of concept, detect drug bioactivity, and inform dosing for later-phase studies. Advances in the precision of current biomarkers, and the identification of new biomarkers with ‘omics-based technologies, are needed to accelerate CF drug development.
ISSN:1569-1993
1873-5010
DOI:10.1016/j.jcf.2016.10.009