Cystic Fibrosis Research Today is a free monthly online journal that collates and summarizes the latest research about Cystic Fibrosis, including details on symptoms, genetics, treatment, information.

Detection of cystic fibrosis transmembrane conductance regulator activity in early-phase clinical trials.

Rowe SM, Accurso F, Clancy JP

Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-0006, USA. smrowe@uab.edu

Advances in our understanding of cystic fibrosis pathogenesis have led to strategies directed toward treatment of underlying causes of the disease rather than treatments of disease-related symptoms. To expedite evaluation of these emerging therapies, early-phase clinical trials require extension of in vivo cystic fibrosis transmembrane conductance regulator (CFTR)-detecting assays to multicenter trial formats, including nasal potential difference and sweat chloride measurements. Both of these techniques can be used to fulfill diagnostic criteria for the disease, and can discriminate various levels of CFTR function. Full realization of these assays in multicenter clinical trials requires identification of sources of nonbiological intra- and intersite variability, and careful attention to study design and statistical analysis of study-generated data. In this review, we discuss several issues important to the performance of these assays, including efforts to identify and address aspects that can contribute to inconsistent and/or potentially erroneous results. Adjunctive means of detecting CFTR including mRNA expression, immunocytochemical localization, and other methods are also discussed. Recommendations are presented to advance our understanding of these biomarkers and to improve their capacity to predict cystic fibrosis outcomes.

Published 26 July 2007 in Proc Am Thorac Soc, 4(4): 387-98.
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