%0 Journal Article
%T Optimization of a high-throughput whole blood expression profiling methodology and its application to assess the pharmacodynamics of interferon (IFN) beta-1a or polyethylene glycol-conjugated IFN beta-1a in healthy clinical trial subjects
%A Normand E Allaire
%A Steven E Bushnell
%A Jadwiga Bienkowska
%A Graham Brock
%A John Carulli
%J BMC Research Notes
%D 2013
%I BioMed Central
%R 10.1186/1756-0500-6-8
%X We have developed a highly reproducible, high-through put, whole blood expression profiling methodology based on sscDNA and used it to analyze human brain reference RNA and universal human reference RNA samples to identify experimental conditions that most highly correlated with a gold standard quantitative polymerase chain reaction reference dataset. We then utilized the optimized method to analyze whole blood samples from healthy clinical trial subjects treated with different versions of interferon (IFN) beta-1a. Analysis of whole blood samples before and after treatment with intramuscular [IM] IFN beta-1a or polyethylene glycol-conjugated IFN (PEG-IFN) beta-1a under optimized experimental conditions demonstrated that PEG-IFN beta-1a induced a more sustained and prolonged pharmacodynamic response than unmodified IM IFN beta-1a. These results provide validation of the utility of this new methodology and suggest the potential therapeutic benefit of a sustained pharmacodynamic response to PEG-IFN beta-1a.This novel microarray methodology is ideally suited for utilization in large clinical studies to identify expressed transcripts for the elucidation of disease mechanisms of action and as prognostic, diagnostic, or toxicity markers.The study of the blood transcriptome in the context of clinical pharmacogenomics has generated much interest in recent years [1,2]. The cellular and molecular components of peripheral blood exhibit dynamic responsiveness to physiological, environmental, or pathological stimuli and are in contact with nearly every tissue in the body, allowing for assessment of systemic responses to disease or treatment. As such, peripheral blood is a source of clinically accessible diagnostic, prognostic and pharmacodynamic (PD) markers [3,4]. This idea is supported by a growing body of research that describes the identification of expressed transcripts from human and animal peripheral blood that can function as indicators of disease, as prognostic markers o
%U http://www.biomedcentral.com/1756-0500/6/8