Transcriptional Biomarkers of LXR Agonists in Blood Cells
Author Information
Author(s): Elizabeth A DiBlasio-Smith, Maya Arai, Elaine M Quinet, Mark J Evans, Tad Kornaga, Michael D Basso, Liang Chen, Irene Feingold, Anita R Halpern, Qiang-Yuan Liu, Ponnal Nambi, Dawn Savio, Shuguang Wang, William M Mounts, Jennifer A Isler, Anna M Slager, Michael E Burczynski, Andrew J Dorner, Edward R LaVallie
Primary Institution: Wyeth Research
Hypothesis
Can peripheral blood biomarkers indicate the activity of synthetic LXR modulators?
Conclusion
Peripheral blood cells can serve as useful biological indicators for the clinical development of synthetic LXR modulators.
Supporting Evidence
- LXR agonists significantly increased ABCA1 and ABCG1 expression in rodent blood.
- In primates, ABCA1 and ABCG1 levels increased dose-dependently after LXR-623 treatment.
- Human PBMCs showed significant upregulation of ABCA1 and ABCG1 after LXR-623 exposure.
Takeaway
This study shows that certain genes in blood can tell us how well a new medicine is working to help with cholesterol problems.
Methodology
The study measured gene expression levels of LXR target genes in blood samples from mice, rats, monkeys, and humans after administering synthetic LXR agonists.
Potential Biases
Potential bias in the selection of biomarkers and the interpretation of results based on specific agonist treatments.
Limitations
The study primarily focused on specific biomarkers and may not encompass all potential effects of LXR agonists.
Participant Demographics
40 healthy human subjects, aged 26-61 years, including 6 males and 5 females.
Statistical Information
P-Value
p<0.001
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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