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Oct 24, 2008

Researchers Identify Three Genes that Better Measure Positive Response to CF Therapy

  • Researchers at National Jewish Health report that they have identified a gene-based blood test that is a quicker and more accurate measure of cystic fibrosis (CF) patients’ response to therapy.

    The research team identified three genes that corresponded with a positive response to treatment. The study was done in a cohort of 18 CF patients, and a 60-patient study is currently being conducted.

    “The currently accepted test, a measure of a patients' ability to exhale air, has several limitations that make it ineffective for some patients and not sensitive enough for clinical trials of many new medications,” says Milene Saavedra, M.D., lead author of the study and assistant professor of medicine. Currently, response to medication is measured by how much air a person can rapidly exhale: forced expiratory volume in one second, or FEV1.

    “By measuring the activity of genes associated with the immune/inflammatory response, we can get a more accurate picture of the biological processes occurring inside the lungs,” continues Dr. Saavedra.

    The investigators thought white blood cells (WBCs) circulating in the blood might be a good source of biomarkers. WBCs are the predominant cell type at sites of tissue destruction in CF patients' lungs. As they circulate in the blood through the lungs they encounter an inflammatory environment and alter their gene expression as a result.

    The scientists evaluated 18 CF patients who were suffering severe exacerbation of their disease. They drew blood before and after two weeks of intravenous antibiotic therapy. The severe exacerbation coupled with the antibiotic therapy served as a condensed model of illness and response to therapy. Usually in these cases antibiotic therapy is successful, and patients' clinical symptoms and FEV1 both improve rapidly.

    Using microarray gene analysis of the blood samples, the researchers recognized 10 genes whose expression differed considerably before and after therapy. Using real-time PCR and additional statistical tools, the researchers then found that three genes, CD36, CD64, and ADAM9, most accurately correlated with a positive therapeutic response.

    “The expression of these genes correlated with FEV1, other inflammatory markers, and various clinical factors,” notes coauthor Jerry Nick, M.D., associate professor of medicine. “When combined with FEV1, they offered a more accurate and sensitive measure of response to therapy than either alone.”

    CD36 and CD64 are genes associated with cells’ absorption of foreign organisms and cellular debris. ADAM9 is associated with tissue destruction that allows inflammatory cells to move through tissue. This process is also believed to contribute to permanent tissue destruction.

    The researchers recently published these results in the online version of American Journal of Respiratory and Critical Care Medicine and will also publish them in a future print issue.



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