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Reports
Serum and urinary biomarker signatures for rapid preclinical in vivo assessment of CDK inhibition as a therapeutic approach for PKD
Sarah Moreno, Oxana Ibraghimov-Beskrovnaya and Nikolay Bukanov
volume 7 | issue 12
15 June 2008Pages: 1856 - 1864
This is an open-access article
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Recent advances in understanding the molecular pathogenesis of polycystic kidney diseases (PKD) are being translated into promising treatments. Currently, a response to therapy in preclinical animal models of PKD can only be evaluated after several weeks of treatment. The availability of biomarkers for rapid efficacy assessment would greatly facilitate the drug development process. Here we applied SELDI-TOF technology to establish serum and urinary biomarker signatures associated with a rapid therapeutic response to cyclin dependent kinase (CDK) inhibitor roscovitine in the jck mouse model of PKD. A set of 74 serum and 56 urinary markers was identified in the group receiving chronic treatment over 5 weeks. This set was further screened for early efficacy biomarkers in acutely (3-5 days) treated animals with mild (26 days of age) and advanced disease (50 days of age). A third group with intermediate disease (33 days of age) received a single injection to monitor rapid changes in protein profiles within 4, 24 or 48 hours after drug administration. Multifactorial comparative analysis of the acutely treated groups identified a set of 20 urinary and 21 serum efficacy biomarkers. This biomarker signature provides a necessary tool for further assessment of CDK inhibitors as therapeutic agents for PKD.
Authors
Sarah Moreno
Genzyme Corporation; Framingham, MA
Oxana Ibraghimov-Beskrovnaya
Genzyme Corporation; Framingham, MA
Nikolay Bukanov
Genzyme Corporation; Framingham, MA
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.