Medizinische Universitaet Graz
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Development of Early Non-Invasive Biomarkers and Means for the Diagnosis and Progression Monitoring of Preeclampsia and Tailoring Putative Therapies

Duration: 2006-2009

Pregenesys is a research project, mainly granted by the EU and carried out within Prioriy 1 of FP6. It is concered with the development of early non-invasive biomarkers and means for the diagnosis and progression monitoring of preeclampsia and tailoring putative therapiesm as suggested by itsfull title. To carry out this project, a 10-member strong consortium has been created, consisting of univerisites, hospitals and industrial companies and private research orgnisations. The countries represented in the consortium are (alphabetically) Austria, Finland, Hungary, Israel, Italy, Portugal, Switzerland and the UK.

Preeclampsia (PET), de-novo hypertension & proteinuria after mid gestation, affects 5-7% of all pregnancies. Cases may develop life threatening haemolysis-elevated liver enzymes-low platelets (HELLP) or renal failure, cerebral haemorrhages & eclampsia, IUGR, placental abruption & death.

We will identify markers for PET risk prediction in the 1st trimester to allow longer time for tailoring putative medications to prevent PET; and assess & characterize plausible links between marker shortage/access, PET & putative medications in in vitro systems to fit putative medications to pre-defined disease-risk women.

Candidates for 1st trimester risk prediction of PET (cell free DNA & RNA, serum PP13, ADAM12, PAPP-A) will be verified with new ones using genomics & proteomics. Our blood, urine & fixed placenta tissue banks of pregnant women enable comparative analysis to build integrative, non-invasive Marker Effectiveness Profiles (MEPs) to PET subtypes (early/late onset, mild/severe, HELLP & IUGR). Disease progressions will be detected by continuous marker monitoring.

Expertise in trophoblast in-vitro systems (placenta explants & cell lines) and quantitative real time PCR, genomics & proteomics, immunohistochemistry & confocal microscopy will verify markers’ roles and identify links to curing effects of putative medications. We will model “Putative Medication Benefit Arrays” (PMBAs) for PET subtypes matched to MEPs.We will develop non-invasive diagnostic kits for 1st trimester PET prediction based on markers, antibodies, oligos & siRNA and others coupled to the power of Doppler ultrasound. Nested case-control clinical studies will test effectiveness of combined diagnosis & drug tailoring. Trans-European prospective clinical study, combining early diagnosis & randomising putative medication will verify findings.

R&D results will be used to train physicians & patients, to implement new prenatal care practice and eradicate preeclampsia.

Team leader at the Institute of Cell Biology, Histology and Embryology
Univ.Prof. Dr. Berthold Huppertz

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