Kits and methods for prediction and treatment of preeclampsia
Inventors
TARCA, Adi L. • Chaemsaithong, Piya • Chaiworapongsa, Tinnakorn • Hassan, Sonia S. • Romero, Roberto
Assignees
Wayne State University • US Department of Health and Human Services
Publication Number
US-11243213-B2
Publication Date
2022-02-08
Expiration Date
2036-11-07
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Abstract
Biomarkers tests which can be used to predict a positive or negative risk of preeclampsia are described. More specifically, a panel of biomarkers including MMP-7 and gpIIbIIIa, described. The test is useful to predict preeclampsia when a biological sample is obtained between the 16th and 22nd week of pregnancy. Prediction later in pregnancy can be achieved by a combination of Siglec-6, Activin A, ALCAM, and/or FCN2.
Core Innovation
The invention provides kits and methods for early prediction of preeclampsia using measurement of levels of six specific biomarkers, including Matrilysin (MMP-7), Integrin alpha-IIb: beta-3 complex (gpIIbIIIa), Sialic acid-binding Ig-like lectin 6 (Siglec-6), Activin A, ALCAM, and/or Ficolin-2 (FCN2). The methods involve determining the levels of one or more of these biomarkers in a biological sample obtained from a pregnant female, generating a dataset based on these levels, assessing the risk or presence of preeclampsia from the dataset, and, where appropriate, determining a treatment regimen to prevent, reduce, or delay preeclampsia symptoms before clinical manifestation.
The problem being solved addresses the need for early and accurate prediction of preeclampsia, a pregnancy syndrome characterized by hypertension and proteinuria that can progress to serious maternal and fetal complications. Current diagnostic criteria for preeclampsia detect onset after 20 weeks of gestation, but early gestational prediction remains a challenge. Preeclampsia affects a significant percentage of pregnancies worldwide and poses increased lifetime cardiovascular risk for affected women and offspring. The invention solves this by identifying biomarker panels that enable prediction as early as 16 to 22 weeks of pregnancy, earlier than existing methods.
The invention also highlights that different biomarker panels can be utilized at different gestational windows for optimal prediction of either early-onset or late-onset preeclampsia, with specific biomarkers performing best in these intervals. For example, MMP-7 and gpIIbIIIa levels taken from 16 to 22 weeks predict early onset preeclampsia, while Siglec-6, Activin A, ALCAM, and FCN2 measured later in pregnancy provide predictive value. The kits include detection mechanisms for these markers along with instructions for data generation, risk assessment, and treatment determination, allowing for clinical decisions and therapeutic interventions based on a patient's biomarker profile.
Claims Coverage
The patent contains 12 method claims covering different aspects of sample obtaining and biomarker assaying for preeclampsia prediction across gestational windows.
Method for assaying plasma or serum samples between 16th and 22nd week using MMP-7 and gpIIbIIIa biomarkers
Obtaining maternal plasma or serum sample from a pregnant human subject between 16 and 22 weeks gestation and contacting the sample with at least two binding ligands that specifically bind biomarker MMP-7 and biomarker gpIIbIIIa respectively.
Method for multi-marker biomarker protein assaying in specified gestational intervals
Assaying expression levels of MMP-7 and gpIIbIIIa in plasma or serum samples obtained between 16 and 22 weeks; assaying Siglec-6 and Activin A between 22 and 28 weeks; and assaying Siglec-6, ALCAM, and FCN2 between 28 and 32 weeks gestation.
Use of well-plate formats coated with specific binding ligands for biomarker detection
Loading plasma or serum samples into wells individually coated with ligands that bind to each biomarker to quantitatively measure levels of MMP-7, gpIIbIIIa, Siglec-6, Activin A, ALCAM, and FCN2 according to gestational period.
The claims collectively cover methods for predicting preeclampsia by assaying specific biomarker proteins in plasma or serum samples collected at defined gestational intervals using binding ligands, with particular emphasis on MMP-7 and gpIIbIIIa between 16 and 22 weeks, and additional biomarkers at later gestational times, employing binding ligand-coated wells for detection.
Stated Advantages
Allows early identification of women at risk for preeclampsia before 22 weeks gestation, enabling timely therapeutic intervention.
Provides improved prediction sensitivity compared to known single biomarker methods during the second trimester.
Enables prediction of both early and late onset preeclampsia by utilizing different biomarker panels at specific gestational windows.
Facilitates use in routine prenatal care via blood samples, enhancing clinical utility and monitoring.
Achieves high specificity (at least 90%) alongside substantial sensitivity levels for preeclampsia prediction.
Documented Applications
Predicting the risk or presence of preeclampsia in pregnant women to determine the need for treatment regimens.
Monitoring and predicting complications of pregnancy including implantation failure, threatened miscarriage, and spontaneous miscarriage.
Clinical decision-making regarding therapeutic interventions aimed to prevent, reduce, or delay preeclampsia symptoms in mother and fetus based on biomarker testing results during pregnancy.
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