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-11782065-B2
Publication Date
2023-10-10
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 to predict the onset of preeclampsia through the measurement of specific biomarkers in maternal plasma or serum. The biomarkers described are Matrilysin (MMP-7), Integrin alpha-IIb: beta-3 complex (gpIIbIIIa), Sialic acid-binding Ig-like lectin 6 (Siglec-6), Activin A, ALCAM, and Ficolin-2 (FCN2). By obtaining and analyzing biological samples from pregnant women at defined gestational intervals and detecting the levels of these markers, clinicians can assess the likelihood of developing preeclampsia before clinical symptoms appear.
The problem addressed by the invention is the lack of adequate predictive diagnostic tools for preeclampsia, a complication characterized by hypertension and proteinuria after 20 weeks of gestation, which is a major cause of maternal and perinatal mortality. Current criteria for preeclampsia diagnosis rely on clinical signs that manifest after onset, making early intervention difficult. Early detection is critical, as preeclampsia originates from impaired implantation and placental development in early gestation.
The invention utilizes the measurement of biomarker panels at specific gestational windows: MMP-7 and gpIIbIIIa between the 16th and 22nd weeks for early prediction, and combinations of Siglec-6, Activin A, ALCAM, and FCN2 at later intervals for extended prediction coverage. The methods involve collecting biological samples, contacting them with binding ligands specific to the relevant biomarkers, generating datasets from the obtained measurements, and using these data to infer preeclampsia risk and inform potential treatment regimens.
Claims Coverage
The patent claims cover three main inventive features described in the independent claims.
Method for detecting MMP-7 and gpIIbIIIa biomarkers in early gestation samples
A method comprising obtaining a plasma or serum sample from a pregnant human subject during the 8th to 16th week of gestation, and contacting the sample with at least two binding ligands: one binding biomarker MMP-7 and one binding biomarker gpIIbIIIa. The process allows for early detection of relevant biomarkers by using binding ligands in wells or other formats.
Sequential sampling and biomarker testing at defined gestational intervals
A method including the steps of obtaining serum or plasma samples from a pregnant subject at specific gestational timepoints (8th–16th, 16th–21st/22nd, 22nd–28th, 28th–32nd weeks), and assaying for: - MMP-7 and gpIIbIIIa in the early interval - Siglec-6 and Activin A in the next interval - Siglec-6, ALCAM, and FCN2 in the later interval. Different binding ligands are used depending on the gestational window to target the appropriate biomarker set.
Assaying biomarker expression levels for MMP-7 and gpIIbIIIa
A method involving assaying a serum or plasma sample from a pregnant human subject for expression levels of MMP-7 and gpIIbIIIa, with the sample obtained between the 8th and 16th week of gestation. This sample is then typically loaded into one or more wells coated with ligands specific for these biomarkers. The method is further extendable by assaying for additional samples and biomarkers during subsequent gestational intervals.
The inventive features provide methodologies for early and sequential detection of a panel of biomarkers associated with preeclampsia, enabling risk assessment at key stages of gestation by testing specifically for MMP-7, gpIIbIIIa, Siglec-6, Activin A, ALCAM, and FCN2.
Stated Advantages
The methods allow earlier identification of women at risk of preeclampsia, enabling prediction before 22 weeks of gestation.
The described methods provide better prediction performance (sensitivity and specificity) for preeclampsia within relevant gestational intervals compared to known biomarkers.
The kits and methods can predict preeclampsia with a specificity of at least 90% and a sensitivity of at least 60%.
Early prediction creates an opportunity for therapeutic intervention to prevent, reduce, or delay symptoms of preeclampsia before they manifest.
Documented Applications
Prediction of preeclampsia in pregnant women using biomarker panels assessed at specific gestational intervals.
Prediction of closely related early gestation pregnancy complications such as implantation failure, and threatened and spontaneous miscarriage.
Determining the presence or risk of preeclampsia in a female to guide the need for a treatment regimen during pregnancy.
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