Systems and methods to identify and treat subjects at risk for obstetrical complications
Inventors
Chaiworapongsa, Tinnakorn • Hassan, Sonia S. • Romero, Roberto
Assignees
Wayne State University • US Department of Health and Human Services
Publication Number
US-10281475-B2
Publication Date
2019-05-07
Expiration Date
2035-03-27
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Provided are systems and methods for assessing the presence or risk of obstetrical complications, particularly those related to an angiogenic and anti-angiogenic imbalance. Also provided are methods of treating an angiogenic and anti-angiogenic imbalance with water-soluble statins, such as pravastatin.
Core Innovation
The invention provides systems and methods for assessing the presence or risk of obstetrical complications associated with an imbalance of angiogenic and anti-angiogenic factors. Specifically, it involves assaying maternal plasma concentrations of angiogenic factors such as placental growth factor (PIGF) and anti-angiogenic factors such as soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin (sEng), calculating their ratios, and determining multiples of the median (MoM) to identify subjects at risk for complications such as preeclampsia, fetal death, small for gestational age neonates, and placental lesions. The methods include obtaining biological samples primarily in the late second or third trimester and comparing the MoM ratios to established thresholds to detect angiogenic imbalance and obstetrical risk.
The problem addressed is the lack of effective means to identify women at increased risk of obstetrical complications associated with angiogenic and anti-angiogenic imbalance, especially late preeclampsia and fetal death at or near term. Existing screening approaches focusing on early gestation have limited predictive value for late-onset complications, and there have been few cohort studies evaluating biomarkers in the third trimester. Furthermore, there was a need for therapeutic methods to treat angiogenic imbalance once risk has been identified, as prior preventive strategies like aspirin were ineffective for late preeclampsia.
The invention also provides methods of treating angiogenic and anti-angiogenic imbalance and related obstetrical complications using water-soluble statins, particularly pravastatin. Pravastatin is shown to reverse biochemical imbalances in angiogenic factors and improve pregnancy outcomes in models of preeclampsia and related placental dysfunctions. The disclosed methods include administering therapeutically effective amounts of pravastatin, alone or with heparin and aspirin, to pregnant subjects identified as at risk by the biomarker assays, thereby offering a novel intervention for preventing or treating pregnancy complications associated with angiogenic imbalance.
Claims Coverage
The patent includes two independent claims covering methods for assessing angiogenic imbalance using specific biomarker ratios and for treating such imbalance with water-soluble statins. The inventive features disclosed focus on biomarker-based risk detection and therapeutic intervention.
Method for assessing angiogenic and anti-angiogenic imbalance using maternal plasma biomarker ratios
A method comprising obtaining a maternal plasma sample, assaying for PIGF and at least one of sVEGFR-1 or sEng, analyzing the ratio(s) of PIGF/sVEGFR-1 and/or PIGF/sEng, determining a Multiple of the Median (MoM) maternal plasma concentration ratio, comparing to thresholds (<0.12 for PIGF/sVEGFR-1, <0.3 for PIGF/sEng), and identifying the presence or risk of angiogenic and anti-angiogenic imbalance based on the MoM comparison.
Treatment of angiogenic imbalance with water-soluble statins based on identified risk
A method including administering a water-soluble statin, such as pravastatin, to a pregnant subject determined to have an angiogenic and anti-angiogenic imbalance based on the biomarker MoM ratios, thereby treating the imbalance and associated obstetrical complications.
The independent claims cover the innovative approach of using specific maternal plasma biomarker ratios with defined MoM thresholds for risk assessment of obstetrical complications related to angiogenic imbalance, and the therapeutic administration of water-soluble statins to treat such identified conditions.
Stated Advantages
The methods enable accurate identification of subjects at risk for severe late preeclampsia and stillbirth using maternal plasma concentrations of angiogenic and anti-angiogenic factors, especially in the third trimester, improving upon earlier trimester screening methods.
The use of multiples of the median (MoM) facilitates generalizable and interpretable assessment of biomarker levels relative to gestational age, enhancing diagnostic performance.
Treatment with water-soluble statins like pravastatin can reverse angiogenic and anti-angiogenic imbalances safely during pregnancy, potentially preventing serious obstetrical complications, including fetal death and preeclampsia.
The biomarker assays can guide timely therapeutic interventions and optimize pregnancy management, such as delivery decisions, thus reducing morbidity and mortality associated with placental dysfunctions.
Documented Applications
Risk assessment for obstetrical complications including preeclampsia, severe late preeclampsia, fetal death (stillbirth), small for gestational age neonates, placental lesions, and maternal vascular underperfusion during pregnancy.
Screening of pregnant subjects in the late second and third trimesters to identify those at high risk of adverse pregnancy outcomes for increased surveillance or intervention.
Treatment of angiogenic and anti-angiogenic imbalances in pregnant subjects, particularly using water-soluble statins such as pravastatin, alone or in combination with heparin and aspirin, to prevent or reduce obstetrical complications.
Use of kits comprising antibodies, binding proteins, primers, or probes to assay angiogenic and anti-angiogenic factors to facilitate the described diagnostic methods.
Interested in licensing this patent?