Systems and methods to identify and treat subjects at risk for obstetrical complications
Inventors
Chaiworapongsa, Tinnakorn • Romero, Roberto • Hassan, Sonia S.
Assignees
Wayne State University • US Department of Health and Human Services
Publication Number
US-11686735-B2
Publication Date
2023-06-27
Expiration Date
2035-03-27
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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 present disclosure provides systems and methods for assessing the presence or risk of obstetrical complications, particularly those related to an angiogenic and anti-angiogenic imbalance, by using concentrations and ratios of angiogenic factors such as placental growth factor (PlGF) and anti-angiogenic factors including soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin (sEng). It involves determining the multiples of the median (MoM) of the maternal plasma concentration ratios of PlGF to sVEGFR-1 and/or PlGF to sEng in biological samples, especially in the third trimester of pregnancy.
The disclosure addresses the currently unmet need for effective ways to identify women at increased risk of obstetrical complications such as late preeclampsia (PE), severe late PE, fetal death (FD), small for gestational age (SGA) neonates, and placental lesions associated with maternal vascular underperfusion, particularly near term. It recognizes that an appropriate balance between angiogenic and anti-angiogenic processes is essential for successful pregnancy, and that imbalances are linked to various complications including miscarriage, implantation failure, and placental pathologies.
In addition to providing diagnostic methods, the invention offers treatments for obstetrical complications associated with angiogenic and anti-angiogenic imbalance by administering water-soluble statins, such as pravastatin. These treatments aim to prevent or reduce the risk of these complications by correcting the imbalance. The utility of such treatments is demonstrated especially when subjects are identified as being at risk by measuring angiogenic factor levels during pregnancy, allowing timely intervention.
Claims Coverage
The patent includes one independent claim covering a method of treating an angiogenic and anti-angiogenic imbalance. The main inventive features are focused on identifying subjects at risk via plasma biomarker ratios and treating with water-soluble statins.
Method to identify angiogenic and anti-angiogenic imbalance using biomarker ratios
A method to identify a female human subject as having or at risk of an angiogenic and anti-angiogenic imbalance by obtaining a sample, assaying for concentrations of PlGF and sVEGFR-1 (and optionally sEng), determining the multiples of the median (MoM) plasma concentration ratios of PlGF/sVEGFR-1 and/or PlGF/sEng, comparing these MoM values to thresholds (MoM <0.12 for PlGF/sVEGFR-1 and MoM <0.3 for PlGF/sEng indicating imbalance), and thus diagnosing the presence or risk of imbalance.
Treatment of angiogenic and anti-angiogenic imbalance with water-soluble statins
Administering an effective amount of a water-soluble statin, such as pravastatin (e.g., 20 mg/day), to a subject identified as having or at risk of an angiogenic and anti-angiogenic imbalance thereby treating the imbalance. The method may further include administering heparin and aspirin to the subject.
The claims cover methods combining diagnostic identification of angiogenic imbalance using specific biomarker plasma ratios with therapeutic administration of water-soluble statins to treat the imbalance and associated obstetrical complications, with detailed thresholds and exemplified dosages provided.
Stated Advantages
Improved identification of subjects at risk for late preeclampsia, severe late preeclampsia, fetal death, and small for gestational age neonates using biomarker ratios measured in the third trimester.
Biomarker-based risk assessment outperforms earlier trimester measurements and uterine artery Doppler velocimetry in predicting obstetrical complications near term.
Water-soluble statins, such as pravastatin, can treat and potentially reverse angiogenic and anti-angiogenic imbalances associated with obstetrical complications.
The use of multiples of the median (MoM) facilitates more generalizable and interpretable biomarker assessments across different gestational ages.
Potential to enable timely clinical interventions, reduce maternal and fetal morbidity and mortality by identifying high-risk subjects that may benefit from targeted surveillance and treatment.
Documented Applications
Assessing the presence or risk of obstetrical complications such as preeclampsia, severe late preeclampsia, fetal death including stillbirth, small for gestational age neonates, and placental lesions through measuring maternal plasma concentrations of angiogenic and anti-angiogenic factors.
Treatment of identified angiogenic and anti-angiogenic imbalances and associated obstetrical complications by administration of water-soluble statins, particularly pravastatin.
Use of biomarker assays as a diagnostic tool in prenatal care for risk stratification of pregnancy complications especially in the third trimester, allowing for enhanced antepartum surveillance and timing of delivery.
Risk assessment for fetal death with placental lesions consistent with maternal vascular underperfusion using biomarker ratios measured between 24 and 28 weeks of gestation.
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