Cradle Genomics, Inc. — Department of Health and Human Services SBIR Phase I: NICHD

Description

Limited information is available about early human placentation when many pregnancy pathologies originateTo address this knowledge gap and begin development of robust diagnostic tool to manage pregnancy complicationswe propose a pilot study based on a highly sensitive immune assay and our company s base technologyTrophoblast Retrieval and Isolation from the CervixTRICTRIC uses a Pap smearconsidered safe during pregnancyto non invasively capture hundreds of homogeneousHLA G expressingfetal cells during ongoing pregnancies attoweeks of gestational ageGAWe propose that these fetal cells are useful for assessing pregnancy status and assessing risk of perinatal disease in vivoOur premise is based on data demonstrating that cells obtained by TRIC express trophoblast extravillous lineage markerse ghCGHLA Gand have molecular profiles affected by pathologySpecificallyimmunocytochemical protein expression analysis of the cells demonstrates altered levels of several key proteins in pregnancies that later develop miscarriagefetal growth restrictionFGRor preeclampsiaWe hypothesize thatbased on robust data obtained in our published studiesthat AFP and PGF levels are significantly altered in EVT cells from pregnancies linked to FGRa key indicator of placenta based perinatal disordersThereforewe will rigorously determine if expression of two proteins identified in our preliminary studies in fetal cells obtained by TRIC correlate with fetal growth ratesconsidering fetal sex and other relevant factorsThe specific aim of this application is to establish the relationship of cervical extravillous trophoblast biomarker levels to pregnancy outcomesWe will quantify AFP and PGF in EVT cells obtained by TRIC in the first trimestercomparing cohorts of subjects with normal term pregnancies to those with adverse outcomes associated with low birth weight for GA at birthThis goal will be accomplished in four milestonesMilestonewe will develop a high sensitivity immune assay to quantify AFP and PGF levels in trophoblast cellsMilestonewe will build a biobank ofspecimens of trophoblast cells isolated by TRIC from pregnant patients in the first trimesteralong with de identified medical records to determine pregnancy outcomesMilestonethe immune assay will be optimized with patient trophoblast samplesMilestonethe remaining patient trophoblast samples will be assayed for AFP and PGF levels and compared to patient outcomesparticularly reduced birth weight for gestational ageThese experiments will validate the testing platform and provide preliminary data for a larger clinical study to establish a perinatal test for maternal fetal disordersOur long term goal is to develop and commercialize products for early diagnosis of perinatal pathologies using EVT cells obtained safely during ongoing pregnancies through TRIC This research provides major public health benefits by leveraging a safenoninvasive method to capture human fetal cells with placental cell properties to develop a method to quantify biomarkers of obstetrical disease during the first trimester of pregnancyThese assays will enable monitoring of pregnancyanalogous to using ultrasound charts to monitor fetal growthbut at a much earlier stage when intervention strategies can be developedOur company will develop a perinatal test that can be commercialized for maternal fetal health managementand that will generate clinical and experimental breakthroughs beneficial to the well being of mothers and their babies