摘要
Rebecca Barney, Arthur Lee, Brandon T. Leader. PATH, 2201 Westlake Avenue, Seattle, Washington.IntroductionAccurate and timely diagnosis of women at high risk for preeclampsia (PE) is key to accessing proper interventions and improving clinical outcomes. New biomarkers for PE have shown potential for earlier and more accurate identification of women at increased risk. While a few biomarkers exist in commercially available diagnostics, these products are often expensive and too complex for use outside of a hospital setting. PATH has developed a point-of-care, field-friendly diagnostic for use in low-resource settings, specifically in regional and local antenatal care programs.ObjectivesPATH conducted research and development (R&D) to produce a new prototype lateral flow rapid diagnostic test (RDT) for detection of promising preeclampsia biomarker candidates.MethodsInitial biomarker candidates were identified in a previously published landscape analysis.1 Two candidates, one blood-based and one urinary biomarker, were chosen for laboratory assay development. We selected these biomarkers based on commercial availability of antibodies, existing patents, and potential for achieving functional analytical sensitivity. Enzyme link immunosorbent assays (ELISAs) were first developed for both biomarkers. The most promising ELISA antibody pairs were transferred and optimized for use in a lateral flow RDT format. In parallel to laboratory activities, early commercial due diligence activities were conducted, including outreach to test developers and reagent manufacturers, as well as a patent review to better understand the potential for future commercialization if the current R&D phase was successful.ResultsBlood-based biomarker R&D was suspended, as we were unable to obtain the necessary limit of detection (LOD) in ELISA development. Resources were then directed into the development of the urinary biomarker assay. Conversely, laboratory-based R&D on the selected urine-based biomarker has not only successfully progressed through ELISA development, but moved into a lateral flow RDT format. Results of initial evaluations of the performance of the new prototype RDT using synthetic urine or buffer spiked with biomarker analyte demonstrated clinically acceptable LOD for use as an assay to differentiate between normal pregnancies and those at increased risk for developing PE. The next step of active work is to validate the new RDT with forthcoming clinical urine specimens.ConclusionsCommercial and technical due diligence have allowed us to identify a pool of promising PE biomarker candidates to move forward into early R&D based on their potential for adaptation into a low-cost, field-friendly RDT format. To date, our program, supported through USAID’s Saving Lives at Birth award, has been successful in developing a promising new alpha-prototype RDT for a urinary biomarker that could potentially have clinical application for identifying women at risk for developing PE. Current efforts are now underway to verify the performance of the new test with characterized urine specimens from women who had normative pregnancies or were diagnosed with PE.1 Towards biomarker-based tests that can facilitate decisions about prevention and management of preeclampsia in low-resource settings. Nathalie Acestor et al, Clin Chem Lab Med. 2016 Jan;54(1):17-27