A Novel Therapy For Preeclampsia

先兆子痫仍然是一个主要的健康问题，影响着美国5-10%的孕妇。这是一个

Preeclampsia remains a major health concern, affecting 5-10% of all pregnancies in the United States. It is a leading cause of maternal and perinatal morbidity and mortality. Currently, there is no effective therapy for the management of the preeclamptic patient, with the disease only remitting after birth. While the underlying mechanisms are not clear, it is believed that inadequate remodeling of the maternal vasculature leads to placental hypo-perfusion, resulting in chronic placental hypoxia/ischemia. In response the placenta releases pathogenic factors into the maternal blood stream, leading to widespread maternal endothelial dysfunction and hypertension. In recent years, a great deal of attention has been focused on the secretion of an anti- angiogenic protein, the fms-like tyrosine kinase-1 (sFlt-1). Despite intensive research into this pathogenic pathway, no therapeutics have emerged which can adequately target sFlt-1 in the preeclampsia patient. In this proposal, we describe a novel therapeutic protein which consists of placental growth factor (PlGF), a VEGF family member specific for Flt-1, fused to the synthetic protein carrier Elastin Like Polypeptide (ELP), which we have recently demonstrated restricts attached therapeutics to the maternal compartment improving fetal safety during administration. We hypothesize that ELP-PlGF will attenuate the maternal and fetal complications associated with placental insufficiency, and may therefore be a potential therapeutic for the management of preeclampsia. This proposal will study the safety and efficacy of this therapeutic in a relevant preclinical animal model of preeclampsia.