Hypertensive disorders of pregnancy such as preeclampsia are among the most important contributors to maternal and fetal morbidity and mortality. Despite the prevalence and impact of these disorders, few effective treatment options exist. The most widely used and effective antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), cannot be used to treat pregnant patients because they cross the placenta and cause developmental abnormalities in the fetus. We propose to develop antibody fragments that can bind to the angiotensin receptor and block its signaling. Since the placenta does not transport proteins (with the exception of IgG), antibody fragment ARBs may be able to treat maternal hypertension while avoiding fetal toxicity. In this project, we will create and optimize antibody fragment ARBs, and we will perform functional characterization to define their molecular pharmacology. This work will serve as a foundation for future efforts to investigate the therapeutic potential of this new ARB class.
Preeclampsia and related conditions pose major health risks in pregnancy, but few effective treatment options are available. This project aims to develop antibody fragments as a new class of angiotensin receptor blockers (ARBs) that may be useful in treating preeclampsia while avoiding fetal toxicity associated with currently available ARBs.