Therapeutics Beyond Delivery: Repurposed Drugs and Biologic Pathways

Pre-eclampsia remains a leading cause of maternal and perinatal morbidity and mortality worldwide, yet no disease-modifying therapy currently exists. This review examines the challenges inherent in developing therapeutics for pre-eclampsia, and evaluates the evidence for repurposing existing drugs and developing novel biologic strategies to treat preterm pre-eclampsia.

Metformin has demonstrated a trend towards prolongation of pregnancy in a randomized controlled trial, with larger trials ongoing. Proton pump inhibitors and sulfasalazine show compelling preclinical efficacy, though neither has yet translated to clinical benefit, possibly reflecting inadequate drug exposure in vivo. Novel biologic approaches, including sFlt-1-targeting siRNA, complement inhibition with eculizumab, and placenta-tropic lipid nanoparticle delivery systems, represent promising emerging strategies. Advancing molecular classification of pre-eclampsia is essential to identifying targetable pathways and selecting patients most likely to benefit from specific interventions. Improved pharmacokinetic evaluation in pregnancy, earlier identification of at-risk women using circulating biomarkers, and regulatory frameworks supportive of obstetric research will be critical to translating promising candidates into effective therapies.