Treating the dysfunctional placenta

Abstract

Placental dysfunction underlies major obstetric diseases such as pre-eclampsia and fetal growth restriction (FGR). Whilst there has been a little progress in prophylaxis, there are still no treatments for placental dysfunction in normal obstetric practice. However, a combination of increasingly well-described in vitro systems for studying the human placenta, together with the availability of more appropriate animal models of pre-eclampsia and FGR, has facilitated a recent surge in work aimed at repurposing drugs and therapies, developed for other conditions, as treatments for placental dysfunction. This review: (1) highlights potential candidate drug targets in the placenta – effectors of improved uteroplacental blood flow, anti-oxidants, heme oxygenase induction, inhibition of HIF, induction of cholesterol synthesis pathways, increasing insulin-like growth factor II availability; (2) proposes an experimental pathway for taking a potential drug or treatment for placental dysfunction from concept through to early phase clinical trials, utilizing techniques for studying the human placenta in vitro and small animal models, particularly the mouse, for in vivo studies; (3) describes the data underpinning sildenafil citrate and adenovirus expressing vascular endothelial growth as potential treatments for placental dysfunction and summarizes recent research on other potential treatments. The importance of sharing information from such studies even when no effect is found, or there is an adverse outcome, is highlighted. Finally, the use of adenoviral vectors or nanoparticle carriers coated with homing peptides to selectively target drugs to the placenta is highlighted: such delivery systems could improve efficacy and reduce the side effects of treating the dysfunctional placenta.