Could targeting inflammation in preeclampsia lower future heart disease in mothers?

Doctor Natasha de Alwis, The University of Melbourne

Postdoctoral Fellowship

Years funded: 2025 - 2026

Preeclampsia is a serious pregnancy complication, featuring major systemic maternal vascular dysfunction. It is associated with up to 5-fold increased risk of maternal cardiovascular disease following pregnancy. As preeclampsia affects 3% of all pregnancies in Australia, and up to 8% worldwide, it is a significant contributor to the overall prevalence of cardiovascular disease. There is currently no effective treatment for preeclampsia and its long term sequalae. Therapeutic development in the obstetric field is slow due to repeated exclusion of pregnant individuals in clinical trials, mainly due to fear of harming the developing fetus. There is urgent need for a treatment that blocks pathology, to improve pregnancy outcomes and prevent long-term cardiovascular disease.

Repurposing immunomodulatory therapies may offer a novel avenue of treatment. This study investigates whether neutralising tumor necrosis factor alpha (a key pathogenic molecule in preeclampsia) will halt the pathophysiology of preeclampsia. Tumor necrosis factor contributes to excessive inflammation in the maternal circulation, resulting in widespread endothelial/vascular damage. I will test whether the biologic tumor necrosis factor inhibitors, etanercept and adalimumab, can mitigate cardiovascular dysfunction during, and following a preeclamptic pregnancy, using human and animal models of preeclampsia.

The tumor necrosis factor inhibitors, etanercept and adalimumab, are currently used in the treatment of chronic immune conditions during pregnancy, and importantly have no associated adverse fetal effects. Their known safety, in combination with their ability to directly target and neutralise tumor necrosis factor, provides strong rationale for evaluation and enhances the feasibility of this proposal. If successful, this preclinical project will provide key data to support the progression of biologic tumor necrosis factor inhibitors into Phase II clinical trials to treat preeclampsia – providing new hope to women and their families affected by this devastating cardiovascular condition.