A candidate mRNA treatment for early-stage pre-eclampsia, which treats abnormal blood vessels in the placenta, has achieved good results in a mouse model.
Pre-eclampsia affects three to five percent of pregnancies and causes maternal high blood pressure and sometimes protein build up, kidney and liver injury, seizures and other neuronal conditions. It can also affect the fetus, causing restricted growth.
Despite being the leading cause of fetal and maternal morbidity worldwide, there is still no treatment for pre-eclampsia other than early delivery of the baby, which is not ideal for the mother or baby.
Pre-eclampsia is due to placental dysfunction caused by abnormal blood vessel formation at the interface between the mother and baby. The condition starts fairly early in pregnancy when these abnormal blood vessels begin to form. Later in gestation, low oxygen levels in the placenta and oxidative stress start to be expressed as maternal symptoms such as high blood pressure.
Developed by Michael Mitchell, PhD, an associate professor at the University of Pennsylvania, and colleagues, the treatment is a vascular endothelial growth factor (VEGF) mRNA encapsulated in a lipid nanoparticle (LNP) that is attracted to the placenta.
As reported in Nature, the researchers first searched for an LNP that had good affinity for the placenta. The selected LNP (LNP 55) allowed 100-fold greater delivery of mRNA to the placenta than an LNP used in a clinically approved RNA treatment (Onpattro).
After a single treatment with the candidate VEGF mRNA therapy, pregnant mice with pre-eclampsia had a reduction in blood pressure that allowed completion of normal pregnancy length and fetal health was also improved.
“Our LNP was able to deliver an mRNA therapeutic that reduced maternal blood pressure through the end of gestation and improved fetal health and blood circulation in the placenta,” said first author Kelsey Swingle, a doctoral student in Mitchell’s lab, in a press statement.
“Additionally, at birth we saw an increase in litter weight of the pups, which indicates a healthy mom and healthy babies. I am very excited about this work and its current stage because it could offer a real treatment for pre-eclampsia in human patients in the very near future.”
Later analysis of the placenta showed that the treatment partially restored normal vasculature and levels of immune biomarkers were also closer to normal levels.
Swingle, Mitchell, and colleagues now want to test their treatment in other animal models before hopefully moving on to human trials.
“We are already in talks about creating a spin-off company and want to work on bringing this LNP-mRNA therapeutic to clinical trials and the market,” said Swingle. “But there will always be more research to do to improve the drug and to truly understand how it works.”
