In order to treat preeclampsia, a potentially fatal condition of pregnancy, scientists from the University of Pennsylvania have created an ionizable lipid nanoparticle (LNP) formulation carrying mRNA for VEGF-A which can be guided to the placenta during pregnancy.
The study was published in the Journal of the American Chemical Society on the 15th of February, and it involved the placentas of mice. Lead author Kelsey Swingle, a Ph.D. student, said, “As we continue to work towards translating these LNPs from bench top to animal models to perhaps patients one day, this therapy has the potential to benefit both maternal and fetal health”.
Preeclampsia affects anywhere from 3 to 8% of pregnancies, leading to early delivery or even stillbirth. Inadequate dilatation of blood vessels in the placenta leads to a decrease in blood circulation from the mother to the fetus; hence, excessive maternal blood pressure is a characteristic of this condition.
Despite being known for at least a century, the actual cause of preeclampsia is still a mystery to medical professionals. Many hypotheses have been proposed for this phenomenon, including an effect of hormones or minerals lacking in the mother’s body, or even inflammation. Along with other problems, people with high blood pressure also experience renal damage, fluid retention in the lungs, low platelet counts and headaches.
Management for a pregnant woman diagnosed with preeclampsia often includes strict dietary restrictions, increased monitoring, the use of blood pressure medication, and, in severe cases, an early induction of labor.
In order to treat preeclampsia, blood vessels must be dilated to restore normal blood circulation to the placenta. Some studies have used adenovirus vectors carrying the VEGF gene to transport the protein to the uterine arteries, while others have injected tiny interfering RNA subcutaneously coupled to cholesterol to inhibit the synthesis of sFlt-1, the receptor for VEGF.
Swingle’s group is the first to use LNPs to successfully transport mRNA to the placenta. LNPs are basically tiny clumps of ionizable fats. They are used to transport gene treatments, small-molecule medicines and other therapeutic mRNAs.
Researchers injected VEGF directly into placental cells in pregnant mice via the tail vein, harnessing the placenta’s normal blood circulation to the fetus in tandem with a highly selective ionizable lipid in the LNP. Placental cells that take in VEGF mRNA produce the protein, which then widens the placental blood channels. As a result, the mother’s blood pressure drops, and the fetus’s circulation is normalized.
Unfortunately, most medications on the marketplace haven’t been evaluated for safety in pregnant women. As disorders that manifest during pregnancy cannot be treated before delivery, this presents a dilemma.
Swingle said that when pregnant women had concerns about the safety of the COVID vaccination back in 2021, she was motivated to investigate targeted medicines and treatments for fetal and maternal welfare. In this regard, both the mother and child would benefit from a greater quality of life and better health in the long run if the underlying cause of the problem could be treated. She went on to say that she has plans to help fillthis research gap in the future.
