A study in mice published in ‘Nature‘demonstrates a possible mRNA-based therapy to treat preeclampsia. The method uses nanoparticles lipids to deliver VEGF mRNA to the placenta, restoring maternal blood pressure and improving fetal health.
The underlying cause of preeclampsia is placental dysfunction and toxins such as sFlt-1, which inhibit VEGF. A single injection of candidate LNP 55 into mice reduced symptoms by improving placental vasculature, increasing fetal weight, and stabilizing maternal blood pressure.
Although more research is needed for humans, these results highlight the potential of this mRNA therapy.
The engineers of the University of Pennsylvania (US) that this is a crucial advance that addresses a significant gap in health equity for pregnant people with preeclampsia.
Preeclampsia is caused by insufficient blood flow to the placenta, causing high blood pressure in the mother and restricting blood flow to the fetus.
It is one of the main causes of stillbirths and premature births worldwide, affecting between 3 and 5% of pregnancies. Pregnant people diagnosed with early preeclampsia face high risks for themselves and their babies, including serious health problems and, in extreme cases, death.
Currently, treatment options only address symptoms, such as blood pressure medications, bed rest, or premature birth, which often involve difficult moral decisions for pregnant people.
For researcher Kelsey Swingle these options are insufficient. Swingle sees gaps in women’s health care as medical challenges that require innovative and urgent scientific solutions.
Lipid nanoparticles
In previous research, Swingle conducted a proof-of-concept study that explored a library of lipid nanoparticles (LNPs), known for their use in mRNA vaccines against covid-19and its ability to reach the placenta in pregnant mice.
In this latest study, published in Nature, Swingle analyzed 98 LNPs to determine their effectiveness in reducing blood pressure and improving vasodilation in mice with preeclampsia. One LNP in particular managed to deliver more than 100 times more mRNA to the placenta than formulations approved by US health authorities (FDA).
The treatment worked. “Our LNP was able to deliver an mRNA therapy that reduced maternal blood pressure through late gestation, improved fetal health and circulation in the placenta,” Swingle explained. “In addition, we observed an increase in the birth weight of litters, indicating healthy mothers and pups.”
The team is now looking to bring this treatment to larger animal models, such as rats and guinea pigs, whose placental systems are more similar to humans. These experiments will explore how many doses would be necessary and the effectiveness in longer gestations.
“We are in talks to create a derivative company and work on bringing this therapy into clinical trials and to market,” said Swingle, who is also leading research to further optimize LNP and better understand how it reaches the placenta.
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