A new study on rodents has found that mRNA therapy could potentially treat the fatal pregnancy disorder preeclampsia, which currently has no cure.
In preeclampsia, pregnant people develop persistent high blood pressure that can lead to organ damage, causing protein to appear in the urine and sometimes organ failure. The condition affects 3% to 5% of pregnancies, usually around 20 weeks after conception, although it can also occur after birth. Preeclampsia is responsible for more than 70,000 maternal deaths and 500,000 fetal deaths worldwide each year.
There are currently no drugs that can slow the progression of preeclampsia. The only way to cure the condition is to deliver the baby. Until then, the mother’s symptoms can be managed using blood pressure-lowering drugs.
To find a potential solution, researchers created an experimental therapy for preeclampsia that uses the same technology found in the Pfizer-BioNTech and Moderna COVID-19 vaccines. This therapy uses small, spherical particles to deliver a type of genetic material called messenger RNA (mRNA) to cells. This mRNA serves as a blueprint for cells to make specific proteins.
During a healthy pregnancy, VEGF helps promote the formation of blood vessels in the placenta, which enables more blood — and the nutrients and oxygen within it — to flow to the growing fetus. However, for unknown reasons, the placenta in patients with preeclampsia does not develop properly, impeding blood flow to it and hindering fetal growth.
The condition also causes placental cells to release toxins that inhibit VEGF, which ultimately damages the cells that line the mother’s blood vessels and raises her blood pressure.
In the new study, published Wednesday (Dec. 11) in the journal Nature, researchers tested the new mRNA therapy in pregnant mice with a condition similar to preeclampsia.
Just one injection of the therapy, given halfway through the mice’s pregnancies, lowered their blood pressure to healthy levels by the time they gave birth. The rodents’ newborns were heavier than those of mice that were not injected with the mRNA. The placental blood vessels of the treated mice were partially restored, making their symptoms less severe.
Commenting on the new research, Dr. Ravi Thadhani, executive vice president for health affairs at Emory University in Georgia and Dr. S. Anantha Karumanchi, professor of medicine at Cedars-Sinai Medical Center in California, said the researchers had “advance the quest to develop a safe and effective treatment for women with preeclampsia.”
However, Thadhani and Karumanchi, neither of whom was involved in the research, said the results “still raise questions” about the suitability of this treatment for preeclampsia. While inhibition of VEGF is a problem in preeclampsia, they added that excessive amounts of the protein in the uterine lining have been linked to pregnancy loss in mice. So the new mRNA may be needed to create the right balance of VEGF.
The study team now plans to test whether the new therapy is safe and effective in larger animals — that is, non-human primates. This level of investigation is necessary for the therapy to be given to human patients someday.
Study lead author Kelsey Swingle, a doctoral candidate at the University of Pennsylvania, told Live Science that “there’s a lot of work to be done to really make sure this is a safe technique, as we’re working to scale it up.” One of the things the team needs to figure out is how often and when the therapy should be given to pregnant people. This is a difficult question to answer at present, given that the average pregnancy duration of a mouse is about 20 days, whereas in humans it is about 40 weeks.