A transcription “switchboard” protein called VGLL3 appears to sit upstream of multiple defects seen in preeclampsia, and early experiments show that dialing it down can ease disease signals in placentas and mouse models, hinting at future treatments that go beyond early delivery.

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A key trigger may lie at the heart of preeclampsia, a dangerous pregnancy complication. Preeclampsia affects roughly 1 in 10 pregnancies. It causes dangerously high blood pressure, damages organs and restricts the baby’s growth. It remains one of the leading causes of maternal and infant death worldwide. The only definitive treatment is delivery, sometimes weeks before the baby is ready. Despite decades of research, why certain women develop preeclampsia has remained unclear. The new discovery marks a crucial step toward understanding why preeclampsia develops and how it might be more effectively treated.

What The Protein Does in the Placenta

A new study has found that a protein called Vestigial Like Family Member 3 may be at the heart of preeclampsia. It acts as a switch, controlling which genes are turned on or off in cells. Too much of this switchboard protein upsets the balance between the placenta and the mother’s immune system. It prevents specialized placental cells called trophoblasts from growing and performing their job properly. This disrupts the normal widening of maternal blood vessels, which can lead to high blood pressure and reduced oxygen and nutrient delivery to the baby.

The study demonstrated that women with preeclampsia had significantly higher levels of this protein in their placentas compared to those with healthy pregnancies. In experiments, mice engineered to overproduce the switchboard protein in their placentas developed hallmark symptoms of preeclampsia: elevated blood pressure, restricted blood flow to the fetus, smaller offspring and increased mortality among the baby mice.

Toward a Treatment

The current standard of care still focuses on controlling blood pressure, preventing seizures with medications such as magnesium sulfate, close monitoring of mother and baby and timing delivery as safely as possible. The definitive “cure” remains delivery of the placenta, which is why severe preeclampsia often leads to early birth.

The study tested whether blocking the switch could reverse the damage. When the protein was blocked in mice, inflammation was reduced, even when the mice were exposed to compounds that normally trigger it. In human preeclamptic placentas treated with a drug that interferes with the protein's ability to activate genes, disease-related signaling decreased across multiple cell types. In other words, instead of only treating the symptoms, it was possible to dial back some of the early changes that drive preeclampsia in the first place.

The drug, called Verteporfin, is already approved for an unrelated eye condition and has well-established safety data in nonpregnant adults. A few case reports describe those who were exposed to the drug very early in pregnancy and later delivered healthy infants, but these small, accidental exposures are not enough to declare it safe for routine use in pregnancy. At higher doses, it can cause birth defects in animals. Even so, the drug's ability to switch off disease pathways in human placental tissue marks a promising first step toward therapies that treat preeclampsia at its source rather than relying solely on early delivery.

Future clinical trials will need to answer key questions: Can a targeted drug be given safely during pregnancy? When should it be started? And does it truly lower the risk of serious complications for mothers and babies? If the answers are yes, a diagnosis of preeclampsia could one day lead to a medicine that calms the overactive immune switchboard without cutting pregnancy short.

A Connection to Autoimmunity

The same switchboard protein has been linked to illnesses that affect mostly women. Autoimmune diseases, where the immune system attacks the body, affect about 15 million people in the United States. Most of them are women. Lupus, for example, is much more common in women than in men. For years, hormones were thought to be the reason. This switchboard protein may offer a new clue.

Women start out with more of the protein, and their immune systems might be closer to being overactive. In earlier studies, when mice produced excess switchboard protein in their skin, they developed symptoms similar to those seen in lupus, including a rash and organ damage. Therefore, a small trigger—like an infection, stress or pregnancy—could push things over the edge.

The connection between preeclampsia and immune diseases is seen outside the lab, too. In a study of almost 290,000 women, those who had high blood pressure during pregnancy had a much higher risk of getting lupus later on, compared to women with normal pregnancies. The risk of other immune system problems, such as joint disease and blood clotting issues, also increased. The worse the preeclampsia, the higher the later risk.

Understanding preeclampsia reframes it not simply as a pregnancy complication but as a window into the broader biology of female immune vulnerability. If ongoing research confirms the protein as a viable therapeutic target, it could eventually benefit not only women facing high-risk pregnancies but also millions of women affected by related disorders.