Toward a New Cure for Pre-eclampsia

Despite its prevalence, the exact cause of pre-eclampsia remains a mystery. While the most visible sign is a sudden spike in the mother’s blood pressure, the condition involves much more than just hypertension. When pre-eclampsia sets in, the mother’s blood vessels begin to malfunction, damaging her kidneys and causing essential proteins to leak into the urine while inflammation spreads throughout her body. 

“If it’s not monitored and treated, it can progress to eclampsia—when it starts affecting the brain, causing seizures, which can be fatal for the mother,” Dr. Majumder said. 

Pre-eclampsia also takes a toll on the baby by disrupting the placenta, the temporary organ that forms during pregnancy as a lifeline connecting mother and baby. For a fetus to develop normally, the placenta must build a complex network of blood vessels to carry oxygen and nutrients from a mother to her baby. In pregnancies complicated by pre-eclampsia, that vascular network often fails to develop properly.

“If the baby is not getting enough oxygen, blood supply, and nutrients from the mother, they will not grow well,” Dr. Majumder explained. “Pre-eclampsia, in most cases, is associated with fetal growth restriction. That’s when the babies are extremely small for their gestational age and not growing properly.”

Doctors and mothers face a frustrating reality: there are no treatments for either pre-eclampsia or fetal growth restriction. Low-dose aspirin is sometimes prescribed to keep the mother’s hypertension in check, but it’s an intervention that doesn’t always work. “The only real treatment is to deliver the baby early to save the mother and baby both,” said Dr. Majumder.

Early delivery is lifesaving, but comes with its own set of risks as well as health consequences that can last a lifetime. 

“The babies are premature. They have longer NICU stays,” Dr. Majumder explained. “Later in life, they tend to develop obesity, cardiometabolic problems, and neurodegeneration. It all starts with the pregnancy and continues throughout life.” 

There was an urgent need for a different approach, one that looked beyond managing symptoms and delivering babies prematurely and, instead, focused on correcting the underlying biological problem in the placenta itself. 

In earlier research studies, Timothy Crombleholme, MD, Director of Connecticut Children’s Fetal Care Center, found that gene therapy using a growth factor called insulin-like growth factor-1 (IGF-1) corrected fetal growth restriction in multiple animal models. Growth factors are naturally occurring proteins that guide how cells grow and develop, and IGF-1 plays an important role in helping the placenta build its network of blood vessels. 

IGF-1 is found to be particularly low in cases of pre-eclampsia and fetal growth restriction, raising the question: Could restoring IGF-1 levels in the placenta repair those blood vessels and reverse the disease the way it had in Dr. Crombleholme’s fetal growth restriction study? It was an idea they wanted to explore together. 

Genes act as instructions for producing proteins—like IGF-1—in the body. If scientists can insert a functioning copy of a gene into a cell, that cell may begin producing the missing protein on its own. Using a mouse model that displays similar features to pre-eclampsia in humans (high blood pressure, kidney injury, and protein leakage during pregnancy), Dr. Majumder and her research team injected a modified virus carrying the IGF-1 gene directly into the placenta at 16 weeks’ gestation (equivalent to 28 to 32 weeks in humans). 

The outcome was striking. “When we introduced the IGF-1, we saw the blood vessel formation in the placenta improve,” she said. It also produced dramatic improvements in the mothers themselves. “It normalized their blood pressure and corrected the kidney pathology. All three major features of pre-eclampsia were reduced.”

These findings suggest that repairing the placenta could relieve the physical stress that pre-eclampsia places on a mother’s body and allow pregnancies to continue safely for a longer period of time—buying a baby valuable time to grow and mature before delivery.

“The results are really promising,” Dr. Majumder said. But what remains unclear is exactly how the IGF-1 gene restores placental function. To answer that question, she is collaborating with researchers at UConn Health and The Jackson Laboratory, where advanced technologies can analyze the molecular activity of placental cells in extraordinary detail. 

Using techniques such as single-cell and single nuclear RNA sequencing, spatial transcriptomics, and biomechanistic studies, the team can examine how genes and molecules are being changed when IGF-1 is introduced and what is happening in the placenta besides blood vessel formation. These insights could help refine the therapy and guide its eventual development for human use. 

Moving from laboratory success to human treatment will take time. The virus used to deliver the gene therapy in the mouse model cannot be used in human patients, so Dr. Majumder and her team are exploring safer alternatives that could deliver the gene in clinical settings. If those hurdles are overcome, the next step would be clinical trials in pregnant women, a goal that’s about five to seven years away.

Still, it’s hard to overstate the potential impact of this research. “Pre-eclampsia can affect any pregnant woman,” Dr. Majumder said. It’s a condition that transcends socio-economic status and even outward health. The 2023 death of Olympic track and field champion Tori Bowie, who died from complications of pre-eclampsia, served as a heartbreaking reminder that it can strike anyone. But Dr. Majumder’s research offers a glimpse into a brighter future where placental function can be restored, allowing mothers with pre-eclampsia to continue their pregnancies to term—and their babies to be born stronger and healthier.