Gene Therapy for Placental Insufficiency Nears Human Trials

Researchers at the University of Wisconsin–Madison and the University of Florida have developed a gene therapy method that enhances placental function, potentially reducing risks associated with low birthweight and preterm delivery. Initial tests in pregnant monkeys indicate the therapy is safe and effective, marking an important step toward human clinical trials. These findings were recently published in Molecular Human Reproduction.

Addressing placental insufficiency with genetic tools

Placental insufficiency occurs when the placenta cannot adequately supply nutrients and oxygen to a developing fetus, leading to low birthweight and complications such as preterm birth. This condition has no direct treatment options, leaving physicians to manage its effects on newborns through intensive care. The researchers aimed to address this gap by improving placental health during pregnancy.

“The placenta, although transient and typically discarded after pregnancy, is an organ that is so critical to ensuring healthy babies. Placental insufficiency contributes to poor nutrient and oxygen transport to the fetus and low birth weight, but there is currently no way to treat the placenta.”

Dr. Jenna Schmidt

The therapy involves injecting nanoparticles into the placenta that deliver DNA encoding insulin-like growth factor 1 (IGF-1), a protein critical for placental development and function. IGF-1 levels are often reduced in pregnancies affected by fetal growth restriction, a condition linked to smaller-than-normal babies and increased risk of adult diseases such as cardiovascular and neurodevelopmental disorders.

Testing the approach in primates

The study involved injecting the nanoparticles into the placentas of pregnant rhesus macaques. Within 24 hours, the DNA was absorbed and expressed without adverse effects on the mothers or their developing fetuses. Expression of the transgene persisted for at least 10 days, suggesting potential for long-lasting benefits.

“This was the first study to test this treatment in macaques, and it worked,” said Jenna Schmidt, a researcher at the Wisconsin National Primate Research Center. Importantly, the study showed no immune response in the mothers or signs of off-target effects, indicating that the therapy might be safe for extended use.

Progressing toward clinical application

Prior studies in mice and guinea pigs with placental insufficiency demonstrated encouraging results, and the success in macaques represents a crucial step toward human trials. Future research will focus on extending therapy into the later stages of pregnancy and measuring its effects through birth outcomes.

The researchers envision this approach as a potential intervention after mid-pregnancy, when abnormalities in fetal growth are typically identified using ultrasound. Regular infusions of the nanoparticles could support placental health and improve outcomes for babies and mothers.

Reference: Wilson RL, Schmidt JK, Davenport BN, et al. Placental gene therapy in nonhuman primates: a pilot study of maternal, placental, and fetal response to non-viral, polymeric nanoparticle delivery of IGF1. Mol Hum Reprod. 2024;30(11):gaae038. doi: 10.1093/molehr/gaae038

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