Janani Ravikumar
Staff Writer

Erkki Ruoslahti — an adjunct professor in the University of California, Santa Barbara Center for Nanomedicine and Department of Molecular, Cellular and Developmental Biology — has found a way to bolster the placenta during pregnancy. Ruoslahti, who is also an adjunct professor at the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, and her team discovered that this can potentially prevent premature deaths and complications such as preeclampsia. Their findings are recorded in the Science Advances journal.

“The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus,” the study’s abstract states. “As enhancement of placental growth in animal models, we have developed a method for targeted delivery of payloads to the placenta.”

The U.S. National Library of Medicine defines placental insufficiency broadly as the placenta not working as well as it should, leading to babies not growing as well, thus causing signs of fetal stress, resulting in a harder time during labor. Placental insufficiency can be caused by diabetes, high blood pressure during pregnancy, medical conditions that increase the mother’s chances of blood clots, smoking and taking cocaine or other drugs.

The placenta may have an abnormal shape, not grow large enough, not attach correctly to the surface of the womb or break away from the surface of the womb and bleed prematurely. But a woman with placental insufficiency usually does not display any symptoms.

“Fetal growth restriction caused by suboptimal placental function is a very common pregnancy complication with potentially serious consequences,” Ruoslahti said in an interview with The Bottom Line. “There are known drugs that help correct this condition, but they can have serious side effects.”

Ruoslahti’s research hopes to avoid these problems by treating the baby in utero and thus avoid induced labor. Two peptides, or chains of amino acids, used to selectively target tumors can deliver drugs that improve the placenta function and benefit the growth of the baby without causing harm.

“Cell-penetrating peptides provide a highly promising strategy for intracellular drug delivery,” wrote Jakob Regberg, Artita Srimanee and Ulo Langel, researchers at Stockholm University in Sweden and Mahidol University in Thailand, in a study published on pharmaceuticals. “One relevant clinical application of cell-penetrating peptides is cancer therapeutics. Peptide-based delivery could increase the uptake of drugs in tumor cells and thereby increase the efficacy of the treatment, either of conventional small molecular drugs or oligonucleotide based therapeutics.”

Ruoslahti’s team applied the same principle to the placenta. With a mouse model, the researchers used peptide-coated nanoparticles to deliver a growth hormone to the placenta. There was no effect on normal-sized fetuses, although undersized fetuses grew. Meanwhile, the targeted drug did not build up in the mother’s organs, and likewise, no level was detected in the fetuses.

“This means that other tissues in the mother and fetus receive relatively less of the drug, which reduces or eliminates the side effects,” Ruoslahti said. “While we demonstrated the principle in fetal growth restriction, this is a platform technology that can be used in delivering any drug in any condition affecting the placenta.”

However, because the drugs primarily target tumors, there is still the potential for harmful effects in mothers who have undiagnosed cancers. A screening program could overcome this problem.

“Only one drug for use during pregnancy has been licensed in the last 20 years,” said the lead author of the study, Lynda Harris of the University of Manchester in England, according to the UC Santa Barbara Current. “By developing this platform, we have opened up the possibility that any number of new drugs can be adapted and then used safely to treat common and serious pregnancy complications.”