Researchers from the University of Wisconsin-Madison and the University of Florida have discovered a treatment for placentas deficient in the growth hormone IGF-1 that may soon be going toward human clinical trials.
Placentas provide oxygen and vital nutrients to the fetus and are “the organ[s] in the middle,” communicating between the mother and fetus with hormones, Dr. Helen Jones, an associate professor at the University of Florida, told The Daily Cardinal. When not properly regulated, those hormones can result in the manifestation of extremes like pre-eclampsia, cardiovascular disease and elevated cortisol in the mother.
Jones has been studying the placenta for over 20 years with a focus on inadequate fetal growth.
“As I went through my training and career, I started to realize that a lot of people were beginning to understand the pregnancy complications but not really looking at how we might be able to actually adjust these complications,” Jones said.
Jones looked for biomarkers of low fetal growth, and one was low placenta growth. She read the literature and decided to avoid viral therapeutics because of how viruses are perceived in society.
“We are trying to improve growth by improving the growth and development of the placenta, in our case the IDF-1 growth factor,” Jones said. “There seems to be a central pathway in the placenta that is sort of downstream of growth factors.”
This pathway was discovered to be an integral part of IGF-1 treatment. Her collaborative therapeutic intervention is a blood transfusion that delivers DNA plasmid to the placenta, which is very accessible because the placenta is bathed in blood.
Subjects have advanced past mice and guinea pigs, and studies from the Wisconsin National Primate Research Center at UW-Madison have shown that the experimental treatment is safe in rhesus macaques.
“From our initial studies that we’ve done now, on the macaques, we’re getting some quite good expression of this gene even 10 days after the treatment,” Jones said.
Dr. Jenna Schmidt is a cell and embryo gene editing researcher at the primate lab and led the study in macaques. She told WPR that macaques are great models for human pregnancies because they share many similarities in their placentas and pregnancy development stages with humans.
Schmidt and Jones have continued to find no negative responses in the subjects, such as unexpected changes in hormones or blood sugar. The only adjustment observed has been a reduction in cortisol, meaning lower stress levels in the mother.
Looking to the future
The treatment developed by Jones and tested by Schmidt can reduce the risk for generations of people from developing cardiovascular disease, metabolic syndrome and other ailments with roots in fetal development. Treating the placenta with IGF-1 allows the fetus to absorb the necessary elements to thrive once born.
“If you’re born at the right weight at the right time, you’ve gotten nutrition and plenty of oxygen supply, so you’re born as you should be, then you’re on the right trajectory for a healthy life,” Jones said.
The future of this research in clinical trials is contingent on funding and the perception of its usefulness in health care. The placenta is “an organ that most people don’t appreciate,” Jones said, and there is “a lot of misunderstanding” about what its role is during a pregnancy. Women’s health care is a notably underfunded area of research, but Jones said it is an inaccurate categorization.
“Every human born on this planet had a placenta,” Jones said. “So it’s not women’s health, it’s human life.”
Despite setbacks with funding, the joint research between Jones and the primate lab is looking toward clinical trials in humans in the next five years.
Schmidt told WPR that their treatment plan is targeted in the third trimester with extended treatment through the end of the pregnancy. Jones suggested mothers could receive their transfusion at their weekly obstetric checkup.
In cases where an unhealthy placenta is misdiagnosed through an inaccurate ultrasound, Jones noted that these transfusions would not likely harm the fetus through extra growth. There is “a built-in safety” inside the placenta that would not react with the excess IGF-1, but further observation and analysis of the babies after delivery would be necessary to fully understand the possible side effects of a misdiagnosis.
