Using mRNA Technology to Treat Pre-eclampsia

Currently, the only way to deal with preeclampsia, a common pregnancy complication, is to deliver the baby early if possible. But researchers have now successfully treated this condition in mice by delivering mRNA molecules to the placenta to stimulate the growth of new blood vessels.

They say the next step is to test this mRNA therapy in larger animals such as guinea pigs and non-human primates. kelsey swingle at the University of Pennsylvania. “That’s something we’ve been talking about starting in the really near future.”

If the treatment proves effective in large animals, the researchers envision testing it first in people who develop preeclampsia early in pregnancy.

“If you have pre-eclampsia in the 8th or 9th month of pregnancy, you are inducing it early, but if you have severe pre-eclampsia in the 4th or 5th month of pregnancy, it is It’s not an option. There’s a very good chance you’ll lose the baby,” the team member says. michael mitchell also at the University of Pennsylvania. “That’s where we can get treatment.” [address] There is a pressing need. ”

It may also be used late in pregnancy to avoid the need for early delivery, which can affect the infant’s health.

Approximately 1 in 25 women will develop preeclampsia during their first pregnancy, which can have serious consequences. It is estimated that 75,000 women die from preeclampsia worldwide. 500,000 infants Every year.

Preeclampsia is usually diagnosed based on high blood pressure after 20 weeks of pregnancy and signs of kidney damage, such as protein in the urine. The underlying reason for this is that the arteries that connect the uterus and placenta fail to develop properly, Swingle said.

Therefore, it could theoretically be possible to treat preeclampsia by promoting the growth of arteries within the placenta. We know that a protein called vascular endothelial growth factor (VEGF) promotes blood vessel growth, but the problem is getting it to the placenta.

Proteins like VEGF are simply injected into the bloodstream and quickly removed, Swingle said. This problem can be overcome by providing a recipe for creating proteins in the form of mRNA molecules wrapped in fatty substances forming lipid nanoparticles (LNPs).

Once LNP is taken up by cells, mRNA molecules tell the cells how to make the desired protein. The effect is temporary, as the molecules break down after a while.

Swingle says this approach has already been tested in pregnancy, as this is how covid-19 mRNA vaccines work. “Many pregnant women have been vaccinated against COVID-19.”

The LNPs used in mRNA covid-19 vaccines are injected directly into muscle cells, so they are taken up by muscle cells. However, when the same LNP is injected into the blood, almost all of it is taken up by liver cells.

Therefore, the big challenge for Swingle and her team was finding a way to get the LNPs to the placenta. To accomplish this, we created and tested about 100 LNPs with slightly different chemical properties.

When the research team used the most promising of these LNPs to deliver an mRNA molecule encoding VEGF to pregnant mice with pre-eclampsia, the mice’s blood pressure returned to normal for the remainder of their pregnancy. .

“This approach merits further study in higher primates and, if animal data suggest both safety and efficacy, in women with preeclampsia,” he says. peter von derdelsen At King’s College London.

Studies in mice using mRNA encoding fluorescent proteins have shown that LNPs are taken up by the spleen and to some extent by the liver and placenta, which is a potential safety issue. Importantly, however, there was no sign that LNPs crossed the mouse placenta and reached the fetus.

There is currently no cure for preeclampsia, but the risks are especially great without advanced medical care. “Injectable therapies that do not require all the highly expensive and complex standard treatments could be transformative for applications in developing countries,” Mitchell said.