Preeclampsia can be treated using mRNA technology

Premature delivery, when possible, is currently the only way to deal with the common pregnancy complication preeclampsia. But this condition has now been successfully treated in mice by delivering mRNA molecules to the placenta to promote the growth of new blood vessels.

The next step is to test this mRNA therapy in larger animals, such as guinea pigs and non-human primates, he says. Kelsey Swingle At the University of Pennsylvania. “This is something we talked about to start in the really near term.”

If the treatment proves effective in larger animals, the team expects to test it first in people who develop preeclampsia early in pregnancy.

“If you develop preeclampsia in the eighth or ninth month of pregnancy, you will be induced early, but that’s not an option if you have severe preeclampsia in the fourth or fifth month of pregnancy. It’s very likely that you will lose the baby,” says a team member. Michael Mitchelland also at the University of Pennsylvania. “This is where treatment can come [address] “Immediate need.”

It is also possible to use it later in pregnancy to avoid the need to induce labor early, which may affect the health of the infant.

About 1 in 25 women develop preeclampsia during their first pregnancy, which can lead to serious consequences. Globally, it is estimated that preeclampsia kills 75,000 women 500,000 infants every year.

Preeclampsia is usually diagnosed on the basis of high blood pressure after the 20th week of pregnancy, along with signs of kidney damage, such as the presence of proteins in the urine. The underlying cause, Swingle says, is a failure of the arteries that connect the uterus to the placenta to develop as fully as usual.

So, in theory, promoting the growth of arteries in the placenta could treat preeclampsia. We know that a protein called vascular endothelial growth factor (VEGF) promotes blood vessel growth – the problem is getting it to the placenta.

If proteins like VEGF are injected into the blood, they are quickly eliminated, Swingle says. This could be overcome by providing recipes for making proteins instead, in the form of mRNA molecules coated with a lipid to form lipid nanoparticles (LNPs).

When cells pick up LNPs, the mRNA molecules tell the cell how to make the desired protein. The molecules break down after a while, so the effect is temporary.

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

The LNPs used in mRNA covid-19 vaccines are absorbed by muscle cells because they are injected directly into them. But if the same LNPs were injected into the blood, almost all of them would be absorbed by liver cells.

So the big challenge for Swingle and her team was to find a way to deliver LNPs to the placenta. To achieve this, they created and tested nearly a hundred LNPs with slightly different chemical properties.

When the team used the most promising of these LNPs to deliver mRNAs encoding VEGF to pregnant mice with preeclampsia, the mice’s blood pressure returned to normal for the remainder of pregnancy.

“This approach merits further study in higher primates, and if the animal data suggest safety and efficacy, it merits further study in women with pre-eclampsia,” he says. Peter von Dadelssen At King’s College London.

Studies in mice using mRNA encoding a fluorescent protein have shown that LNPs are taken up by the spleen, and to some extent the liver, as well as the placenta, a potential safety issue. But more importantly, there was no sign of the LNPs crossing the placenta of the mice into the fetuses.

Although there is no current cure for preeclampsia, the risks are especially high without advanced medical care. “Injectable therapy, which doesn’t require that complex level of care and is very expensive, could be transformative in developing world applications,” says Mitchell.

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