High blood pressure is a common symptom of preeclampsia
Nataliya Piatrovitx/Alay
Delivering babies early, when possible, is the only way to deal with the norm these days pregnancy preeclampsia complication. But the condition has been successfully treated in mice by delivering mRNA molecules to the placenta to stimulate 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. Kelsey Swingle at the University of Pennsylvania. “We’ve talked about it to start in the short term.”
If the therapy proves effective in larger animals, the team plans to test it first in humans who develop preeclampsia early in pregnancy.
“If you get pre-eclampsia at eight or nine months of pregnancy, you’re going to induce early, but it’s not an option if you have severe pre-eclampsia at four or five months of pregnancy. It is likely that the child will be lost,” says the team member Michael MitchellAlso at the University of Pennsylvania. “So the treatment can address an immediate need.”
It could also be used later in pregnancy to prevent the need for premature birth, which can have an effect. the health of children
About 1 in 25 women develop preeclampsia during their first pregnancy, which can cause serious complications. the consequences. Worldwide, preeclampsia is estimated to kill 75,000 women 500,000 children every year
Preeclampsia is often diagnosed high blood pressure after the 20th week of pregnancy, along with signs of kidney damage, such as protein in the urine. The underlying reason for this is the failure of the arteries connecting the uterus and placenta to develop as fully as they normally would, Swingle says.
So in theory, stimulating the growth of placental arteries could treat preeclampsia. We know that a protein called vascular endothelial growth factor (VEGF) encourages the growth of blood vessels; the problem is getting to the placenta.
If proteins like VEGF are simply injected into the bloodstream, they are cleared quickly, Swingle says. Instead, it can be overcome by providing recipes for proteins to form lipid nanoparticles (LNPs) in the form of mRNA molecules embedded in a fatty substance.
When LNPs are taken up by cells, the mRNA molecules tell the cell how to make the desired protein. The molecules break up a bit, so the effect is temporary.
It’s like this COVID-19 Swingle says mRNA vaccines work, so the approach has already been tested in pregnancy. “Many pregnant women were vaccinated against covid-19”.
The LNPs used in mRNA covid-19 vaccines are taken up by muscle cells because they are injected directly. But if the same LNPs are injected the bloodalmost all are taken up by liver cells.
So the big challenge for Swingle and his team was to find a way to get the LNPs into the placenta. To achieve this, they created and tested a hundred LNPs with slightly different chemical properties.
The team used the most promising of these LNPs to deliver mRNA molecules encoding VEGF to pregnant mice with preeclampsia, and the mice’s blood pressure returned to normal for the rest of the pregnancy.
“This approach deserves further study in higher primates and, if animal data indicate safety and efficacy, in women with preeclampsia,” he says. Peter von Dadelszen at King’s College London.
Studies in mice using mRNA coding for a fluorescent protein show that LNPs involve the spleen and to some extent the liver, as well as the placenta, a potential safety concern. Importantly, however, there was no evidence of LNPs crossing mouse placentas to fetuses.
Although there is no cure for preeclampsia, the risks are especially high without advanced medical care. “An injectable therapy that doesn’t require that complicated, expensive standard of care could be transformative for developing applications around the world,” says Mitchell.
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