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RNA Therapy Helps Reduce Preeclampsia Symptoms

Pregnant woman

(Sergio Santos, nursingschoolsnearme.com, Flickr)

20 November 2018. Experimental treatments with engineered RNA are shown in lab animals to reduce symptoms of preeclampsia, a disorder causing high blood pressure in pregnant women. A team from University of Massachusetts Medical School in Worcester and other institutions, and the company Moderna Therapeutics, report their findings in yesterday’s issue of the journal Nature Biotechnology (paid subscription required).

Researchers led by UMass medical chemistry professor Anastasia Khvorova, Moderna Therapeutics chief scientist Melissa Moore, and Ananth Karumanchi at Harvard Medical School and Beth Israel medical center in Boston are seeking better treatments for preeclampsia, a life-threatening condition resulting from a sudden rise in blood pressure in a pregnant woman, affecting blood flow to the placenta, and excess protein in the urine.

The only known cure for preeclampsia is delivery of the baby, which in some cases can be dangerous for the baby as well as the mother. Severe cases of preeclampsia can result in break downs in red blood cells, impaired liver and kidney function, and fluid in the lungs. The earlier in the pregnancy preeclampsia occurs, the riskier to outcomes for both mother and baby. The Preeclampsia Foundation says the condition occurs in 5 to 8 percent of all pregnancies.

The research team focused on a characteristic protein associated with preeclampsia, called soluble vascular endothelial growth factor receptor FLT1, or sFLT1, often found overproduced in women with the condition. This protein, at high levels and in soluble forms, limits development of new blood vessels, thus the team looked for ways to block production of this protein in order to treat preeclampsia.

The researchers designed a form of RNA, amino acids with coding instructions for proteins to cells, to interrupt production of sFLT1. The treatment is known as RNA interference, a natural process to silence the expression of genes causing disease. RNA interference targets specific genes, making it a potentially powerful therapeutic technique, while minimizing damage to other genes, thus limiting side effects. In this case, the interfering RNA molecules are small in size, with limited numbers of amino acids, and are known as short interfering RNAs or siRNAs.

The team designed their siRNAs to target FLT1 genes responsible for three specific types of sFLT1 proteins, without completely blocking all FLT1 genes. The researchers formulated the siRNAs to accumulate in the placenta, where harmful sFLT1 proteins also congregate. In tests with lab mice, the team found the siRNAs reduced sFLT1 proteins by half. Working with colleagues at Western Sydney University in Australia, the researchers also tested the treatment in pregnant baboons, a proxy model for humans, and found the siRNAs suppressed sFLT1 production and reduced symptoms of preeclampsia, including high blood pressure and protein accumulations in urine.

However, the baboons also gave birth to offspring with lower birth rates, which will need further study and resolution before advancing the treatment to clinical trials. Moore, who still holds a faculty position at UMass Medical School, suffered from preeclampsia 15 years ago, so this research is more than a professional exercise. “This project is near and dear to my heart,” says Moore in a UMass statement. “As exciting as these results are, it still feels like we’re half done. It won’t be complete until we can get a therapy to women. Getting pregnant shouldn’t be one of the most dangerous things a woman can do.”

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