When three-time Olympic track and field medalist Tori Bowie, a Black woman, was found dead in her apartment last spring, eight months pregnant and in labor, many people had never heard of eclampsia, identified as a contributing factor, much less knew that Black women are far more likely to be affected.
Now, a new RNA therapeutic for preeclampsia, a hypertensive disorder of pregnancy that can progress to eclampsia, may soon be able to reduce the condition’s deadly toll.
A novel small interfering RNA (siRNA) treatment developed by Comanche Biopharma Corp., based on work by UMass Chan researchers and collaborating scientists, was cleared by the U.S. Food and Drug Administration as an investigational new drug earlier this year. This milestone allows for first-in-human clinical trials of the subcutaneously delivered therapy, CBP-4888, to begin.
But UMass Chan researchers also say a multipronged approach to addressing factors underlying health disparities is key. Preeclampsia and eclampsia are responsible for more than 70,000 maternal deaths and 500,000 fetal and newborn deaths annually worldwide, according to the Centers for Disease Control and Prevention. In the U.S., the risk of dying of eclampsia and preeclampsia is about five times greater for Black individuals (3.93 maternal deaths per 100,000 live births) than for white individuals (0.78 maternal deaths per 100,000 live births), according to a recommendation statement from the U.S. Preventive Services Task Force (USPSTF) published in September.
Women experiencing preeclampsia suffer from the onset of high blood pressure and excess protein in the urine, called proteinuria, beginning around 20 weeks of pregnancy. In severe cases, red blood cells can break down, blood platelet counts fall, liver and kidney function become impaired, and fluid can fill the lungs. A complication in 2 to 8 percent of all pregnancies, the only treatment for severe preeclampsia is delivery of the baby and placenta. Preeclampsia mortality risks continue to the immediate postpartum period, so the USPSTF statement recommends continued blood pressure and clinical monitoring.
A primary cause of preeclampsia is excess production of the protein sFLT1 by the placenta, which enters the mother’s bloodstream.
“A huge amount of work by different laboratories and medical professionals came into play to understand that we can make an siRNA having the ability to selectively eliminate the overexpressed disease-causing protein from the bloodstream without affecting normal processes,” said Anastasia Khvorova, PhD, the Remondi Family Chair in Biomedical Research, professor of RNA therapeutics and Comanche scientific advisory board member. Even allowing the pregnancy to continue for a few more weeks can make a difference in the health of the baby, she said.
Melissa J. Moore, PhD, professor of RNA therapeutics, former co-director of the RNA Therapeutics Institute at UMass Chan, former chief scientific officer at Moderna and Comanche scientific advisory board member, has been working on a therapy for preeclampsia since she developed the condition herself 20 years ago.
Dr. Moore had many of the risk factors for preeclampsia, which is more likely to occur in a first pregnancy. She had undergone in vitro fertilization and was overweight, older and had spent a lot of time at high altitude.
Her symptoms included swollen ankles, high blood pressure and protein in her urine. Other symptoms may include severe headaches, vision changes and abdominal pain.
As Moore was being prepped for an emergency cesarean section, she met a doctor studying preeclampsia, Ananth Karumanchi, MD, then of Beth Israel and Harvard Medical School. The two ultimately collaborated in developing siRNA therapy to treat the disease, joined by Dr. Khvorova and Annemarie Hennessy, PhD, MBA, MBBS, dean of medicine at Western Sydney University.
“I really have faith that this siRNA therapy is going to work,” said Moore. “There really haven’t been any new treatments or medicines for pregnancy-related disorders since the 1960s, because of thalidomide (which caused birth defects).”
While she praised the potential new treatment for preeclampsia, Crista Johnson-Agbakwu, MD, professor of obstetrics & gynecology and executive director of the UMass Chan Collaborative in Health Equity, said Bowie’s death was just “the tip of the iceberg.”
“Despite so many advances in the science and understanding disease processes, we really haven’t reckoned with addressing pervasive racism and some of the underlying structural and systemic forces that have perpetuated harm on communities of color,” Dr. Johnson-Agbakwu said.
“We’ve kind of created a monster. Black women across the country are now afraid when they become pregnant, they think, ‘Oh my goodness, am I going to die?’” she said. So, they often take pregnancy care into their own hands, which could cause even more harm.
Johnson-Agbakwu called for a holistic approach that includes first building trust by carefully listening to women, paying attention and showing respect. Women of color need to be represented more in medicine and academic medical leadership, she said, and representative samples of women of color must be included in clinical trials.
“We need to nurture a stronger partnership with communities of color to recognize that there are social drivers of persistent inequities that go beyond the disease process,” said Johnson-Agbakwu.
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