A treatment for pre-eclampsia may be on the horizon

Blood filtering has performed well in early trials

FEW PROBLEMS in pregnancy are as mysterious and dangerous as pre-eclampsia. The condition, which causes a sudden spike in the mother’s blood pressure, can quickly lead to organ failure and death. It is hard to see coming and the only known treatment is to deliver the baby fast, often by emergency C-section.

If the pregnancy is 32 weeks or less along at this point, as is the case for roughly 20,000 such births in America each year, the baby’s chances of survival and healthy development are significantly lower. Even a small extension of the pregnancy in such cases could have huge benefits, if ways to safely achieve it could be found.

There is now a glimmer of hope that this can be done. On April 27th an international collaboration led by Ravi Thadhani and Ananth Karumanchi from the Cedars-Sinai Medical Centre in Los Angeles reported the early results for a promising novel treatment. In a study published in Nature Medicine, they showed that filtering the blood of women with pre-eclampsia to remove a troublesome protein can safely slow its progression.

As promising as its results sound, the trial represents a proof-of-concept study that tested the treatment in only 16 women. To more accurately test the efficacy of the approach, and to work out whether it could one day become standard treatment, bigger trials will be needed. Even so, according to James Walker from the University of Leeds, “The study marks the first credible step beyond symptom control toward a true disease-modifying treatment.”

There is enormous room for improvement. Doctors have been managing pre-eclampsia in much the same way for the past 50 years, says Dr Karumanchi. The current standard of care for pre-eclampsia is watchful waiting, interspersed with drugs to prevent seizures in the mother as well as steroids to prepare the baby’s lungs for an early birth. Such steps can buy a few additional days but cannot stop the progression of pre-eclampsia.

Part of the reason for this stagnation is the difficulty involved in developing new medicines for pregnant women. Most obviously, some molecules could cross from the mother’s bloodstream into the placenta where they could affect the developing fetus in unforeseen ways.

To sidestep this issue, Dr Karumanchi’s team decided to remove problematic components from a woman’s blood rather than adding anything new. The target they settled on was a protein called soluble Fms-like tyrosine kinase 1 (sFlt-1) which is secreted by the placenta in order to boost blood flow. Scientists have known for about 15 years that this protein spikes in pre-eclampsia and plays a direct causal role in the development of the disease in the mother. But nobody had previously managed to safely lower its levels in a woman’s blood.

Drs Thadhani and Karumanchi, alongside their collaborators, hoped to solve the problem with the help of a standard medical protocol known as aphaeresis, which has long been used to clean up blood. Blood is taken from a patient, passed through a filter and then returned to the body. It is used to reduce cholesterol levels in people with high inherited levels of the stuff, and helps remove certain dangerous types of blood cells in patients with cancer or sickle cell anaemia.

To remove sFlt-1 from a patient’s blood, the researchers designed an antibody capable of binding to that specific protein. They then equipped a filter with enough of these antibodies to reduce the sFlt-1 concentration in blood plasma that was passed through. Although sFlt-1 rebounded in some patients, its level plateaued rather than continuing to rise as would otherwise have been the case.

Neither the women with pre-eclampsia on the trial nor their babies had any ill effects. The median extension of pregnancy in the treated women was ten days—meaningfully longer than the four days current treatment offers, and long enough for some babies to be classified as “moderately” rather than “very” preterm. After decades of better risk prediction without better treatment, adds Dr Walker, this study offers genuine grounds for optimism. ■