Pilot study suggests removing a placental protein from circulation could prolong high-risk pregnancies and reduce preterm birth.
The first in-human trial of a potential treatment for preeclampsia has shown encouraging early results, with researchers reporting it may slow progression of the condition and allow pregnancies to continue for longer.
The pilot study, performed by researchers from Australia, the US, the UK and Germany, removed the placental protein soluble Fms-like tyrosine kinase-1 (sFlt-1) from circulation via apheresis. This protein has been strongly linked to the development and progression of preeclampsia, with levels rising as the condition progresses.
The only definitive treatment for preeclampsia, which affects around one in 10 pregnancies in Australia, is delivery of the baby and placenta. It is strongly associated with preterm birth and increased intervention rates, contributing to a substantial proportion of labour inductions and Caesarean sections.
The experimental apheresis treatment was first tested in three pregnant baboons with preeclampsia. Each apheresis session reduced circulating sFlt-1 levels by around 50%, and two of the three animals went on to deliver healthy babies. The third neonatal death was reported as unrelated to the treatment.
Initial safety testing was then performed on five healthy non-pregnant women before the first in-human trial of 16 women with very early preeclampsia which required hospital management before 32 weeks’ gestation. Multiple treatment sessions were received by nine of the 16, with the other seven undertaking a single apheresis treatment.
The apheresis sessions – where blood was removed, passed through an external filter that selectively bound sFlt-1 then returned to circulation – took between one to two hours depending on the volume of plasma processed.
In those who underwent repeated cycles, sFlt-1 levels fell by an average of 16.7% following each session. Mean arterial blood pressure fell by an average of 4.1mmHg after treatment, with researchers reporting that reductions in blood pressure closely correlated with the drop in circulating sFlt-1.
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The study did not report pooled efficacy outcomes for women who underwent a single apheresis treatment. However, the authors noted that in two of the seven participants, sFlt-1 levels remained at or below baseline for several days after treatment.
Maternal and foetal vital signs remained stable throughout the sessions and reported side effects were mild, including temporary low calcium levels in three participants, minor bleeding at the venepuncture site in one participant and one case of false labour. No foetal adverse events were attributed to the procedure.
One of the most notable findings was the potential extension of pregnancy duration. Women who received treatment remained pregnant for a median of 10 days after hospital admission, compared with around four days in a contemporaneous untreated comparison group receiving standard care.
The authors noted that even modest prolongation of pregnancy in very preterm preeclampsia may be clinically meaningful, potentially allowing additional foetal growth and more time for standard interventions such as corticosteroids before delivery.
While the findings suggested the treatment was safe, tolerable and may have helped slow the progression of very early preeclampsia, the authors cautioned that the study was small, non-randomised and designed primarily to assess safety rather than effectiveness.
If confirmed in larger controlled trials, they said the therapy could offer one of the first disease-targeted treatment options for preeclampsia.
