Researchers from Western University and Brown University have made groundbreaking progress toward identifying the root cause and potential therapy for preeclampsia.
Preeclampsia is a pregnancy complication that affects up to eight per cent of pregnancies globally and is the leading cause of maternal and fetal mortality due to premature delivery, complications with the placenta, and lack of oxygen.
The research, led by Drs. Kun Ping Lu and Xiao Zhen Zhou at Western, and Drs. Surendra Sharma and Sukanta Jash at Brown, have identified a toxic protein, cis P-tau, in the blood and placenta of preeclampsia patients.
According to the study, cis P-tau plays a major role in causing the deadly complication.
“The root cause of preeclampsia has (so far) remained unknown, and without a known cause there has been no cure. Preterm delivery is the only life-saving measure,” said Lu, professor of biochemistry and oncology at Schulich School of Medicine & Dentistry.
Until now, cis P-tau was mainly associated with neurological disorders like Alzheimer’s disease, traumatic brain injuries (TBI), and stroke.
In 2012, Zhou developed an antibody to target the toxic protein. It is currently undergoing clinical trials in human patients suffering from TBI and Alzheimer’s. The antibody has shown promising results in animal models and human cell cultures in treating the brain conditions.
The researchers were curious whether the same antibody could work as a potential treatment for preeclampsia. Upon testing the antibody in mouse models they found astonishing results.
“In this study, we found the cis P-tau antibody efficiently depleted the toxic protein in the blood and placenta, and corrected all features associated with preeclampsia in mice. Clinical features of preeclampsia, like elevated blood pressure, excessive protein in urine, and fetal growth restriction, among others, were eliminated and pregnancy was normal,” said Sharma, professor of pediatrics and professor of pathology and laboratory medicine at Brown.
Recent research has also identified preeclampsia’s long-term impacts and possible links to brain health.
“Preeclampsia presents immediate dangers to both the mother and fetus, but its long-term effects are less understood and still unfolding,” said Sharma. “Research has suggested a heightened risk of dementia later in life for both mothers who have experienced preeclampsia and their children.”
The researchers say this new study suggests a deeper connection between preeclampsia and brain-related issues.
As researchers delve deeper, how bodies respond to stress is also emerging as a potential factor in the onset of preeclampsia.
“Understanding how stress and other environmental factors intersect with biological markers like cis P-tau may offer a more complete picture,” said Jash, the lead author of the study.
In 1996 and 1997, Lu and Zhou made the groundbreaking discovery of Pin1, which turned out to be a stress-response enzyme. Pin1 becomes active or changes its behaviour in response to stressors, such as environmental challenges, toxins, or physiological changes.
“Essentially, when Pin1 is activated, it can lead to cancer. On the other hand, when there’s a decrease or deactivation in Pin1, it results in the formation of the toxic protein cis P-tau, which leads to memory loss in Alzheimer’s and after TBI or stroke. Now, we’ve uncovered its connection to preeclampsia as well,” said Zhou.
The researchers continue to work on developing an assay for early detection of preeclampsia and therapies to treat the condition.
