Identifying the Cause and Potential Therapy for Preeclampsia: A Groundbreaking Discovery
Preeclampsia, a pregnancy complication that affects up to eight percent of pregnancies worldwide, has long been shrouded in mystery. In the absence of a known cause, it has posed a significant challenge for healthcare professionals, leading to high maternal and fetal mortality rates due to premature birth, placental complications, and lack of oxygen. However, researchers at Western and Brown University have recently made groundbreaking progress in understanding the root cause of preeclampsia and have even identified a potential therapy.
The Identification of a Troublemaker
Leading the research efforts, Drs. Kun Ping Lu and Xiao Zhen Zhou at Western, along with Drs. Surendra Sharma and Sukanta Jash at Brown, have discovered a toxic protein called cis P-tau in the blood and placenta of patients with preeclampsia. According to their study published in Nature Communications, cis P-tau is a central circulating factor in preeclampsia and plays a crucial role in causing this deadly complication.
Previously, cis P-tau had primarily been associated with neurological disorders such as Alzheimer’s disease, traumatic brain injury (TBI), and stroke. However, Lu and Zhou’s earlier research into the role of the tau protein in cancer and Alzheimer’s led them to uncover this unexpected association. In fact, an antibody developed by Zhou in 2012 to target the toxic protein has shown promising results in clinical trials for TBI and Alzheimer’s. This prompted the researchers to investigate whether the same antibody could potentially be used to treat preeclampsia.
Potential Therapeutic Breakthrough
When the researchers tested the cis P-tau antibody in mouse models, they were met with surprising results. The antibody efficiently depleted the toxic protein in the blood and placenta, effectively eliminating the clinical features of preeclampsia, such as elevated blood pressure, excess protein in urine, and fetal growth restriction. The pregnancy in the mouse models returned to normal. This breakthrough discovery marks a crucial development in the quest for a therapy for preeclampsia.
“Our study identifies cis P-tau as a crucial culprit and biomarker of preeclampsia. It can be used for early diagnosis of the complication and is a crucial therapeutic target,” said Dr. Sharma, one of the leading preeclampsia researchers at Brown. Being able to diagnose and target preeclampsia early on has the potential to save countless lives and improve maternal and fetal outcomes.
A Closer Look at Preeclampsia
Preeclampsia has long been known to disproportionately affect black and Hispanic women. The recent tragic death of American track and field champion Tori Bowie, who was found dead in her bed while approximately eight months pregnant, further shed light on this issue. An autopsy report suggested that complications related to preeclampsia may have been a contributing factor.
Research has indicated that women of certain races may possess genes that predispose them to higher than average blood pressure levels, potentially setting the stage for preeclampsia during pregnancy. However, the exact relationship between race, genetics, and environmental factors is still not fully understood. The lack of comprehensive registries in many low-level countries further complicates the investigation into these interconnections. As research continues, it is vital to strive for a more comprehensive understanding of preeclampsia and its impact on maternal health.
Preeclampsia and Brain Health
Emerging research has also pointed to a potential link between preeclampsia and long-term brain health. Studies have suggested an increased risk of dementia in mothers who have experienced preeclampsia, as well as in their children. However, the causal connection between preeclampsia and dementia remains unknown.
The recent study conducted by Lu, Zhou, Sharma, and Jash has shed new light on this complex relationship. For the first time, significant levels of cis P-tau have been detected outside the brain in the placenta and blood of patients with preeclampsia. This finding suggests a deeper connection between preeclampsia and brain-related problems. Further investigation is necessary to unravel the intricacies of this relationship and its potential implications for both mothers and their children.
The Role of Stress and Pin1 Enzyme
While genetics play a role in the development of preeclampsia, emerging evidence suggests that factors like stress may also contribute to the onset of this condition. Understanding how stress and other environmental factors intersect with biological markers like cis P-tau may provide a more complete picture of the underlying mechanisms.
A key player in stress response is an enzyme called Pin1, which Drs. Lu and Zhou discovered in 1996 and 1997. Pin1 is a specific protein in cells that activates or alters its behavior in response to stressors. It plays a critical role in maintaining the functional form of proteins, including the tau protein, during periods of stress. When Pin1 is inactivated, it leads to the formation of the toxic cis P-tau protein responsible for memory loss seen in conditions like Alzheimer’s, traumatic brain injury, stroke, and now preeclampsia.
The significance of this discovery reaches far beyond preeclampsia. Pin1 has been found to be highly active in many human cancers, particularly in cancer stem cells that are believed to drive tumor growth and spread. Understanding the role of Pin1 and its connection to various conditions, from pregnancy-related complications to brain disorders and cancer, presents new possibilities for developing targeted therapies and revolutionizing our approach to these conditions.
Collaboration and Future Directions
The collaborative efforts between the researchers at Western and Brown universities have proven to be transformative. The unexpected collaboration, sparked by a lecture given by Dr. Lu, highlights the serendipitous nature of scientific progress. By breaking down barriers and combining expertise from different fields, groundbreaking discoveries can be made, leading to significant advances in our understanding and treatment of various conditions.
Their groundbreaking research on preeclampsia, cis P-tau, and Pin1 opens up new avenues for investigation and potential therapeutic approaches. From early diagnosis to targeted therapies, their findings have the potential to revolutionize the management of preeclampsia, improve maternal and fetal outcomes, and shed light on the intricate relationship between preeclampsia and brain health.
As researchers continue to delve deeper into the complexities of preeclampsia, stress, and biological markers, a more comprehensive understanding of this condition and its underlying mechanisms will emerge. This knowledge will pave the way for innovative interventions and personalized approaches, ultimately improving the lives of millions of women and their children worldwide.
Summary
In a groundbreaking study, researchers from Western and Brown University have made significant progress in identifying the root cause of preeclampsia, a pregnancy complication that affects up to eight percent of pregnancies worldwide. They have discovered a toxic protein called cis P-tau in the blood and placenta of patients with preeclampsia, which plays a central role in causing this deadly condition. The researchers have tested an antibody that targets this toxic protein in mouse models and found promising results, which brings hope for a potential therapy for preeclampsia. Preeclampsia has long been known to disproportionately affect black and Hispanic women, and an increased risk of dementia has been observed in both mothers who have experienced preeclampsia and their children. The recent study has also revealed a possible connection between preeclampsia and brain-related problems, adding further complexity to the understanding of this condition. Additionally, stress and an enzyme called Pin1 have been identified as potential factors contributing to the onset of preeclampsia. Collaborative efforts between researchers at Western and Brown universities have led to transformative discoveries, highlighting the value of multidisciplinary collaboration in advancing scientific knowledge. These groundbreaking findings have far-reaching implications and may revolutionize the understanding and treatment of not only preeclampsia but also various other conditions.
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Researchers at Western and Brown University have made groundbreaking progress toward identifying the root cause and potential therapy for preeclampsia.
Pregnancy complication affects up to eight percent of pregnancies worldwide and is the leading cause of maternal and fetal mortality due to premature birth, complications with the placenta and lack of oxygen.
The research, led by Drs. Kun Ping Lu and Xiao Zhen Zhou of Western, and Drs. Surendra Sharma and Sukanta Jash at Brown, have identified a toxic protein, cis P-tau, in the blood and placenta of patients with preeclampsia.
According to the study published in Nature Communications, cis P-tau is a central circulating factor in preeclampsia, a “troublemaker” that plays an important role in causing this deadly complication.
“The fundamental cause of preeclampsia (until now) remains unknown, and without a known cause there has been no cure. Preterm birth is the only life-saving measure,” said Lu, professor of biochemistry and oncology at the School of Medicine. Schulich and Dentistry. Lu is also a Western research professor in biotherapeutics.
“Our study identifies cis P-tau as a crucial culprit and biomarker of preeclampsia. It can be used for early diagnosis of the complication and is a crucial therapeutic target,” said Sharma, who recently retired from his roles at Brown as professor of pathology and laboratory medicine (research) and professor of pediatrics (research).
In 2016, Sharma, a leading preeclampsia researcher, and his team identified that preeclampsia and diseases like Alzheimer’s had similar root causes related to protein problems. This research is based on that finding.
Until now, cis P-tau was mainly associated with neurological disorders such as Alzheimer’s disease, traumatic brain injury (TBI), and stroke. This association was discovered by Lu and Zhou in 2015 as a result of decades of research into the role of the tau protein in cancer and Alzheimer’s.
An antibody developed by Zhou in 2012 to attack only the toxic protein and leave its healthy counterpart unharmed is currently in clinical trials in human patients suffering from TBI and Alzheimer’s disease. The antibody has shown promising results in animal models and human cell cultures in the treatment of brain conditions.
The researchers were curious to know if the same antibody could work as a potential treatment for preeclampsia. When testing the antibody in mouse models, they found surprising results.
“In this study, we found the cis The P-tau antibody efficiently depleted the toxic protein in the blood and placenta, and corrected all features associated with preeclampsia in mice. The clinical features of preeclampsia such as elevated blood pressure, excess protein in urine and fetal growth restriction, among others, were eliminated and the pregnancy was normal,” Sharma said.
Sharma and his team at Brown have been working on developing an assay for early detection of preeclampsia and therapies to treat the condition. He believes the findings of this study have brought them closer to their goal.
Black and Hispanic women are more susceptible
The tragic death of American track and field champion Tori Bowie earlier this year put a spotlight on preeclampsia, which disproportionately affects black and Hispanic women.
Bowie, 32, a gold, silver and bronze medalist at the 2016 Olympics, was found dead in her bed on May 2, 2023, while she was approximately eight months pregnant. According to the autopsy report, complications may have involved eclampsia, a severe form of preeclampsia.
“Research has shown that women of certain races have genes that could possibly lead to higher than average blood pressure levels, eventually creating conditions for preeclampsia during pregnancy. However, it is also true that in many low-level countries There is no registry to record PD cases, so its relationship with other environmental factors is still unclear,” Sharma said.
Preeclampsia and the brain
Recent research has also shed light on the long-term impacts of preeclampsia and its possible links to brain health.
“Preeclampsia poses immediate dangers to both mother and fetus, but its long-term effects are less understood and are still developing,” Sharma said. “Research has suggested an increased risk of dementia later in life for both mothers who have experienced preeclampsia and their children.” However, the causal link between preeclampsia and dementia is unknown.
Researchers say this new study has identified a possible underlying cause for the complex relationship between preeclampsia and brain health.
“Our study adds another layer to this complexity. For the first time, we have identified significant levels of cis P-tau outside the brain in the placenta and blood of patients with preeclampsia. “This suggests a deeper connection between preeclampsia and brain-related problems,” said Jash, lead author of the study.
As researchers dig deeper, the way our bodies respond to stress is also emerging as a potential factor in the onset of preeclampsia.
“While genetics play a role, factors like stress could be an important piece of the puzzle. Understanding how stress and other environmental factors intersect with biological markers like cis “P-tau may offer a more complete picture,” said Jash, assistant professor of molecular biology, cell biology and biochemistry (research), and pediatrics (research) at Brown.
A stress response enzyme called Pin1
In 1996 and 1997, Lu and Zhou made the groundbreaking discovery of Pin1, which turns out to be a stress response enzyme. It is a specific protein in cells that activates or changes its behavior in response to stressors, such as environmental challenges, toxins or physiological changes.
“Pin1 plays a critical role in maintaining proteins, including the tau protein, in their functional form during stress. When Pin1 is inactivated, it leads to the formation of a toxic and deformed variant of tau… cis P-tau,” said Zhou, associate professor of pathology and laboratory medicine at Schulich Medicine & Dentistry.
Interestingly, Pin1 is a key player in cancer signaling networks, activating numerous proteins that cause cancer and deactivating many that suppress it. It is found at high levels in most human cancers and is particularly active in cancer stem cells, which are believed to be critical in starting and spreading tumors and are difficult to target with existing treatments.
“Essentially, when Pin1 is activated, it can cause cancer. On the other hand, when there is a decrease or deactivation of Pin1, the formation of the toxic protein occurs. cis P-tau, which causes memory loss in Alzheimer’s and after traumatic brain injury or stroke. Now, we have also discovered its connection with preeclampsia,” Zhou said.
“The results have far-reaching implications. This could revolutionize the way we understand and treat a variety of conditions, from pregnancy-related problems to brain disorders,” Lu said.
Lu and Sharma met at Brown in 2019, where Lu was invited to give a lecture about his research. After an interesting session and some dinners together, a collaboration was forged between the Western researchers and Brown.
“The science surprises us. I had never thought about working to find a therapy for preeclampsia. It also shows that collaboration can be transformative.”
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