Breakthrough Finding: How a Bacterial Molecule Coudl Revolutionize Sepsis Treatment
Sepsis, a life-threatening condition triggered by the body’s extreme response to infection, claims approximately 8 million lives annually. Now, researchers at Oregon Health & Science University (OHSU) have uncovered a critical link between a bacterial molecule and the deadly blood clotting that often accompanies sepsis. Their findings,published in the Journal of Biological Chemistry,could pave the way for groundbreaking treatments to save millions of lives.
The Role of Lipopolysaccharide in Sepsis
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At the heart of this discovery is lipopolysaccharide (LPS), a molecule found on the surface of certain bacteria, including E. coli. The OHSU team, led by Owen McCarty, Ph.D., a professor of biomedical engineering in the OHSU school of Medicine, found that LPS can directly activate proteins in the blood that trigger clotting. This process, known as the “contact pathway,” involves a chain reaction where proteins work together to form clots, potentially blocking blood flow and damaging vital organs.
“Your blood normally forms tiny clots to contain certain bacteria to clear them from the bloodstream,” McCarty explained. “But if there are too many bacteria, the system gets overwhelmed, using up all the platelets and clotting factors. The result is catastrophic — you can’t stop clotting or bleeding.”
The researchers identified a specific type of LPS, called O26:B6, as especially effective at initiating this clotting cascade. This discovery sheds light on why sepsis patients often experience disseminated intravascular coagulation (DIC), a condition characterized by simultaneous widespread clotting and bleeding.
sepsis: A Global Health Crisis
Sepsis occurs when the body’s immune response to an infection spirals out of control, leading to widespread inflammation, organ failure, and, in severe cases, death. Gram-negative bacteria, such as E.coli, are common culprits because they release LPS when they invade the bloodstream. This molecule not only triggers inflammation but also activates the clotting pathway, exacerbating the condition.
The OHSU team’s research, conducted in the cardiovascular engineering lab, highlights the dual role of LPS in sepsis.By understanding how LPS drives clotting, researchers hope to develop targeted therapies that can interrupt this deadly process.
Implications for Treatment
The findings could lead to new interventions for sepsis, a condition that currently lacks effective treatments.By targeting the contact pathway or specific types of LPS, such as O26:B6, scientists might potentially be able to prevent the excessive clotting and bleeding that frequently enough prove fatal in sepsis patients.
This research builds on previous studies linking coagulopathy (a disorder of blood clotting) to sepsis outcomes. For instance,a 2021 study highlighted how coagulopathy ranges from mild thrombocytopenia to severe DIC, underscoring the need for precise therapeutic strategies.
Key Findings at a glance
| Key Insight | Details |
|————————————-|—————————————————————————–|
| Molecule Studied | Lipopolysaccharide (LPS) on bacteria like E. coli |
| Clotting Mechanism | Activation of the contact pathway by LPS |
| Critical LPS Type | O26:B6,which is highly effective at triggering clotting |
| Clinical Impact | Potential to prevent DIC and improve sepsis outcomes |
| Research Team | OHSU’s cardiovascular engineering lab,led by Owen McCarty,Ph.D. |
A Call to Action
The OHSU team’s work is a significant step forward in the fight against sepsis, but much remains to be done. As McCarty and his colleagues continue to explore the mechanisms of LPS-induced clotting, their findings could inspire new clinical trials and therapeutic approaches.For now, their research offers hope to millions of patients and families affected by this devastating condition.
To learn more about the groundbreaking work being done at OHSU, visit their biomedical engineering department.—
This article is based on research published in the Journal of Biological Chemistry and insights from the OHSU team.For further reading, explore the full study here.
Targeting Factor XII: A Promising Approach to Combat Sepsis Without Causing Bleeding
Sepsis, a life-threatening condition triggered by infections, remains a significant challenge in modern medicine. Though, groundbreaking research led by scientists at Oregon Health & Science University (OHSU) is shedding light on a potential solution: targeting factor XII, a protein involved in blood clotting. This innovative approach could help prevent dangerous clots in sepsis patients without increasing the risk of bleeding.
The Role of Factor XII in Sepsis
Sepsis occurs when the body’s response to an infection spirals out of control,leading to widespread inflammation and blood clotting. This imbalance can cause organ failure and death.Researchers have long focused on the contact activation system, a part of the clotting cascade that includes factor XII.
“People who are born without factor XII are healthy and don’t bleed abnormally,” said Joseph shatzel, M.D., a physician-scientist at OHSU specializing in clotting and bleeding disorders. “That makes it a great target for therapies — blocking it might help stop dangerous clots without causing bleeding.”
Shatzel, an associate professor of biomedical engineering at the OHSU School of Medicine and a researcher at the OHSU Knight Cancer Institute, has been instrumental in bridging the gap between lab research and patient care. His work focuses on translating innovative discoveries into treatments that can directly benefit patients.
how Bacteria Trigger Clotting
The study, conducted in nonhuman primates, revealed that when bacteria containing lipopolysaccharide (LPS) enter the bloodstream, they rapidly activate the clotting system. This includes proteins like factor XII, which initiates a chain reaction leading to clot formation.
André L. Lira, Ph.D., a postdoctoral scholar and lead author of the study, explained that his research focuses on how the physical properties of bacterial surfaces trigger this clotting response. “Even when we know the bacteria causing the infection, different strains can behave differently,” he said. “By understanding this, we hope to develop precision therapies.”
Experimental Treatments Targeting Factor XII
The OHSU team is developing experimental treatments that target factor XII, including antibodies designed to block its activity. This builds on their previous work targeting factor XI, another protein in the clotting cascade. Their research on factor XI has already advanced to human clinical trials, with promising results published in 2023.
By focusing on factor XII, the team aims to create therapies that can prevent the dangerous clotting seen in sepsis without disrupting the body’s ability to stop bleeding. This dual benefit makes factor XII an attractive target for future treatments.
Key Insights from the Study
| Key Finding | Implication |
|————————————-|———————————————————————————|
| Factor XII initiates clotting in sepsis | Blocking it could prevent dangerous clots without increasing bleeding risk. |
| Bacterial LPS activates clotting | Understanding this mechanism could lead to precision therapies for infections. |
| Factor XII deficiency is harmless | People without factor XII are healthy,making it a safe therapeutic target. |
A Path Forward
The OHSU team’s work represents a significant step forward in the fight against sepsis. By targeting factor XII,they hope to develop treatments that can save lives without the side effects of traditional anticoagulants.
“The systems that control blood clotting and bleeding become dangerously unbalanced in sepsis,” Shatzel said. “Our group has focused on part of the clotting system that has traditionally been ignored. My personal work has been to take the innovation from this lab and bring it directly to the patients.”
As research continues,the potential for factor XII-targeted therapies to revolutionize sepsis treatment grows. With further development, these treatments could offer hope to millions of patients worldwide.
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For more details on the OHSU Knight Cancer Institute and their groundbreaking research, visit their official website.
Breakthrough Antibody Therapy Offers Hope for Sepsis Patients
Sepsis, a life-threatening condition triggered by the body’s extreme response to infection, claims millions of lives annually. Despite its devastating impact, treatment options have remained stagnant for decades. Now, a team of researchers at Oregon Health & Science University (OHSU) is pioneering a groundbreaking approach using antibody therapy to combat sepsis-related blood clotting without increasing the risk of bleeding.
“We’re optimistic that this approach could prevent dangerous clots in sepsis patients without increasing their risk of bleeding,” said Owen McCarty, one of the lead researchers.
The antibodies, developed at OHSU, have shown promising results in early-stage clinical trials and animal models. “We’ve seen promising results,” said André Lira, another key researcher. “The antibodies seem to stop the clotting caused by certain bacterial infections without harming the patient’s ability to heal.”
The Urgency for New Sepsis therapies
Sepsis is a global health crisis, with mortality rates in the U.S. reaching as high as 50%. “The mortality rate of sepsis in the United States can be as high as 50%,and there haven’t been major breakthroughs in decades,” said Joseph Shatzel,a clinician involved in the research. “We’re still treating it with antibiotics, supportive care, maybe steroids to modulate the immune system, but it is not developed like oncology. We don’t have targeted therapies that really improve outcomes. This research could be a game-changer.”
The interdisciplinary team at OHSU includes basic scientists, clinicians, and researchers from institutions like the oklahoma Medical Research Foundation, Case Western Reserve University, and Vanderbilt University Medical Centre. Their collaborative efforts span from lab research to clinical trials, creating a unique environment for innovation.
“This is one of the rare programs that truly spans the gap between lab research and patient care,” Shatzel said. “we’re working from test tubes to animal models to clinical trials — it’s all happening here.”
A Collaborative Approach to Innovation
McCarty emphasized the importance of the team’s diverse expertise. “We have basic scientists like André, who think about the physics of how bacteria interact with blood, and clinicians like Joe, who see the real-world challenges in the ICU,” he said.“That kind of collaboration is what makes breakthroughs possible.”
The research has been supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases, both part of the National Institutes of Health. These funds have enabled the team to advance their studies and explore the potential of their antibody therapy.
What’s Next?
the team is now focused on ongoing studies and grant applications to fund further research and clinical trials. “We’re excited about the potential impact this could have,” Lira said.“There’s a long way to go,but the possibility of helping patients drives us forward.”
Key Points at a Glance
| aspect | Details |
|————————–|—————————————————————————–|
| therapy | Antibody therapy targeting sepsis-related blood clotting |
| current Stage | Early-stage clinical trials and animal models |
| potential Impact | Prevents clotting without increasing bleeding risk |
| Mortality rate | Up to 50% in the U.S. |
| Funding | Supported by NIH grants |
| Collaborators | OHSU, oklahoma Medical Research Foundation, Case Western, Vanderbilt |
Clarity and Integrity
OHSU is committed to maintaining the integrity of its research. Christina U. lorentz and Erik I. Tucker, employees of Aronora, Inc., and Joseph Shatzel, a medical consultant for the company, have disclosed their affiliations. Aronora,Inc. may have a commercial interest in the results of this research. For more details, review OHSU’s conflict of interest program.
This breakthrough in sepsis treatment offers a glimmer of hope for patients and healthcare providers alike. As the research progresses, the potential to save lives and improve outcomes becomes increasingly tangible.
Stay informed about the latest advancements in medical research by following OHSU’s updates.At Oregon Health & Science University (OHSU), the welfare of animal research subjects is a top priority. All research involving animals must undergo a thorough review and approval process by the university’s Institutional Animal Care and Use Committee (IACUC). This committee ensures that the health and safety of both the animals and the researchers are upheld to the highest standards.
The IACUC’s mission is clear: to rigorously evaluate every animal research proposal.Their goal is to confirm that the studies demonstrate significant scientific value and justify the use of live animals.“The IACUC’s priority is to ensure the health and safety of animal research subjects,” states the university’s guidelines.Additionally, the committee reviews procedures to safeguard the well-being of the people who work with these animals.This meticulous process reflects OHSU’s commitment to ethical research practices. By balancing scientific advancement with animal welfare,the university sets a benchmark for responsible research.
| Key Responsibilities of the IACUC |
|—————————————|
| Review and approve all animal research proposals |
| Ensure the health and safety of animal subjects |
| Safeguard the well-being of researchers |
| Confirm scientific value and ethical justification of studies |
For more information on OHSU’s research protocols, visit their official research page. The IACUC’s rigorous standards ensure that OHSU remains a leader in ethical and impactful scientific research.
Here’s a summary of the key insights and potential advancements in sepsis treatment, focusing on Factor XII as a therapeutic target:
key Insights from the Study
| Key Finding | Implication |
|————————————-|———————————————————————————|
| Factor XII initiates clotting in sepsis | Blocking it could prevent perilous clots without increasing bleeding risk. |
| bacterial LPS activates clotting | understanding this mechanism could lead to precision therapies for infections. |
| Factor XII deficiency is harmless | People without factor XII are healthy, making it a safe therapeutic target. |
A Path Forward
The OHSU team’s research represents a critically important step forward in the fight against sepsis.By targeting Factor XII, they aim to develop treatments that save lives without the side effects of traditional anticoagulants.
- Quote from Shatzel:
“The systems that control blood clotting and bleeding become dangerously unbalanced in sepsis. Our group has focused on part of the clotting system that has traditionally been ignored. My personal work has been to take the innovation from this lab and bring it directly to the patients.”
As research progresses, Factor XII-targeted therapies hold the potential to revolutionize sepsis treatment, offering hope to millions of patients worldwide.
Breakthrough Antibody Therapy Offers Hope for Sepsis Patients
Sepsis, a life-threatening condition triggered by infection, claims millions of lives annually. The OHSU team is pioneering an antibody therapy targeting Factor XII, which shows promise in preventing sepsis-related blood clotting without increasing bleeding risk.
- Early-stage trials and animal models have demonstrated promising results.
- Quote from McCarty:
“We’re optimistic that this approach could prevent dangerous clots in sepsis patients without increasing their risk of bleeding.”
- Quote from Lira:
“The antibodies seem to stop the clotting caused by certain bacterial infections without harming the patient’s ability to heal.”
The Urgency for New Sepsis Therapies
With mortality rates in the U.S. as high as 50%, sepsis remains a global health crisis. Current treatments are limited to antibiotics and supportive care, lacking targeted therapies to improve outcomes.
- Quote from Shatzel:
“This research could be a game-changer.”
A Collaborative Approach to Innovation
The OHSU team brings together basic scientists, clinicians, and researchers from institutions like:
- Oklahoma Medical Research Foundation
- Case Western Reserve University
- Vanderbilt University Medical Center
Supported by grants from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases, the team bridges the gap between lab research and patient care.
What’s Next?
The team is focused on ongoing studies and grant applications to fund further research and clinical trials.
Key Points at a Glance
| Aspect | Details |
|————————–|—————————————————————————–|
| Therapy | antibody therapy targeting sepsis-related blood clotting |
| Current Stage | Early-stage clinical trials and animal models |
| target | Factor XII, a safe and effective clotting inhibitor |
| Collaborators | OHSU, OMRF, Case Western, Vanderbilt |
| Funding | National Institutes of Health (NIH) grants |
| Impact | Potential to revolutionize sepsis treatment and save lives globally |
For more details on the OHSU Knight Cancer Institute and their groundbreaking research, visit their official website.
