In a development that could transform how doctors diagnose and monitor various diseases, researchers at Case Western Reserve University have identified specific chemical markers that could lead to blood tests detecting inflammation in specific organs. The finding addresses a longstanding challenge in medicine: while inflammation plays a role in nearly every disease, current blood tests cannot pinpoint which organs or tissues are affected.
The research, published today in the Proceedings of the National Academy of Sciences (PNAS), centers on compounds formed during inflammatory processes that leave distinct chemical signatures in different parts of the body.
“This research opens up an amazing number of pathways for future studies,” said Greg Tochtrop, professor of chemistry at Case Western Reserve who led the investigation. “It will lead directly to better understanding inflammation and detecting diseases, as well as to discovering new drugs.”
The discovery focuses on how reactive oxygen species (ROS) – highly reactive chemicals produced by immune cells to fight pathogens – interact with fatty acids found in cell membranes. These interactions create compounds called epoxyketooctadecanoic acids (EKODEs) that accumulate differently in various tissues experiencing oxidative stress, from the brain to the heart and liver.
The potential implications extend beyond just detection. The approach could mirror the widely-used A1C test for diabetes, which measures glucose-bound hemoglobin to track blood sugar levels over three months. Similarly, an EKODE-based test could reveal abnormal oxidative stress patterns unique to specific organs, potentially flagging early signs of conditions like heart disease, Alzheimer’s, and various cancers before they become severe.
The path to this discovery required significant innovation in the laboratory. “We had to develop many of the tools in the lab to search for them in the first place,” Tochtrop explained. His team synthesized model compounds and methodically studied their reactions with different amino acids, ultimately finding that the amino acid cysteine formed lasting bonds with EKODEs.
The work has drawn attention from pharmaceutical researchers, as identifying reactive cysteines has become increasingly important in drug development. “Identifying reactive cysteines is central to drug discovery right now,” Tochtrop noted. “This could help uncover many reactive cysteines that could be targeted for drug discovery, which is a valuable offshoot of our research.”
Environmental factors like ultraviolet light, pollution, radiation, and smoking can also generate the ROS that lead to EKODE formation, suggesting potential applications in monitoring exposure to environmental stressors. The research team validated their findings using both mouse models and human tissues, developing antibodies that could detect different types of EKODEs and their varying concentrations across different organs.
Looking ahead, Tochtrop’s team is particularly focused on identifying EKODE markers associated with eye conditions like age-related macular degeneration and diabetic retinopathy. These conditions, which can lead to vision loss, might be detected earlier through blood tests based on this research.
The approach reflects a fundamental shift in how researchers might detect disease-specific biomarkers. “We looked at the inherent chemistry of the system, predicted what would form and then searched for them,” Tochtrop said. “There are very important translational implications, but this is an example of how looking at things from first principles can really inform the next steps to developing clinical tests.”
As the research progresses, the next phase involves correlating specific EKODE patterns with particular diseases, potentially leading to a new generation of diagnostic tools that could detect inflammation with unprecedented precision. For patients and healthcare providers, this could mean earlier detection and more targeted treatment approaches for a wide range of inflammatory conditions.
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