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Inflammation is a common factor across nearly all diseases, but traditional blood tests have limitations in identifying inflammation in particular organs or tissues within the body.
Researchers at Case Western Reserve University have pioneered a method that utilizes antibodies to detect inflammation, which could pave the way for blood tests targeting disease-specific biomarkers linked to conditions such as heart disease, Alzheimer’s disease, and various cancers. This innovative approach may also enhance drug discovery processes.
According to Greg Tochtrop, a chemistry professor at Case Western Reserve and the lead researcher of this study, “This research opens up an amazing number of pathways for future studies. It will lead directly to better understanding inflammation and detecting diseases, as well as to discovering new drugs.”
The findings of this research have been published in the journal Proceedings of the National Academy of Sciences (PNAS).
Inflammation Leaves a Trace
The research team, led by Tochtrop, made a significant discovery regarding specific compounds that arise from interactions with reactive oxygen species (ROS). These highly reactive molecules can cause damage to essential cellular components, including DNA, proteins, and lipids. During inflammatory responses, immune cells produce ROS to combat bacteria and pathogens, but these reactive species can also emerge from external sources such as pollution, UV radiation, and smoking, potentially causing damage to cells.
In their investigations, Tochtrop and his colleagues focused on the reaction of ROS with linoleic acid, a fat found in cell membranes. This interaction results in the formation of compounds known as epoxyketooctadecanoic acids (EKODEs), which have the capability to bind with RNA, DNA, and proteins.
An intriguing aspect of this research is Tochtrop’s finding that EKODEs react uniquely with the nucleic acid cysteine, leading to stable bonds that accumulate in tissues undergoing oxidative stress, including vital organs like the brain, heart, and liver. By developing antibodies aimed at detecting these EKODEs, the team was able to quantify their presence in both mouse models and human tissues.
“What makes this so interesting and so potentially valuable,” Tochtrop noted, “is that we could detect unique compounds and concentrations in different tissues and organs. This means there is potential to identify a range of diseases through a simple blood test.”
This test could function similarly to the A1C test used for diabetes, which gauges the percentage of hemoglobin coated with glucose, reflecting glucose levels over the past three months. In a similar way, an EKODE test could indicate abnormal oxidative stress in specific organs.
Searching for Disease-Specific Biomarkers
Tochtrop indicated that the next steps involve identifying various EKODE targets associated with distinct organs and diseases. He expressed particular interest in the EKODEs linked to age-related macular degeneration and diabetic retinopathy, both conditions that significantly impact vision.
Reflecting on why these biomarkers had not been previously identified, Tochtrop explained, “We had to develop many of the tools in the lab to search for them in the first place.”
The team synthesized EKODE model compounds and examined their reactions with different amino acids, concluding that cysteine is the only one to form stable bonds with EKODE for extended durations.
“Our approach was based on understanding the underlying chemistry of the system, predicting possible products, and then searching for them,” Tochtrop said. “There are substantial translational implications, showcasing how a fundamental perspective can steer future clinical test development.”
Potential for Discovering New Drugs
This research not only offers potential insights into disease detection but also stands to impact drug discovery efforts, particularly concerning reactive cysteines sought by pharmaceutical developers.
“Identifying reactive cysteines is currently a critical focus in drug discovery,” Tochtrop explained. “Our findings could reveal numerous reactive cysteines to target for new drug development, representing a valuable extension of our research.”
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