Case Western Reserve University-led researchers have pioneered a method to detect organ-specific inflammation using antibodies. This breakthrough promises advancements in diagnosing diseases such as heart disease, Alzheimer’s and cancer, as well as aiding drug discovery.
Researchers led by Case Western Reserve University have developed a novel method to detect inflammation in specific organs and tissues, potentially revolutionizing how diseases like heart disease, Alzheimer’s and cancer are diagnosed.
Nearly all diseases have inflammation at their core. However, current blood tests fall short of pinpointing where inflammation occurs.
Now, the team has identified a way to use antibodies to detect inflammation, which may lead to the development of disease-specific biomarkers. This advancement could also fuel new drug discoveries.
“This research opens up an amazing number of pathways for future studies,” corresponding author Greg Tochtrop, a professor of chemistry at Case Western Reserve, said in a news release. “It will lead directly to better understanding inflammation and detecting diseases, as well as to discovering new drugs.”
Published in the Proceedings of the National Academy of Sciences (PNAS), this research could mark a turning point in medical diagnostics and therapeutic development.
Detecting the Indelible Trace of Inflammation
When the body faces inflammation, it often results in producing highly reactive oxygen species (ROS). These molecules, while crucial for defending against pathogens, can inflict severe damage on DNA, proteins and lipids.
Exposure to factors like ultraviolet light, pollution and smoking can exacerbate ROS production, leading to oxidative stress.
Tochtrop and his team delved into the interaction between ROS and linoleic acid, a common fatty acid in cell membranes.
They discovered that this interaction produced unique compounds, known as epoxyketooctadecanoic acids (EKODEs), which bind firmly to cysteine, an amino acid. These stable compounds accumulate in various tissues affected by oxidative stress, such as the brain, heart,and liver.
Using mouse models, the researchers developed antibodies to detect different types of EKODEs, successfully identifying their presence in both mouse and human tissues.
“What makes this so interesting and so potentially valuable is that we could detect unique compounds and concentrations in different tissues and organs, which means that you could potentially detect a variety of diseases with a blood test,” Tochtrop added.
The envisioned test could function similarly to the A1C test for diabetes, which measures glucose-coated hemoglobin levels in the blood over a three-month period. An EKODE test could potentially reveal oxidative stress in specific organs.
On the Hunt for Disease-Specific Biomarkers
The next phase, according to Tochtrop, involves identifying specific EKODE targets in various organs to link them with particular diseases.
One area of interest includes EKODEs produced in the eye due to conditions like age-related macular degeneration or diabetic retinopathy.
“We had to develop many of the tools in the lab to search for them in the first place,” Tochtrop added, elaborating on why these biomarkers hadn’t been identified previously.
The researchers synthesized EKODE model compounds and examined their reactions with different amino acids, discovering that cysteine consistently formed a stable bond with EKODEs.
“We looked at the inherent chemistry of the system, predicted what would form, and then searched for them,” added Tochtrop. “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.”
Implications for Drug Discovery
Apart from diagnostic applications, this research could significantly impact drug discovery. With drug developers currently seeking reactive cysteines as drug targets, the research could unveil new reactive cysteines for therapeutic targeting.
“Identifying reactive cysteines is central to drug discovery right now. This could help uncover many reactive cysteines that could be targeted for drug discovery, which is a valuable offshoot of our research,” Tochtrop concluded.