Inflammatory diseases like rheumatoid arthritis, Crohn’s disease, and ulcerative colitis have complex disease mechanisms that can differ from patient to patient with the same diagnosis. Now, researchers at Karolinska Institute report a potential path of personalized treatment of inflammatory diseases. Using digital twins, the researchers have obtained a deeper understanding of the “off and on” proteins that control these diseases.

The findings are published in the journal Cell Reports Medicine in a paper entitled “Multi-organ single cell analysis reveals an on/off switch system with potential for personalized treatment of immunological diseases.”

“Prioritization of disease mechanisms, biomarkers, and drug targets in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions between thousands of genes,” wrote the researchers.” Our multi-organ single-cell RNA sequencing of a mouse IMID model, namely collagen-induced arthritis, shows highly complex and heterogeneous expression changes in all analyzed organs.”

The researchers report the solution lies in molecular programs.

“Our analyses of patients who responded or didn’t respond to TNF therapy revealed different switch proteins in different individuals,” says the study’s corresponding author Mikael Benson, researcher at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet. “Another important discovery was that the proteins did not switch off the diseases but were more like dimmer switches that raised or lowered the disease programs.”

“The methods can be developed to tailor the right combination of drugs for “on” proteins for individual patients,” Benson added. “The programs we describe will be made available to the research community so that more clinical studies can be done of patients with different immune diseases.”

In the current study, the researchers combined analyses of a mouse model of rheumatoid arthritis and digital twins of human patients with various inflammatory diseases.

“Even though only the joints were inflamed in mice, we found that thousands of genes changed their activity in different cell types in ten organs, including the skin, spleen, liver and lungs,” said Benson. “As far as I’m aware, this is the first time science has obtained such a broad picture of how many organs are affected in rheumatoid arthritis. This is partly due to the difficulty of physically sampling so many different organs.”

The study was done in close collaboration with Linköping University in Sweden, Harvard University and other universities in the U.S., China and Korea.

Previous articleThe State of Global Fermentation
Next articleAlzheimer’s Model Mice Treated Using Targeted Protein Degradation