Rheumatoid arthritis is the most common inflammatory joint disorder, affecting over 60,000 people in Austria alone, with women being three times as likely to suffer from the condition as men. While treatment advances over the past decades have led to the development of numerous drugs with varying mechanisms of action, many patients still fail to achieve clinical remission due to a lack of tools to help find the right treatment, leaving their symptoms inadequately controlled.
Clinicians are left with a "trial-and-error" approach to therapy, where one drug is tested after another. While some biomarkers exist to help predict treatment outcomes, they are not yet suitable for routine clinical use or require invasive procedures.
In a long-standing collaboration, the team led by Giulio Superti-Furga at CeMM and the Medical University of Vienna has, for the first time, tested a precision medicine method that could enable more targeted and accurate therapy selection for rheumatoid arthritis and likely other autoimmune diseases. The findings, published in EBioMedicine (DOI: 10.1016/j.ebiom.2024.105522), represent a major step forward in this field.
Cell Types Influence Disease and Therapy
The method is based on cutting-edge microscopy technology capable of generating and analysing vast amounts of imaging data in a fully automated manner. Developed at CeMM under the name "Pharmacoscopy"1, 2, it enables the direct measurement of drug effects on a wide variety of individual immune cells—a task that would be far too labour-intensive to perform at this scale using conventional molecular biology techniques. Additionally, it allows the observation of drug effects without the need to elucidate the underlying molecular mechanisms.
In the current study, the microscopy method was combined with a so-called "ex vivo" stimulation process. Immune cells from blood samples from patients are treated outside the body ("ex vivo") with medications used for rheumatoid arthritis, and the effects of the drugs on immune cells are analysed microscopically.
Through this approach, the researchers could take a snapshot of the behaviour of immune cells in various conditions allowing for the identification of so-called "cellular phenotypes," that correlate with disease activity and therapeutic response. These phenotypes could potentially be used in the future to predict the success of different treatments on a blood sample before administering them to patients.
"The presented work is the first showcase for the application of imaging-based ex vivo screening in combination with ex vivo drug treatment as an approach to rheumatic diseases. This forms the basis for the future development of novel assays for precision medicine and preferential treatment selection," explains Felix Kartnig, a PhD student in the group of Giulio Superti-Furga at CeMM and first author of the study.
"The establishment of this tool and its proof of concept forms a formidable scientific basis for the evaluation of this technology in the context of envisioned clinical trials and therefore highlights the value of innovative translational research." states Leonhard Heinz co-corresponding author and principal investigator at the Division of Rheumatology of the Medical University of Vienna.
"Our approach is a remarkable example for a precision medicine of the future," says study leader Giulio Superti-Furga. "Once again, our long-standing collaboration with the Medical University of Vienna has proven fruitful. We demonstrated that systematic and fully automated analyses of drug effects on individual cells can provide valuable insights into the mechanisms of action in human therapies."
