Applied precision medicine: High-tech microscopy enables tailored rheumatology therapies

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.”

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Cited Literature:

1: Vladimer, G., Snijder, B., Krall, N. et al. Global survey of the immunomodulatory potential of common drugs. Nat Chem Biol 13, 681–690 (2017). https://doi.org/10.1038/nchembio.2360
2: Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study

Snijder, Berend et al. The Lancet Haematology, Volume 4, Issue 12, e595 - e606

Pictures attached:

1: The authors of the study Giulio Superti-Furga, Felix Kartnig, and Leonhard Heinz (f.l.t.r.) © Andreas Angermayr / CeMM2: The authors of the study Giulio Superti-Furga, Felix Kartnig, and Leonhard Heinz (f.l.t.r.) © Andreas Angermayr / CeMM
3: Example image of the high-throughput microscopy method used in the study, showing individual blood cells stained with different fluorescence markers. © Felix Kartnig / CeMM / MedUni Vienna

The Study “Ex vivo imaging-based high content phenotyping of patients with rheumatoid arthritis” was published in eBioMedicine on December 26, 2024. DOI: 10.1016/j.ebiom.2024.105522

Authors: Felix Kartnig, Michael Bonelli, Ulrich Goldmann, Noemi Mészáros, Nikolaus Krall, Daniel Aletaha, Leonhard X. Heinz, and Giulio Superti-Furga.

Funding: This work was supported by the Austrian Academy of Sciences, the Medical University of Vienna and a grant (RMG2235 to L.X.H.) from the European Alliance of Associations for Rheumatology (EULAR).

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The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences is an international, independent and interdisciplinary research institution for molecular medicine under the scientific direction of Giulio Superti-Furga. CeMM is oriented towards medical needs and integrates basic research and clinical expertise to develop innovative diagnostic and therapeutic approaches for precision medicine. Research focuses on cancer, inflammation, metabolic and immune disorders, rare diseases and aging. The Institute's research building is located on the campus of the Medical University and the Vienna General Hospital.

www.cemm.at

The Medical University of Vienna (MedUni Vienna) is one of the longest-established medical education and research facilities in Europe. With almost 8,600 students, it is currently the largest medical training centre in the German-speaking countries. With more than 6,500 employees, 30 departments and two clinical institutes, twelve medical theory centres and numerous highly specialized laboratories, it is one of Europe's leading research establishments in the biomedical sector. MedUni Vienna also has a medical history museum, the Josephinum.

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