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Systems biology for battling rheumatoid arthritis: Application of the Entelos PhysioLab platform

Systems biology for battling rheumatoid arthritis: Application of the Entelos PhysioLab platform

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A large-scale mathematical model, the Entelos® Rheumatoid Arthritis (RA) PhysioLab® platform, has been developed to describe the inflammatory and erosive processes in afflicted joints of people suffering from RA. The platform represents the life cycle of inflammatory cells, endothelium, synovial fibroblasts, and chondrocytes, as well as their products and interactions. The interplay between these processes culminates in clinically relevant measures for inflammation and erosion. The simulation model is deterministic, which allows tracing back the mechanism of action for a particular simulation result. Different patient phenotypes are represented by different virtual patients. The RA PhysioLab platform has been used to systematically and quantitatively study the predicted therapeutic effect of modulating several molecular targets, which resulted in a ranking of putative drug targets and a workflow to confirm the simulations experimentally. In addition, critical pathways were identified that drive the predicted disease outcome. Within these pathways, targets were identified from public literature that were not previously associated with arthritis. The model provides insights into the biology of RA and can be used as a platform for hypothesis-driven research. Case studies of therapies directed against IL-12 and IL-15 illustrate the approach, with emphasis on the analysis of system dynamics.

Inspec keywords: bone; biomechanics; physiological models; drugs; cellular biophysics; diseases; wear

Other keywords: molecular targets; afflicted joints; synovial fibroblasts; chondrocytes; putative drug targets; systems biology; Entelos PhysioLab platform; rheumatoid arthritis; erosion; inflammation; large-scale mathematical model; inflammatory cells; endothelium

Subjects: General, theoretical, and mathematical biophysics; Mechanical properties of tissues and organs; Biology and medical computing; Patient care and treatment; Cellular biophysics

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