Extending on our previous work on the treatment of arthritis with combination therapies of dasatinib with subtherapeutic doses of anti-TNF biologics, we explore here in this collaborative research project the interplay of inflammation and senescence in the context of combination treatments.
Published in Mechanisms of Ageing and Development 2023, 214, 111856.
In the frame of a collaborative project co-financed by the European Union and Greek national funds (BreastCaRANKL project code: T1EDK-02829), Biomedcode has collaborated with Dr. Douni’s lab at BSRC Al. Fleming and the companies Bioemtech and Protavio to develop an innovative human-RANKL dependent breast cancer mouse model aiming to study RANKL dependent breast cancer mechanisms and to establish novel integrated preclinical platforms with modules of advanced imaging and molecular analysis for the evaluation of human therapeutics targeting cancer.
Published in Cancers 2023, 15(15), 4006.
In the frame of a collaborative drug development project scientists from Biomedcode and BSRC Al. Fleming using bioinformatics tools, have repurposed the neuroleptic drug amisulpride for the reversal of the pathogenic expression signature of synovial fibroblasts and the treatment of arthritis pathology.
Published in JCI Insight 2023 May 8;8(9):e165024. doi: 10.1172/jci.insight.165024.
Our paper in Journal of Translational Medicine shows that combination of dasatinib and other kinase inhibitors with a subtherapeutic anti‐hTNF dose effectively treats arthritis pathology.
Published in Journal of Translational Medicine 2021 Apr 23;19(1):165. doi: 10.1186/s12967-021-02764-y.
With a new publication in Arthritis Research and Therapy, entitled “Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis”, Biomedcode in collaboration with George Kollias Lab at BSRC Al. Fleming, introduce the TgA86 transmembrane TNF transgenic mouse as a novel model of human spondyloarthritis (SpA).
The authors show that the TgA86 mouse model develops spontaneously peripheral arthritis and axial pathologies that closely reproduce key pathogenic features of human SpA, including distinct stages of inflammation and ectopic new bone formation. This is a chronic and complex disease model that similar to human patients also develops extraarticular comorbidities such as heart valve pathology and systemic bone loss. As with human patients in the clinic, all the pathologies of the TgA86 mouse model are reversed following early treatment with anti-hTNF therapeutics.
This novel model of SpA that captures not only specific features, but also the complexity of human disease, can prove to be an invaluable translational tool in the study of SpA pathogenesis as well as in the evaluation of human therapeutics.
Published in Arthritis Research and Therapy 2020 Oct 6;22(1):232. doi: 10.1186/s13075-020-02327-4.
Scientists of Biomedcode present in PLOS Computational Biology a new computational framework revealing key differences between four rheumatoid arthritis medications and their impact on biological pathways in mice.
Published in PLoS Computational Biology 2019 May 9;15(5):e1006933. doi: 10.1371/journal.pcbi.1006933
Patients with rheumatoid arthritis and spondyloarthritis show higher mortality rates, mainly caused by cardiac comorbidities. The TghuTNF (Tg197) arthritis model develops tumour necrosis factor (TNF)-driven and mesenchymal synovial fibroblast (SF)-dependent polyarthritis. Here, we investigate whether this model develops, similarly to human patients, comorbid heart pathology and explore cellular and molecular mechanisms linking arthritis to cardiac comorbidities.
Published in Annals of Rheumatic Diseases 2018 Jun;77(6):926-934. doi: 10.1136/annrheumdis-2017-212597.
Mesenchymal TNF signaling is etiopathogenic for inflammatory diseases such as rheumatoid arthritis and spondyloarthritis (SpA). The role of Tnfr1 in arthritis has been documented; however, Tnfr2 functions are unknown. Here, we investigate the mesenchymal-specific role of Tnfr2 in the TnfΔARE mouse model of SpA in arthritis and heart valve stenosis comorbidity by cell-specific, Col6a1-cre-driven gene targeting. We find that TNF/Tnfr2 signaling in resident synovial fibroblasts (SFs) and valvular interstitial cells (VICs) is detrimental for both pathologies, pointing to common cellular mechanisms. In contrast, systemic Tnfr2 provides protective signaling, since its complete deletion leads to severe deterioration of both pathologies. SFs and VICs lacking Tnfr2 fail to acquire pathogenic activated phenotypes and display increased expression of antiinflammatory cytokines associated with decreased Akt signaling.
Published in JCI Insight 2018 Apr 5;3(7):e98864. doi: 10.1172/jci.insight.98864
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Biomedcode coauthors a publication in the Journal of Proteome Research on the identification of a biomarker with translational value for the diagnosis and monitoring of rheumatoid arthritis disease and therapy.
Published in Journal of Proteome Research 2016 Dec 2;15(12):4579-4590. doi: 10.1021/acs.jproteome.6b00654.
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