Technology

ISD-Immunotech is developing a first-in-class therapy to treat the most severe Systemic lupus erythematosus (SLE)  patients. The therapy works by dampening the action of an intracellular protein called STimulator of INterferon Genes (STING). STING is part of the innate immune system, the body’s first line of defense against pathogen invaders like bacteria and viruses. When activated, STING ramps up production of inflammatory proteins called interferons and cytokines. STING overactivity has recently been linked to severe SLE. SLE is an autoimmune disease that can affect any organ of the body including the skin, joints, heart, kidneys, lungs, nervous system and others. As immune cells attack the body, inflammation, scarring, and permanent damage ensue, leading to worsened function and sometimes even organ failure and death.

Source: Membranous lupus nephritis showing thickened glomerular basement membrane. International Society of Nephrology/Renal Pathology Society 2003 class V (×200, silver stain).

Today there is no drug that can significantly alter the disease for severe SLE patients.  ISD has shown that our lead prevents the development of SLE in a mouse model of SLE and reduces the interferon signature in a benchtop test of human patient blood samples.  ISD-Immunotech's approach is unique in targeting STING, a new molecular target for SLE, eliciting dampening of multiple events implicated in SLE including IFN-1 levels, other cytokines and apoptosis for broader efficacy. Furthermore, ISD seeks to reduce the complexity of SLE clinical development by using a benchtop test to pre-select severe patients who respond the therapy instead of targeting the heterogenous SLE population. 

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• Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations  J Clin Invest. 2014;124(12):5516-5520. https://doi.org/10.1172/JCI79100.

• Structures of STING protein illuminate this key regulator of inflammation, Published online: 06 March 2019; doi:10.1038/d41586-019-00707-8

Tara Heitner

CEO

Kristian Hansen

CDO

Prof. Søren Riis Paludan

CSO

Publications

Scientific Papers 

Articles by Betty Diamond

• Porat, A., Giat, E., Kowal, C., He, M., Son, M., Latz, E., Ben-Zvi, I., Al-Abed, Y., … Diamond, B. (2018). DNA-Mediated Interferon Signature Induction by SLE Serum Occurs in Monocytes Through Two Pathways: A Mechanism to Inhibit Both Pathways. Frontiers in immunology, 9, 2824. doi:10.3389/fimmu.2018.02824

• Malkiel, S., Barlev, A. N., Atisha-Fregoso, Y., Suurmond, J., & Diamond, B. (2018). Plasma Cell Differentiation Pathways in Systemic Lupus Erythematosus. Frontiers in immunology, 9, 427. doi:10.3389/fimmu.2018.00427

• Suurmond, J., Calise, J., Malkiel, S., & Diamond, B. (2016). DNA-reactive B cells in lupus. Current opinion in immunology, 43, 1-7.

• Bhattacharya, J., Pappas, K., Toz, B., Aranow, C., Mackay, M., Gregersen, P. K., Doumbo, O., Traore, A. K., Lesser, M. L., McMahon, M., Utset, T., Silverman, E., Levy, D., McCune, W. J., Jolly, M., Wallace, D., Weisman, M., Romero-Diaz, J., … Diamond, B. (2018). Serologic features of cohorts with variable genetic risk for systemic lupus erythematosus. Molecular medicine (Cambridge, Mass.), 24(1), 24. doi:10.1186/s10020-018-0019-4

Articles by Søren Riis Paludan

• Luecke, S., Holleufer, A., Christensen, M. H., Jønsson, K. L., Boni, G. A., Sørensen, L. K., Johannsen, M., Jakobsen, M. R., Hartmann, R., … Paludan, S. R. (2017). cGAS is activated by DNA in a length-dependent manner. EMBO reports, 18(10), 1707-1715.

• Holm, C. K., Rahbek, S. H., Gad, H. H., Bak, R. O., Jakobsen, M. R., Jiang, Z., Hansen, A. L., Jensen, S. K., Sun, C., Thomsen, M. K., Laustsen, A., Nielsen, C. G., Severinsen, K., Xiong, Y., Burdette, D. L., Hornung, V., Lebbink, R. J., Duch, M., Fitzgerald, K. A., Bahrami, S., Mikkelsen, J. G., Hartmann, R., … Paludan, S. R. (2016). Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses. Nature communications, 7, 10680. doi:10.1038/ncomms10680

• Christensen, M. H., & Paludan, S. R. (2016). Viral evasion of DNA-stimulated innate immune responses. Cellular & molecular immunology, 14(1), 4-13.

About iSD Immunotech

iSD Immunotech is a spin-out of Aarhus University, Denmark and is dedicated to developing the first efficacious treatment - a targeted molecular therapy for the most severe SLE patients.

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