Fibrin deposition and impaired fibrinolysis has long been implicated as a driver of chronic inflammation secondary to loss of vascular integrity in a large number of central nervous system (CNS) and peripheral inflammatory diseases. However, a lack of understanding of the cellular and molecular innate immune mechanisms responsible for fibrin-driven inflammation and an inability to target the inflammatory aspects of fibrin, while sparing any downstream impact on its role in hemostasis has prevented therapeutic intervention along this axis.
We are harnessing the unique insights that we possess at Therini Bio along with our founder, Dr. Katerina Akassoglou, Senior Investigator, Gladstone Institutes and Professor of Neurology, UCSF, to progress fibrin-targeting therapies that solve for these issues. Our therapies block fibrin-mediated inflammatory activation of the innate immune system specifically in diseased tissue, sparing any systemic immunosuppression to the patient, and without any impact on the hemostatic function of fibrin.
Coagulation and immunity: Caught in the fibrin web
Sozmen EG, Akassoglou K.
Immunity. 2021 Nov 9;54(11):2439-2441.
The immunology of blood: connecting the dots at the neurovascular interface
Nat Immunol. 2020 Jul;21(7):710-712.
Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model
Merlini M, Rafalski VA, Rios Coronado PE, Gill TM, Ellisman M, Muthukumar G, Subramanian KS, Ryu JK, Syme CA, Davalos D, Seeley WW, Mucke L, Nelson RB, Akassoglou K.
Neuron. 2019 Mar 20;101(6):1099-1108.
Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration
Ryu JK, Rafalski VA, Meyer-Franke A, Adams RA, Poda SB, Rios Coronado PE, Pedersen LØ, Menon V, Baeten KM, Sikorski SL, Bedard C, Hanspers K, Bardehle S, Mendiola AS, Davalos D, Machado MR, Chan JP, Plastira I, Petersen MA, Pfaff SJ, Ang KK, Hallenbeck KK, Syme C, Hakozaki H, Ellisman MH, Swanson RA, Zamvil SS, Arkin MR, Zorn SH, Pico AR, Mucke L, Freedman SB, Stavenhagen JB, Nelson RB, Akassoglou K.
Nat Immunol. 2018 Nov;19(11):1212-1223.
Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics
Petersen MA, Ryu JK, Akassoglou K. Fibrinogen in neurological diseases: mechanisms, imaging, and therapeutics.
Nat Rev Neurosci. 2018, 19(5):283-301.
Fibrinogen as a key regulator of inflammation in disease
Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease.
Semin Immunopathol. 2012. 34:43-62.