Sujana Biotech is developing novel therapeutics for Inflammatory and Vascular Diseases
Binding of the leukocyte-expressed integrin macrophage-1 antigen (Mac-1) to platelet-expressed glycoprotein Ibα (GPIbα) is a key event mediating inflammation-associated transmigration of leukocytes out of the vasculature. The Scientific Founders, Dan Simon, Ed Plow, and Yunmei Wang have shown that the strong interaction between Mac-1 and GPIbα is critically dependent on a short segment of Mac-1 (“M2”). They have also demonstrated that M2 is not critical for the binding of Mac-1 to other important ligands such as fibrinogen, and that selective inhibition of the GPIbα interaction through M2-directed strategies is possible without effecting Mac-1 interactions with other binding partners. These observations suggest that novel therapeutics targeting M2 may inhibit a number of pathological inflammatory conditions without compromising other innate immune or hemostatic functions.
Preclinical studies in a variety of animal models indicate that leukocyte engagement of platelet GPIbα via Mac-1 is critical for the pathophysiological response to mechanical vascular injury, and also implicate the GPIba-Mac-1 interaction in the development and progression of thrombosis, vasculitis, glomerulonephritis and multiple sclerosis.
Collectively, the data advance the hypothesis that inflammation is broadly platelet-dependent, and that therapeutic strategies directed against M2 may offer an innovative, effective approach to diverse inflammatory diseases.