Actelion's efforts in the field of selective S1P1 receptor modulation started in 1999 by focusing on receptors found on the endothelium, the inner lining of blood vessels.
In the presence of a selective S1P1 receptor modulators, lymphocytes lose their ability to sense S1P concentration gradients. As a consequence, selective S1P1 receptor modulators block lymphocyte migration out of lymphoid tissue into the lymphatic and blood circulation, thereby reducing peripheral lymphocyte counts and preventing lymphocyte recruitment to sites of inflammation.
This new strategy for therapeutic immunomodulation offers potential advantages over existing therapies. Sequestration of T cells in lymphoid organs is expected to prevent the processes that contribute to inflammatory diseases, such as tissue invasion, local cytokine release, macrophage recruitment, and direct cell killing, while sparing functions that do not rely on homing mechanisms. These include antibody generation by B lymphocytes, first-line immunological protection by neutrophils and monocytes, and antigen-dependent T cell activation and expansion.