GMI-1070: Pan-selectin antagonist treatment of sickle cell disease

GMI-1070 is a rationally designed carbohydrate molecule created as an antagonist of all selectin proteins. Selectins are adhesion molecules expressed by many hematopoietic and endothelial cells. They mediate early stages of cell adhesion and are therefore critical in a wide variety of cell-cell interactions, including hematopoietic stem cell interactions with the bone marrow microenvironment, lymphocyte homing to lymphoid tissue, inflammatory leukocyte adhesion to the endothelium, and cancer cell adhesion during metastasis. In sickle cell disease, both red cell and leukocyte adhesion appears to be at least partially selectin-dependent, suggesting that blockade of selectin-mediated interactions might ameliorate or prevent vaso-occlusive events. GMI-1070 has been shown to have activity in many of these processes in a variety of in vitro and in vivo models. In addition, it has been tested in humans in phase I studies, and it is now undergoing phase II evaluation in the setting of sickle cell disease vaso-occlusive events. This compound thus represents one of the earliest attempts at anti-adhesive therapy in sickle cell disease. Copyright © 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Duke Scholars

Author Marilyn Jo Telen Medicine, Hematology