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Updated: Apr 27, 2026
Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium
Published on: February 11, 2009
Phase 1 study of the E-selectin inhibitor GMI 1070 in patients with sickle cell anemia
Ted Wun1, Lori Styles2, Laura DeCastro3
1Division of Hematology Oncology, University of California Davis School of Medicine, Sacramento, California, United States of America; Clinical and Translational Sciences Center, UC Davis School of Medicine, Sacramento, California, United States of America; Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Sacramento, California, United States of America; VA Northern California Health Care System, Sacramento, California, United States of America.
Background:
Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease.
Methods:
We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions.
Results:
The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied.
Conclusions:
GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing.
Trial Registration:
ClinicalTrials.gov NCT00911495.
