Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 49 · Cited by 69
Research works printed but not linked: 3
- [43]Wun T, Paglieroni T, Rangaswami A, Gosselin R, Cheung ATW (1999) Platelet-monocyte aggregates (PMA) in patients with sickle cell disease. Blood 94: 198A– 198A. 11985552
- [45]Flanner H, Kramer W, Magnani JL, Thackray H (2009) Single and Multiple Ascending Dose Pharmacokinetics of the Novel Pan Selectin Antagonist GMI-1070 after Intravenous Infusions of 2, 5, 10, 20 and 40 Mg/Kg to Healthy Volunteers. Journal of Clinical Pharmacology 49: 1105– 1105.
- [46]Flanner HH, Kramer WG, Thackray HM, Magani JL (2010) Single Dose Pharmacokinetics of the Novel Pan Selectin Antagonist GMI-1070 after Intravenous Infusions to Adults with Sickle Cell Disease. Journal of Clinical Pharmacology 50: 1081– 1081.
- Authors
- Wun, T., Styles, L., DeCastro, L., Telen, M. J., Kuypers, F., Cheung, A., Kramer, W., Flanner, H., Rhee, S., Magnani, J. L., & Thackray, H.
- Affiliations
- VA Northern California Health Care System (US)
- University of Pittsburgh (US)
- University of California Davis Medical Center (US)
- GlycoMimetics (United States) (US)
- Rho (United States) (US)
- Corresponding author
- Wun, Ted
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-07-02
- Volume
- 9
- Issue
- 7
- Pages
- e101301
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4079300
- OpenAlex
- W2034914402
- Cited by
- 69
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 5 · 2021: 8 · 2020: 3 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 12 · 2015: 12 · 2014: 1
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-10-17)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UL1TR000002)
- University of California, Davis
- National Center for Advancing Translational Sciences (#TR 000002)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- sickle cell disease, vascular occlusion, leukocyte adhesion, drug safety, pharmacokinetics, leukocyte activation, tissue factor, thrombin-antithrombin complex, intravital microscopy
- MeSH terms
- Adult, Anemia, Sickle Cell, Blood Flow Velocity, Female, Glycolipids, Humans, Leukocytes, Male, Middle Aged, E-Selectin, Young Adult, Administration, Intravenous
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
