ArticleBlood2021
Treatment of sickle cell disease by increasing oxygen affinity of hemoglobin.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 82 citations in OpenAlex.
- Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease.American journal of hematology · 2025Trial
- One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study.Blood advances · 2023Trial
- Nanozymes for Advanced Hemoglobin-Based Oxygen Carriers: Applications in Blood Substitution, Wound Healing, Antitumor Therapy, and Beyond.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mitapivat for sickle cell disease: the time is ripe for a new therapy.Annals of translational medicine · 2026Article
- Updated Review of Current Therapeutic Approaches for the Management of Sickle Cell Disease.Cardiovascular & hematological disorders drug targets · 2026Review
- Potent Antisickling Furaldehyde Analogs for Acute Sickle Cell Therapy: Enhanced Efficacy and Intravenous Formulation Potential.ChemMedChem · 2025Article
- Discovery of Osivelotor (GBT021601): A Potent, Next-Generation Sickle Hemoglobin Polymerization Inhibitor.ACS medicinal chemistry letters · 2025Article
- Accelerated drug approvals and patient trust: impact of voxelotor and crizanlizumab for sickle cell disease.Blood advances · 2025Article
- A retrospective research of adverse event reporting system events for voxelotor based on the FAERS database.BMC pharmacology & toxicology · 2025Article
- Therapeutic potential of the latest oxygen affinity-modifying agent, GBT021601, for treating sickle cell disease is questionable.British journal of haematology · 2024Article
- Sickle Cell Hemoglobin "Drugged" with Cyclic Peptides Is Aggregation Incompetent.The journal of physical chemistry. B · 2024Article
- Article
- Effect of voxelotor on murine bone marrow and peripheral blood with hematopoietic progenitor cell mobilization for gene therapy of sickle cell disease.Blood cells, molecules & diseases · 2024Article
- A framework of computer vision-enhanced microfluidic approach for automated assessment of the transient sickling kinetics in sickle red blood cells.Frontiers in physics · 2024Article
- Therapeutics for sickle cell disease intravascular hemolysis.Frontiers in physiology · 2024Review
- Hope on the Horizon: New and Future Therapies for Sickle Cell Disease.Journal of clinical medicine · 2023Review
- Voxelotor does not inhibit sickle hemoglobin fiber formation upon complete deoxygenation.Biophysical journal · 2023Article
- SGK1 inhibition induces fetal hemoglobin expression and delays polymerization in sickle erythroid cells.Blood advances · 2023Article
- Resveratrol, a New Allosteric Effector of Hemoglobin, Enhances Oxygen Supply Efficiency and Improves Adaption to Acute Severe Hypoxia.Molecules (Basel, Switzerland) · 2023Article
- Neuregulin-1 attenuates hemolysis- and ischemia induced-cerebrovascular inflammation associated with sickle cell disease.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2023Article
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12 authors at 2 institutions in 1 country.
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Abstract
The issue of treating sickle cell disease with drugs that increase hemoglobin oxygen affinity has come to the fore with the US Food and Drug Administration approval in 2019 of voxelotor, the only antisickling drug approved since hydroxyurea in 1998. Voxelotor reduces sickling by increasing the concentration of the nonpolymerizing, high oxygen affinity R (oxy) conformation of hemoglobin S (HbS). Treatment of sickle cell patients with voxelotor increases Hb levels and decreases indicators of hemolysis, but with no indication as yet that it reduces the frequency of pain episodes. In this study, we used the allosteric model of Monod, Wyman, and Changeux to simulate whole-blood oxygen dissociation curves and red cell sickling in the absence and presence of voxelotor under the in vivo conditions of rapid oxygen pressure decreases. Our modeling agrees with results of experiments using a new robust assay, which shows the large, expected decrease in sickling from the drug. The modeling indicates, however, that the increase in oxygen delivery from reduced sickling is largely offset by the increase in oxygen affinity. The net result is that the drug increases overall oxygen delivery only at the very lowest oxygen pressures. However, reduction of sickling mitigates red cell damage and explains the observed decrease in hemolysis. More importantly, our modeling of in vivo oxygen dissociation, sickling, and oxygen delivery suggests that drugs that increase fetal Hb or decrease mean corpuscular hemoglobin concentration (MCHC) should be more therapeutically effective than drugs that increase oxygen affinity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.