ArticleBlood cells, molecules & diseases2022
Mitapivat increases ATP and decreases oxidative stress and erythrocyte mitochondria retention in a SCD mouse model.
Article in Blood cells, molecules & diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026Review
- Mitapivat for sickle cell disease: the time is ripe for a new therapy.Annals of translational medicine · 2026Article
- Pyruvate kinase deficiency modifies sickle hemoglobin carrier and sickle cell disease phenotypes in mice.JCI insight · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Erythropoiesis in health and disease: Distinguishing defective and ineffective erythropoiesis.HemaSphere · 2026Review
- Mitochondrial retention and autophagy dysregulation drive oxidative stress in sickle cell disease erythrocytes.Experimental hematology · 2025Article
- Mitapivat-Associated Adverse Effects and Potential Mechanistic: Insights From Real-World Data.Journal of cellular and molecular medicine · 2025Article
- Article
- Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia.Haematologica · 2025Article
- Are Mitochondria a Potential Target for Treating β-Thalassemia?Journal of clinical medicine · 2025Review
- Article
- Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation.Scientific reports · 2024Article
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
- Beyond adenosine triphosphate: unveiling the pleiotropic effects of pyruvate kinase activation in sickle cell anemia.Haematologica · 2024Article
- Biopreservation and Reversal of Oxidative Injury During Blood Storage by a Novel Curcumin-based Gel Formulation.Research square · 2024Article
- Article
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport.Frontiers in physiology · 2024Review
- Pyruvate kinase activators: targeting red cell metabolism in sickle cell disease.Hematology. American Society of Hematology. Education Program · 2023Article
- Mitapivat reprograms the RBC metabolome and improves anemia in a mouse model of hereditary spherocytosis.JCI insight · 2023Article
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Authors and funding
22 authors at 7 institutions in 1 country.
Funding
Abstract
Polymerization of deoxygenated sickle hemoglobin (HbS) leads to erythrocyte sickling. Enhancing activity of the erythrocyte glycolytic pathway has anti-sickling potential as this reduces 2,3-diphosphoglycerate (2,3-DPG) and increases ATP, factors that decrease HbS polymerization and improve erythrocyte membrane integrity. These factors can be modulated by mitapivat, which activates erythrocyte pyruvate kinase (PKR) and improves sickling kinetics in SCD patients. We investigated mechanisms by which mitapivat may impact SCD by examining its effects in the Townes SCD mouse model. Control (HbAA) and sickle (HbSS) mice were treated with mitapivat or vehicle. Surprisingly, HbSS had higher PKR protein, higher ATP, and lower 2,3-DPG levels, compared to HbAA mice, in contrast with humans with SCD, in whom 2,3-DPG is elevated compared to healthy subjects. Despite our inability to investigate 2,3-DPG-mediated sickling and hemoglobin effects, mitapivat yielded potential benefits in HbSS mice. Mitapivat further increased ATP without significantly changing 2,3-DPG or hemoglobin levels, and decreased levels of leukocytosis, erythrocyte oxidative stress, and the percentage of erythrocytes that retained mitochondria in HbSS mice. These data suggest that, even though Townes HbSS mice have increased PKR activity, further activation of PKR with mitapivat yields potentially beneficial effects that are independent of changes in sickling or hemoglobin levels.
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