ArticleThe Journal of clinical investigation2021
The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 75 citations in OpenAlex.
- Long-term efficacy and safety of mitapivat in non-transfusion-dependent α- or β-thalassaemia: An open-label phase 2 study.British journal of haematology · 2025Trial
- Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency.Blood advances · 2024Trial
- Contemporary Management of Thalassemia: A Perspective on Current Standards and the Emergence of FDA-Approved Oral Therapy.Health science reports · 2026Article
- Thalassaemia.Nature reviews. Disease primers · 2026Review
- Article
- Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026Review
- CCND3 Suppression Ameliorates β-Thalassaemia in a Murine Disease Model: A Potential Therapeutic Strategy.Cells · 2026Article
- Pyruvate kinase deficiency modifies sickle hemoglobin carrier and sickle cell disease phenotypes in mice.JCI insight · 2026Article
- Case series: a rare dominant form of β-thalassemia successfully treated by luspatercept.Annals of hematology · 2026Article
- SNH-119014, a novel pyruvate kinase activator, enhances ATP production and reduces oxidative stress in erythroid cells from patients with β-thalassemia major.Frontiers in pharmacology · 2026Article
- Fertility and endocrinopathies among adults with β-thalassemia major treated at Dubai thalassemia center.Frontiers in endocrinology · 2026Observational
- Unveiling molecular mechanisms and therapeutic targets in HbH-CS disease: a focus on oxidative stress and mitochondrial dysfunction.Open life sciences · 2026Article
- Genetic Engineering in Hematopoietic Stem Cells for β-Hemoglobinopathies Treatment: Advances, Challenges, and Clinical Translation.International journal of hematology-oncology and stem cell research · 2025Review
- Luspatercept versus mitapivat for non-transfusion-dependent β-thalassemia: Dare to compare?HemaSphere · 2025Article
- Mitapivat metabolically reprograms human β-thalassemic erythroblasts, increasing their responsiveness to oxidation.Blood advances · 2025Article
- Cholesterol-conjugated miR-29b induces fetal haemoglobin expression via γ-globin promoter demethylation in the Townes mouse model for sickle cell anaemia.British journal of haematology · 2025Article
- Premature skeletal muscle aging in VPS13A deficiency relates to impaired autophagy.Acta neuropathologica communications · 2025Article
- Are Mitochondria a Potential Target for Treating β-Thalassemia?Journal of clinical medicine · 2025Review
- Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation.Blood advances · 2024Article
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anemia in β-thalassemia is related to ineffective erythropoiesis and reduced red cell survival. Excess free heme and accumulation of unpaired α-globin chains impose substantial oxidative stress on β-thalassemic erythroblasts and erythrocytes, impacting cell metabolism. We hypothesized that increased pyruvate kinase activity induced by mitapivat (AG-348) in the Hbbth3/+ mouse model for β-thalassemia would reduce chronic hemolysis and ineffective erythropoiesis through stimulation of red cell glycolytic metabolism. Oral mitapivat administration ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice. Increased ATP, reduced reactive oxygen species production, and reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance suggested enhanced metabolism following mitapivat administration in β-thalassemia. The amelioration of responsiveness to erythropoietin resulted in reduced soluble erythroferrone, increased liver Hamp expression, and diminished liver iron overload. Mitapivat reduced duodenal Dmt1 expression potentially by activating the pyruvate kinase M2-HIF2α axis, representing a mechanism additional to Hamp in controlling iron absorption and preventing β-thalassemia-related liver iron overload. In ex vivo studies on erythroid precursors from patients with β-thalassemia, mitapivat enhanced erythropoiesis, promoted erythroid maturation, and decreased apoptosis. Overall, pyruvate kinase activation as a treatment modality for β-thalassemia in preclinical model systems had multiple beneficial effects in the erythropoietic compartment and beyond, providing a strong scientific basis for further clinical trials.
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