ArticleJCI insight2019
Bitopertin, a selective oral GLYT1 inhibitor, improves anemia in a mouse model of β-thalassemia.
Article in JCI insight, 2019. 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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The trial behind it
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- Safety and pharmacodynamics of the ferroportin inhibitor vamifeport in patients with non-transfusion-dependent β-thalassemia: results from a randomized phase 2a study.Orphanet journal of rare diseases · 2025Trial
- Results from the first clinical trial of bitopertin for steroid-relapsed/refractory Diamond-Blackfan anemia.Blood red cells & iron · 2026Article
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Multiomics analysis of red blood cells reveals thalassemia severity beyond globin gene mutations.Blood advances · 2026Article
- The GLYT1 inhibitor bitopertin mitigates erythroid PPIX production and liver disease in erythroid protoporphyria.The Journal of clinical investigation · 2025Article
- Restricting glycine uptake with bitopertin improves erythropoiesis in preclinical models of Diamond-Blackfan anemia.Blood red cells & iron · 2025Article
- Mitapivat metabolically reprograms human β-thalassemic erythroblasts, increasing their responsiveness to oxidation.Blood advances · 2025Article
- HRI protein kinase in cytoplasmic heme sensing and mitochondrial stress response: Relevance to hematological and mitochondrial diseases.The Journal of biological chemistry · 2025Review
- Mitoxantrone ameliorates ineffective erythropoiesis in a β-thalassemia intermedia mouse model.Blood advances · 2024Article
- Nrf2 Plays a Key Role in Erythropoiesis during Aging.Antioxidants (Basel, Switzerland) · 2024Article
- Preliminary screening of biomarkers and drug candidates in a mouse model of β-thalassemia based on quasi-targeted metabolomics.Frontiers in physiology · 2024Article
- AZD8055 Is More Effective Than Rapamycin in Inhibiting Proliferation and Promoting Mitochondrial Clearance in Erythroid Differentiation.Analytical cellular pathology (Amsterdam) · 2024Article
- Novel potential therapeutics to modify iron metabolism and red cell synthesis in diseases associated with defective erythropoiesis.Haematologica · 2023Review
- In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell-Related Injury.HemaSphere · 2023Article
- Erythroid Cell Research: 3D Chromatin, Transcription Factors and Beyond.International journal of molecular sciences · 2022Review
- Redox Balance in β-Thalassemia and Sickle Cell Disease: A Love and Hate Relationship.Antioxidants (Basel, Switzerland) · 2022Review
- Advancing the care of β-thalassaemia patients with novel therapies.Blood transfusion = Trasfusione del sangue · 2022Review
- Iron, Heme Synthesis and Erythropoietic Porphyrias: A Complex Interplay.Metabolites · 2021Review
- The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model.The Journal of clinical investigation · 2021Article
- Therapeutic targeting of Lyn kinase to treat chorea-acanthocytosis.Acta neuropathologica communications · 2021Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 4 countries.
Funding
Abstract
Anemia of β-thalassemia is caused by ineffective erythropoiesis and reduced red cell survival. Several lines of evidence indicate that iron/heme restriction is a potential therapeutic strategy for the disease. Glycine is a key initial substrate for heme and globin synthesis. We provide evidence that bitopertin, a glycine transport inhibitor administered orally, improves anemia, reduces hemolysis, diminishes ineffective erythropoiesis, and increases red cell survival in a mouse model of β-thalassemia (Hbbth3/+ mice). Bitopertin ameliorates erythroid oxidant damage, as indicated by a reduction in membrane-associated free α-globin chain aggregates, in reactive oxygen species cellular content, in membrane-bound hemichromes, and in heme-regulated inhibitor activation and eIF2α phosphorylation. The improvement of β-thalassemic ineffective erythropoiesis is associated with diminished mTOR activation and Rab5, Lamp1, and p62 accumulation, indicating an improved autophagy. Bitopertin also upregulates liver hepcidin and diminishes liver iron overload. The hematologic improvements achieved by bitopertin are blunted by the concomitant administration of the iron chelator deferiprone, suggesting that an excessive restriction of iron availability might negate the beneficial effects of bitopertin. These data provide important and clinically relevant insights into glycine restriction and reduced heme synthesis strategies for the treatment of β-thalassemia.
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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.